Prognostic value of albumin-bilirubin score in hepatocellular carcinoma patients treated with Lenvatinib: A Real-world South Indian cohort study

Prognostic value of albumin-bilirubin score in hepatocellular carcinoma patients treated with Lenvatinib: A Real-world South Indian cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prognostic value of albumin-bilirubin score in hepatocellular carcinoma patients treated with Lenvatinib: A Real-world South Indian cohort study Merin Babu, Rakesh M.P, Princy Louis Palatty, Arun Valsan, Shine Sadasivan, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9161824/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background In advanced hepatocellular carcinoma (HCC), baseline liver function is crucial for predicting survival, therapeutic effectiveness, and safety outcomes. A proven, objective indicator of hepatic reserve, the albumin–bilirubin (ALBI) score may be a better indicator of prognosis for patients undergoing systemic therapy. Objective This study examines the effects of baseline Child Pugh score and ALBI grade on patients with hepatocellular cancer who were treated with lenvatinib. Methods All patients who received lenvatinib as a first- or second-line therapy for advanced HCC at our hospital between 2020 and 2024 were included in this retrospective study. The Child-Pugh score and ALBI grade were used to classify baseline liver function. The objective response rate (mRECIST), time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), and treatment discontinuation due to adverse events (AEs) were the primary outcomes evaluated. The patients were divided into four groups: Child-Pugh A5/ALBI 1, Child-Pugh A5/ALBI 2, Child-Pugh A6, and Child-Pugh ≥ 7. To identify determinants of response and discontinuation, univariate and multivariate analyses were conducted. Results The cohort's median overall survival (OS) and progression-free survival (PFS) were 27.4 months and 13.5 months, respectively. The OS (38.4 vs. 20.4 months) and PFS (15.3 vs. 11.5 months) of patients with ALBI grade 1 were considerably longer. Group 4 had the lowest survival rate, while Group 1 had the highest. The most frequent adverse events were fatigue (30%) and anorexia (22%). Disease progression was independently predicted by higher initial dosages and extrahepatic distribution. Conclusion The prognosis of HCC patients on lenvatinib was effectively stratified by baseline ALBI grade. The higher survival and tolerability of patients with preserved liver function (ALBI grade 1) suggest ALBI as a crucial adjunct to the Child-Pugh score in treatment planning. Hepatocellular carcinoma ALBI grade Child Pugh score Lenvatinib liver function real-world evidence Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 INTRODUCTION Globally, liver cancer, particularly hepatocellular carcinoma (HCC), ranks third in cancer-related mortality and sixth in terms of incidence¹. HCC is a formidable malignancy, frequently diagnosed at advanced stages, underscoring the critical need for effective prognostic indicators to guide therapeutic strategies 2 . In India, it ranks 11th in cancer incidence and 8th in mortality, with 38,703 new cases and 36,953 deaths annually 3 , 4 . In South India, MASLD has been identified as a significant etiological factor for HCC, surpassing the viral causes. Notably, 14.5% of biopsy samples revealed steatohepatitis coexisting with HCC, highlighting the metabolic basis of malignancy in this region. Musunuri et al 5 reported that over half of HCC cases in a tertiary-care cohort from coastal South India were cryptogenic/NAFLD-related, with many patients presenting at advanced BCLC stages and only a minority detected through surveillance. Similarly, the results from a large multicentre Kerala HCC survey conducted by Koshy et al 6 showed that 44% of HCC patients had metabolic syndrome or NAFLD, with a high prevalence of diabetes (64%) and hypertension (38%), and the majority of them presented at stages where curative therapy was not practical. These convergent datasets show that MASLD is a fast-increasing oncogenic driver in South India, highlighting the need for earlier surveillance mechanisms and improved metabolic risk classification. There is an evolving landscape involving a multi-disciplinary team in the treatment options available for various stages of liver cancer 7 . Targeted multi-kinase inhibitor therapy and immune checkpoint inhibitors are the systemic therapies for unresectable HCC. The paradigm for treating HCC has changed with the introduction of targeted treatments like lenvatinib 8 – 10 . Lenvatinib, a multi-potent tyrosine kinase inhibitor that targets the vascular endothelial growth factor receptors 1–3, fibroblast growth factor receptor 1–4, platelet-derived growth factor receptor α, RET, and KIT, has gained popularity over sorafenib after the REFLECT trial. The study showed lenvatinib had a tolerable safety profile, non-inferior overall survival, and a greater response rate in comparison to sorafenib 10 , 11 . The recent ASCO 2024 guidelines suggest the immune checkpoint inhibitors (Atezolizumab–bevacizumab/Durvalumab–tremelimumab) for Child-Pugh A patients with a good performance score of 0–1. Lenvatinib remains a vital option when the above therapies are contraindicated 12 . Real-world studies suggest that lenvatinib has demonstrated improved overall survival and a better safety profile in the HCC population. The response achieved with lenvatinib is, however, significantly influenced by the patients' baseline liver function. Deteriorated liver function not only limits the treatment options but can also increase the risk of adverse events and alter the well-being of the patient and his/her family 13 – 15 . The Child–Pugh scoring system is one of the traditional methods used to assess liver function and includes subjective parameters such as hepatic encephalopathy and ascites grading. However, considerable interobserver variability has been reported among clinicians, limiting its reproducibility. Due to this lack of objectivity and specificity, newer grading systems based on quantitative parameters—such as the albumin–bilirubin (ALBI) grade—were developed to provide a more standardized assessment of liver function 16 , 17 . The ALBI grade, a recently developed scoring system based on two objective biochemical parameters—serum albumin and bilirubin—is used for liver function assessment in patients with hepatic diseases, particularly HCC. It has emerged as a promising tool for risk stratification and prognostication in various liver diseases, including HCC 18 . Several studies have demonstrated the significance of the ALBI grade in predicting overall survival, guiding treatment strategies, and determining the toxicity profile in patients with HCC 18 . Studies from India consistently demonstrate that the ALBI grade offers better predictive discrimination than the conventional Child-Pugh score, especially for patients who are categorized as Child-Pugh A 19 . A real-world tertiary cancer center cohort presented at ASCO confirmed ALBI's stronger prognostic value in advanced HCC under systemic therapy 20 , while a retrospective cohort from Eastern India showed that ALBI more accurately stratified survival and liver-related complications than Child–Pugh 19 . These results are consistent with larger analyses conducted in Asia and South Asia, where ALBI consistently performs better than Child-Pugh in resection, trans arterial chemoembolization (TACE), and systemic-therapy settings 21 . Our study endeavours to evaluate the prognostic utility of the albumin-bilirubin score in a South Indian cohort of HCC patients undergoing lenvatinib treatment, addressing a critical regional gap in current literature. METHODS 2.1 Study design : The medical records of 502 consecutive patients diagnosed with advanced HCC and treated with lenvatinib as first /second line treatment between 2019 to 2024 at our institution were reviewed. This retrospective single-centre study was approved by the institutional ethics committee of Amrita School of Medicine, ECASM-AIMS-2021-293 on 15-06-2021, and was conducted as per the principles of the Declaration of Helsinki and guidelines of the Indian Council of Medical Research. 2.2 Inclusion criteria : Unresectable adult HCC patients substantiated by radiographic or histological findings, Barcelona Clinic Liver Cancer (BCLC) stage B or C; Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1; Child-Pugh score received lenvatinib as 1st or 2nd line therapy, were included. Exclusion criteria Patients were excluded if they had incomplete patient data history and were not willing to take part in the study. 2.3 Lenvatinib treatment regimen : Lenvatinib (Lenvima ®, Eisai Co Ltd, Tokyo, Japan; or Lentykine ®, Intas Pharmaceuticals; or Lenvat ®, Natco Pharma Ltd; or Adlante ®, Adley formulations) was given orally to advanced HCC patients. As per the Food and Drug Administration (FDA), the approved dose of oral lenvatinib was 8mg/day in patients with < 60kg body weight and 12 mg/day in patients with ≥ 60kg body weight. To prevent early cessation due to adverse events, a lower initial dose of lenvatinib is prescribed in patients with non-Child Pugh A illness, the elderly population, low body weight, pleural effusion, ascites, or gastrointestinal varices at risk of bleeding. Any unacceptable or severe side effects or clinical progression resulted in discontinuation of lenvatinib. In accordance with the lenvatinib administration recommended, patients who experienced grade ≥ 3 severe adverse events or any unacceptable grade 2 related adverse events had their drug dosage either decreased or their therapy stopped. The National Cancer Institute Common Terminology criteria for adverse events (CTCAE), version 5.0, were used to evaluate the adverse events. 2.5 Treatment Protocol Lenvatinib’s effectiveness and safety in treating individuals with incurable HCC were assessed by grouping patients based on their Child-Pugh score and ALBI grade. The patients were categorised into four groups: Group 1: Child-Pugh score A5, ALBI grade 1 Group 2: Child-Pugh score A5, ALBI grade 2 Group 3: Child-Pugh score A6 Group 4: Child-Pugh score A ≥ 7 (B or C) 2.6 Data Collection and Treatment Assessment Clinical, demographic, and treatment-related data were retrospectively collected from electronic medical records. The collected parameters included patient age, sex, aetiology of liver disease, ECOG performance status, Child–Pugh classification, and details of systemic therapy received. Laboratory data at baseline and during treatment were extracted for biochemical and pharmacokinetic analysis. ALBI score was calculated using serum albumin and bilirubin, thereby eliminating the subjective variables present in the Child–Pugh classification using the formula 14 : ALBI score= (log10 bilirubin ×0.66) +(albumin ×−0.085) where bilirubin is expressed in µmol/L and albumin in g/L . Patients were categorized into three grades based on the calculated score: Grade 1 : ≤ − 2.60 Grade 2 : > − 2.60 to ≤ − 1.39 Grade 3 : > − 1.39 Treatment response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) using dynamic contrast-enhanced CT or MRI scans. Imaging assessments were performed at baseline and at regular follow-up intervals as per institutional protocol. Efficacy outcomes were assessed using key clinical endpoints, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and time to treatment failure (TTF) defined as time from initial administration to the time of treatment failure, which can be either due to treatment discontinuation or progression or death). 