Liver Fibrosis Despite Normal Aminotransferases – Implications for Hepatitis B Management and Treatment Eligibility in Viet Nam: A Cross-Sectional Study

Liver Fibrosis Despite Normal Aminotransferases – Implications for Hepatitis B Management and Treatment Eligibility in Viet Nam: A Cross-Sectional 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 Liver Fibrosis Despite Normal Aminotransferases – Implications for Hepatitis B Management and Treatment Eligibility in Viet Nam: A Cross-Sectional Study Thi Ai Phuong Truong, Thi Kim Lan Nguyen, Quang Thien Phu Pham, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9362409/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 10 You are reading this latest preprint version Abstract Background Chronic hepatitis B (CHB) is a major public health challenge in Viet Nam. Many patients have normal alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, yet clinically relevant fibrosis may progress silently. This study assessed fibrosis prevalence using transient elastography (FibroScan®) and identified factors associated with significant fibrosis (≥ F2) in CHB patients with normal aminotransferases. Methods We conducted a cross-sectional study among CHB patients aged ≥ 18 years at the Gastroenterology Clinic of 115 People’s Hospital, Ho Chi Minh City, from April 2024 to March 2025. Eligible patients were treatment-naïve with normal ALT and AST (Viet Nam Ministry of Health 2019 definition). Clinical, laboratory, and virological data were collected, and liver stiffness was measured by transient elastography. Logistic regression was used to assess predictors of fibrosis. Results Among 220 patients, 86.4% had no or mild fibrosis (F0–F1), 12.3% had significant fibrosis (F2), and 1.3% had advanced fibrosis (F3); none had cirrhosis (F4). In multivariable analysis, older age (OR 1.06; 95% CI 1.02–1.11) and lower platelet count (OR 0.98; 95% CI 0.98–0.99) were independent predictors of significant fibrosis. According to the 2019 Viet Nam Ministry of Health guidelines, 23.2% of patients with normal aminotransferases met indications for antiviral therapy, whereas application of the 2024 WHO criteria increased eligibility to 34.1%. Conclusions A substantial proportion of CHB patients with normal aminotransferases had significant fibrosis, underscoring the limitations of aminotransferase-based monitoring. Incorporating non-invasive fibrosis assessment into HBV programs could support earlier treatment and accelerate elimination efforts. Chronic hepatitis B liver fibrosis transient elastography FibroScan® aminotransferases Viet Nam Key Message Over one in eight Viet Namese CHB patients with normal ALT had significant fibrosis. Liver enzyme-based monitoring misses many treatment-eligible patients, delaying care and worsening outcomes. WHO 2024 guidelines expand eligibility: 34% qualified vs. 23% under Viet Nam 2019 criteria. Integrating non-invasive fibrosis assessment into national HBV programs can accelerate elimination progress. INTRODUCTION Chronic hepatitis B virus (HBV) infection remains a pressing global public health challenge, driving substantial morbidity and mortality through chronic liver disease, cirrhosis, and hepatocellular carcinoma. In 2019, approximately 295.9 million people—3.8% of the global population—were living with chronic HBV, resulting in more than 820,000 deaths, yet only about 6.6 million were receiving antiviral therapy [ 1 ]. The World Health Organization (WHO) Global Hepatitis Report 2024 highlights persistent obstacles in achieving elimination goals, particularly in low- and middle-income countries where access to diagnosis and treatment remains limited [ 2 ]. These gaps represent a major barrier to reaching the United Nations Sustainable Development Goal (SDG) of ending viral hepatitis as a public health threat by 2030. Viet Nam continues to face one of the highest HBV burdens in the Western Pacific region. A recent community-based seroprevalence survey reported HBsAg prevalence at 7.5% and evidence of past HBV exposure in nearly 50% of the population [ 3 ]. Such high prevalence not only places millions of individuals at risk for cirrhosis and liver cancer but also poses significant strain on the health system. HBV’s natural course is complex—progressing through immune tolerance, immune clearance, inactive carrier, and reactivation phases—and patients in so-called “low-risk” phases may still progress silently to advanced liver disease [ 4 ]. Studies have shown that even among patients with normal aminotransferases, up to one quarter may already have moderate-to-severe histologic disease [ 5 , 6 ]. From a public health perspective, these findings suggest that reliance on liver enzyme testing alone risks missing a substantial proportion of patients in need of earlier intervention. Effective antiviral therapy is available and proven to reduce the risk of cirrhosis and hepatocellular carcinoma [ 4 ]. However, guidelines from AASLD, EASL, APASL, and Viet Nam’s Ministry of Health emphasize that treatment eligibility should not be based solely on ALT or HBV DNA, but rather should incorporate fibrosis stage, age, family history, and other clinical factors [ 7 , 8 ]. In practice, many primary care health facilities—especially at the district and provincial levels—continue to depend primarily on liver enzyme monitoring, reflecting limitations in health system resources and diagnostic infrastructure. Wider adoption of non-invasive tools such as transient elastography (FibroScan®) could help bridge this gap, providing an accurate and accessible method for fibrosis staging that can be integrated into public health programs [ 9 ]. Despite Viet Nam’s high HBV prevalence and recent progress in vaccination and surveillance, limited data exist on the burden of fibrosis among patients with persistently normal aminotransferases. This knowledge gap has direct public health implications that without accurate detection of silent fibrosis, opportunities for early treatment and prevention of cancer and cirrhosis are lost. Addressing this challenge is critical to advancing HBV micro-elimination strategies and achieving equitable health outcomes. Taken all together, this study aims to 1) assess the distribution of fibrosis stages using transient elastography among chronic HBV patients with normal aminotransferases; 2) identify factors associated with significant fibrosis (≥ F2); and 3) examine associations between liver stiffness and clinical or laboratory markers such as age, platelet count, and HBV DNA levels. METHODS Study Population and Setting The study recruited adults aged ≥ 18 years with chronic HBV infection, normal alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and no history of antiviral therapy. The sampling frame was patients meeting these criteria who attended the Gastroenterology Clinic of 115 People’s Hospital, Ho Chi Minh City, between April 2024 and March 2025. Eligible participants were enrolled consecutively. Chronic HBV infection was defined as persistent positivity for hepatitis B surface antigen (HBsAg) and/or detectable HBV DNA for ≥ 6 months, or positivity for HBsAg with negativity for anti-HBc IgM. Normal aminotransferase levels were defined as ALT < 25 IU/L for women and < 35 IU/L for men. Participants were required to be treatment-naïve, not receiving medications known to lower aminotransferase levels, and to have complete laboratory and imaging results (blood count, ALT, AST, HBV DNA, HBeAg, anti-HCV, abdominal ultrasound, and FibroScan®). Written informed consent was obtained from all participants. Exclusion criteria were alternative causes of liver fibrosis, including anti-HCV positivity, hepatic steatosis on ultrasound, or significant alcohol use (≥ 20 g/day or ≥ 140 g/week for men; ≥10 g/day or ≥ 70 g/week for women for at least two consecutive years). Patients were also excluded if they had autoimmune hepatitis, hemochromatosis, Wilson’s disease, or if they were pregnant or breastfeeding. Study Design and Sample Size We conducted a cross-sectional study. The required sample size was calculated using the single-proportion formula with a 95% confidence level (Z = 1.96), a precision of 6%, and an estimated prevalence of significant fibrosis (≥ F2) of 28.7% based on a previous study in Spain [ 5 ]. The minimum required sample size was 219 participants. A consecutive sampling method was used until the target was achieved. Data Collection and Measures Data were collected using structured case report forms, including demographics (age, sex, anthropometrics), past medical history (hypertension, diabetes, dyslipidemia, family history of HBV or hepatocellular carcinoma), duration of HBV infection, and alcohol use. Laboratory assessments included complete blood count, ALT, aspartate aminotransferase (AST), HBeAg, HBV DNA, and anti-HCV. Abdominal ultrasound was performed in all participants. Liver fibrosis was assessed using transient elastography (FibroScan®, Echosens, Paris, France) performed by a single experienced radiologist using the M probe. Measurements were obtained from the right lobe through the intercostal space. Each patient underwent at least 10 valid measurements; results were considered reliable if the success rate exceeded 60% and the interquartile range (IQR) was < 30% of the median liver stiffness measurement (LSM). Fibrosis stages were classified according to the 2019 Viet Nam Ministry of Health guidelines: F0–F1 (< 7.0 kPa), F2 (7.0–<9.5 kPa), F3 (9.5–<11.0 kPa), and F4 (≥ 11.0 kPa). Statistical Analysis Data were entered into Microsoft Excel 2019 and analyzed using IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation (SD) or median with interquartile range (IQR), depending on distribution. Categorical variables were reported as frequencies and percentages. Comparisons between groups were conducted using Student’s t test or Mann–Whitney U test for continuous variables and chi-square test for categorical variables. Factors associated with significant fibrosis (≥ F2) were examined using univariable and multivariable logistic regression. Variables with p < 0.10 in univariable analyses were entered into the multivariable model. Statistical significance was set at p < 0.05. Potential confounders considered in regression analysis included age, sex, body mass index (BMI), diabetes, hypertension, platelet count, and HBV DNA level. Missing data were minimal (< 5% for all variables). Patients with missing values were excluded from regression analyses but included in descriptive statistics. Ethical Considerations The study adhered to the principles of the Declaration of Helsinki. As an observational, non-interventional study, no additional risks were posed to participants. All patients were informed of the study objectives and procedures and provided written informed consent prior to enrollment. Personal identifiers were removed, and data were coded to maintain confidentiality throughout the study. Approval was obtained from the Institutional Review Board of 115 People’s Hospital, Ho Chi Minh City. RESULTS Patients’ characteristics Between April 2024 and March 2025, a total of 220 patients with chronic HBV infection and normal ALT and AST levels were enrolled. The baseline characteristics are summarized in Table 1 . The mean age was 41.9 ± 11.3 years, with most participants aged 30–60 years (81%). Females accounted for 59.5% of the study population. More than half of patients (55.0%) reported HBV infection for over 10 years. At the time of enrollment, most were asymptomatic, with 58.2% having no clinical symptoms and 65.9% showing no abnormal physical findings. The median BMI was 21.6 kg/m². According to WHO criteria, 65.9% had a normal BMI, with women tending to have lower BMI than men. The median platelet count was 236 K/µL, and 95% of patients had values ≥ 150 K/µL. Mean ALT and AST levels were within the normal range (ALT with 20.74 ± 5.8 U/L and AST with 21.28 U/L). The majority