The associated between ALDH2 rs671 polymorphism and clinical prognosis in alcohol- related hepatocellular carcinoma after curative resection

The associated between ALDH2 rs671 polymorphism and clinical prognosis in alcohol- related hepatocellular carcinoma after curative resection | 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 The associated between ALDH2 rs671 polymorphism and clinical prognosis in alcohol- related hepatocellular carcinoma after curative resection Chih-Jan Ko, Wen-Lung Wang, Hung-Yu Lin, Pei-Min Hsieh, Szu-Ying Chen, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4506472/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Whether ALDH2 rs671 polymorphism predicts clinical prognosis in alcoholic liver disease (ALD)-related hepatocellular carcinoma (HCC) after hepatectomy remains unclear. Aims This study aims to investigate the association between ALDH2 rs671 polymorphism and HCC recurrence and mortality in patients with ALD-related HCC who underwent hepatectomy. We also explored the risk factors for HCC recurrence and mortality in this population of patients. Methods This prospective cohort study enrolled 238 ALD-related HCC patients underwent hepatectomy from 2011 to 2022 at the E-Da Hospital, I-Shou University. Data analyses were finalized on October, 2023. Alcoholism was defined as consuming over 20 g of ethanol each day for at least 5 years. Patients with HBsAg-positive or/and HCV-positive status were excluded. ALDH2 rs671 polymorphism was analyzed. The endpoint was HCC recurrence and overall mortality. Results Of the 238 patients enrolled, 196 (82.4%) were men, and the mean (SD) age was 62.3 (10.2) years. HCC recurrence occurred in 70 patients, and 64 patients died. ALDH2 rs671 polymorphism was significantly associated with HCC recurrence and mortality. The 10-year cumulative HCC recurrence and mortality rates were significantly higher in patients with the ALDH2 rs671 genotype GA/AA relative to those with the ALDH2 rs671 genotype GG. In the Cox proportional analyses, the ALDH2 rs671 genotypes GA/AA (hazard ratio [HR]: 2.66, 95% confidence interval [CI]: 1.59–4.43, P < 0.001) and AST ≥ 40 IU/L (HR: 1.93, 95% CI: 1.18–3.17, P = 0.009) were significantly associated with increased HCC recurrence. Furthermore, the ALDH2 rs671 genotype GA/AA (HR: 2.02, 95% CI: 1.17–3.49, P = 0.012) and age ≥ 65 years (HR: 1.67, 95% CI: 1.01–2.78, P = 0.048) were significantly associated with increased mortality. Conclusions The ALDH2 rs671 genotype GA/AA is significantly associated with unfavorable clinical prognosis in ALD-related HCC after hepatectomy. Hepatocellular carcinoma ALDH2 rs671 polymorphism predictors recurrence mortality hepatectomy. Figures Figure 1 Figure 2 Figure 3 Introduction Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality globally [1–5]. In Taiwan, HCC often results from viral- and alcohol-related cirrhosis [6, 7]. Moreover, early-stage HCC is difficult to diagnose, resulting in elevated HCC recurrence and mortality rates after surgical resection [8–13]. Despite the use of highly sensitive tumor markers to predict clinical outcomes after hepatectomy in patients with HCC, the result remains unsatisfactory [14]. Therefore, the identification of predictors for HCC recurrence and mortality could help improve the clinical prognosis of patients with HCC undergoing hepatectomy. The aldehyde dehydrogenase 2 (ALDH2) polymorphism influences the development of HCC in alcoholic patients with or without viral hepatitis [15–18] and nonalcoholic patients [19, 20]. Several studies have demonstrated that the ALDH2 rs671 polymorphism is not associated with HCC in East Asians [21–24]. Our previous study revealed a significant increase in the risk of HCC development and mortality in HBV-related cirrhotic patients with heavy alcohol drinking and ALDH2 rs671 polymorphism [6]. Moreover, a previous study