2.7 Statistical analysis Statistical analysis was used using IBM SPSS version 20.00. Continuous variables are shown as medians (range). To test the statistical significance of the association of risk factors with dose reduction, progression, the Pearson chi-square test was applied. Multivariate logistic regression was done to examine the most significant risk factors after adjusting for the confounding factors. To find the survival probability of overall survival and progression-free survival, Kaplan Meier analysis was computed, and also comparison was also determined using log log-rank test. A p-value < 0.05 was considered to be statistically significant. RESULTS 3.1 Baseline characteristics of the study population A total of 502 patients with HCC were screened for eligibility between 2019 and 2024. Of these, 22 patients were excluded due to incomplete clinical data (n = 10), unwillingness to participate in the study (n = 5), or being second-opinion/one-time-visit cases (n = 7). After applying the exclusion criteria, 480 patients were finally included in the analysis (Fig. 1 ). Table 1 Baseline characteristics Characteristics Number Percentage Age Mean age, years (range) 65.11 ± 8.9 (27–90) Gender Male 441 91.9 Female 39 8.1 Aetiology MASLD 176 37 Alcohol 155 32.3 Unknown 107 22.3 Hepatitis B 30 6.25 Hepatitis C 14 3 Lenvatinib starting dose 4mg OD 340 70.8 8mg OD 126 26.3 12mg OD 14 2.9 Comorbidities Diabetes mellitus 339 70.6 Hypertension 246 51.2 Dyslipidaemia 65 13.5 Baseline liver function Median Total bilirubin (mg/dl) 1.08 Median Serum albumin (g/dl) 3.67 Median INR (sec) 1.14 Tumour markers Median Alpha feto protein (ng/ml) 29.72 Median PIVKA (mAU/ml) 1090.11 Child Pugh Score A5 227 47.3 A6 116 24.2 B7 44 9.2 B8 33 6.9 B9 32 6.7 C10 14 2.9 C11 12 2.5 C12 2 0.4 ALBI grade 1 154 32.1 2 269 56 3 57 11.9 BCLC score A 149 31 B 101 21 C 230 47.9 Site of tumour Right lobe 288 60 Left lobe 76 16 Both lobes 116 24 Number of liver lesions 1 177 36.9 2 174 36.3 3 63 13.1 > 3 66 13.8 Portal vein thrombosis Main trunk 27 5.6 Right anterior or posterior 56 11.7 Right or left 27 5.6 Segmental PV invasion 11 2.3 Extrahepatic spread Lymph node 20 4.2 Lung 16 3.3 Bone 6 1.2 Adrenal 2 0.4 Brain 1 0.2 Peritoneal 1 0.2 Cancer-directed therapies Total patients undergone cancer-directed therapies 325 67.7 MWA 93 29 TACE 86 26.4 RFA 55 17 SBRT 43 13.2 Liver resection 25 8 Liver transplantation 14 4.3 TARE 9 3 Abbreviations: MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease; INR - International Normalized Ratio; PIVKA-Protein Induced by Vitamin K Absence or antagonist-II; ALBI-Albumin-Bilirubin; BCLC - Barcelona Clinic Liver Cancer staging system; PV- portal vein; MWA-Microwave Ablation; TACE-Trans arterial chemoembolization; RFA-Radiofrequency ablation; SBRT-Stereotactic body radiation therapy; TARE-Trans arterial Radioembolization. A summary of 480 eligible patients with baseline characteristics is presented in Table 1. There were 39 females and 441 males, with a mean age was 65.11 years. The most common aetiology was MASLD in 176 (37%) and alcohol in 155 (32.3%), followed by hepatitis B in 30 (6.2%) and hepatitis C in 14 (3%). The majority of the patients (340, 70.8%) were started with a lower dose of lenvatinib 4mg OD, irrespective of the FDA guidelines, followed by 126 (26.3%) with 8mg OD. The most prevalent comorbidities were diabetes mellitus (70.6%) and hypertension (51.2%). The majority of patients belonged to Child Pugh Class A (71.5%), whereas ALBI grade 2 (56%) was the most prevalent. Of the cohort, nearly half (47.9%) were in BCLC stage C. Single or double focal lesions were the most common (73.2%), and the right lobe accounted for 60% of the tumour involvement. One hundred twenty-one patients (25.2%) had portal vein thrombosis, mainly in the right portal vein branches (11.7%), and 9.5% cases had an extrahepatic dissemination, mostly to the lymph nodes (4.2%) and lungs (3.3%). Microwave ablation (29%) and TACE (26.4%) were the most common cancer-directed therapies reported in 67.7% patients. (55.4%) 3.2 Association Between ALBI Grade and Child–Pugh Classification Of the 480 patients enrolled, 154 patients (32%) were classified as ALBI grade 1, 270 patients (56%) as ALBI grade 2, and 56 patients (12%) as ALBI grade 3 (Table 2). Most of the patients with ALBI grade 1 (144 out of 154 patients, 93.5%) had a Child Pugh score of A. Patients were categorised into 4 groups based on their Child Pugh score and ALBI grade (Table 3) Table 2: Correlation between the ALBI grade and Child Pugh score ALBI/Child Pugh score Child Pugh Score – n (%) 5 6 ≥ 7 Total ALBI grade 1 131 (85.1) 13 (8.4) 10 (6.5) 154 2 96 (35.7) 98 (36.4) 76 (28.2) 270 3 0 5 (8.8) 51 (89.5) 56 Total 227 116 137 480 Abbreviations: ALBI-Albumin-Bilirubin Table 3: Patient Distribution According to Child–Pugh Classification and ALBI Grade Group Group details N Group 1 Child Pugh score A5 with ALBI grade 1 131 Group 2 Child Pugh score A5 with ALBI grade 2 96 Group 3 Child Pugh score A6 with ALBI grade 1,2,3 116 Group 4 Child Pugh score ≥ 7 with ALBI grade 1,2,3 137 Abbreviations: ALBI-Albumin-Bilirubin 3.3 Response to lenvatinib Out of the 480 patients, only 373 (77.7%) were evaluable according to mRECIST criteria, as 107 patients did not undergo repeat imaging as recommended by the HCC management guidelines. Repeat imaging as per mRECIST was advised every six months; however, only a limited number of patients underwent imaging at the recommended interval, with many receiving follow-up scans only when liver function tests became abnormal or when clinical progression was suspected. No patient had a complete response, and only 9 (2.4%) had a partial response to lenvatinib treatment. Stable disease or progressive disease was observed in the majority of patients, 169 (45.3%) and 196 (52.5%), respectively. Tumour response to lenvatinib according to mRECIST is summarised in Table 4. Table 4: Tumour Response to lenvatinib According to mRECIST Criteria Group n PR SD PD Total evaluable DCR (%) Group 1 131 5 (55.6) 51 (30.2) 57 (29.1) 113 49.6 Group 2 96 2 (22.2) 41 (24.3) 42 (21.4) 84 51.2 Group 3 116 0 42 (25) 42 (21.4) 84 50.0 Group 4 137 2 (22.2) 55 (33) 55 (28.1) 92 61.9 Total 480 9 169 196 373 47.7 Abbreviations: ALBI-Albumin-Bilirubin; PR-Partial response; SD- stable disease; PD- progressive disease; DCR: disease control rate Group 1 (ALBI grade 1) demonstrated comparatively better disease control than the other groups. In particular, the disease control rate (DCR = PR + SD / total number of evaluable patients) for group 1 was 49%, whereas 51.2% for group 2, 50% for group 3, and 61.9% for group 4. Group 1 showed better clinical efficacy among the patients with preserved hepatic function. These findings suggest that, in comparison to patients with higher ALBI grades, group 1 represents patients with preserved liver function and better disease stabilisation during lenvatinib therapy. 3.4 Treatment modifications and discontinuations The dose modifications and therapy discontinued profiles for each of the four study groups are summarised in Table 5. Forty-two patients had a dose reduction, with group 1 having 36% followed by group 2 (29%) and group 3 (21.4%). Sixty-six individuals experienced drug interruptions, with group 4 experiencing the highest frequency (33.3%). Group 1 showed the highest likelihood of continued treatment (68, 29.2%), whereas treatment discontinuation due to adverse events/progression was more frequent in group 4 (53, 38.1%). Table 5: Dose Adjustment and Therapy Discontinuation Profile Group n DR DI DC due to adverse events DC due to progression Ongoing Group 1 131 15 (36) 17 (26) 7 (25) 24 (22) 68 (29.2) Group 2 96 12 (29) 14 (21.2) 3 (10.7) 23 (20) 44 (18.9) Group 3 116 9 (21.4) 13 (19.7) 10 (35.7) 19 (17) 65 (28) Group 4 137 6 (14.3) 22 (33.3) 8 (28.6) 45 (41) 56 (24) Total 480 42 66 28 111 233 Abbreviations: DR- Dose reduction; DI- Drug interruptions, DC-Discontinued 3.5 Survival outcomes (OS, PFS, and TTF) according to ALBI grade and Child Pugh score The median OS of the present study population was 27.4 months (95% CI 19.2 – 35.5 months). The median OS of patients with groups 1,2,3, and 4 were 38.4, 27.4,32 and 12 months, respectively, with a significant difference among the 4 groups (p <0.001) [Figure 2]. The median OS of patients with ALBI grade 1 and ALBI grade ≥ 2 were 38.4 and 20.4 months, respectively (p <0.001) [Figure 3]. The median PFS of patients with groups 1,2,3, and 4 were 15, 14.1,10 and 9.7 months, respectively, with a significant difference among the 4 groups (p = 0.03) [Figure 4]. The median PFS of patients with ALBI grade 1 and ≥ 2 were 15.3 and 11.5 months, respectively (p = 0.022) [Figure 5]. The median survival was 17 months (95% CI 14 – 20.1 months). Kaplan Meier estimates of TTF according to ALBI grade and Child Pugh score are shown in Figure 6. The median TTF was 19, 19.4, 17, and 14.4 months in groups 1,2,3, and 4, respectively. Liver function according to the ALBI grade and Child Pugh score was significantly associated with TTF patients of group 2 had the longest TTF, whereas the group 4 patients had the shortest TTF (p = 0.023). 3.6 Treatment-related adverse events stratified by ALBI grade The distribution of treatment-related adverse events among patients categorised by ALBI is shown in Table 6. Patients with ALBI grade 2 had a higher overall incidence of any grade adverse events than those with grade 1, but those with ALBI grade 3 had fewer total adverse events, which is probably due to shorter treatment duration and lower hepatic reserve. The most frequent adverse event in the present study population was fatigue (144, 30%); loss of appetite (106, 22.1%); hand-foot skin reaction (66, 14%); elevated aspartate aminotransferase/ alanine transaminase (49,10.2%); abdominal pain (39, 8.1%), and mucositis (39, 8.1%). Table 6: Comparison of Treatment-related Adverse Events Among ALBI Grades Adverse events ALBI grade 1 (n = 154) ALBI grade 2 (n = 270) ALBI grade 3 (n = 56) Any grade Grade ≥ 2 Any grade Grade ≥ 2 Any grade Grade ≥ 2 Fatigue 46 3 84 7 14 0 Loss of appetite 24 1 61 4 16 2 HFSR 21 9 41 20 4 1 Elevated AST/ALT 8 0 27 1 14 1 Abdominal pain 7 0 28 2 4 0 Mucositis 10 0 27 4 2 0 Hypoalbuminemia 9 4 16 6 12 6 Loss of weight 14 1 20 1 1 0 Constipation 9 0 18 0 2 0 Ascites 2 0 16 0 9 1 Diarrhoea 6 1 19 2 2 0 Edema 3 0 17 0 1 0 Dysphonia 8 0 10 1 0 0 Hyperbilirubinemia 3 0 11 1 2 1 Abbreviations: ALBI-Albumin-Bilirubin; HSFR- Hand–Foot Skin Reaction ; AST- Aspartate Aminotransferase; ALT- Alanine Aminotransferase The most often reported adverse event, mostly of grade 1 severity among ALBI grade 1 patients, was fatigue (29.9%), loss of appetite (15.6%), and HFSR (13.6%). These adverse events were similarly prevalent in ALBI grade 2, whereas grade ≥ 2 events, such as HFSR (7.4%), fatigue (2.6%), and hypoalbuminemia (2.2%), were more prevalent. Overall, patients with ALBI grade 1 showed a decreased likelihood of experiencing severe (grade ≥ 2) adverse events, indicating that hepatic function preservation may improve the treatment tolerance and lessen the risk of toxicity during lenvatinib therapy. 