of patients were HBeAg negative (74.5%), and 45.0% had undetectable HBV DNA. Abdominal ultrasound revealed abnormalities in 50.5% of cases, though most were extrahepatic; only a small proportion showed changes suggestive of cirrhosis. Table 1 Patients’ characteristics (n = 220) Characteristics Values Demographics Age (years) , mean ± SD 41.95 ± 11.29 Age groups , n (%) 60 years 13 (5.9%) Sex Female , n (%) 131 (59.5%) Clinical characteristics Duration of HBV infection , n (%) 6 months – 5 years 24 (10.9%) 5–10 years 75 (34.1%) > 10 years 121 (55.0%) Past medical history , n (%) None 140 (63.6%) Family history of HCC/cirrhosis/HBV 86 (39.1%) Hypertension 26 (11.8%) Hyperlipidemia 17 (7.7%) Diabetes mellitus 13 (5.9%) Other comorbidities (e.g., gastritis, varices) 45 (20.5%) Clinical symptoms , n (%) None 128 (58.2%) Bloating 27 (12.3%) Loss of appetite 19 (8.6%) RUQ tenderness 14 (6.4%) Others (heartburn, weight loss, nausea, etc.) 25 (11.4%) Physical signs , n (%) None 145 (65.9%) Jaundice/spider angiomas/palmar erythema 4 (1.8%) Hepatomegaly/splenomegaly 9 (4.1%) Others (edema, erythema) 28 (12.7%) BMI (kg/m²) , median (IQR) 21,60 (20.00–23.50) WHO BMI Classification , n (%) Normal (18.5–22.9) 145 (65.9%) Overweight (23–24.9) 54 (24.5%) Obese (25–29.9) 21 (9.5%) Laboratory and imaging characteristics Platelet counts (K/µL) , median (IQR) 236 (200–283) AST (U/L) , median (IQR) 21.28 (18.42–24.00) ALT (U/L) , mean ± SD 20.74 ± 5.78 HBeAg , n (%) 56 (25.5%) HBV DNA levels , n (%) Undetectable 99 (45.0%) 20,000 IU/ml 32 (14.5%) Abdominal sonography , n (%) None detected 108 (49.1%) Others (kidney stone, liver cyst, liver hemangioma, uterine fibroids) 104 (47.3%) Coarsened hepatic echotexture and/or cirrhosis 7 (3.2%) Liver stiffness by FibroScan (kPa) , median (IQR) 5.50 (4.80–6.30) Fibrosis stage by FibroScan , n (%) F0–F1 190 (86.4%) F2 27 (12.3%) F3 3 (1.3%) F4 0 (0.0%) Liver Fibrosis by Transient Elastography The median liver stiffness measurement was 5.5 kPa (IQR 4.8–6.3), ranging from 2.9 to 10.7 kPa (Table 2 ). Based on fibrosis staging criteria, 86.4% of patients were classified as F0–F1, 12.3% as F2 (significant fibrosis), and 1.3% as F3 (advanced fibrosis). No patients had cirrhosis (F4). Overall, 13.6% of participants had significant fibrosis or worse (≥ F2) despite having persistently normal aminotransferase levels. Factors Associated with Significant Liver Fibrosis Compared to patients without fibrosis or with only mild fibrosis (F0–F1), those with significant fibrosis (≥ F2) were older (mean age 48.93 ± 11.46 vs. 40.84 ± 10.89 years, p < 0.001). The prevalence of overweight or obesity was also higher in this group (53.3% vs. 31.1%, p = 0.035). Median platelet count was lower among patients with ≥F2 fibrosis (208 K/µL vs. 241 K/µL, p < 0.001), and 30% had thrombocytopenia (< 150 K/µL). In terms of virological markers, the proportion of HBeAg positivity was greater in the significant fibrosis group (46.7% vs. 22.1%, p = 0.004). Likewise, a higher proportion had HBV DNA levels ≥ 2000 IU/mL (80.0% vs. 21.6%, p < 0.001). No significant differences were observed in ALT or AST levels between the two groups. Table 2 Associations of fibrosis stages with patients’ characteristics Characteristics Fibrosis staging P values F0–F1(n = 190) ≥ F2(n = 30) Sex , n (%) 0.122ᵃ Female 117 (61.60%) 14 (46.70%) Male 73 (38.40%) 16 (53.30%) Age (years) , mean ± SD 40.84 ± 10.89 48.93 ± 11.46 < 0.001ᵈ Age groups , n (%) 0.001ᵇ 60 years 7 (3.70%) 6 (20.00%) Duration of HBV infection , n (%) 0.847ᵇ 6 months – 5 years 22 (11.60%) 2 (6.70%) 5–10 years 64 (33.70%) 11 (36.70%) > 10 years 104 (54.70%) 17 (56.70%) BMI (kg/m²) , median (IQR) 21.55 (19.98–23.33) 22.55 (20.90–23.83) 0.173ᶜ WHO BMI Classification , n (%) 0.035ᵇ Normal (18.5–22.9) 131 (68.90%) 14 (46.70%) Overweight (23–24.9) 41 (21.60%) 13 (43.30%) Obese (25–29.9) 18 (9.50%) 3 (10.00%) Platelet counts (K/µL) , median (IQR) 241 (203–287) 208 (144–249) < 0,001ᶜ Classification of platelet counts . n (%) < 0.001ᵇ ≥ 150,000/µL 188 (98.90%) 21 (70.00%) < 150,000/µL 2 (1.10%) 9 (30.00%) AST (U/L) , median (IQR) 21.32 (18.40–24.00) 21.00 (19.09–24.24) 0.830ᶜ ALT (U/L) , mean ± SD 20.55 ± 5.79 21.96 ± 5.66 0.214ᵈ HBeAg , n (%) 0.004ᵃ Positive 42 (22.10%) 14 (46.70%) Negative 148 (77.90%) 16 (53.30%) HBV DNA levels , n (%) < 0.001ᵃ < 2000 IU/ml 149 (78.40%) 6 (20.00%) ≥ 2000 IU/ml 41 (21.60%) 24 (80.00%) ᵃChi-square test; ᵇFisher’s exact test; ᶜMann–Whitney test (non-normal distribution); ᵈIndependent-Samples T Test (normal distribution) Univariable logistic regression identified age (OR = 1.06, 95% CI = 1.03–1.10), platelet count (OR = 0.98, 95% CI = 0.97–0.99), and HBV DNA load (OR = 1.00; p = 0.037) as significant predictors of fibrosis ≥F2. In the multivariable model, only age and platelet count remained independent predictors (Table 3 ). Table 3 Logistic regresion analysis of factors associated with significant fibrosis (≥ F2) Predictors OR 95% Confidence Interval Adjusted OR 95% Confidence Interval Age 1.06 1.03–1.10 1.06 1.02–1.11 BMI 1.14 0.97–1.35 — — Platelet counts (K/µL) 0.98 0.97–0.99 0.98 0.98–0.99 HBV DNA levels (IU/mL) 1.00 1.00–1.00 — — Correlation Between Liver Stiffness and Clinical or Laboratory Parameters The correlations between liver stiffness measurements (kPa) and selected clinical and laboratory variables are presented in Table 4 . Liver stiffness showed weak but statistically significant positive correlations with age ( r = 0.268, p < 0.001). body mass index (BMI) ( r = 0.195, p = 0.004), and HBV DNA levels ( r = 0.296, p < 0.001). Conversely, platelet count demonstrated a weak negative correlation with liver stiffness ( r = − 0.202, p = 0.003). Although these associations were statistically significant, all correlation coefficients were below 0.3, indicating only weak relationships between liver stiffness and the examined variables. Table 4 Correlation of liver stiffness (kPa) with clinical and laboratory characteristics Characteristics r coefficients p values Age 0.268 < 0.001 BMI 0.195 0.004 Platelet counts (K/µL) -0.202 0.003 HBV DNA levels (IU/mL) 0.296 < 0.001 Proportion of Patients Meeting Antiviral Treatment Criteria The proportion of patients eligible for antiviral therapy according to two current guideline systems is presented in Table 5 . Based on the 2019 Viet Nam Ministry of Health (MOH) guidelines, 23.2% of patients (51/220) met treatment indications. Specifically, 5.9% had significant fibrosis (≥ F2) with HBV DNA ≥ 2000 IU/mL and were HBeAg-negative; 2.7% had significant fibrosis with HBV DNA ≥ 20,000 IU/mL and were HBeAg-positive; and 14.6% had a family history of hepatocellular carcinoma or cirrhosis. Using the updated World Health Organization (WHO) 2024 guidelines, the proportion of eligible patients increased to 34.1% (75/220). Among these, 13.6% had significant fibrosis (≥ F2), 5.9% had diabetes mellitus, and 14.6% reported a family history of liver disease. Table 5 Proportion of patients eligible for antiviral therapy according to WHO (2024) and Viet Nam Ministry of Health (2019) guidelines Treatment eligibility Viet Nam Ministry of Health 2019 WHO 2024 Fibrosis ≥ F2, HBV DNA ≥ 2000 IU/mL, and HBeAg (+) 13 (5.91%) — Fiborsis ≥ F2, HBV DNA ≥ 20.000 IU/mL, and HBeAg (+) 6 (2.72%) — Family history of HCC and/or cirrhosis 32 (14.55%) 32 (14.55%) Fibrosis ≥ F2 — 30 (13.64%) Concurrent Diabetes mellitus — 13 (5.91%) Total eligible 51 (23.2%) 75 (34.1%) DISCUSSION In this cross-sectional study, we found that while the majority had minimal fibrosis (F0–F1, 86.4%), a clinically significant proportion already showed evidence of significant (F2, 12.3%) or advanced (F3, 1.3%) fibrosis, despite the absence of elevated liver enzymes. Several factors differed significantly between patients with and without significant fibrosis, including age, body mass index (BMI), HBeAg status, platelet count, and HBV DNA levels. Liver stiffness was positively correlated with age, BMI, and HBV DNA, and negatively correlated with platelet count. Importantly, age emerged as an independent predictor of fibrosis ≥F2 (OR 1.06; 95% CI 1.02–1.11), underscoring that the risk of liver damage increases progressively with advancing age, even among asymptomatic individuals with normal aminotransferases. From a public health perspective, these findings highlight the limitations of relying solely on ALT for patient monitoring and treatment eligibility, and strengthen the case for incorporating non-invasive fibrosis assessment into HBV control programs to prevent missed opportunities for early intervention. In this study, the median liver stiffness among chronic hepatitis B (CHB) patients with normal aminotransferases was 5.5 kPa, comparable to findings from Viet Nam (5.3 kPa) [ 10 ] and lower than values reported in Spain (6.3 ± 5.8 kPa) [ 5 ]. The lower stiffness in our cohort may reflect exclusion of patients with hepatic steatosis or significant alcohol use—both known contributors to increased stiffness [ 11 ]. Although most patients (86.4%) were classified as F0–F1, a notable 13.6% had significant or advanced fibrosis (≥ F2). This aligns with prior biopsy-based studies showing that 20–30% of CHB patients with persistently normal ALT still had histological fibrosis ≥F2 [ 12 ]. Kumar et al. reported a higher prevalence (56.6%) in India, which may be attributable to older ALT cutoffs (40 U/L) and reliance on biopsy rather than transient elastography [ 13 ]. San Juan López et al. also observed higher rates, likely influenced by different fibrosis cutoffs (≥ 7.9 kPa) and higher obesity prevalence (62% vs. 9.5% in our study) [ 5 ]. These findings highlight that even patients with normal ALT may harbor progressive disease, underscoring the need for comprehensive fibrosis assessment in CHB management. We identified older age and lower platelet count as independent predictors of significant fibrosis. Each additional year of age increased the risk of fibrosis by 6%, consistent with prior evidence that host factors such as age, sex, and family history shape fibrosis progression [ 14 , 15 ]. Similar findings have been reported in China and Korea, where older patients showed more advanced histological changes despite normal ALT [ 22 , 23 ]. BMI was also higher in patients with fibrosis ≥F2. This association is consistent with evidence linking metabolic syndrome and obesity with fibrosis progression in CHB [ 16 , 24 ]. Metabolic cofactors may act synergistically with HBV to accelerate fibrogenesis, even in the absence of elevated liver enzymes. Platelet count was inversely correlated with liver stiffness (r = − 0.202, p = 0.003). This supports its role as a surrogate marker of fibrosis, explained by reduced thrombopoietin synthesis, hypersplenism, or portal hypertension [ 17 – 19 ]. Thrombocytopenia has been widely validated as a component of non-invasive fibrosis indices such as APRI and FIB-4, which remain particularly valuable in low-resource settings [ 25 , 26 ]. Notably, ALT and AST levels did not differ significantly between fibrosis groups, supporting the argument that aminotransferases are unreliable markers of disease severity [ 20 , 21 ]. Recent data confirm that a substantial proportion of CHB patients with normal ALT exhibit moderate-to-severe histological activity, reinforcing calls to broaden treatment eligibility beyond ALT thresholds [ 27 ]. Applying the 2019 Viet Nam Ministry of Health (MOH) guidelines, only 23.2% of patients met treatment criteria, whereas the proportion increased to 34.1% under the 2024 WHO guidelines. This reflects a paradigm shift in HBV management, where non-invasive fibrosis assessment and broader clinical criteria identify more patients at risk of progression [ 2 , 7 ]. Recent studies confirm that earlier antiviral therapy reduces the risk of cirrhosis and hepatocellular carcinoma, even in patients with normal ALT [ 8 , 27 ]. From a public health perspective, these findings underscore the importance