demonstrated that the ALDH2 rs671 genotype GG correlated significantly with shorter overall survival, but not with recurrence-free survival, particularly in patients with viral-related HCC who underwent surgical resection [25]. However, the effect of ALDH2 rs671 polymorphism on HCC recurrence and mortality in patients with alcoholic liver disease (ALD)-related HCC who underwent surgical resection remains unclear. Hence, we investigated the association between ALDH2 rs671 polymorphism and HCC recurrence and mortality in patients with ALD-related HCC who underwent hepatectomy. We also explored the risk factors for HCC recurrence and mortality in this population of patients. Materials and Methods Patients and follow-up This prospective cohort study enrolled 238 patients with ALD-related HCC who underwent surgical resection from October 2011 to December 2022 at the E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. All patients underwent liver function tests, α-fetoprotein (AFP) tests, and imaging examinations, including ultrasonography, computed tomography, and magnetic resonance imaging examinations. These clinical investigations were conducted every 3–6 months or as deemed necessary for the detection of HCC. The data analyses were finalized on October 31, 2023. Patients with alcoholism were included in this study, and alcoholism was defined as consuming at least 20 g of ethanol each day for more than 5 years. However, patients with (1) hepatitis B virus infection; (2) hepatitis C virus infection; (3) alcohol intake of < 20 g/day and for < 5 years; and (4) HCC recurrence and mortality within 6 months after surgical resection were all excluded from the excluded. The presence of ALDH2 rs671 polymorphism was determined by using blood analysis. The primary endpoint was HCC recurrence whereas the secondary endpoint was overall mortality. The follow-up time was defined as the time from the date of inclusion to the date of death, the last follow-up, or the end of the study (October 31, 2023), whichever was earliest. The occurrence time was defined as the time from the date of inclusion to the date of HCC diagnosis, the date of death, the last follow-up, or the end of the study (October 31, 2023), whichever was earliest. HCC recurrence was established based on histology or at least two typical HCC imaging methods, as outlined by the HCC guidelines of the American Association for the Study of Liver Disease[26]. The clinicopathological features of the patients, including demographic data and tumor characteristics, were recorded. This research was approved by the Institutional Review Board of E-DA Hospital (EMRP41111N). Additionally, the research was conducted per the guidelines of the International Conference on Harmonization for Good Clinical Practice. Notably, all participants were adults and provided written informed consent for study participation. ALDH2 rs671 polymorphism ALDH2 is a major enzyme involved in the elimination of acetaldehyde from the body. The ALDH2*2 allele variant is a single point mutation (G to A) in exon 12, resulting in a change from glutamine (Glu) to lysine (Lys) at codon 487 and the inactivation of ALDH2 enzyme activity in humans, causing deficiency. The presence of a single polymorphism (Glu to Lys, G to A, or *1 to *2) was evaluated using blood samples. The ALDH2 rs671 polymorphism causes one of three genotypes: GG, AA, and GA. To evaluate ALDH2 deficiency, patients with the GA and AA genotypes were merged into a single GA/AA group. Statistical analysis Continuous data are expressed as the mean and standard deviation (SD). Categorical data are described using numbers and percentages. Normally distributed continuous variables were compared using the Student’s t- test, and the Wilcoxon rank-sum test was applied for comparisons of two groups when continuous variables were not normally distributed. The chi-squared