3.7 Univariate and multivariate analysis Univariate logistic regression was performed to evaluate the association between baseline clinical variables and lenvatinib discontinuation. Factors assessed included age, sex, viral aetiology, AFP levels, BCLC stage, ALBI grade, portal vein thrombosis, number of focal lesions, extrahepatic spread, and initial dose. In the univariate analysis, the presence of portal vein thrombosis (OR = 1.56; 95% CI: 0.99–2.46; p = 0.052), multiple focal lesions (OR = 1.51; 95% CI: 0.97–2.35; p = 0.064), and extrahepatic spread (OR = 1.82; 95% CI: 0.93–3.56; p = 0.078) showed a trend toward higher odds of discontinuation, though not statistically significant. Variables with p < 0.1 in the univariate analysis were included in the multivariate logistic regression model. In the multivariate analysis, none of the factors retained statistical significance; however, portal vein thrombosis (adjusted OR = 1.47; 95% CI: 0.93–2.33; p = 0.097), extrahepatic spread (adjusted OR = 1.75; 95% CI: 0.89–3.46; p = 0.107), and multiple focal lesions (adjusted OR = 1.49; 95% CI: 0.95–2.33; p = 0.079) remained near-significant predictors of lenvatinib discontinuation (Supplementary material 1). With regard to factors contributing to disease progression, the results of univariate analysis suggest that both initial dose and extrahepatic spread showed a statistically significant association with disease progression (p < 0.001 for both). Patients receiving higher initial doses (8 or 12 mg) had an increased likelihood of progression (OR = 2.10, 95% CI 1.39–3.16), and those with extrahepatic spread demonstrated a markedly higher risk (OR = 3.69, 95% CI 1.79–7.63). The multivariate analysis confirmed initial dose (OR = 1.95, 95% CI 1.29–2.97, p = 0.002) and extrahepatic spread (OR = 3.59, 95% CI 1.69–7.60, p = 0.001) as independent predictors of disease progression. Although BCLC stage C showed a trend toward higher risk (OR = 1.66, 95% CI 0.97–2.85, p = 0.064), it did not reach statistical significance (Supplementary material 2). Patients who received cancer-directed therapy demonstrated significantly longer survival outcomes compared to those who did not. The mean OS was 46 months in patients who underwent cancer-directed therapy versus 17.6 months in those without (p < 0.001). Similarly, the mean PFS was significantly higher among patients receiving cancer-directed therapy (33.7 months vs. 12.9 months; p = 0.003). Among individual treatment modalities, TACE showed a significant improvement in both OS (62.1 months vs. 28.8 months; p < 0.001) and PFS (43 months vs. 22.5 months; p = 0.029). Liver transplantation also demonstrated a significant benefit in PFS (p = 0.047). Other modalities such as RFA, MWA, TARE, and SBRT did not show statistically significant differences in survival outcomes (Supplementary material 3). DISCUSSION Our study is one of the largest real-world assessments from South India evaluating the prognostic role of ALBI score in patients receiving lenvatinib treatment for advanced HCC. These findings demonstrate a correlation between the treatment outcomes and survival in this cohort. The treatment paradigm for advanced HCC has changed as a result of recent advancements in systemic therapy. In patients with Child Pugh A liver function and an ECOG performance status of 0-1, the ASCO 2024 guidelines suggest immune checkpoint inhibitor combinations, such as atezolizumab plus bevacizumab or durvalumab plus tremelimumab, as the preferred first-line treatment 7,12 . However, lenvatinib continues to play a crucial role in clinical practice when immunotherapy is contraindicated or unavailable 8 . The study cohort’s demographic profile is consistent with regional and global HCC epidemiology, which consistently shows a predominance of older age and males 22-24 . The epidemiological landscape of HCC in India is evolving with alcohol related liver disease and metabolic dysfunction-associated steatosis (MASLD) exceeding the viral causes in recent years 25,26 . These changes emphasize the importance of regional real-world data to comprehend treatment outcomes in a variety of hepatic backgrounds. Given that other studies have demonstrated equivalent efficacy but superior safety profiles at lower doses in patients with impaired hepatic reserve, the larger percentage of patients receiving a lower dose of lenvatinib (4mg OD) may reflect the dosage individualization based on hepatic function and tolerability 11,27 . The overall objective response rate (ORR) was low (2.4%), and the disease control rate (DCR) was 47.7% in this real-world cohort. When compared to the pivotal REFLECT study, which revealed an ORR of 24.1% and DCR of 75.5% according to mRECIST criteria, these results are modest 11 . The inclusion of individuals with impaired hepatic function (ALBI grade 2 and 3), varying drug exposure, could be the reason for the reduced efficacy seen in our study. Group 1 (ALBI grade 1) demonstrated a comparatively positive response profile with a lower rate of PD and a greater PR proportion. This suggests that disease stabilisation with ALBI grade 1 patients is more durable and linked to better survival outcomes. Prior research has shown that patients with baseline liver function (ALBI grade 1 or Child Pugh A) achieve significantly improved ORR, DCR, PFS, and OS 28-30 . According to Hiraoka et al, DCR for ALBI grades 1 and 2 were 3% and 55% respectively, along with a median PFS of 8.9 and 4.2 months 28 . Early detection of biochemical and radiological responses is considered a prognostic marker of better survival in patients with preserved hepatic function, as reported by Kodama K et al 24 . A study by Shimozato et al 31 and Cheon et al 32 from Japanese and Korean cohorts, respectively, reported that lenvatinib yielded better outcomes among patients with ALBI grade 1. The above studies support the need for preserved liver function can enhance lenvatinib’s anti-cancer activity and disease control potential. The key factors for tolerability and safety in lenvatinib-treated HCC patients are treatment modifications and discontinuation. Group 1 showed a lower frequency of dose interruptions and adverse event-related discontinuations compared to other groups. A higher rate of ongoing therapy (29.2%) was also observed in this group. Consistent with our findings, prior real-world studies have demonstrated that 10-25% of patients on lenvatinib discontinue treatment due to adverse events. According to Kudo et al, 18% of the participants of the REFLECT study 11 discontinued due to adverse events, demonstrating controllable toxicity with suitable dose modification techniques. Ikeda et al also showed that dose reductions and interruptions did not substantially affect treatment efficacy, highlighting the significance of personalised dosing to preserve tolerability 33 . The higher discontinuation rates in group 4 of our cohort could be attributed to advanced disease stage or impaired hepatic function 34,35 . These results emphasize that, especially in individuals with good hepatic reserve, dose individualization and close monitoring of adverse events can help maintain therapy with enhanced outcomes. Our results are in line with other international studies by Tada et al and Hiraoka et al, which showed that the patients with ALBI grade 1 had considerably longer PFS and OS than patients with higher ALBI grades 18,14 . The median OS for ALBI grade 1 patients in our dataset was 38.4 months, while the median OS for ALBI grade ≥ 2 was 20.4 months, which closely matches the real-world assessments conducted in Italy and Japan 13,36 . Hepatic reserve is crucial for maintaining lenvatinib therapy as it is linked to fewer treatment discontinuations and dose interruptions. Compared to patients treated with lenvatinib alone, those who received prior or concurrent cancer-directed therapy, such as TACE, MWA, resection, or liver transplantation, have noticeably better survival rates. These findings support the concept of multimodal management with both locoregional and systemic treatment to promote tumour control 7,37 . Specifically, our study’s median OS exceeded 60 months when TACE and lenvatinib were combined, which is consistent with emerging data from East Asian cohorts that sequential or combinational treatment can improve outcomes in well-compensated patients 38 . Fatigue, anorexia, and HFSR were the most common toxicities in our study’s adverse event profile, which was similar to earlier real-world findings 39 . As hepatic function declined (ALBI grade ≥2), their occurrence increased, highlighting the significance of liver function-based dose selection. These insights align with the earlier empirical findings. Compared to ALBI grade 1, Hiraoki et al 28 found that ALBI grade 2 patients had a greater risk of therapy termination and dose reductions due to hepatotoxicity. Similarly, in HCC patients receiving lenvatinib, Ueshima et al 38 found that baseline ALBI grade was an independent predictor of both survival and hepatic adverse events. Increased toxicity and decreased dosage intensity were also observed in patients with poorer baseline liver function in an Indian multi-centric experience by Rauthan A et al, 40 , confirming the use of ALBI grade as a useful tool for treatment planning. In line with the findings of Burgio V et al 36 , multivariate analysis showed that extra-hepatic spread and higher initial dose independently predict the progression of disease. Since the patients with advanced tumour burden or BCLC stage C usually receive higher initial doses, the correlation between the higher dosage and advanced disease may be due to aggressive disease biology. All of these findings substantiate the current study’s findings that lenvatinib’s anti-cancer efficacy and disease control rate are enhanced by preserved liver function (ALBI grade 1). For HCC patients on lenvatinib therapy, baseline ALBI assessment should be regarded as a crucial stratification tool for maximizing treatment results, identifying the best dose, forecasting tolerance, and guiding clinical decision-making on patients receiving sequential or combinational therapy. There are certain limitations of our study. Due to the single-centre retrospective nature of the analysis, selection bias and missing imaging data are present. Furthermore, the measurement of temporal changes in hepatic reserve was not possible due to the lack of a dynamic assessment of ALBI during therapy. Despite these drawbacks, our results are strengthened by the large cohort size and uniform treatment protocol. Notably, our study offers region-specific data from an Indian population where HCC aetiology, comorbidities, and clinical presentation differ from Western and East Asian cohorts, thereby helping to bridge a key evidence gap. Conclusion In conclusion, lenvatinib improved tumour response and disease control in patients with ALBI grade 1, which may result in increased treatment efficacy and longer survival. The prognostic and predictive utility of ALBI grading in clinical practice is supported by these results. Declarations Acknowledgements: The authors would like to thank Amrita Institute of Medical Sciences and Research Centre, Kochi, for providing research support. Conflicts of Interest: All the authors declare no competing interests. Funding statement: This research received no external funding. Data Availability: All data generated or analysed during this study are included in this published article [and its supplementary information files] Ethical approval and consent to participate: This study was approved by the Institutional Ethics Committee of Amrita School of Medicine ECASM-AIMS-2021-293 on 15-06-2021 and was conducted as per the principles of the Declaration of Helsinki and guidelines of the Indian Council of Medical Research. All the authors certify that they have obtained all the appropriate patient consent for the study. Author contributions: Conceptualization: MB, KP, SHS Data curation: MB, SHS, RMP Formal analysis: MB, AK, NK Funding acquisition: KP Investigation: MB, RMP, KP Methodology: KP Project administration: KP Resources: SHS, RMP Software: AK, NK Supervision: KP Validation: KP Visualization: MB, KP Writing-original draft: MB, KP Writing-review & editing: RMP, AV, SHS, KP Approval of final manuscript: All authors References Siegel RL, Giaquinto AN, Jemal A (2024) Cancer statistics, 2024. CA Cancer J Clin 74(1):12–49 Ferlay J, Ervik M, Lam F et al (2024) [Internet] Global Cancer Observatory: Cancer Today. Lyon: IARC; Available from: https://gco.iarc.who.int/today . Accessed 22 Oct 2025 Giri S, Singh A (2024) Epidemiology of hepatocellular carcinoma in India—an updated review for 2024. J Clin Exp Hepatol 14(6):101447 International Agency for Research on Cancer. GLOBOCAN 2022 India fact sheet, Lyon (2022) [Internet] IARC; Available from: https://gco.iarc.who.int/media/globocan/factsheets/populations/356-india-fact-sheet.pdf . Accessed 27 Oct 2025 Musunuri B, Shetty S, Bhat G, Udupa K, Pai A (2022) Profile of patients with hepatocellular carcinoma: An experience from a tertiary care centre in India. Indian J Gastroenterol 41(2):127–134 Koshy A, Devadas K, Panackel C, Philip M, Premaletha N, Zacharias P et al (2023) Kerala Hepatocellular Carcinoma Study Group. Multi-center prospective survey of hepatocellular carcinoma in Kerala: More than 1,200 cases. Indian J Gastroenterol 42(2):233–240 Kumar K, Saraswat VA (2025) Evolving landscape of systemic therapy for hepatocellular carcinoma in 2025. J Clin Exp Hepatol 102547. 