of integrating transient elastography into national HBV programs. FibroScan® offers a scalable and reproducible alternative to biopsy [ 9 , 28 ], and when combined with simple markers like platelet count, can enable effective stratification in resource-limited settings [ 25 ]. Wider adoption could prevent missed treatment opportunities and accelerate progress toward HBV elimination goals by 2030 [ 2 ]. This study has several limitations. First, it was conducted among outpatients at a single tertiary hospital in Ho Chi Minh City, which may limit the generalizability of findings to all chronic hepatitis B patients in Viet Nam. Hospitalized patients, who often have more severe or complex disease, were not represented and may have a different fibrosis burden. However, outpatients constitute the majority of individuals living with chronic HBV in the community, and their clinical profile may be more comparable to the general population, particularly for public health surveillance and programmatic planning. Future studies with larger, multicenter cohorts will be important to confirm and extend these findings. Second, liver fibrosis was assessed exclusively with transient elastography (FibroScan®). Although FibroScan is a reliable, non-invasive method that is highly suitable for large-scale screening and public health programs, it cannot fully replace liver biopsy, the histological gold standard. Biopsy, however, is invasive, carries procedural risks, and is not realistic for routine practice or population-level studies. As such, the reliance on FibroScan may have underestimated the true prevalence of fibrosis in this cohort. Future research should consider combining transient elastography with other non-invasive markers to further enhance diagnostic accuracy in real-world settings. CONCLUSION Although most chronic hepatitis B patients with normal aminotransferases had minimal fibrosis, more than one in eight were already living with significant disease that would have been missed using current ALT-based monitoring alone. This evidence shows that liver enzyme testing is insufficient as a population-level screening tool and that broader, risk-based approaches are urgently needed. Public health programs in Viet Nam and other high-burden countries should integrate non-invasive fibrosis assessment into routine HBV care, alongside systematic evaluation of family history, metabolic risk, and virological markers, to enable earlier treatment. Embedding these strategies in national elimination plans will not only improve individual outcomes but also strengthen progress toward the 2030 Sustainable Development Goal of ending viral hepatitis as a public health threat. Declarations Funding This study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Conflicts of Interest The authors declare that they have no competing interests. Ethics Approval and Consent to Participate The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of 115 People’s Hospital, Ho Chi Minh. Written informed consent was obtained from all participants prior to enrollment. Consent to Publish declaration Not applicable Data Availability The datasets generated and analyzed during the current study are not publicly available due to patient confidentiality but are available from the corresponding author on reasonable request. Code Availability This study used standard software packages as described in the Methods section; no custom code was developed. Author Contributions Truong Thi Ai Phuong: Conceptualization, Methodology, Data Curation, Formal Analysis, Writing – Original Draft. Nguyen Thi Kim Lan: Investigation, Resources, Data Collection, Writing – Review & Editing. Pham Quang Thien Phu: Methodology, Investigation, Data Collection, Project Administration. Tran Vy Thao: Writing – Original Draft, Writing – Review & Editing, Visualization. Thanh Van Kim: Methodology, Writing – Original Draft, Writing – Review & Editing, Literature Review. Tran Kinh Thanh: Conceptualization, Methodology, Supervision, Formal Analysis, Writing – Review & Editing, Project Administration. Acknowledgements The authors thank the clinical staff of the Gastroenterology Clinic, 115 People’s Hospital, Ho Chi Minh City, for their support in patient recruitment and data collection. We also acknowledge the patients who generously participated in this study. Clinical trial number Not applicable References Cui F, Blach S, Mingiedi CM, et al. Global reporting of progress towards elimination of hepatitis B and hepatitis C. Lancet Gastroenterol Hepatol. 2023;8(10):915–28. https://doi.org/10.1016/S2468-1253(22)00386-7 . World Health Organization. Global hepatitis report 2024: action for access in low- and middle-income countries. Geneva: WHO; 2024. https://www.who.int/publications/i/item/9789240091672 . Pham TND, Le DH, Dao DVB, et al. Establishing baseline framework for hepatitis B virus micro-elimination in Ho Chi Minh City, Viet Nam: a community-based seroprevalence study. Lancet Reg Health West Pac. 2023;30:100620. https://doi.org/10.1016/j.lanwpc.2022.100620 . Zhou J, Wang FD, Wang ML, et al. Antiviral therapy for chronic HBV infection with persistently normal alanine aminotransferase: controversy and consensus. Front Med. 2021;8:717125. https://doi.org/10.3389/fmed.2021.717125 . San Juan López C, Marta CM, Mercedes GS, et al. Characterization and evaluation of liver fibrosis grade in patients with chronic hepatitis B virus infection and normal transaminases. Clin Mol Hepatol. 2018;24(4):384–91. https://doi.org/10.3350/cmh.2018.0004 . Wang H, Ru GQ, Yan R, et al. Histologic disease in Chinese chronic hepatitis B patients with low viral loads and persistently normal alanine aminotransferase levels. J Clin Gastroenterol. 2016;50(9):790–6. https://doi.org/10.1097/mcg.0000000000000544 . Cornberg M, Sandmann L, Jaroszewicz J, et al. EASL Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2025;S0168. https://doi.org/10.1016/j.jhep.2025.03.018 . -8278(25)00052 – 1. Lim YS, Kim WR, Dieterich D, et al. Evidence for benefits of early treatment initiation for chronic hepatitis B. Viruses. 2023;15(4):997. https://doi.org/10.3390/v15040997 . Wong GLH. Transient elastography (FibroScan®): a new look of liver fibrosis and beyond. Euroasian J Hepatogastroenterol. 2013;3(1):70–7. https://doi.org/10.5005/jp-journals-10018-1067 . Vu Hai V, Shimakawa Y, Kim J, et al. Assessment and simplification of treatment eligibility among patients with chronic hepatitis B infection in Viet Nam. Clin Infect Dis. 2021;73(5):e1072–7. https://doi.org/10.1093/cid/ciaa1814 . Wong VWS, Chan WK, Chitturi S, et al. Asia–Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines 2017—part 1: definition, risk factors and assessment. J Gastroenterol Hepatol. 2018;33(1):70–85. https://doi.org/10.1111/jgh.13857 . Bárcena Marugán R, García Garzón S. DNA-guided hepatitis B treatment: viral load is essential, but not sufficient. World J Gastroenterol. 2009;15(4):423–30. https://doi.org/10.3748/wjg.15.423 . Kumar M, Sarin SK, Hissar S, et al. Virologic and histologic features of chronic hepatitis B virus-infected asymptomatic patients with persistently normal ALT. Gastroenterology. 2008;134(5):1376–84. https://doi.org/10.1053/j.gastro.2008.02.075 . Zheng B, Zhu YJ, Wang HY, Chen L. Gender disparity in hepatocellular carcinoma: multiple underlying mechanisms. Sci China Life Sci. 2017;60(6):575–84. https://doi.org/10.1007/s11427-016-9043-9 . Wang SH, Chen PJ, Yeh SH. Gender disparity in chronic hepatitis B: mechanisms of sex hormones. J Gastroenterol Hepatol. 2015;30(8):1237–45. https://doi.org/10.1111/jgh.12934 . Mena Á, Pedreira JD, Castro Á, et al. Metabolic syndrome association with fibrosis development in chronic hepatitis B virus inactive carriers. J Gastroenterol Hepatol. 2014;29(1):173–8. https://doi.org/10.1111/jgh.12432 . Aiolfi R, Sitia G. Chronic hepatitis B: role of anti-platelet therapy in inflammation control. Cell Mol Immunol. 2015;12(3):264–8. https://doi.org/10.1038/cmi.2014.124 . Balaphas A, Meyer J, Sadoul K, et al. Platelets and platelet-derived extracellular vesicles in liver physiology and disease. Hepatol Commun. 2019;3(7):855–66. https://doi.org/10.1002/hep4.1358 . Afdhal N, McHutchison J, Brown R, et al. Thrombocytopenia associated with chronic liver disease. J Hepatol. 2008;48(6):1000–7. https://doi.org/10.1016/j.jhep.2008.03.009 . Zhao Q, Liu K, Zhu X, et al. Antiviral effect in chronic hepatitis B patients with normal or mildly elevated alanine aminotransferase. Antiviral Res. 2020;184:104953. https://doi.org/10.1016/j.antiviral.2020.104953 . Gong X, Yang J, Tang J, et al. A mechanistic assessment of the discordance between normal serum alanine aminotransferase levels and altered liver histology in chronic hepatitis B. PLoS ONE. 2015;10(7):e0134532. https://doi.org/10.1371/journal.pone.0134532 . Kim JH, Kim MN, Han KH, Kim SU. Clinical application of transient elastography in patients with chronic viral hepatitis receiving antiviral treatment. Liver Int. 2015;35(4):1103–15. https://doi.org/10.1111/liv.12628 . Liu J, Wang J, Yan X, et al. Presence of Liver Inflammation in Asian Patients With Chronic Hepatitis B With Normal ALT and Detectable HBV DNA in Absence of Liver Fibrosis. Hepatol Commun. 2022;6(4):855–66. https://doi.org/10.1002/hep4.1859 . Zhang L, Wu HD, Qian YF, Xu HY. Prevalence of nonalcoholic fatty liver disease in patients with hepatitis B: A meta-analysis. World J Clin Cases. 2024;12(25):5749–60. https://doi.org/10.12998/wjcc.v12.i25.5749 . Lemoine M, Shimakawa Y, Nayagam S, et al. The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa. Gut. 2016;65(8):1369–76. https://doi.org/10.1136/gutjnl-2015-309260 . Zeng DW, Dong J, Liu YR, Jiang JJ, Zhu YY. Noninvasive models for assessment of liver fibrosis in patients with chronic hepatitis B virus infection. World J Gastroenterol. 2016;22(29):6663–72. https://doi.org/10.3748/wjg.v22.i29.6663 . Tseng TC, Kao JH. Treating Immune-tolerant Hepatitis B. J Viral Hepat. 2015;22(2):77–84. https://doi.org/10.1111/jvh.12370 . Marcellin P, Ziol M, Bedossa P, et al. Non-invasive assessment of liver fibrosis by stiffness measurement in patients with chronic hepatitis B. Liver Int. 2009;29(2):242–7. https://doi.org/10.1111/j.1478-3231.2008.01802.x . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 18 May, 2026 Reviews received at journal 16 May, 2026 Reviews received at journal 07 May, 2026 Reviewers agreed at journal 30 Apr, 2026 Reviewers agreed at journal 27 Apr, 2026 Reviewers agreed at journal 27 Apr, 2026 Reviewers invited by journal 15 Apr, 2026 Editor assigned by journal 14 Apr, 2026 Submission checks completed at journal 13 Apr, 2026 First submitted to journal 08 Apr, 2026 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-9362409","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":623702508,"identity":"4e888334-eaa3-44ee-bca7-80fa83de6ee6","order_by":0,"name":"Thi Ai Phuong Truong","email":"","orcid":"","institution":"115 People Hospital","correspondingAuthor":false,"prefix":"","firstName":"Thi","middleName":"Ai Phuong","lastName":"Truong","suffix":""},{"id":623702509,"identity":"033cead8-ce90-4889-96d1-e9a69bb83234","order_by":1,"name":"Thi Kim Lan Nguyen","email":"","orcid":"","institution":"115 People Hospital","correspondingAuthor":false,"prefix":"","firstName":"Thi","middleName":"Kim Lan","lastName":"Nguyen","suffix":""},{"id":623702510,"identity":"7b18e063-3636-49b2-b5ff-16709ba6d3a5","order_by":2,"name":"Quang Thien Phu Pham","email":"","orcid":"","institution":"115 People Hospital","correspondingAuthor":false,"prefix":"","firstName":"Quang","middleName":"Thien Phu","lastName":"Pham","suffix":""},{"id":623702511,"identity":"2eed0e5d-ec26-4fbe-a25b-39d4d38391ac","order_by":3,"name":"Vy Thao Tran","email":"","orcid":"","institution":"Viet Nam National University","correspondingAuthor":false,"prefix":"","firstName":"Vy","middleName":"Thao","lastName":"Tran","suffix":""},{"id":623702512,"identity":"a8edf3e3-2d3b-469f-8f6c-0269cb0df4c9","order_by":4,"name":"Thanh Van Kim","email":"","orcid":"","institution":"Pham Ngoc Thach University of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Thanh","middleName":"Van","lastName":"Kim","suffix":""},{"id":623702513,"identity":"fa197f6b-18b3-4543-877e-5bad6dcbb9fa","order_by":5,"name":"Kinh Thanh Tran","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBklEQVRIiWNgGAWjYJACxgYDhgQGCQYGZsZ//+VAIgce4FHOA9PCA9LCwMZsDNaSQFALA0JLYgNIGJ8We+nDzx7OKLiTZy/d/OxxAQ9b+vywww+BttjJ6TbgsIUvzdxwg8GzYh6ZY+bGMyR4cjfeTjMAakk2NjuAQwsPg5nkA4PDiT0SCWbSPAYSuRtnJ4C0HEjchlML+zeolvRv0jwJBumGs9M/ENDCYya5AawlB2jLgYQEeekcArac4SmTnAHSciOnTJq34YDhBumcggMJBrj9wt7Dvk2y58/hxPYZ6dtAWuTlZ6dv/vChwk4OlxZMYABWaUCschCQbyBF9SgYBaNgFIwEAAB1x11E+3wANwAAAABJRU5ErkJggg==","orcid":"","institution":"115 People Hospital","correspondingAuthor":true,"prefix":"","firstName":"Kinh","middleName":"Thanh","lastName":"Tran","suffix":""}],"badges":[],"createdAt":"2026-04-09 03:08:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9362409/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9362409/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107706702,"identity":"5c6dbe8d-28ec-4f09-9e9b-0d8c7e91d9cc","added_by":"auto","created_at":"2026-04-24 09:18:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":412845,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9362409/v1/46e08cb0-1a51-49b4-9d7d-bc5e5d626929.