test was used to compare categorical variables. The cumulative HCC recurrence and mortality rates were evaluated using the Kaplan–Meier method. Recognizing that patients who died were no longer at risk for HCC recurrence, competing risk analyses were conducted. These analyses aimed to evaluate the cumulative HCC recurrence, with mortality considered a competing risk. Both univariable and multivariable analyses were used to evaluate the risk predictors associated with HCC recurrence and mortality. The multivariable analyses were conducted using Cox proportional regression modes for HCC. P < 0.05 indicated statistical significance. All analyses were performed using the Statistical Package for Social Sciences (SPSS, version 23.0; Chicago, IL). Results Baseline demographic data The demographic and clinicopathological features of the study participants are presented in Table 1 . Notably, 196 (82.4%) were men, and the mean (SD) age was 62.3 (10.2) years. HCC recurrence occurred in 70 patients, and 64 patients died. Additionally, one-fourth of the patients had liver cirrhosis. Regarding tumor stage, 15.5% and 14.7% of the patients were Barcelona clinic liver cancer (BCLC) stage B-C and TNM stage III-IV, respectively. Table 1 Basic demographic data of all patients and correlations between ALDH2 polymorphisms and clinicopathologic features. Characteristics All patients (n = 238) ALDH2 rs671 genotype P -value GG (n = 111) GA/AA (n = 127) Gender Female 42 (17.6) 20 (18.0) 22 (17.3) 0.888 Male 196 (82.4) 91 (82.0) 105 (82.7) Age (years) 62.3 ± 10.2 62.8 ± 9.7 61.9 ± 11.1 0.510 BMI (kg/m 2 ) 24.8 ± 3.8 25.0 ± 3.5 24.7 ± 3.6 0.078 HTN 103 (43.3) 52 (46.8) 51 (40.2) 0.299 DM 59 (24.8) 30 (27.0) 29 (22.8) 0.455 Smoking 64 (26.9) 38 (34.2) 26 (20.5) 0.017 AST (IU/L) 48 ± 32 45 ± 26 50 ± 37 0.167 ALT (IU/L) 49 ± 45 50 ± 53 48 ± 37 0.780 Total Bilirubin (mg/dl) 0.9 ± 0.5 0.9 ± 0.6 0.9 ± 0.4 0.978 Albumin (g/dl) 4.2 ± 0.3 4.2 ± 0.3 4.2 ± 0.3 0.918 Creatinine 1.3 ± 0.9 1.3 ± 1.0 1.3 ± 0.8 0.601 Platelet count (x10 3 /ml) 188 ± 70 188 ± 68 188 ± 72 0.726 INR 1.0 ± 0.1 1.0 ± 0.1 1.0 ± 0.1 0.428 AFP (ng/dl) 3295 ± 21189 4342 ± 26918 2380 ± 14497 0.477 ICG (%) 11.9 ± 6.7 12.1 ± 6.6 11.8 ± 6.9 0.732 Liver cirrhosis Absent 174 (73.1) 85 (76.6) 89 (70.1) 0.259 Present 64 (26.9) 26 (23.4) 38 (29.9) Child-Pugh class class A 236(99.2) 109(98.2) 127(100) 0.419 class B 2(0.8) 2(1.8) 0(0.0) Operative margin (> 1 cm) Absent 168(70.6) 78 (70.2) 90 (70.8) 0.906 Present 70(29.4) 33 (29.8) 37 (29.2) Edmondson-Steiner Grades I-II 23(9.7) 6 (5.4) 17 (13.4) 0.038 III-IV 215(90.3) 105 (94.6) 110 (86.6) Macrovascular invasion Absent 215 (90.3) 97 (87.4) 118 (92.9) 0.150 Present 23 (9.7) 14 (12.6) 9 (7.1) Microvascular invasion Absent 184 (77.3) 83 (74.8) 101 (79.5) 0.473 Present 54 (22.7) 28 (25.2) 26 (20.5) Lymph node invasion Absent 232 (97.5) 110 (99.1) 122 (96.1) 0.136 Present 6 (2.5) 1 (0.9) 5 (3.9) Tumor number Single 218 (91.6) 102 (91.9) 116 (91.3) 0.878 Multiple 20 (8.4) 9 (8.1) 11 (8.7) Tumor size (cm) 4.8 ± 2.9 4.8 ± 2.6 4.8 ± 3.1 0.912 Tumor size < 5 cm 145(60.9) 61 (55.0) 84 (66.1) 0.078 ≥5 cm 93 (39.1) 50 (45.0) 43 (33.9) TNM stage I-II 201 (84.5) 93 (83.8) 108 (85.0) 0.791 III-IV 37 (15.5) 18 (16.2) 19 (15.0) BCLC stage 0-A 203 (85.3) 94 (84.7) 109 (85.8) 0.804 B-C 35 (14.7) 17 (15.3) 18 (14.2) Recurrence Absent 168 (70.6) 89 (80.2) 79 (62.2) 0.002 Present 70 (29.4) 22 (19.8) 48 (37.8) Recurrence time 4.6 ± 3.1 5.5 ± 3.2 3.8 ± 2.8 < 0.001 Mortality Absent 174 (73.1) 88 (79.3) 86 (67.7) 0.045 Present 64 (26.9) 23 (20.7) 41 (32.3) Follow up time 5.5 ± 3.1 6.2 ± 3.1 4.9 ± 3.0 0.003 Data shown as mean ± standard deviation or number (%). BMI: Body mass index; HTN: Hypertension; DM: Diabetes Mellitus; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; INR: International normalized ratio; AFP: Alpha-fetoprotein; ICG: Indocyanine green; BCLC stage: Barcelona