10.1016/j.jceh.2025.102547 Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY et al (2020) Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 382(20):1894–1905 Kudo M (2017) Lenvatinib versus sorafenib in first-line treatment of unresectable hepatocellular carcinoma: REFLECT trial and beyond. Liver Cancer 6(1):1–9. 10.1159/000452868 Chen Y, Dai S, Cheng C, Cheng L (2024) Lenvatinib and immune checkpoint inhibitors in hepatocellular carcinoma: mechanistic insights, clinical efficacy and future perspectives. J Hematol Oncol 17(1):130 Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F et al (2018) Lenvatinib versus sorafenib in first-line treatment of unresectable HCC (REFLECT). Lancet 391(10126):1163–1173 Gordan JD, Kennedy EB, Abou-Alfa GK, Beal E, Finn RS, Gade TP et al (2024) Systemic therapy for advanced hepatocellular carcinoma: ASCO guideline update. J Clin Oncol 42(15):1830–1850 Persano M, Rimini M, Tada T, Suda G, Shimose S, Kudo M, Cheon J et al (2023) Clinical outcomes with atezolizumab plus bevacizumab or lenvatinib in hepatocellular carcinoma: real-world study. J Cancer Res Clin Oncol 149(9):5591–5602 Kang W, Kim YJ, Kim SU, Seo YS, Kim JW, Kim JH et al (2024) Real-world effectiveness and safety of lenvatinib in unresectable hepatocellular carcinoma in Korea: post marketing study. Future Oncol 20(37):2949–2959 Casadei-Gardini A, Rimini M, Kudo M, Shimose S, Tada T, Suda G et al (2022) Real life Study of Lenvatinib therapy for hepatocellular carcinoma: RELEVANT study. Liver Cancer 11(6):527–539 Johnson PJ, Berhane S, Kagebayashi C, Satomura S, Teng M, Reeves HL et al (2015) Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach- the ALBI grade. J Clin Oncol 33(6):550–558 Toyoda H, Johnson PJ (2022) The ALBI score: From liver function in patients with HCC to a general measure of liver function. JHEP Rep 4(10):10057 Tada T, Kumada T, Hiraoka A, Atsukawa M, Hirooka M, Tsuji K, Ishikawa T et al (2021) Impact of modified albumin-bilirubin grade on survival in patients with HCC who received lenvatinib. Sci Rep 11:14474 Shafiq S, Khan MN, Majumder B, Alam MS, Islam MS, Sultana T (2019) Correlation of Albumin-Bilirubin (ALBI) score with Child-Turcotte-Pugh (CTP) score in the evaluation of liver cirrhosis. Am J Lab Med 4(3):60–64 Sinha N, Porwal J, Sehrawat A, Mitra R, Gargy S (2023) Comparison of Child–Turcotte–Pugh score and albumin–bilirubin index score for advanced hepatocellular carcinoma at an LMIC tertiary cancer facility. J Clin Oncol 41(16 Suppl):e16174 Peng Y, Wei Q, He Y, Xie Q, Liang Y, Zhang L et al (2020) ALBI versus Child-Pugh in predicting outcome of patients with HCC: A systematic review. Expert Rev Gastroenterol Hepatol 14(5):383–400 Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR (2019) A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol 16(10):589–604 Villanueva A (2019) Hepatocellular carcinoma. N Engl J Med 380(15):1450–1462 Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S et al (2021) Hepatocellular carcinoma. Nat Rev Dis Primers 7(1):6 Eslam M, Sanyal AJ, George J (2020) International Consensus Panel. MAFLD: A consensus-driven proposed nomenclature for Metabolic Associated Fatty Liver Disease. Gastroenterology 158(7):1999–2014e1 Duseja A, Chalasani N (2013) Epidemiology and risk factors of NAFLD. Hepatol Int 7(S2):755–764 Pires Amaro C, Allen MJ, Knox JJ, Tsang ES, Lim HJ, Richard M et al (2022) Dosing, efficacy and safety of lenvatinib—Canadian real-world data. Liver Cancer Int 3:119–127 Hiraoka A, Kumada T, Kariyama K, Takaguchi K, Atsukawa M, Itobayashi E et al (2019) Clinical features of lenvatinib for unresectable HCC: multicenter analysis. Cancer Med 8(1):137–146 Kodama K, Kawaoka T, Namba M, Uchikawa S, Ohya K, Morio K et al (2019) Correlation between early tumor marker response and imaging response in patients with advanced hepatocellular carcinoma treated with lenvatinib. Oncology 97(2):75–81 Kuzuya T, Ishigami M, Ito T, Ishizu Y, Honda T, Ishikawa T et al (2020) Favorable radiological antitumor response at 2 weeks after starting lenvatinib for patients with advanced hepatocellular carcinoma. Hepatol Res 50(3):374–381 Shimozato N, Namisaki T, Okano A, Ohana M, Kinoshita D, Kawasaki T et al (2022) Efficacy and safety of lenvatinib for patients with advanced hepatocellular carcinoma: A retrospective, real world study conducted in Japan. Anticancer Res 42(1):173–183 Cheon J, Chon HJ, Bang Y, Park NH, Shin JW, Kim KM et al (2020) Real-world efficacy and safety of lenvatinib in Korean patients with advanced hepatocellular carcinoma: a multicenter retrospective analysis. Liver Cancer 9(5):613–624 Ikeda M, Okusaka T, Mitsunaga S, Ueno H, Tamai T, Suzuki T et al (2016) Safety and pharmacokinetics of lenvatinib in advanced HCC. Clin Cancer Res 22(6):1385–1394 Hiraoka A, Kumada T, Atsukawa M, Hirooka M, Tsuji K, Ishikawa T et al (2019) Early relative change in hepatic function with lenvatinib. Oncology 97(6):334–340 Reig M, Forner A, Rimola J, Ferrer-Fabrega J, Burrel M, Garcia-Criado A et al (2022) BCLC strategy for HCC: 2022 update. J Hepatol 76(3):681–693 Burgio V, Iavarone M, Di Costanzo GG, Marra F, Lonardi S, Tamburini E et al (2021) Real life data of Lenvatinib vs sorafenib for unresectable HCC in Italy. Cancer Manag Res 13:9379–9389 Peng Z, Fan W, Zhu B, Wang G, Sun J, Xiao C et al (2023) Lenvatinib plus Transarterial Chemoembolization as first-line treatment for Advanced Hepatocellular carcinoma: A Phase III, Randomized Clinical Trial (LAUNCH). J Clin Oncol 41(1):117–127 Ueshima K, Nishida N, Hagiwara S, Aoki T, Minami T, Chishina H et al (2019) Impact of baseline ALBI grade on the outcomes of hepatocellular carcinoma patients treated with lenvatinib. Cancers (Basel) 11(7):952 Sho T, Suda G, Ogawa K, Kimura M, Shimazaki T, Maehara O et al (2019) Early response and safety of lenvatinib for patients with advanced hepatocellular carcinoma in a real world setting. JGH Open 4(1):54–60 Rauthan A, Somashekhar SP, Patil P, Zaveri S (2020) Real-world experience with lenvatinib in HCC—Indian single-center experience. J Clin Oncol 38(15suppl):e16596 Additional Declarations No competing interests reported. Supplementary Files Suppl1.Univariateandmultivariateanalysisonfactorsaffectingdrugdiscontinuation.docx Suppl2.Univariateandmultivariateanalysisonfactorsaffectingdiseaseprogression.docx Suppl3.Cancerdirectedtherapieseffectonoverallsurvivalandprogressionfreesurvival.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9161824","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":614899585,"identity":"9f391fa7-103e-400a-8920-97c534d0add5","order_by":0,"name":"Merin Babu","email":"","orcid":"","institution":"Amrita Institute of Medical Sciences and Research Centre, Amrita School of Medicine, Amrita Vishwa Vidyapeetham","correspondingAuthor":false,"prefix":"","firstName":"Merin","middleName":"","lastName":"Babu","suffix":""},{"id":614899586,"identity":"ac23ec92-5bac-44b8-9155-9aa76dcf9b6d","order_by":1,"name":"Rakesh 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2\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-9161824/v1/0d258c085caafc1426f49606.png"},{"id":106093119,"identity":"55e00d09-4f5c-4b28-b4a2-c0db7934d6f6","added_by":"auto","created_at":"2026-04-03 11:35:05","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":47059,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curve with a table depicting the progression-free survival between 4 groups\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-9161824/v1/7f42f5d60e3d300bb25b8665.png"},{"id":106093451,"identity":"67f98dac-f974-47b4-aeb0-2257feeee25e","added_by":"auto","created_at":"2026-04-03 11:37:25","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":35738,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan Meir curve with a table depicting the 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treated with Lenvatinib: A Real-world South Indian cohort study","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eGlobally, liver cancer, particularly hepatocellular carcinoma (HCC), ranks third in cancer-related mortality and sixth in terms of incidence\u0026sup1;. HCC is a formidable malignancy, frequently diagnosed at advanced stages, underscoring the critical need for effective prognostic indicators to guide therapeutic strategies\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. In India, it ranks 11th in cancer incidence and 8th in mortality, with 38,703 new cases and 36,953 deaths annually \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. In South India, MASLD has been identified as a significant etiological factor for HCC, surpassing the viral causes. Notably, 14.5% of biopsy samples revealed steatohepatitis coexisting with HCC, highlighting the metabolic basis of malignancy in this region. Musunuri et al\u003csup\u003e5\u003c/sup\u003e reported that over half of HCC cases in a tertiary-care cohort from coastal South India were cryptogenic/NAFLD-related, with many patients presenting at advanced BCLC stages and only a minority detected through surveillance. Similarly, the results from a large multicentre Kerala HCC survey conducted by Koshy et al\u003csup\u003e6\u003c/sup\u003e showed that 44% of HCC patients had metabolic syndrome or NAFLD, with a high prevalence of diabetes (64%) and hypertension (38%), and the majority of them presented at stages where curative therapy was not practical. These convergent datasets show that MASLD is a fast-increasing oncogenic driver in South India, highlighting the need for earlier surveillance mechanisms and improved metabolic risk classification. There is an evolving landscape involving a multi-disciplinary team in the treatment options available for various stages of liver cancer \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Targeted multi-kinase inhibitor therapy and immune checkpoint inhibitors are the systemic therapies for unresectable HCC. The paradigm for treating HCC has changed with the introduction of targeted treatments like lenvatinib\u003csup\u003e\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eLenvatinib, a multi-potent tyrosine kinase inhibitor that targets the vascular endothelial growth factor receptors 1\u0026ndash;3, fibroblast growth factor receptor 1\u0026ndash;4, platelet-derived growth factor receptor α, RET, and KIT, has gained popularity over sorafenib after the REFLECT trial. The study showed lenvatinib had a tolerable safety profile, non-inferior overall survival, and a greater response rate in comparison to sorafenib\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e The recent ASCO 2024 guidelines suggest the immune checkpoint inhibitors (Atezolizumab\u0026ndash;bevacizumab/Durvalumab\u0026ndash;tremelimumab) for Child-Pugh A patients with a good performance score of 0\u0026ndash;1. Lenvatinib remains a vital option when the above therapies are contraindicated\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Real-world studies suggest that lenvatinib has demonstrated improved overall survival and a better safety profile in the HCC population. The response achieved with lenvatinib is, however, significantly influenced by the patients' baseline liver function. Deteriorated liver function not only limits the treatment options but can also increase the risk of adverse events and alter the well-being of the patient and his/her family\u003csup\u003e\u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe Child\u0026ndash;Pugh scoring system is one of the traditional methods used to assess liver function and includes subjective parameters such as hepatic encephalopathy and ascites grading. However, considerable interobserver variability has been reported among clinicians, limiting its reproducibility. Due to this lack of objectivity and specificity, newer grading systems based on quantitative parameters\u0026mdash;such as the albumin\u0026ndash;bilirubin (ALBI) grade\u0026mdash;were developed to provide a more standardized assessment of liver function\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe ALBI grade, a recently developed scoring system based on two objective biochemical parameters\u0026mdash;serum albumin and bilirubin\u0026mdash;is used for liver function assessment in patients with hepatic diseases, particularly HCC. It has emerged as a promising tool for risk stratification and prognostication in various liver diseases, including HCC\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Several studies have demonstrated the significance of the ALBI grade in predicting overall survival, guiding treatment strategies, and determining the toxicity profile in patients with HCC\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Studies from India consistently demonstrate that the ALBI grade offers better predictive discrimination than the conventional Child-Pugh score, especially for patients who are categorized as Child-Pugh A\u003csup\u003e19\u003c/sup\u003e. A real-world tertiary cancer center cohort presented at ASCO confirmed ALBI's stronger prognostic value in advanced HCC under systemic therapy\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e, while a retrospective cohort from Eastern India showed that ALBI more accurately stratified survival and liver-related complications than Child\u0026ndash;Pugh\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. These results are consistent with larger analyses conducted in Asia and South Asia, where ALBI consistently performs better than Child-Pugh in resection, trans arterial chemoembolization (TACE), and systemic-therapy settings\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Our study endeavours to evaluate the prognostic utility of the albumin-bilirubin score in a South Indian cohort of HCC patients undergoing lenvatinib treatment, addressing a critical regional gap in current literature.