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Liver Fibrosis Despite Normal Aminotransferases – Implications for Hepatitis B Management and Treatment Eligibility in Viet Nam: A Cross-Sectional Study","fulltext":[{"header":"Key Message","content":"\u003cul\u003e\n \u003cli\u003eOver one in eight Viet Namese CHB patients with normal ALT had significant fibrosis.\u003c/li\u003e\n \u003cli\u003eLiver enzyme-based monitoring misses many treatment-eligible patients, delaying care and worsening outcomes.\u003c/li\u003e\n \u003cli\u003eWHO 2024 guidelines expand eligibility: 34% qualified vs. 23% under Viet Nam 2019 criteria.\u003c/li\u003e\n \u003cli\u003eIntegrating non-invasive fibrosis assessment into national HBV programs can accelerate elimination progress.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"INTRODUCTION","content":"\u003cp\u003eChronic hepatitis B virus (HBV) infection remains a pressing global public health challenge, driving substantial morbidity and mortality through chronic liver disease, cirrhosis, and hepatocellular carcinoma. In 2019, approximately 295.9\u0026nbsp;million people\u0026mdash;3.8% of the global population\u0026mdash;were living with chronic HBV, resulting in more than 820,000 deaths, yet only about 6.6\u0026nbsp;million were receiving antiviral therapy [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The World Health Organization (WHO) Global Hepatitis Report 2024 highlights persistent obstacles in achieving elimination goals, particularly in low- and middle-income countries where access to diagnosis and treatment remains limited [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. These gaps represent a major barrier to reaching the United Nations Sustainable Development Goal (SDG) of ending viral hepatitis as a public health threat by 2030.\u003c/p\u003e \u003cp\u003eViet Nam continues to face one of the highest HBV burdens in the Western Pacific region. A recent community-based seroprevalence survey reported HBsAg prevalence at 7.5% and evidence of past HBV exposure in nearly 50% of the population [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Such high prevalence not only places millions of individuals at risk for cirrhosis and liver cancer but also poses significant strain on the health system. HBV\u0026rsquo;s natural course is complex\u0026mdash;progressing through immune tolerance, immune clearance, inactive carrier, and reactivation phases\u0026mdash;and patients in so-called \u0026ldquo;low-risk\u0026rdquo; phases may still progress silently to advanced liver disease [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Studies have shown that even among patients with normal aminotransferases, up to one quarter may already have moderate-to-severe histologic disease [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. From a public health perspective, these findings suggest that reliance on liver enzyme testing alone risks missing a substantial proportion of patients in need of earlier intervention.\u003c/p\u003e \u003cp\u003eEffective antiviral therapy is available and proven to reduce the risk of cirrhosis and hepatocellular carcinoma [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, guidelines from AASLD, EASL, APASL, and Viet Nam\u0026rsquo;s Ministry of Health emphasize that treatment eligibility should not be based solely on ALT or HBV DNA, but rather should incorporate fibrosis stage, age, family history, and other clinical factors [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In practice, many primary care health facilities\u0026mdash;especially at the district and provincial levels\u0026mdash;continue to depend primarily on liver enzyme monitoring, reflecting limitations in health system resources and diagnostic infrastructure. Wider adoption of non-invasive tools such as transient elastography (FibroScan\u0026reg;) could help bridge this gap, providing an accurate and accessible method for fibrosis staging that can be integrated into public health programs [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite Viet Nam\u0026rsquo;s high HBV prevalence and recent progress in vaccination and surveillance, limited data exist on the burden of fibrosis among patients with persistently normal aminotransferases. This knowledge gap has direct public health implications that without accurate detection of silent fibrosis, opportunities for early treatment and prevention of cancer and cirrhosis are lost. Addressing this challenge is critical to advancing HBV micro-elimination strategies and achieving equitable health outcomes. Taken all together, this study aims to 1) assess the distribution of fibrosis stages using transient elastography among chronic HBV patients with normal aminotransferases; 2) identify factors associated with significant fibrosis (\u0026ge;\u0026thinsp;F2); and 3) examine associations between liver stiffness and clinical or laboratory markers such as age, platelet count, and HBV DNA levels.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population and Setting\u003c/h2\u003e \u003cp\u003eThe study recruited adults aged\u0026thinsp;\u0026ge;\u0026thinsp;18 years with chronic HBV infection, normal alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and no history of antiviral therapy. The sampling frame was patients meeting these criteria who attended the Gastroenterology Clinic of 115 People\u0026rsquo;s Hospital, Ho Chi Minh City, between April 2024 and March 2025. Eligible participants were enrolled consecutively.\u003c/p\u003e \u003cp\u003eChronic HBV infection was defined as persistent positivity for hepatitis B surface antigen (HBsAg) and/or detectable HBV DNA for \u0026ge;\u0026thinsp;6 months, or positivity for HBsAg with negativity for anti-HBc IgM. Normal aminotransferase levels were defined as ALT\u0026thinsp;\u0026lt;\u0026thinsp;25 IU/L for women and \u0026lt;\u0026thinsp;35 IU/L for men. Participants were required to be treatment-na\u0026iuml;ve, not receiving medications known to lower aminotransferase levels, and to have complete laboratory and imaging results (blood count, ALT, AST, HBV DNA, HBeAg, anti-HCV, abdominal ultrasound, and FibroScan\u0026reg;). Written informed consent was obtained from all participants.\u003c/p\u003e \u003cp\u003eExclusion criteria were alternative causes of liver fibrosis, including anti-HCV positivity, hepatic steatosis on ultrasound, or significant alcohol use (\u0026ge;\u0026thinsp;20 g/day or \u0026ge;\u0026thinsp;140 g/week for men; \u0026ge;10 g/day or \u0026ge;\u0026thinsp;70 g/week for women for at least two consecutive years). Patients were also excluded if they had autoimmune hepatitis, hemochromatosis, Wilson\u0026rsquo;s disease, or if they were pregnant or breastfeeding.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy Design and Sample Size\u003c/h3\u003e\n\u003cp\u003eWe conducted a cross-sectional study. The required sample size was calculated using the single-proportion formula with a 95% confidence level (Z\u0026thinsp;=\u0026thinsp;1.96), a precision of 6%, and an estimated prevalence of significant fibrosis (\u0026ge;\u0026thinsp;F2) of 28.7% based on a previous study in Spain [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The minimum required sample size was 219 participants. A consecutive sampling method was used until the target was achieved.\u003c/p\u003e\n\u003ch3\u003eData Collection and Measures\u003c/h3\u003e\n\u003cp\u003eData were collected using structured case report forms, including demographics (age, sex, anthropometrics), past medical history (hypertension, diabetes, dyslipidemia, family history of HBV or hepatocellular carcinoma), duration of HBV infection, and alcohol use. Laboratory assessments included complete blood count, ALT, aspartate aminotransferase (AST), HBeAg, HBV DNA, and anti-HCV. Abdominal ultrasound was performed in all participants.\u003c/p\u003e \u003cp\u003eLiver fibrosis was assessed using transient elastography (FibroScan\u0026reg;, Echosens, Paris, France) performed by a single experienced radiologist using the M probe. Measurements were obtained from the right lobe through the intercostal space. Each patient underwent at least 10 valid measurements; results were considered reliable if the success rate exceeded 60% and the interquartile range (IQR) was \u0026lt;\u0026thinsp;30% of the median liver stiffness measurement (LSM). Fibrosis stages were classified according to the 2019 Viet Nam Ministry of Health guidelines: F0\u0026ndash;F1 (\u0026lt;\u0026thinsp;7.0 kPa), F2 (7.0\u0026ndash;\u0026lt;9.5 kPa), F3 (9.5\u0026ndash;\u0026lt;11.0 kPa), and F4 (\u0026ge;\u0026thinsp;11.0 kPa).\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eData were entered into Microsoft Excel 2019 and analyzed using IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) or median with interquartile range (IQR), depending on distribution. Categorical variables were reported as frequencies and percentages. Comparisons between groups were conducted using Student\u0026rsquo;s \u003cem\u003et\u003c/em\u003e test or Mann\u0026ndash;Whitney U test for continuous variables and chi-square test for categorical variables. Factors associated with significant fibrosis (\u0026ge;\u0026thinsp;F2) were examined using univariable and multivariable logistic regression. Variables with \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.10 in univariable analyses were entered into the multivariable model. Statistical significance was set at \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Potential confounders considered in regression analysis included age, sex, body mass index (BMI), diabetes, hypertension, platelet count, and HBV DNA level. Missing data were minimal (\u0026lt;\u0026thinsp;5% for all variables). Patients with missing values were excluded from regression analyses but included in descriptive statistics.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEthical Considerations\u003c/h3\u003e\n\u003cp\u003e The study adhered to the principles of the Declaration of Helsinki. As an observational, non-interventional study, no additional risks were posed to participants. All patients were informed of the study objectives and procedures and provided written informed consent prior to enrollment. Personal identifiers were removed, and data were coded to maintain confidentiality throughout the study. Approval was obtained from the Institutional Review Board of 115 People\u0026rsquo;s Hospital, Ho Chi Minh City.