clinic liver cancer; ALDH2 rs671 polymorphism is associated with advanced clinicopathological features Notably, 44.6% (111) and 56.04% (127) of the 238 patients had ALDH2 rs671 genotype GG and genotype GA/AA, respectively (Table 1 ). The ALDH2 rs671 genotype was significantly correlated with advanced clinicopathological features, including Edmondson–Steiner Grades [105 (94.6) vs. 110 (86.6), P = 0.038], recurrence [22 (19.8) vs. 48 (37.8), P < 0.001], and mortality [23 (20.7) vs. 41 (32.3), P = 0.003]. Predictive factors associated with tumor recurrence in patients with HCC who underwent hepatectomy HCC recurrence was observed in 70 patients after hepatectomy, with 1-, 3-, 5-, and 10-year cumulative incidence rates of 2.6%, 12.0%, 23.8%, and 37.7%, respectively (Fig. 1 A). The univariate analysis revealed that ALDH2 rs671 genotype GA/AA, AST ≥ 40 IU/L, and TNM stage III-IV were significantly correlated with increased HCC recurrence (Table 2 ). Furthermore, the multivariate Cox regression analysis revealed that the ALDH2 rs671 genotype GA/AA was significantly correlated with increased HCC recurrence (hazard ratio [HR]: 2.66, 95% confidence interval [CI]: 1.59–4.43, P < 0.001), followed by those with AST ≥ 40 IU/L (HR: 1.93, 95% CI: 1.18–3.17, P = 0.009) (Table 2 ). Table 2 Univariate and multivariate analyses of factors associated with tumor recurrence of hepatocellular carcinoma patients who underwent curative resection. Characteristics Univariate analyses Multivariate analyses HR (95% CI) P -value HR (95% CI) P- value Gender, Female vs. Male 1.43 (0.73–2.80 0.292 Age (years), < 65 vs. ≥ 65 0.78 (0.48–1.29) 0.337 Body Mass Index, (kg/m2) 0.94 (0.59–1.50) 0.796 Diabetes Mellitus, Absent vs. Presence 0.90 (0.51–1.6) 0.715 Hypertension, Absent vs. Presence 0.86 (0.53–1.4) 0.863 Smoking, Absent vs. Presence 1.02 (0.60–1.72) 0.946 AST (IU/L), < 40 vs. ≥ 40 2.08 (1.29–3.37) 0.003 1.93 (1.18–3.17) 0.009 ALT (IU/L), < 40 vs. ≥ 40 1.39 (0.87–2.23) 0.167 Total Bilirubin (mg/dl), < 1.2 vs. ≥ 1.2 1.10 (0.62–1.95) 0.740 Albumin (g/dl), < 3.5 vs. ≥ 3.5 0.46 (1.7–1.27) 0.133 Platelet count (x10 3 /ml), < 100K vs. ≥ 100K 0.98 (0.36–2.68) 0.960 INR, < 1.0 vs. ≥ 1.0 1.16 (0.65–2.05) 0.62 AFP (ng/dl) < 200 vs. ≥ 200 0.95 (0.52–1.74) 0.877 Liver cirrhosis, Absent vs. Presence 1.34 (0.81–2.21) 0.250 Child-Pugh class, A vs. B 0.05 (0.01–131) 0.636 Operative margin (cm), < 1.0 vs. ≥ 1.0 1.39 (0.84–2.31) 0.199 Tumor number, Single vs. Multiple 1.47 (0.70–3.08) 0.306 Tumor size (cm), < 5 vs. ≥ 5 1.06 (0.66–1.72) 0.806 Edmondson-Steiner Grade I-II vs. III-IV Macrovascular invasion, Absent vs. Presence 1.12 (0.51–2.45) 0.778 Microvascular invasion, Absent vs. Presence 1.05 (0.58–1.89) 0.868 Lymph node invasion, Absent vs. Presence 1.69 (0.41–6.92) 0.464 TNM stage, I-II vs. III-IV 1.89 (1.08–3.40) 0.026 1.62 (0.92–2.87) 0.098 BCLC stage, 0-A vs. B-C 1.72 (0.96–3.09) 0.070 ALDH2 rs671 genotype, GG vs. GA/AA 2.63 (1.58–4.38) < 0.001 2.66 (1.59–4.43) < 0.001 AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; INR: International normalized ratio; AFP: Alpha-fetoprotein; BCLC stage: Barcelona clinic liver cancer; The Kaplan-Meier analysis revealed that patients with ALDH2 rs671 genotype GA/AA had a significantly higher HCC recurrence rate than those with ALDH2 rs671 genotype GG. Additionally, for patients with ALDH2 rs671 genotype GA/AA, the 1-, 3-, 5- and 10-year cumulative HCC recurrence rates were 7.2%, 30.1%, 43.2%, and 59.0%, respectively. By contrast, those with genotype GG had 1-, 3-, 5- and 10-year cumulative HCC recurrence rates of 6.6%, 11.5%, 17.4%, and 23.8%, respectively (Fig. 1 B). In addition, patients with AST ≥ 40 IU/L had a significantly higher HCC recurrence rate than those with AST < 40 IU/L. For those AST ≥ 40 IU/L, the 1-, 3-, 5- and 10-year HCC recurrence rates were 8.9%, 28.9%, 39.5% and 53.2%, respectively. In contrast, those