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e2.1 \u003cem\u003eStudy design\u003c/em\u003e: The medical records of 502 consecutive patients diagnosed with advanced HCC and treated with lenvatinib as first /second line treatment between 2019 to 2024 at our institution were reviewed. This retrospective single-centre study was approved by the institutional ethics committee of Amrita School of Medicine, ECASM-AIMS-2021-293 on 15-06-2021, and was conducted as per the principles of the Declaration of Helsinki and guidelines of the Indian Council of Medical Research.\u003c/p\u003e\u003cp\u003e2.2 \u003cem\u003eInclusion criteria\u003c/em\u003e: Unresectable adult HCC patients substantiated by radiographic or histological findings, Barcelona Clinic Liver Cancer (BCLC) stage B or C; Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1; Child-Pugh score received lenvatinib as 1st or 2nd line therapy, were included.\u003c/p\u003e\u003cp\u003e \u003cstrong\u003eExclusion criteria\u003c/strong\u003e \u003c/p\u003e\u003cp\u003ePatients were excluded if they had incomplete patient data history and were not willing to take part in the study.\u003c/p\u003e \u003cp\u003e2.3 \u003cem\u003eLenvatinib treatment regimen\u003c/em\u003e: Lenvatinib (Lenvima \u0026reg;, Eisai Co Ltd, Tokyo, Japan; or Lentykine \u0026reg;, Intas Pharmaceuticals; or Lenvat \u0026reg;, Natco Pharma Ltd; or Adlante \u0026reg;, Adley formulations) was given orally to advanced HCC patients.\u003c/p\u003e \u003cp\u003eAs per the Food and Drug Administration (FDA), the approved dose of oral lenvatinib was 8mg/day in patients with \u0026lt;\u0026thinsp;60kg body weight and 12 mg/day in patients with \u0026ge;\u0026thinsp;60kg body weight. To prevent early cessation due to adverse events, a lower initial dose of lenvatinib is prescribed in patients with non-Child Pugh A illness, the elderly population, low body weight, pleural effusion, ascites, or gastrointestinal varices at risk of bleeding.\u003c/p\u003e \u003cp\u003eAny unacceptable or severe side effects or clinical progression resulted in discontinuation of lenvatinib. In accordance with the lenvatinib administration recommended, patients who experienced grade\u0026thinsp;\u0026ge;\u0026thinsp;3 severe adverse events or any unacceptable grade 2 related adverse events had their drug dosage either decreased or their therapy stopped. The National Cancer Institute Common Terminology criteria for adverse events (CTCAE), version 5.0, were used to evaluate the adverse events.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.5 \u003cem\u003eTreatment Protocol\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eLenvatinib\u0026rsquo;s effectiveness and safety in treating individuals with incurable HCC were assessed by grouping patients based on their Child-Pugh score and ALBI grade.\u003c/p\u003e \u003cp\u003eThe patients were categorised into four groups:\u003c/p\u003e \u003cp\u003eGroup 1: Child-Pugh score A5, ALBI grade 1\u003c/p\u003e \u003cp\u003eGroup 2: Child-Pugh score A5, ALBI grade 2\u003c/p\u003e \u003cp\u003eGroup 3: Child-Pugh score A6\u003c/p\u003e \u003cp\u003eGroup 4: Child-Pugh score A\u0026thinsp;\u0026ge;\u0026thinsp;7 (B or C)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.6 \u003cem\u003eData Collection and Treatment Assessment\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eClinical, demographic, and treatment-related data were retrospectively collected from electronic medical records. The collected parameters included patient age, sex, aetiology of liver disease, ECOG performance status, Child\u0026ndash;Pugh classification, and details of systemic therapy received. Laboratory data at baseline and during treatment were extracted for biochemical and pharmacokinetic analysis.\u003c/p\u003e \u003cp\u003eALBI score was calculated using serum albumin and bilirubin, thereby eliminating the subjective variables present in the Child\u0026ndash;Pugh classification using the formula\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e:\u003c/p\u003e \u003cp\u003eALBI score= (log10 bilirubin \u0026times;0.66) +(albumin \u0026times;\u0026minus;0.085)\u003c/p\u003e \u003cp\u003ewhere \u003cb\u003ebilirubin\u003c/b\u003e is expressed in \u003cb\u003e\u0026micro;mol/L\u003c/b\u003e and \u003cb\u003ealbumin\u003c/b\u003e in \u003cb\u003eg/L\u003c/b\u003e.\u003c/p\u003e \u003cp\u003ePatients were categorized into three grades based on the calculated score:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eGrade 1\u003c/b\u003e: \u0026le; \u0026minus;\u0026thinsp;2.60\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eGrade 2\u003c/b\u003e: \u0026gt; \u0026minus;\u0026thinsp;2.60 to \u0026le; \u0026minus;\u0026thinsp;1.39\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eGrade 3\u003c/b\u003e: \u0026gt; \u0026minus;\u0026thinsp;1.39\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eTreatment response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) using dynamic contrast-enhanced CT or MRI scans. Imaging assessments were performed at baseline and at regular follow-up intervals as per institutional protocol. Efficacy outcomes were assessed using key clinical endpoints, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and time to treatment failure (TTF) defined as time from initial administration to the time of treatment failure, which can be either due to treatment discontinuation or progression or death).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.7 Statistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was used using IBM SPSS version 20.00. Continuous variables are shown as medians (range). To test the statistical significance of the association of risk factors with dose reduction, progression, the Pearson chi-square test was applied. Multivariate logistic regression was done to examine the most significant risk factors after adjusting for the confounding factors. To find the survival probability of overall survival and progression-free survival, Kaplan Meier analysis was computed, and also comparison was also determined using log log-rank test. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered to be statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Baseline characteristics of the study population\u003c/h2\u003e \u003cp\u003eA total of 502 patients with HCC were screened for eligibility between 2019 and 2024. Of these, 22 patients were excluded due to incomplete clinical data (n\u0026thinsp;=\u0026thinsp;10), unwillingness to participate in the study (n\u0026thinsp;=\u0026thinsp;5), or being second-opinion/one-time-visit cases (n\u0026thinsp;=\u0026thinsp;7). After applying the exclusion criteria, 480 patients were finally included in the analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNumber\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePercentage\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean age, years (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65.11\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(27\u0026ndash;90)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e441\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e91.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eAetiology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMASLD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e176\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAlcohol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e155\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e107\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHepatitis B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHepatitis C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eLenvatinib starting dose\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4mg OD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e340\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e70.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8mg OD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e126\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12mg OD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eComorbidities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e339\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e70.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e246\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDyslipidaemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eBaseline liver function\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedian Total bilirubin (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedian Serum albumin (g/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedian INR (sec)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTumour markers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedian Alpha feto protein (ng/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedian PIVKA (mAU/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1090.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003eChild Pugh Score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e227\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eB7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eB8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eB9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eALBI grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e154\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e269\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eBCLC score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e149\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e230\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eSite of tumour\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRight lobe\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e288\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLeft lobe\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBoth lobes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eNumber of liver lesions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e177\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003ePortal vein thrombosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMain trunk\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRight anterior or posterior\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRight or left\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSegmental PV invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003eExtrahepatic spread\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLymph node\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLung\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAdrenal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBrain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePeritoneal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"7\" rowspan=\"8\"\u003e \u003cp\u003eCancer-directed therapies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal patients undergone cancer-directed therapies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e325\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e67.