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u0026rsquo; characteristics\u003c/h2\u003e \u003cp\u003eBetween April 2024 and March 2025, a total of 220 patients with chronic HBV infection and normal ALT and AST levels were enrolled. The baseline characteristics are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The mean age was 41.9\u0026thinsp;\u0026plusmn;\u0026thinsp;11.3 years, with most participants aged 30\u0026ndash;60 years (81%). Females accounted for 59.5% of the study population. More than half of patients (55.0%) reported HBV infection for over 10 years. At the time of enrollment, most were asymptomatic, with 58.2% having no clinical symptoms and 65.9% showing no abnormal physical findings. The median BMI was 21.6 kg/m\u0026sup2;. According to WHO criteria, 65.9% had a normal BMI, with women tending to have lower BMI than men. The median platelet count was 236 K/\u0026micro;L, and 95% of patients had values\u0026thinsp;\u0026ge;\u0026thinsp;150 K/\u0026micro;L. Mean ALT and AST levels were within the normal range (ALT with 20.74\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8 U/L and AST with 21.28 U/L). The majority of patients were HBeAg negative (74.5%), and 45.0% had undetectable HBV DNA. Abdominal ultrasound revealed abnormalities in 50.5% of cases, though most were extrahepatic; only a small proportion showed changes suggestive of cirrhosis.\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\u003ePatients\u0026rsquo; characteristics (n\u0026thinsp;=\u0026thinsp;220)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValues\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDemographics\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (years)\u003c/b\u003e, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41.95\u0026thinsp;\u0026plusmn;\u0026thinsp;11.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge groups\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;30 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (13.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30\u0026ndash;44 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e118 (53.6% )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e45\u0026ndash;60 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60 (27.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;60 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (5.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex Female\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e131 (59.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical characteristics\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDuration of HBV infection\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6 months \u0026ndash; 5 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (10.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u0026ndash;10 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75 (34.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;10 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e121 (55.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePast medical history\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e140 (63.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFamily history of HCC/cirrhosis/HBV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e86 (39.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (11.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperlipidemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (7.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (5.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther comorbidities (e.g., gastritis, varices)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45 (20.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical symptoms\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e128 (58.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBloating\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (12.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLoss of appetite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (8.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRUQ tenderness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (6.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers (heartburn, weight loss, nausea, etc.)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (11.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePhysical signs\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e145 (65.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJaundice/spider angiomas/palmar erythema\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (1.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHepatomegaly/splenomegaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (4.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers (edema, erythema)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (12.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI (kg/m\u0026sup2;)\u003c/b\u003e, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21,60 (20.00\u0026ndash;23.50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWHO BMI Classification\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal (18.5\u0026ndash;22.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e145 (65.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOverweight (23\u0026ndash;24.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54 (24.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eObese (25\u0026ndash;29.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (9.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLaboratory and imaging characteristics\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePlatelet counts (K/\u0026micro;L)\u003c/b\u003e, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e236 (200\u0026ndash;283)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAST (U/L)\u003c/b\u003e, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.28 (18.42\u0026ndash;24.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eALT (U/L)\u003c/b\u003e, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.74\u0026thinsp;\u0026plusmn;\u0026thinsp;5.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHBeAg\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56 (25.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHBV DNA levels\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUndetectable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e99 (45.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;2000 IU/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56 (25.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2000\u0026ndash;20,000 IU/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33 (15.0%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;20,000 IU/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (14.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAbdominal sonography\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone detected\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e108 (49.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers (kidney stone, liver cyst, liver hemangioma, uterine fibroids)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e104 (47.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoarsened hepatic echotexture and/or cirrhosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (3.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLiver stiffness by FibroScan (kPa)\u003c/b\u003e, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.50 (4.80\u0026ndash;6.30)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFibrosis stage by FibroScan\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF0\u0026ndash;F1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e190 (86.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (12.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (1.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eF4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\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\u003ch3\u003eLiver Fibrosis by Transient Elastography\u003c/h3\u003e\n\u003cp\u003eThe median liver stiffness measurement was 5.5 kPa (IQR 4.8\u0026ndash;6.3), ranging from 2.9 to 10.7 kPa (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Based on fibrosis staging criteria, 86.4% of patients were classified as F0\u0026ndash;F1, 12.3% as F2 (significant fibrosis), and 1.3% as F3 (advanced fibrosis). No patients had cirrhosis (F4). Overall, 13.6% of participants had significant fibrosis or worse (\u0026ge;\u0026thinsp;F2) despite having persistently normal aminotransferase levels.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eFactors Associated with Significant Liver Fibrosis\u003c/h2\u003e \u003cp\u003eCompared to patients without fibrosis or with only mild fibrosis (F0\u0026ndash;F1), those with significant fibrosis (\u0026ge;\u0026thinsp;F2) were older (mean age 48.93\u0026thinsp;\u0026plusmn;\u0026thinsp;11.46 vs. 40.84\u0026thinsp;\u0026plusmn;\u0026thinsp;10.89 years, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The prevalence of overweight or obesity was also higher in this group (53.3% vs. 31.1%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.035). Median platelet count was lower among patients with \u0026ge;F2 fibrosis (208 K/\u0026micro;L vs. 241 K/\u0026micro;L, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and 30% had thrombocytopenia (\u0026lt;\u0026thinsp;150 K/\u0026micro;L).\u003c/p\u003e \u003cp\u003eIn terms of virological markers, the proportion of HBeAg positivity was greater in the significant fibrosis group (46.7% vs. 22.1%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004). Likewise, a higher proportion had HBV DNA levels\u0026thinsp;\u0026ge;\u0026thinsp;2000 IU/mL (80.0% vs. 21.6%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). No significant differences were observed in ALT or AST levels between the two groups.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociations of fibrosis stages with patients\u0026rsquo; 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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eFibrosis staging\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP values\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF0\u0026ndash;F1(n\u0026thinsp;=\u0026thinsp;190)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026ge; F2(n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.122ᵃ\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e117 (61.60%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (46.70%)\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\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73 (38.40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (53.30%)\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\"\u003e \u003cp\u003e\u003cb\u003eAge (years)\u003c/b\u003e, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.84\u0026thinsp;\u0026plusmn;\u0026thinsp;10.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48.93\u0026thinsp;\u0026plusmn;\u0026thinsp;11.