AST < 40 IU/L had 1-, 3-, 5- and 10-year mortality rates of 2.5%, 14.1%, 22.3%, and 29.1%, respectively (Fig. 1 C). Furthermore, in the competing risk analysis, patients with ALDH2 rs671 genotype GA/AA still had a significantly higher HCC recurrence rate than those with ALDH2 rs671 genotype GG ( P < 0.001, Fig. 2 ). Additionally, for patients with ALDH2 rs671 genotype GA/AA, the 1-, 3-, 5- and 10-year cumulative HCC recurrence rates were 9.7%, 34.7%, 48%, and 62.7%, respectively. By contrast, those with genotype GG had 1-, 3-, 5- and 10-year cumulative HCC recurrence rates of 3.1%, 13%, 19.3%, and 25.7%, respectively (Fig. 2 ). Predictive factors associated with mortality in patients with HCC who underwent hepatectomy During the mean follow-up time of 5.5 years, 64 patients died. The cumulative mortality rates at 1, 3, 5, and 10 years after resection were 3.6%, 13.0%, 23.8%, and 37.7%, respectively (Fig. 3 A). The univariate analysis revealed that the following factors were significantly correlated with increased mortality: age ≥ 65 years, ALDH2 rs671 genotype GA/AA, AST ≥ 40 IU/L, TNM stage III-IV, platelet count < 100 K, multiple tumor number, Barcelona clinic liver cancer (BCLC) stage B-C, and HCC recurrence (Table 3 ). The multivariate Cox regression analysis revealed that patients with ALDH2 rs671 genotype GA/AA had the highest mortality rate (HR: 2.02, 95% CI: 1.17–3.49, P = 0.012), followed by those with age ≥ 65 years (HR: 1.67, 95% CI: 1.01–2.78, P = 0.048) (Table 3 ). Table 3 Univariate and multivariate analyses of factors associated with mortality of hepatocellular carcinoma patients who underwent curative resection. Characteristics Univariate analyses Multivariate analyses HR (95% CI) P -value HR (95% CI) P -value Gender, Female vs. Male 1.38 (0.68–2.79) 0.373 Age (years), < 65 vs. ≥ 65 1.68 (1.03–2.75) 0.037 1.67 (1.01–2.78) 0.048 Body Mass Index, (kg/m2) 0.63 (0.38–1.04) 0.073 Diabetes Mellitus, Absent vs. Presence 1.30 (0.76–2.25) 0.342 Hypertension, Absent vs. Presence 1.45 (0.89–2.36) 0.139 Smoking, Absent vs. Presence 1.17 (0.69–1.93) 0.551 AST (IU/L), < 40 vs. ≥ 40 1.84 (1.12–3.05) 0.017 1.53 (0.88–2.66) 0.135 ALT (IU/L), < 40 vs. ≥ 40 1.01 (0.62–1.67) 0.959 Total Bilirubin (mg/dl), < 1.2 vs. ≥ 1.2 1.36 (0.77–2.39) 0.291 Albumin (g/dl), < 3.5 vs. ≥ 3.5 0.40 (0.14–1.09) 0.073 Platelet count (x10 3 /ml), < 100K vs. ≥ 100K 0.40 (0.19–0.84) 0.016 0.53 (0.25–1.14) 0.103 Prothrombin time,, < 1.0 vs. ≥ 1.0 1.78 (0.90–3.5) 0.095 AFP (ng/dl) < 200 vs. ≥ 200 1.17 (0.65–2.12) 0.596 Liver cirrhosis, Absent vs. Presence 1.01 (0.58–1.75) 0.982 Child-Pugh class, A vs. B 3.45 (0.47–25.2) 0.223 Operative margin (cm), < 1.0 vs. ≥ 1.0 1.01 (0.59–1.74) 0.971 Tumor number, Single vs. Multiple 2.29 (1.19–4.38) 0.013 1.70 (0.78–3.69) 0.179 Tumor size (cm), < 5 vs. ≥ 5 1.56 (0.96–2.55) 0.076 Edmondson-Steiner Grade I-II vs. III-IV Macrovascular invasion, Absent vs. Presence 2.48 (1.35–4.57) 0.003 1.70 (0.81–3.56) 0.159 Microvascular invasion, Absent vs. Presence 1.73 (0.99–2.99) 0.052 TNM stage, I-II vs. III-IV 2.99 (1.76–5.08) < 0.001 1.89 (0.87–4.13) 0.108 BCLC stage, 0-A vs. B-C 2.56 (1.48–4.42) 0.001 0.94 (0.42–2.12) 0.881 Recurrence, Absent vs. Presence 1.66 (1.01–2.73) 0.044 1.30 (0.77–2.19) 0.326 ALDH2 rs671 genotype, GG vs. GA/AA 1.90 (1.14–3.16) 0.014 2.02 (1.17–3.49) 0.012 AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; INR: International normalized ratio; AFP: Alpha-fetoprotein; BCLC stage: Barcelona clinic liver cancer; Patients with ALDH2 rs671 genotype GA/AA had a significantly higher mortality rate than those with ALDH2 rs671 genotype GG. For those with ALDH2 rs671 genotype GA/AA, the 1-, 3-, 5- and 10-year mortality rates were 3.2%, 17.9%, 29.8%, and 46.2%, respectively. In contrast, patients with genotype GG had 1-, 3-, 5- and 10-year mortality rates of 1.8%, 7.5%, 7.3%, and 28.7%, respectively (Fig. 3 B). In