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMWA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTACE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRFA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSBRT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLiver resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLiver transplantation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTARE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e\n\u003cp\u003eAbbreviations: MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease; INR - International Normalized Ratio; PIVKA-Protein Induced by Vitamin K Absence or antagonist-II; ALBI-Albumin-Bilirubin; BCLC - Barcelona Clinic Liver Cancer staging system; PV- portal vein; MWA-Microwave Ablation; TACE-Trans arterial chemoembolization; RFA-Radiofrequency ablation; SBRT-Stereotactic body radiation therapy; TARE-Trans arterial Radioembolization.\u003c/p\u003e\n\u003cp\u003eA summary of 480 eligible patients with baseline characteristics is presented in Table 1. There were 39 females and 441 males, with a mean age was 65.11 years. The most common aetiology was MASLD in 176 (37%) and alcohol in 155 (32.3%), followed by hepatitis B in 30 (6.2%) and hepatitis C in 14 (3%). \u0026nbsp; The majority of the patients (340, 70.8%) were started with a lower dose of lenvatinib 4mg OD, irrespective of the FDA guidelines, followed by 126 (26.3%) with 8mg OD. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe most prevalent comorbidities were diabetes mellitus (70.6%) and hypertension (51.2%). The majority of patients belonged to Child Pugh Class A (71.5%), whereas ALBI grade 2 (56%) was the most prevalent. Of the cohort, nearly half (47.9%) were in BCLC stage C. Single or double focal lesions were the most common (73.2%), and the right lobe accounted for 60% of the tumour involvement. One hundred twenty-one patients (25.2%) had portal vein thrombosis, mainly in the right portal vein branches (11.7%), and 9.5% cases had an extrahepatic dissemination, mostly to the lymph nodes (4.2%) and lungs (3.3%). Microwave ablation (29%) and TACE (26.4%) were the most common cancer-directed therapies reported in 67.7% patients. (55.4%)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3.2 Association Between ALBI Grade and Child\u0026ndash;Pugh Classification\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOf the 480 patients enrolled, 154 patients (32%) were classified as ALBI grade 1, 270 patients (56%) as ALBI grade 2, and 56 patients (12%) as ALBI grade 3 (Table 2). Most of the patients with ALBI grade 1 (144 out of 154 patients, 93.5%) had a Child Pugh score of A. Patients were categorised into 4 groups based on their Child Pugh score and ALBI grade (Table 3)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: Correlation between the ALBI grade and Child Pugh score\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eALBI/Child Pugh score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\"\u003e\n \u003cp\u003e\u003cstrong\u003eChild Pugh Score \u0026ndash; n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026ge; 7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e\n \u003cp\u003e\u003cstrong\u003eALBI grade\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e131 (85.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e13 (8.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10 (6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e154\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e96 (35.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e98 (36.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e76 (28.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e270\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5 (8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e51 (89.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e56\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e227\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e116\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e137\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e480\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: ALBI-Albumin-Bilirubin\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3: Patient Distribution According to Child\u0026ndash;Pugh Classification and ALBI Grade\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eGroup details\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGroup 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eChild Pugh score A5 with ALBI grade 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e131\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGroup 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eChild Pugh score A5 with ALBI grade 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e96\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGroup 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eChild Pugh score A6 with ALBI grade 1,2,3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e116\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGroup 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eChild Pugh score \u0026ge; 7 with ALBI grade 1,2,3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e137\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: ALBI-Albumin-Bilirubin\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3.3 Response to lenvatinib\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOut of the 480 patients, only 373 (77.7%) were evaluable according to mRECIST criteria, as 107 patients did not undergo repeat imaging as recommended by the HCC management guidelines. Repeat imaging as per mRECIST was advised every six months; however, only a limited number of patients underwent imaging at the recommended interval, with many receiving follow-up scans only when liver function tests became abnormal or when clinical progression was suspected. No patient had a complete response, and only 9 (2.4%) had a partial response to lenvatinib treatment. Stable disease or progressive disease was observed in the majority of patients, 169 (45.3%) and 196 (52.5%), respectively. Tumour response to lenvatinib according to mRECIST is summarised in Table 4.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4: Tumour Response to lenvatinib According to mRECIST Criteria\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ePR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ePD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eTotal evaluable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDCR (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e131\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5 (55.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e51 (30.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e57 (29.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e113\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e49.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2 (22.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e41 (24.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e42 (21.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e84\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e51.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e116\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e42 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e42 (21.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e84\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e50.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e137\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2 (22.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e55 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e55 (28.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e92\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e61.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e480\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e169\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e196\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e373\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e47.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: ALBI-Albumin-Bilirubin; PR-Partial response; SD- stable disease; PD- progressive disease; DCR: disease control rate\u003c/p\u003e\n\u003cp\u003eGroup 1 (ALBI grade 1) demonstrated comparatively better disease control than the other groups. In particular, the disease control rate (DCR = PR + SD / total number of evaluable patients) for group 1 was 49%, whereas 51.2% for group 2, 50% for group 3, and 61.9% for group 4. Group 1 showed better clinical efficacy among the patients with preserved hepatic function. These findings suggest that, in comparison to patients with higher ALBI grades, group 1 represents patients with preserved liver function and better disease stabilisation during lenvatinib therapy.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e3.4 Treatment modifications and discontinuations\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe dose modifications and therapy discontinued profiles for each of the four study groups are summarised in Table 5. Forty-two patients had a dose reduction, with group 1 having 36% followed by group 2 (29%) and group 3 (21.4%). Sixty-six individuals experienced drug interruptions, with group 4 experiencing the highest frequency (33.3%). Group 1 showed the highest likelihood of continued treatment (68, 29.2%), whereas treatment discontinuation due to adverse events/progression was more frequent in group 4 (53, 38.1%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5: Dose Adjustment and Therapy Discontinuation Profile\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eDR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eDI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eDC due to adverse events\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eDC due to progression\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eOngoing\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGroup 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e131\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e15 (36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e17 (26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7 (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e24 (22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e68 (29.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGroup 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e12 (29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e14 (21.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3 (10.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e23 (20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e44 (18.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGroup 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e116\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9 (21.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e13 (19.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10 (35.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e19 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e65 (28)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eGroup 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e137\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6 (14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e22 (33.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8 (28.