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001ᵈ\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge groups\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001ᵇ\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;30 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (14.70%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (3.30%)\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\"\u003e \u003cp\u003e30\u0026ndash;44 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e107 (56.30%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (36.70%)\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\"\u003e \u003cp\u003e45\u0026ndash;60 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48 (25.30%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (40.00%)\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\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;60 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (3.70%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (20.00%)\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\"\u003e \u003cp\u003e\u003cb\u003eDuration of HBV infection\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.847ᵇ\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6 months \u0026ndash; 5 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (11.60%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (6.70%)\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\"\u003e \u003cp\u003e5\u0026ndash;10 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64 (33.70%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (36.70%)\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\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;10 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e104 (54.70%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (56.70%)\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\"\u003e \u003cp\u003e\u003cb\u003eBMI (kg/m\u0026sup2;)\u003c/b\u003e, \u003c/p\u003e \u003cp\u003emedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.55 (19.98\u0026ndash;23.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.55 (20.90\u0026ndash;23.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.173ᶜ\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWHO BMI Classification\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.035ᵇ\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal (18.5\u0026ndash;22.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e131 (68.90%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (46.70%)\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\"\u003e \u003cp\u003eOverweight (23\u0026ndash;24.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (21.60%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (43.30%)\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\"\u003e \u003cp\u003eObese (25\u0026ndash;29.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (9.50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (10.00%)\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\"\u003e \u003cp\u003e\u003cb\u003ePlatelet counts (K/\u0026micro;L)\u003c/b\u003e, \u003c/p\u003e \u003cp\u003emedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e241 (203\u0026ndash;287)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e208 (144\u0026ndash;249)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0,001ᶜ\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClassification of platelet counts\u003c/b\u003e. n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001ᵇ\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;150,000/\u0026micro;L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e188 (98.90%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (70.00%)\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\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;150,000/\u0026micro;L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1.10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (30.00%)\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\"\u003e \u003cp\u003e\u003cb\u003eAST (U/L)\u003c/b\u003e, \u003c/p\u003e \u003cp\u003emedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.32 (18.40\u0026ndash;24.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.00 (19.09\u0026ndash;24.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.830ᶜ\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eALT (U/L)\u003c/b\u003e, \u003c/p\u003e \u003cp\u003emean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.55\u0026thinsp;\u0026plusmn;\u0026thinsp;5.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.96\u0026thinsp;\u0026plusmn;\u0026thinsp;5.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.214ᵈ\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHBeAg\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.004ᵃ\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42 (22.10%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (46.70%)\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\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e148 (77.90%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (53.30%)\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\"\u003e \u003cp\u003e\u003cb\u003eHBV DNA levels\u003c/b\u003e, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001ᵃ\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;2000 IU/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e149 (78.40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (20.00%)\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\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;2000 IU/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (21.60%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (80.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eᵃChi-square test; ᵇFisher\u0026rsquo;s exact test; ᶜMann\u0026ndash;Whitney test (non-normal distribution); ᵈIndependent-Samples T Test (normal distribution)\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eUnivariable logistic regression identified age (OR\u0026thinsp;=\u0026thinsp;1.06, 95% CI\u0026thinsp;=\u0026thinsp;1.03\u0026ndash;1.10), platelet count (OR\u0026thinsp;=\u0026thinsp;0.98, 95% CI\u0026thinsp;=\u0026thinsp;0.97\u0026ndash;0.99), and HBV DNA load (OR\u0026thinsp;=\u0026thinsp;1.00; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.037) as significant predictors of fibrosis \u0026ge;F2. In the multivariable model, only age and platelet count remained independent predictors (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLogistic regresion analysis of factors associated with significant fibrosis (\u0026ge;\u0026thinsp;F2)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePredictors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% Confidence Interval\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAdjusted OR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e95% Confidence Interval\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.03\u0026ndash;1.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.02\u0026ndash;1.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.97\u0026ndash;1.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet counts (K/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.97\u0026ndash;0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.98\u0026ndash;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHBV DNA levels (IU/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.00\u0026ndash;1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026mdash;\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 \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eCorrelation Between Liver Stiffness and Clinical or Laboratory Parameters\u003c/h2\u003e \u003cp\u003eThe correlations between liver stiffness measurements (kPa) and selected clinical and laboratory variables are presented in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. Liver stiffness showed weak but statistically significant positive correlations with age (\u003cem\u003er\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.268, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). body mass index (BMI) (\u003cem\u003er\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.195, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004), and HBV DNA levels (\u003cem\u003er\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.296, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Conversely, platelet count demonstrated a weak negative correlation with liver stiffness (\u003cem\u003er\u003c/em\u003e = \u0026minus;\u0026thinsp;0.202, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003). Although these associations were statistically significant, all correlation coefficients were below 0.3, indicating only weak relationships between liver stiffness and the examined variables.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCorrelation of liver stiffness (kPa) with clinical and laboratory characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003er coefficients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep values\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.268\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.195\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet counts (K/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.202\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHBV DNA levels (IU/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.296\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\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 \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eProportion of Patients Meeting Antiviral Treatment Criteria\u003c/h2\u003e \u003cp\u003eThe proportion of patients eligible for antiviral therapy according to two current guideline systems is presented in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. Based on the 2019 Viet Nam Ministry of Health (MOH) guidelines, 23.2% of patients (51/220) met treatment indications. Specifically, 5.9% had significant fibrosis (\u0026ge;\u0026thinsp;F2) with HBV DNA\u0026thinsp;\u0026ge;\u0026thinsp;2000 IU/mL and were HBeAg-negative; 2.7% had significant fibrosis with HBV DNA\u0026thinsp;\u0026ge;\u0026thinsp;20,000 IU/mL and were HBeAg-positive; and 14.6% had a family history of hepatocellular carcinoma or cirrhosis.\u003c/p\u003e \u003cp\u003e Using the updated World Health Organization (WHO) 2024 guidelines, the proportion of eligible patients increased to 34.1% (75/220). Among these, 13.6% had significant fibrosis (\u0026ge;\u0026thinsp;F2), 5.9% had diabetes mellitus, and 14.6% reported a family history of liver disease.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eProportion of patients eligible for antiviral therapy according to WHO (2024) and Viet Nam Ministry of Health (2019) guidelines\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment eligibility\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eViet Nam Ministry of Health 2019\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWHO 2024\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFibrosis\u0026thinsp;\u0026ge;\u0026thinsp;F2, HBV DNA\u0026thinsp;\u0026ge;\u0026thinsp;2000 IU/mL, and HBeAg (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (5.91%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFiborsis\u0026thinsp;\u0026ge;\u0026thinsp;F2, HBV DNA\u0026thinsp;\u0026ge;\u0026thinsp;20.000 IU/mL, and HBeAg (+)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (2.72%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFamily history of HCC and/or cirrhosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (14.55%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (14.55%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFibrosis\u0026thinsp;\u0026ge;\u0026thinsp;F2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (13.64%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConcurrent Diabetes mellitus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (5.91%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal eligible\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (23.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75 (34.1%)\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"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this cross-sectional study, we found that while the majority had minimal fibrosis (F0\u0026ndash;F1, 86.4%), a clinically significant proportion already showed evidence of significant (F2, 12.3%) or advanced (F3, 1.3%) fibrosis, despite the absence of elevated liver enzymes. Several factors differed significantly between patients with and without significant fibrosis, including age, body mass index (BMI), HBeAg status, platelet count, and HBV DNA levels. Liver stiffness was positively correlated with age, BMI, and HBV DNA, and negatively correlated with platelet count. Importantly, age emerged as an independent predictor of fibrosis \u0026ge;F2 (OR 1.06; 95% CI 1.02\u0026ndash;1.11), underscoring that the risk of liver damage increases progressively with advancing age, even among asymptomatic individuals with normal aminotransferases. From a public health perspective, these findings highlight the limitations of relying solely on ALT for patient monitoring and treatment eligibility, and strengthen the case for incorporating non-invasive fibrosis assessment into HBV control programs to prevent missed opportunities for early intervention.