addition, patients with age ≥ 65 years had a significantly higher mortality rate than those with age < 65 years. For those aged ≥ 65 years, the 1-, 3-, 5- and 10-year mortality rates were 6.2%, 17.2%, 18.2% and 47.9%, respectively. In contrast, those aged < 65 years had 1-, 3-, 5- and 10-year mortality rates of 0%, 10%, 20.7%, and 31%, respectively (Fig. 3 C). Discussion This study, involving 238 patients with ALD-related HCC who underwent curative resection, aimed to identify predictive factors for HCC recurrence and mortality. Notably, the ALDH2 rs671 genotype GA/AA exhibited a remarkable correlation with higher rates of HCC recurrence and mortality relative to ALDH2 rs671 genotype GG. In addition, the multivariable Cox regression analysis revealed the significance of the ALDH2 rs671 genotype GA/AA (HR: 2.66, P < 0.001) and AST ≥ 40 IU/L (HR: 1.93, P = 0.009) as risk factors for HCC recurrence. Furthermore, the study revealed risk factors for mortality, with ALDH2 rs671 genotype GA/AA (HR: 2.02, P = 0.012) and age ≥ 65 years (HR: 1.67, P = 0.048) emerging as significant risk factors. These findings suggest that the ALDH2 rs671 genotype may serve as valuable predictors of HCC recurrence and mortality in ALD-related HCC after hepatectomy. To the best of our knowledge, this study is the first to highlight the significant association between ALDH2 rs671 polymorphisms and HCC recurrence and mortality in ALD-related HCC after hepatectomy. Several studies have revealed that ALDH2 polymorphism impacts HCC occurrence in alcoholic liver disease [16, 18]. However, some studies have reported that ALDH2 rs671 polymorphism is not correlated with HCC development [21, 24]. Our previous study revealed that ALDH2 rs671 polymorphism, along with heavy alcohol consumption, remarkably affects the development of HCC and mortality in patients with alcohol-related cirrhosis [6]. The ALDH2*2 allele variant is a single point mutation (G to A) that results in the inactivation of ALDH2 enzyme activity in humans, causing deficiency. Notably, the ALDH2 rs671 genotype GG effectively metabolizes alcohol and is thus less likely to cause the accumulation of carcinogenic acetaldehyde [6, 25]. Our study reveals that the ALDH2 rs671 genotype GA/AA increased the risk of HCC recurrence and mortality relative to ALDH2 rs671 genotype GG in ALD-related HCC following hepatectomy. Taken together, alcoholism with ALDH2 rs671 genotype GA/AA increased the incidence of HCC development and promoted the risk of HCC recurrence after hepatectomy. Therefore, clinicians should determine the presence of ALDH2 rs671 polymorphisms to predict HCC recurrence in ALD-related HCC after resection. Previous studies have reported that the ALDH2 rs671 genotype GA/AA is not correlated with recurrence-free survival in viral- and alcohol-related HCC after resection. In that study, 96% of patients had HBV or HCV infection and only 25% had alcoholism [25]. However, the present study indicates that the ALDH2 rs671 genotype GA/AA is significantly associated with higher HCC recurrence relative to the ALDH2 rs671 genotype GG in ALD-related HCC after hepatectomy. Notably, 100% of patients drank more than 20 g of ethanol each day for at least 5 years, and we excluded those with HBV or HCV infection. The findings in our study differ from those of a previous study that suggested no correlation between the ALDH2 rs671 genotype GA/AA and recurrence-free survival [25]. This disparity may be attributed to the fact that the previous study primarily included patients with viral- and alcohol-related HCC, whereas our study included only patients who had alcoholism without viral hepatitis. Moreover, ALDH2 polymorphism is inconsistent with HCC development in viral-related HCC [6, 15, 17, 21–23]. However, alcoholism with ALDH2 polymorphism increased the incidence of HCC and the risk of HCC recurrence after