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e45 (41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e56 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e480\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e111\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e233\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: DR- Dose reduction; DI- Drug interruptions, DC-Discontinued\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e3.5 Survival outcomes (OS, PFS, and TTF) according to ALBI grade and Child Pugh score\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe median OS of the present study population was 27.4 months (95% CI 19.2 \u0026ndash; 35.5 months). The median OS of patients with groups 1,2,3, and 4 were 38.4, 27.4,32 and 12 months, respectively, with a significant difference among the 4 groups (p \u0026lt;0.001) [Figure 2]. The median OS of patients with ALBI grade 1 and ALBI grade \u0026ge; 2 were 38.4 and 20.4 months, respectively (p \u0026lt;0.001) [Figure 3].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe median PFS of patients with groups 1,2,3, and 4 were 15, 14.1,10 and 9.7 months, respectively, with a significant difference among the 4 groups (p = 0.03) [Figure 4]. The median PFS of patients with ALBI grade 1 and \u0026ge; 2 were 15.3 and 11.5 months, respectively (p = 0.022) [Figure 5].\u003c/p\u003e\n\u003cp\u003eThe median survival was 17 months (95% CI 14 \u0026ndash; 20.1 months). Kaplan Meier estimates of TTF according to ALBI grade and Child Pugh score are shown in Figure 6. The median TTF was 19, 19.4, 17, and 14.4 months in groups 1,2,3, and 4, respectively. Liver function according to the ALBI grade and Child Pugh score was significantly associated with TTF patients of group 2 had the longest TTF, whereas the group 4 patients had the shortest TTF (p = 0.023).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e3.6 Treatment-related adverse events stratified by ALBI grade\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe distribution of treatment-related adverse events among patients categorised by ALBI is shown in Table 6. Patients with ALBI grade 2 had a higher overall incidence of any grade adverse events than those with grade 1, but those with ALBI grade 3 had fewer total adverse events, which is probably due to shorter treatment duration and lower hepatic reserve. The most frequent adverse event in the present study population was fatigue (144, 30%); loss of appetite (106, 22.1%); hand-foot skin reaction (66, 14%); elevated aspartate aminotransferase/ alanine transaminase (49,10.2%); abdominal pain (39, 8.1%), and mucositis (39, 8.1%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 6: Comparison of Treatment-related Adverse Events Among ALBI Grades\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdverse events\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eALBI grade 1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(n = 154)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eALBI grade 2\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(n = 270)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 136px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eALBI grade 3\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e(n = 56)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAny grade\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade \u0026ge; 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAny grade\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade \u0026ge; 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAny grade\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade \u0026ge; 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFatigue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLoss of appetite\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHFSR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eElevated AST/ALT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbdominal pain\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMucositis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHypoalbuminemia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLoss of weight\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eConstipation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAscites\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiarrhoea\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEdema\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDysphonia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 159px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHyperbilirubinemia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: ALBI-Albumin-Bilirubin; HSFR- Hand\u0026ndash;Foot Skin Reaction ; AST- Aspartate Aminotransferase; ALT- Alanine Aminotransferase\u003c/p\u003e\n\u003cp\u003eThe most often reported adverse event, mostly of grade 1 severity among ALBI grade 1 patients, was fatigue (29.9%), loss of appetite (15.6%), and HFSR (13.6%). These adverse events were similarly prevalent in ALBI grade 2, whereas grade \u0026ge; 2 events, such as HFSR (7.4%), fatigue (2.6%), and hypoalbuminemia (2.2%), were more prevalent. Overall, patients with ALBI grade 1 showed a decreased likelihood of experiencing severe (grade \u0026ge; 2) adverse events, indicating that hepatic function preservation may improve the treatment tolerance and lessen the risk of toxicity during lenvatinib therapy.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e3.7 Univariate and multivariate analysis\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eUnivariate logistic regression was performed to evaluate the association between baseline clinical variables and lenvatinib discontinuation. Factors assessed included age, sex, viral aetiology, AFP levels, BCLC stage, ALBI grade, portal vein thrombosis, number of focal lesions, extrahepatic spread, and initial dose.\u003c/p\u003e\n\u003cp\u003eIn the univariate analysis, the presence of portal vein thrombosis (OR = 1.56; 95% CI: 0.99\u0026ndash;2.46; p = 0.052), multiple focal lesions (OR = 1.51; 95% CI: 0.97\u0026ndash;2.35; p = 0.064), and extrahepatic spread (OR = 1.82; 95% CI: 0.93\u0026ndash;3.56; p = 0.078) showed a trend toward higher odds of discontinuation, though not statistically significant.\u003c/p\u003e\n\u003cp\u003eVariables with p \u0026lt; 0.1 in the univariate analysis were included in the multivariate logistic regression model. In the multivariate analysis, none of the factors retained statistical significance; however, portal vein thrombosis (adjusted OR = 1.47; 95% CI: 0.93\u0026ndash;2.33; p = 0.097), extrahepatic spread (adjusted OR = 1.75; 95% CI: 0.89\u0026ndash;3.46; p = 0.107), and multiple focal lesions (adjusted OR = 1.49; 95% CI: 0.95\u0026ndash;2.33; p = 0.079) remained near-significant predictors of lenvatinib discontinuation (Supplementary material 1).\u003c/p\u003e\n\u003cp\u003eWith regard to factors contributing to disease progression, the results of univariate analysis suggest that both initial dose and extrahepatic spread showed a statistically significant association with disease progression (p \u0026lt; 0.001 for both). Patients receiving higher initial doses (8 or 12 mg) had an increased likelihood of progression (OR = 2.10, 95% CI 1.39\u0026ndash;3.16), and those with extrahepatic spread demonstrated a markedly higher risk (OR = 3.69, 95% CI 1.79\u0026ndash;7.63). The multivariate analysis confirmed initial dose (OR = 1.95, 95% CI 1.29\u0026ndash;2.97, p = 0.002) and extrahepatic spread (OR = 3.59, 95% CI 1.69\u0026ndash;7.60, p = 0.001) as independent predictors of disease progression. Although BCLC stage C showed a trend toward higher risk (OR = 1.66, 95% CI 0.97\u0026ndash;2.85, p = 0.064), it did not reach statistical significance (Supplementary material 2).\u003c/p\u003e\n\u003cp\u003ePatients who received cancer-directed therapy demonstrated significantly longer survival outcomes compared to those who did not. The mean OS was 46 months in patients who underwent cancer-directed therapy versus 17.6 months in those without (p \u0026lt; 0.001). Similarly, the mean PFS was significantly higher among patients receiving cancer-directed therapy (33.7 months vs. 12.9 months; p = 0.003). Among individual treatment modalities, TACE showed a significant improvement in both OS (62.1 months vs. 28.8 months; p \u0026lt; 0.001) and PFS (43 months vs. 22.5 months; p = 0.029). Liver transplantation also demonstrated a significant benefit in PFS (p = 0.047). Other modalities such as RFA, MWA, TARE, and SBRT did not show statistically significant differences in survival outcomes (Supplementary material 3).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eOur study is one of the largest real-world assessments from South India evaluating the prognostic role of ALBI score in patients receiving lenvatinib treatment for advanced HCC. These findings demonstrate a correlation between the treatment outcomes and survival in this cohort. The treatment paradigm for advanced HCC has changed as a result of recent advancements in systemic therapy. In patients with Child Pugh A liver function and an ECOG performance status of 0-1, the ASCO 2024 guidelines suggest immune checkpoint inhibitor combinations, such as atezolizumab plus bevacizumab or durvalumab plus tremelimumab, as the preferred first-line treatment\u003csup\u003e7,12\u003c/sup\u003e. However, lenvatinib continues to play a crucial role in clinical practice when immunotherapy is contraindicated or unavailable\u003csup\u003e8\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study cohort’s demographic profile is consistent with regional and global HCC epidemiology, which consistently shows a predominance of older age and males\u003csup\u003e22-24\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe epidemiological landscape of HCC in India is evolving with alcohol related liver disease and metabolic dysfunction-associated steatosis (MASLD) exceeding the viral causes in recent years\u003csup\u003e25,26\u003c/sup\u003e. These changes emphasize the importance of regional real-world data to comprehend treatment outcomes in a variety of hepatic backgrounds.\u003c/p\u003e\n\u003cp\u003eGiven that other studies have demonstrated equivalent efficacy but superior safety profiles at lower doses in patients with impaired hepatic reserve, the larger percentage of patients receiving a lower dose of lenvatinib (4mg OD) may reflect the dosage individualization based on hepatic function and tolerability\u003csup\u003e11,27\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe overall objective response rate (ORR) was low (2.4%), and the disease control rate (DCR) was 47.7% in this real-world cohort. When compared to the pivotal REFLECT study, which revealed an ORR of 24.1% and DCR of 75.5% according to mRECIST criteria, these results are modest\u003csup\u003e11\u003c/sup\u003e. The inclusion of individuals with impaired hepatic function (ALBI grade 2 and 3), varying drug exposure, could be the reason for the reduced efficacy seen in our study. Group 1 (ALBI grade 1) demonstrated a comparatively positive response profile with a lower rate of PD and a greater PR proportion. This suggests that disease stabilisation with ALBI grade 1 patients is more durable and linked to better survival outcomes. Prior research has shown that patients with baseline liver function (ALBI grade 1 or Child Pugh A) achieve significantly improved ORR, DCR, PFS, and OS\u003csup\u003e28-30\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eAccording to Hiraoka et al, DCR for ALBI grades 1 and 2 were 3% and 55% respectively, along with a median PFS of 8.9 and 4.2 months\u003csup\u003e28\u003c/sup\u003e. Early detection of biochemical and radiological responses is considered a prognostic marker of better survival in patients with preserved hepatic function, as reported by Kodama K et al\u003csup\u003e24\u003c/sup\u003e. A study by Shimozato et al\u003csup\u003e31\u003c/sup\u003e and Cheon et al\u003csup\u003e32\u003c/sup\u003e from Japanese and Korean cohorts, respectively, reported that lenvatinib yielded better outcomes among patients with ALBI grade 1. The above studies support the need for preserved liver function can enhance lenvatinib’s anti-cancer activity and disease control potential.