\u003c/p\u003e \u003cp\u003eIn this study, the median liver stiffness among chronic hepatitis B (CHB) patients with normal aminotransferases was 5.5 kPa, comparable to findings from Viet Nam (5.3 kPa) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] and lower than values reported in Spain (6.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8 kPa) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The lower stiffness in our cohort may reflect exclusion of patients with hepatic steatosis or significant alcohol use\u0026mdash;both known contributors to increased stiffness [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Although most patients (86.4%) were classified as F0\u0026ndash;F1, a notable 13.6% had significant or advanced fibrosis (\u0026ge;\u0026thinsp;F2). This aligns with prior biopsy-based studies showing that 20\u0026ndash;30% of CHB patients with persistently normal ALT still had histological fibrosis \u0026ge;F2 [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Kumar et al. reported a higher prevalence (56.6%) in India, which may be attributable to older ALT cutoffs (40 U/L) and reliance on biopsy rather than transient elastography [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. San Juan L\u0026oacute;pez et al. also observed higher rates, likely influenced by different fibrosis cutoffs (\u0026ge;\u0026thinsp;7.9 kPa) and higher obesity prevalence (62% vs. 9.5% in our study) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. These findings highlight that even patients with normal ALT may harbor progressive disease, underscoring the need for comprehensive fibrosis assessment in CHB management.\u003c/p\u003e \u003cp\u003eWe identified older age and lower platelet count as independent predictors of significant fibrosis. Each additional year of age increased the risk of fibrosis by 6%, consistent with prior evidence that host factors such as age, sex, and family history shape fibrosis progression [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Similar findings have been reported in China and Korea, where older patients showed more advanced histological changes despite normal ALT [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. BMI was also higher in patients with fibrosis \u0026ge;F2. This association is consistent with evidence linking metabolic syndrome and obesity with fibrosis progression in CHB [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Metabolic cofactors may act synergistically with HBV to accelerate fibrogenesis, even in the absence of elevated liver enzymes.\u003c/p\u003e \u003cp\u003ePlatelet count was inversely correlated with liver stiffness (r = \u0026minus;\u0026thinsp;0.202, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003). This supports its role as a surrogate marker of fibrosis, explained by reduced thrombopoietin synthesis, hypersplenism, or portal hypertension [\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Thrombocytopenia has been widely validated as a component of non-invasive fibrosis indices such as APRI and FIB-4, which remain particularly valuable in low-resource settings [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Notably, ALT and AST levels did not differ significantly between fibrosis groups, supporting the argument that aminotransferases are unreliable markers of disease severity [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Recent data confirm that a substantial proportion of CHB patients with normal ALT exhibit moderate-to-severe histological activity, reinforcing calls to broaden treatment eligibility beyond ALT thresholds [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e Applying the 2019 Viet Nam Ministry of Health (MOH) guidelines, only 23.2% of patients met treatment criteria, whereas the proportion increased to 34.1% under the 2024 WHO guidelines. This reflects a paradigm shift in HBV management, where non-invasive fibrosis assessment and broader clinical criteria identify more patients at risk of progression [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Recent studies confirm that earlier antiviral therapy reduces the risk of cirrhosis and hepatocellular carcinoma, even in patients with normal ALT [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. From a public health perspective, these findings underscore the importance of integrating transient elastography into national HBV programs. FibroScan\u0026reg; offers a scalable and reproducible alternative to biopsy [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], and when combined with simple markers like platelet count, can enable effective stratification in resource-limited settings [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Wider adoption could prevent missed treatment opportunities and accelerate progress toward HBV elimination goals by 2030 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, it was conducted among outpatients at a single tertiary hospital in Ho Chi Minh City, which may limit the generalizability of findings to all chronic hepatitis B patients in Viet Nam. Hospitalized patients, who often have more severe or complex disease, were not represented and may have a different fibrosis burden. However, outpatients constitute the majority of individuals living with chronic HBV in the community, and their clinical profile may be more comparable to the general population, particularly for public health surveillance and programmatic planning. Future studies with larger, multicenter cohorts will be important to confirm and extend these findings. Second, liver fibrosis was assessed exclusively with transient elastography (FibroScan\u0026reg;). Although FibroScan is a reliable, non-invasive method that is highly suitable for large-scale screening and public health programs, it cannot fully replace liver biopsy, the histological gold standard. Biopsy, however, is invasive, carries procedural risks, and is not realistic for routine practice or population-level studies. As such, the reliance on FibroScan may have underestimated the true prevalence of fibrosis in this cohort. Future research should consider combining transient elastography with other non-invasive markers to further enhance diagnostic accuracy in real-world settings.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eAlthough most chronic hepatitis B patients with normal aminotransferases had minimal fibrosis, more than one in eight were already living with significant disease that would have been missed using current ALT-based monitoring alone. This evidence shows that liver enzyme testing is insufficient as a population-level screening tool and that broader, risk-based approaches are urgently needed. Public health programs in Viet Nam and other high-burden countries should integrate non-invasive fibrosis assessment into routine HBV care, alongside systematic evaluation of family history, metabolic risk, and virological markers, to enable earlier treatment. Embedding these strategies in national elimination plans will not only improve individual outcomes but also strengthen progress toward the 2030 Sustainable Development Goal of ending viral hepatitis as a public health threat.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of 115 People’s Hospital, Ho Chi Minh. Written informed consent was obtained from all participants prior to enrollment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are not publicly available due to patient confidentiality but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study used standard software packages as described in the Methods section; no custom code was developed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTruong Thi Ai Phuong: Conceptualization, Methodology, Data Curation, Formal Analysis, Writing – Original Draft.\u003c/p\u003e\n\u003cp\u003eNguyen Thi Kim Lan: Investigation, Resources, Data Collection, Writing – Review \u0026amp; Editing.\u003c/p\u003e\n\u003cp\u003ePham Quang Thien Phu: Methodology, Investigation, Data Collection, Project Administration.\u003c/p\u003e\n\u003cp\u003eTran Vy Thao: Writing – Original Draft, Writing – Review \u0026amp; Editing, Visualization.\u003c/p\u003e\n\u003cp\u003eThanh Van Kim: Methodology, Writing – Original Draft, Writing – Review \u0026amp; Editing, Literature Review.\u003c/p\u003e\n\u003cp\u003eTran Kinh Thanh: Conceptualization, Methodology, Supervision, Formal Analysis, Writing – Review \u0026amp; Editing, Project Administration.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the clinical staff of the Gastroenterology Clinic, 115 People’s Hospital, Ho Chi Minh City, for their support in patient recruitment and data collection. We also acknowledge the patients who generously participated in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCui F, Blach S, Mingiedi CM, et al. Global reporting of progress towards elimination of hepatitis B and hepatitis C. Lancet Gastroenterol Hepatol. 2023;8(10):915\u0026ndash;28. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S2468-1253(22)00386-7\u003c/span\u003e\u003cspan address=\"10.1016/S2468-1253(22)00386-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorld Health Organization. Global hepatitis report 2024: action for access in low- and middle-income countries. Geneva: WHO; 2024. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.who.int/publications/i/item/9789240091672\u003c/span\u003e\u003cspan address=\"https://www.who.int/publications/i/item/9789240091672\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePham TND, Le DH, Dao DVB, et al. Establishing baseline framework for hepatitis B virus micro-elimination in Ho Chi Minh City, Viet Nam: a community-based seroprevalence study. Lancet Reg Health West Pac. 2023;30:100620. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.lanwpc.2022.100620\u003c/span\u003e\u003cspan address=\"10.1016/j.lanwpc.2022.100620\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou J, Wang FD, Wang ML, et al. Antiviral therapy for chronic HBV infection with persistently normal alanine aminotransferase: controversy and consensus. Front Med. 2021;8:717125. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fmed.2021.717125\u003c/span\u003e\u003cspan address=\"10.3389/fmed.2021.717125\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSan Juan L\u0026oacute;pez C, Marta CM, Mercedes GS, et al. Characterization and evaluation of liver fibrosis grade in patients with chronic hepatitis B virus infection and normal transaminases. Clin Mol Hepatol. 2018;24(4):384\u0026ndash;91. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3350/cmh.2018.0004\u003c/span\u003e\u003cspan address=\"10.3350/cmh.2018.0004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang H, Ru GQ, Yan R, et al. Histologic disease in Chinese chronic hepatitis B patients with low viral loads and persistently normal alanine aminotransferase levels. J Clin Gastroenterol. 2016;50(9):790\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/mcg.0000000000000544\u003c/span\u003e\u003cspan address=\"10.1097/mcg.0000000000000544\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCornberg M, Sandmann L, Jaroszewicz J, et al. EASL Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol. 2025;S0168. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jhep.2025.03.018\u003c/span\u003e\u003cspan address=\"10.1016/j.jhep.2025.03.018\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. -8278(25)00052\u0026thinsp;\u0026ndash;\u0026thinsp;1.