\u003c/p\u003e\n\u003cp\u003eThe key factors for tolerability and safety in lenvatinib-treated HCC patients are treatment modifications and discontinuation. Group 1 showed a lower frequency of dose interruptions and adverse event-related discontinuations compared to other groups. A higher rate of ongoing therapy (29.2%) was also observed in this group.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConsistent with our findings, prior real-world studies have demonstrated that 10-25% of patients on lenvatinib discontinue treatment due to adverse events. According to Kudo et al, 18% of the participants of the REFLECT study\u003csup\u003e11\u003c/sup\u003e discontinued due to adverse events, demonstrating controllable toxicity with suitable dose modification techniques. Ikeda et al also showed that dose reductions and interruptions did not substantially affect treatment efficacy, highlighting the significance of personalised dosing to preserve tolerability\u003csup\u003e33\u003c/sup\u003e. The higher discontinuation rates in group 4 of our cohort could be attributed to advanced disease stage or impaired hepatic function\u003csup\u003e34,35\u003c/sup\u003e. \u0026nbsp;These results emphasize that, especially in individuals with good hepatic reserve, dose individualization and close monitoring of adverse events can help maintain therapy with enhanced outcomes.\u003c/p\u003e\n\u003cp\u003eOur results are in line with other international studies by Tada et al and Hiraoka et al, which showed that the patients with ALBI grade 1 had considerably longer PFS and OS than patients with higher ALBI grades\u003csup\u003e18,14\u003c/sup\u003e. The median OS for ALBI grade 1 patients in our dataset was 38.4 months, while the median OS for ALBI grade ≥ 2 was 20.4 months, which closely matches the real-world assessments conducted in Italy and Japan\u003csup\u003e13,36\u003c/sup\u003e. Hepatic reserve is crucial for maintaining lenvatinib therapy as it is linked to fewer treatment discontinuations and dose interruptions. Compared to patients treated with lenvatinib alone, those who received prior or concurrent cancer-directed therapy, such as TACE, MWA, resection, or liver transplantation, have noticeably better survival rates. These findings support the concept of multimodal management with both locoregional and systemic treatment to promote tumour control\u003csup\u003e7,37\u003c/sup\u003e. Specifically, our study’s median OS exceeded 60 months when TACE and lenvatinib were combined, which is consistent with emerging data from East Asian cohorts that sequential or combinational treatment can improve outcomes in well-compensated patients\u003csup\u003e38\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eFatigue, anorexia, and HFSR were the most common toxicities in our study’s adverse event profile, which was similar to earlier real-world findings\u003csup\u003e39\u003c/sup\u003e. As hepatic function declined (ALBI grade ≥2), their occurrence increased, highlighting the significance of liver function-based dose selection. These insights align with the earlier empirical findings. Compared to ALBI grade 1, Hiraoki et al\u003csup\u003e28\u003c/sup\u003e found that ALBI grade 2 patients had a greater risk of therapy termination and dose reductions due to hepatotoxicity. \u0026nbsp;Similarly, in HCC patients receiving lenvatinib, Ueshima et al\u003csup\u003e38\u003c/sup\u003e found that baseline ALBI grade was an independent predictor of both survival and hepatic adverse events.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIncreased toxicity and decreased dosage intensity were also observed in patients with poorer baseline liver function in an Indian multi-centric experience by Rauthan A et al, \u003csup\u003e40\u003c/sup\u003e, confirming the use of ALBI grade as a useful tool for treatment planning.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn line with the findings of\u0026nbsp;Burgio V\u0026nbsp;et al\u003csup\u003e36\u003c/sup\u003e, multivariate analysis showed that extra-hepatic spread and higher initial dose independently predict the progression of disease. Since the patients with advanced tumour burden or BCLC stage C usually receive higher initial doses, the correlation between the higher dosage and advanced disease may be due to aggressive disease biology. All of these findings substantiate the current study’s findings that lenvatinib’s anti-cancer efficacy and disease control rate are enhanced by preserved liver function (ALBI grade 1). For HCC patients on lenvatinib therapy, baseline ALBI assessment should be regarded as a crucial stratification tool for maximizing treatment results, identifying the best dose, forecasting tolerance, and guiding clinical decision-making on patients receiving sequential or combinational therapy.\u003c/p\u003e\n\u003cp\u003eThere are certain limitations of our study. Due to the single-centre retrospective nature of the analysis, selection bias and missing imaging data are present. Furthermore, the measurement of temporal changes in hepatic reserve was not possible due to the lack of a dynamic assessment of ALBI during therapy. Despite these drawbacks, our results are strengthened by the large cohort size and uniform treatment protocol. Notably, our study offers region-specific data from an Indian population where HCC aetiology, comorbidities, and clinical presentation differ from Western and East Asian cohorts, thereby helping to bridge a key evidence gap.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, lenvatinib improved tumour response and disease control in patients with ALBI grade 1, which may result in increased treatment efficacy and longer survival. The prognostic and predictive utility of ALBI grading in clinical practice is supported by these results. \u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank Amrita Institute of Medical Sciences and Research Centre, Kochi, for providing research support.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the authors declare no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding statement:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no external funding.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article [and its supplementary information files]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Institutional Ethics Committee of Amrita School of Medicine ECASM-AIMS-2021-293 on 15-06-2021 and was conducted as per the principles of the Declaration of Helsinki and guidelines of the Indian Council of Medical Research. All the authors certify that they have obtained all the appropriate patient consent for the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: MB, KP, SHS\u003c/p\u003e\n\u003cp\u003eData curation: MB, SHS, RMP\u003c/p\u003e\n\u003cp\u003eFormal analysis: MB, AK, NK\u003c/p\u003e\n\u003cp\u003eFunding acquisition: KP\u003c/p\u003e\n\u003cp\u003eInvestigation: MB, RMP, KP\u003c/p\u003e\n\u003cp\u003eMethodology: KP\u003c/p\u003e\n\u003cp\u003eProject administration: KP\u003c/p\u003e\n\u003cp\u003eResources: SHS, RMP\u003c/p\u003e\n\u003cp\u003eSoftware: AK, NK\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSupervision: KP\u003c/p\u003e\n\u003cp\u003eValidation: KP\u003c/p\u003e\n\u003cp\u003eVisualization: MB, KP\u003c/p\u003e\n\u003cp\u003eWriting-original draft: MB, KP\u003c/p\u003e\n\u003cp\u003eWriting-review \u0026amp; editing: RMP, AV, SHS, KP\u003c/p\u003e\n\u003cp\u003eApproval of final manuscript: All authors\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSiegel RL, Giaquinto AN, Jemal A (2024) Cancer statistics, 2024. 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J Hepatol 76(3):681\u0026ndash;693\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBurgio V, Iavarone M, Di Costanzo GG, Marra F, Lonardi S, Tamburini E et al (2021) Real life data of Lenvatinib vs sorafenib for unresectable HCC in Italy. Cancer Manag Res 13:9379\u0026ndash;9389\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeng Z, Fan W, Zhu B, Wang G, Sun J, Xiao C et al (2023) Lenvatinib plus Transarterial Chemoembolization as first-line treatment for Advanced Hepatocellular carcinoma: A Phase III, Randomized Clinical Trial (LAUNCH). J Clin Oncol 41(1):117\u0026ndash;127\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUeshima K, Nishida N, Hagiwara S, Aoki T, Minami T, Chishina H et al (2019) Impact of baseline ALBI grade on the outcomes of hepatocellular carcinoma patients treated with lenvatinib. Cancers (Basel) 11(7):952\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSho T, Suda G, Ogawa K, Kimura M, Shimazaki T, Maehara O et al (2019) Early response and safety of lenvatinib for patients with advanced hepatocellular carcinoma in a real world setting. JGH Open 4(1):54\u0026ndash;60\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRauthan A, Somashekhar SP, Patil P, Zaveri S (2020) Real-world experience with lenvatinib in HCC\u0026mdash;Indian single-center experience. J Clin Oncol 38(15suppl):e16596\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Hepatocellular carcinoma, ALBI grade, Child Pugh score, Lenvatinib, liver function, real-world evidence","lastPublishedDoi":"10.21203/rs.3.rs-9161824/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9161824/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eIn advanced hepatocellular carcinoma (HCC), baseline liver function is crucial for predicting survival, therapeutic effectiveness, and safety outcomes. A proven, objective indicator of hepatic reserve, the albumin\u0026ndash;bilirubin (ALBI) score may be a better indicator of prognosis for patients undergoing systemic therapy.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThis study examines the effects of baseline Child Pugh score and ALBI grade on patients with hepatocellular cancer who were treated with lenvatinib.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eAll patients who received lenvatinib as a first- or second-line therapy for advanced HCC at our hospital between 2020 and 2024 were included in this retrospective study. The Child-Pugh score and ALBI grade were used to classify baseline liver function. The objective response rate (mRECIST), time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), and treatment discontinuation due to adverse events (AEs) were the primary outcomes evaluated. The patients were divided into four groups: Child-Pugh A5/ALBI 1, Child-Pugh A5/ALBI 2, Child-Pugh A6, and Child-Pugh\u0026thinsp;\u0026ge;\u0026thinsp;7. To identify determinants of response and discontinuation, univariate and multivariate analyses were conducted.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe cohort's median overall survival (OS) and progression-free survival (PFS) were 27.4 months and 13.5 months, respectively. The OS (38.4 vs. 20.4 months) and PFS (15.3 vs. 11.5 months) of patients with ALBI grade 1 were considerably longer. Group 4 had the lowest survival rate, while Group 1 had the highest. The most frequent adverse events were fatigue (30%) and anorexia (22%). Disease progression was independently predicted by higher initial dosages and extrahepatic distribution.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe prognosis of HCC patients on lenvatinib was effectively stratified by baseline ALBI grade. The higher survival and tolerability of patients with preserved liver function (ALBI grade 1) suggest ALBI as a crucial adjunct to the Child-Pugh score in treatment planning.\u003c/p\u003e","manuscriptTitle":"Prognostic value of albumin-bilirubin score in hepatocellular carcinoma patients treated with Lenvatinib: A Real-world South Indian cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-01 13:20:12","doi":"10.21203/rs.3.rs-9161824/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0fe283c7-bbad-4e14-a1fc-ad2e5c32d20c","owner":[],"postedDate":"April 1st, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-02T16:54:47+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-01 13:20:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9161824","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9161824","identity":"rs-9161824","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}