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLim YS, Kim WR, Dieterich D, et al. Evidence for benefits of early treatment initiation for chronic hepatitis B. Viruses. 2023;15(4):997. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/v15040997\u003c/span\u003e\u003cspan address=\"10.3390/v15040997\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWong GLH. Transient elastography (FibroScan\u0026reg;): a new look of liver fibrosis and beyond. Euroasian J Hepatogastroenterol. 2013;3(1):70\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.5005/jp-journals-10018-1067\u003c/span\u003e\u003cspan address=\"10.5005/jp-journals-10018-1067\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVu Hai V, Shimakawa Y, Kim J, et al. Assessment and simplification of treatment eligibility among patients with chronic hepatitis B infection in Viet Nam. Clin Infect Dis. 2021;73(5):e1072\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/cid/ciaa1814\u003c/span\u003e\u003cspan address=\"10.1093/cid/ciaa1814\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWong VWS, Chan WK, Chitturi S, et al. Asia\u0026ndash;Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines 2017\u0026mdash;part 1: definition, risk factors and assessment. J Gastroenterol Hepatol. 2018;33(1):70\u0026ndash;85. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/jgh.13857\u003c/span\u003e\u003cspan address=\"10.1111/jgh.13857\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eB\u0026aacute;rcena Marug\u0026aacute;n R, Garc\u0026iacute;a Garz\u0026oacute;n S. DNA-guided hepatitis B treatment: viral load is essential, but not sufficient. World J Gastroenterol. 2009;15(4):423\u0026ndash;30. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3748/wjg.15.423\u003c/span\u003e\u003cspan address=\"10.3748/wjg.15.423\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKumar M, Sarin SK, Hissar S, et al. Virologic and histologic features of chronic hepatitis B virus-infected asymptomatic patients with persistently normal ALT. Gastroenterology. 2008;134(5):1376\u0026ndash;84. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1053/j.gastro.2008.02.075\u003c/span\u003e\u003cspan address=\"10.1053/j.gastro.2008.02.075\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZheng B, Zhu YJ, Wang HY, Chen L. Gender disparity in hepatocellular carcinoma: multiple underlying mechanisms. Sci China Life Sci. 2017;60(6):575\u0026ndash;84. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s11427-016-9043-9\u003c/span\u003e\u003cspan address=\"10.1007/s11427-016-9043-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang SH, Chen PJ, Yeh SH. Gender disparity in chronic hepatitis B: mechanisms of sex hormones. J Gastroenterol Hepatol. 2015;30(8):1237\u0026ndash;45. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/jgh.12934\u003c/span\u003e\u003cspan address=\"10.1111/jgh.12934\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMena \u0026Aacute;, Pedreira JD, Castro \u0026Aacute;, et al. Metabolic syndrome association with fibrosis development in chronic hepatitis B virus inactive carriers. J Gastroenterol Hepatol. 2014;29(1):173\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/jgh.12432\u003c/span\u003e\u003cspan address=\"10.1111/jgh.12432\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAiolfi R, Sitia G. Chronic hepatitis B: role of anti-platelet therapy in inflammation control. Cell Mol Immunol. 2015;12(3):264\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/cmi.2014.124\u003c/span\u003e\u003cspan address=\"10.1038/cmi.2014.124\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBalaphas A, Meyer J, Sadoul K, et al. Platelets and platelet-derived extracellular vesicles in liver physiology and disease. Hepatol Commun. 2019;3(7):855\u0026ndash;66. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/hep4.1358\u003c/span\u003e\u003cspan address=\"10.1002/hep4.1358\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAfdhal N, McHutchison J, Brown R, et al. Thrombocytopenia associated with chronic liver disease. J Hepatol. 2008;48(6):1000\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jhep.2008.03.009\u003c/span\u003e\u003cspan address=\"10.1016/j.jhep.2008.03.009\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao Q, Liu K, Zhu X, et al. Antiviral effect in chronic hepatitis B patients with normal or mildly elevated alanine aminotransferase. Antiviral Res. 2020;184:104953. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.antiviral.2020.104953\u003c/span\u003e\u003cspan address=\"10.1016/j.antiviral.2020.104953\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGong X, Yang J, Tang J, et al. A mechanistic assessment of the discordance between normal serum alanine aminotransferase levels and altered liver histology in chronic hepatitis B. PLoS ONE. 2015;10(7):e0134532. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1371/journal.pone.0134532\u003c/span\u003e\u003cspan address=\"10.1371/journal.pone.0134532\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim JH, Kim MN, Han KH, Kim SU. Clinical application of transient elastography in patients with chronic viral hepatitis receiving antiviral treatment. Liver Int. 2015;35(4):1103\u0026ndash;15. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/liv.12628\u003c/span\u003e\u003cspan address=\"10.1111/liv.12628\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu J, Wang J, Yan X, et al. Presence of Liver Inflammation in Asian Patients With Chronic Hepatitis B With Normal ALT and Detectable HBV DNA in Absence of Liver Fibrosis. Hepatol Commun. 2022;6(4):855\u0026ndash;66. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/hep4.1859\u003c/span\u003e\u003cspan address=\"10.1002/hep4.1859\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang L, Wu HD, Qian YF, Xu HY. Prevalence of nonalcoholic fatty liver disease in patients with hepatitis B: A meta-analysis. World J Clin Cases. 2024;12(25):5749\u0026ndash;60. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.12998/wjcc.v12.i25.5749\u003c/span\u003e\u003cspan address=\"10.12998/wjcc.v12.i25.5749\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLemoine M, Shimakawa Y, Nayagam S, et al. The gamma-glutamyl transpeptidase to platelet ratio (GPR) predicts significant liver fibrosis and cirrhosis in patients with chronic HBV infection in West Africa. Gut. 2016;65(8):1369\u0026ndash;76. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1136/gutjnl-2015-309260\u003c/span\u003e\u003cspan address=\"10.1136/gutjnl-2015-309260\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZeng DW, Dong J, Liu YR, Jiang JJ, Zhu YY. Noninvasive models for assessment of liver fibrosis in patients with chronic hepatitis B virus infection. World J Gastroenterol. 2016;22(29):6663\u0026ndash;72. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3748/wjg.v22.i29.6663\u003c/span\u003e\u003cspan address=\"10.3748/wjg.v22.i29.6663\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTseng TC, Kao JH. Treating Immune-tolerant Hepatitis B. J Viral Hepat. 2015;22(2):77\u0026ndash;84. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/jvh.12370\u003c/span\u003e\u003cspan address=\"10.1111/jvh.12370\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarcellin P, Ziol M, Bedossa P, et al. Non-invasive assessment of liver fibrosis by stiffness measurement in patients with chronic hepatitis B. Liver Int. 2009;29(2):242\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/j.1478-3231.2008.01802.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1478-3231.2008.01802.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Chronic hepatitis B, liver fibrosis, transient elastography, FibroScan®, aminotransferases, Viet Nam","lastPublishedDoi":"10.21203/rs.3.rs-9362409/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9362409/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eChronic hepatitis B (CHB) is a major public health challenge in Viet Nam. Many patients have normal alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, yet clinically relevant fibrosis may progress silently. This study assessed fibrosis prevalence using transient elastography (FibroScan\u0026reg;) and identified factors associated with significant fibrosis (\u0026ge;\u0026thinsp;F2) in CHB patients with normal aminotransferases.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe conducted a cross-sectional study among CHB patients aged\u0026thinsp;\u0026ge;\u0026thinsp;18 years at the Gastroenterology Clinic of 115 People\u0026rsquo;s Hospital, Ho Chi Minh City, from April 2024 to March 2025. Eligible patients were treatment-na\u0026iuml;ve with normal ALT and AST (Viet Nam Ministry of Health 2019 definition). Clinical, laboratory, and virological data were collected, and liver stiffness was measured by transient elastography. Logistic regression was used to assess predictors of fibrosis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 220 patients, 86.4% had no or mild fibrosis (F0\u0026ndash;F1), 12.3% had significant fibrosis (F2), and 1.3% had advanced fibrosis (F3); none had cirrhosis (F4). In multivariable analysis, older age (OR 1.06; 95% CI 1.02\u0026ndash;1.11) and lower platelet count (OR 0.98; 95% CI 0.98\u0026ndash;0.99) were independent predictors of significant fibrosis. According to the 2019 Viet Nam Ministry of Health guidelines, 23.2% of patients with normal aminotransferases met indications for antiviral therapy, whereas application of the 2024 WHO criteria increased eligibility to 34.1%.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eA substantial proportion of CHB patients with normal aminotransferases had significant fibrosis, underscoring the limitations of aminotransferase-based monitoring. Incorporating non-invasive fibrosis assessment into HBV programs could support earlier treatment and accelerate elimination efforts.\u003c/p\u003e","manuscriptTitle":"Liver Fibrosis Despite Normal Aminotransferases – Implications for Hepatitis B Management and Treatment Eligibility in Viet Nam: A Cross-Sectional Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-23 18:49:48","doi":"10.21203/rs.3.rs-9362409/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-18T08:32:25+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-17T00:38:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-07T12:57:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"216123127205471761661682001393654559967","date":"2026-05-01T03:23:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"79308044450309171110512924892687400614","date":"2026-04-27T21:53:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"51026427440675732776659906678534718242","date":"2026-04-27T15:33:07+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-15T09:45:37+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-14T05:41:14+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-14T01:16:46+00:00","index":"","fulltext":""},{"type":"submitted","content":"SN Comprehensive Clinical Medicine","date":"2026-04-09T02:51:24+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"59353d37-7bbb-44e4-95e1-9e00aa139471","owner":[],"postedDate":"April 23rd, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-18T08:32:25+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-17T00:38:35+00:00","index":41,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-07T12:57:15+00:00","index":40,"fulltext":""},{"type":"reviewerAgreed","content":"216123127205471761661682001393654559967","date":"2026-05-01T03:23:42+00:00","index":39,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-18T08:40:42+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-23 18:49:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9362409","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9362409","identity":"rs-9362409","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}