hepatectomy. Our previous study revealed that the ALDH2 rs671 genotype GA/AA is significantly associated with higher mortality relative to the ALDH2 rs671 genotype GG in ALD-related cirrhosis [6]. In our current study, we observed a similar trend in ALD-related HCC after hepatectomy. However, previous studies have revealed that the ALDH2 rs671 genotype GA/AA is highly correlated with longer overall survival in viral- and alcohol-related HCC after surgical resection. In that study, 96% of patients had HBV or HCV infection and only 25% had alcoholism [25]. Our study shows that 100% of patients had alcohol drinking more than 20 g of ethanol each day for at least 5 years, and we excluded those with HBV or HCV infection. Our results differ from those of a previous study that suggested a significant correlation between the ALDH2 rs671 genotype GA/AA and overall survival [25]. This disparity may be because the previous study included only patients with viral-related HCC but our study included only patients who had alcoholism without viral hepatitis. In addition, alcoholism with ALDH2 polymorphism increased the incidence of mortality and promoted the risk of mortality after hepatectomy. The ALDH2 rs671 genotype GA/AA is significantly associated with higher HCC recurrence and mortality relative to the ALDH2 rs671 genotype GG in ALD-related HCC after hepatectomy. This study is the first to demonstrate that the ALDH2 rs671 genotype GA/AA is significantly associated with unfavorable clinical prognosis in ALD-related HCC after hepatectomy. Therefore, clinicians should assess ALDH2 rs671 polymorphism to determine the risk of HCC recurrence and mortality in ALD-related HCC after surgical resection. Declarations Ethical statement This study was carried out in accordance with the Declara- tion of Helsinki. This research was approved by the Institutional Review Board of E-DA Hospital (EMRP41111N). All participants were adults and provided written informed consent for study participation. Conflict of interest The authors declare that there are no competing interests. Funding This study was partly supported by grants from Ministry of Science and Technology (MOST 111-2314-B-214-008), E-Da Hospital (EDAHI113002, EDAHP113013, EDAHP112026, EDAHP112006, EDAHP109057, EDAHP108037, EDAHP107041, EDAHP104047, and EDAHS111040), China Medical University Hsinchu Hospital (CMUHCH-DMR-113-029), E-Da Hospital-National Taiwan University Hospital Joint Research Program (112-EDN0004), and National Health Research Institutes (NHRI-109BCCO-MF202016-03). Author Contribution C.K.: Funding acquisition, Writing-origin draft, Writing-review and editing. W.W.: Writing-origin draft, Conceptualization, Methodology. H.L.: Writing-origin draft, Data curation, Formal analysis. P.H.: Funding acquisition, Writing-origin draft, Project administration. S.C.: Writing-origin draft, Investigation. S.L.: Writing-origin draft, Software. L.C.: Writing-origin draft, Resources. Y.C.: Funding acquisition, Writing-origin draft, Funding acquisition, Supervision. Y.H.: Funding acquisition, Writing-origin draft, Validation. W.H.: Funding acquisition, Supervision, Writing-origin draft, Writing-review and editing. C.L.: Funding acquisition, Supervision, Writing-origin draft, Writing-review and editing. All authors reviewed the manuscript. Acknowledgement none Data Availability The data and materials in the current study are available from the corresponding author on reasonable request. Data is provided within supplementary information files. References Llovet JM, Kelley RK, Villanueva A et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021;7(1):6. https://doi.org/10.1038/s41572-020-00240-3. McGlynn KA, Petrick JL, El-Serag HB. Epidemiology of Hepatocellular Carcinoma. Hepatology. 2021;73 Suppl 1(Suppl 1):4-13. https://doi.org/10.1002/hep.31288. Marrero JA, Kulik LM, Sirlin CB et al. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68(2):723-50. https://doi.org/10.1002/hep.29913. European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018;69(1):182-236. https://doi.org/10.1016/j.jhep.2018.03.019. Omata M, Cheng AL, Kokudo N et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int. 2017;11(4):317-70. https://doi.org/10.1007/s12072-017-9799-9. Tsai MC, Yang SS, Lin CC et al. Association of Heavy Alcohol Intake and ALDH2 rs671 Polymorphism With Hepatocellular Carcinoma and Mortality in Patients With Hepatitis B Virus-Related Cirrhosis. JAMA Netw Open. 2022;5(7):e2223511. https://doi.org/10.1001/jamanetworkopen.2022.23511. Lin CW, Lin CC, Mo LR et al. Heavy alcohol consumption increases the incidence of hepatocellular carcinoma in hepatitis B virus-related cirrhosis. J Hepatol. 2013;58(4):730-5. https://doi.org/10.1016/j.jhep.2012.11.045. Roayaie S, Obeidat K, Sposito C et al. Resection of hepatocellular cancer </=2 cm: results from two Western centers. Hepatology. 2013;57(4):1426-35. https://doi.org/10.1002/hep.25832. Forner A, Vilana R, Ayuso C et al. Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma. Hepatology. 2008;47(1):97-104. https://doi.org/10.1002/hep.21966. Tabrizian P, Jibara G, Shrager B et al. Recurrence of hepatocellular cancer after resection: patterns, treatments, and prognosis. Ann Surg. 2015;261(5):947-55. https://doi.org/10.1097/SLA.0000000000000710. Lin CW, Chen YS, Lin CC et al. Autophagy-related gene LC3 expression in tumor and liver microenvironments significantly predicts recurrence of hepatocellular carcinoma after surgical resection. Clin Transl Gastroenterol. 2018;9(6):166. https://doi.org/10.1038/s41424-018-0033-4. Lin CW, Chen YS, Lin CC et al. Significant predictors of overall survival in patients with hepatocellular carcinoma after surgical resection. PLoS One. 2018;13(9):e0202650. https://doi.org/10.1371/journal.pone.0202650. Hsu CC, Hsieh PM, Chen YS et al. Axl and autophagy LC3 expression in tumors is strongly associated with clinical prognosis of hepatocellular carcinoma patients after curative resection. Cancer Med. 2019;8(7):3453-63. https://doi.org/10.1002/cam4.2229. Toyoda H, Kumada T, Tada T et al. Changes in highly sensitive alpha-fetoprotein for the prediction of the outcome in patients with hepatocellular carcinoma after hepatectomy. Cancer Med. 2014;3(3):643-51. https://doi.org/10.1002/cam4.218. Seo W, Gao Y, He Y et al. ALDH2 deficiency promotes alcohol-associated liver cancer by activating oncogenic pathways via oxidized DNA-enriched extracellular vesicles. J Hepatol. 2019;71(5):1000-11. https://doi.org/10.1016/j.jhep.2019.06.018. Abe H, Aida Y, Seki N et al. Aldehyde dehydrogenase 2 polymorphism for development to hepatocellular carcinoma in East Asian alcoholic liver cirrhosis. J Gastroenterol Hepatol. 2015;30(9):1376-83. https://doi.org/10.1111/jgh.12948. Liu J, Yang HI, Lee MH et al. Alcohol Drinking Mediates the Association between Polymorphisms of ADH1B and ALDH2 and Hepatitis B-Related Hepatocellular Carcinoma. Cancer Epidemiol Biomarkers Prev. 2016;25(4):693-9. https://doi.org/10.1158/1055-9965.EPI-15-0961. Sakamoto T, Hara M, Higaki Y et al. Influence of alcohol consumption and gene polymorphisms of ADH2 and ALDH2 on hepatocellular carcinoma in a Japanese population. Int J Cancer. 2006;118(6):1501-7. https://doi.org/10.1002/ijc.21505. Ye X, Wang X, Shang L et al. Genetic variants of ALDH2-rs671 and CYP2E1-rs2031920 contributed to risk of hepatocellular carcinoma susceptibility in a Chinese population. Cancer Manag Res. 2018;10(1037-50. https://doi.org/10.2147/CMAR.S162105. Tomoda T, Nouso K, Sakai A et al. Genetic risk of hepatocellular carcinoma in patients with hepatitis C virus: a case control study. J Gastroenterol Hepatol. 2012;27(4):797-804. https://doi.org/10.1111/j.1440-1746.2011.06948.x. Chen J, Pan W, Chen Y et al. Relationship of ALDH2 rs671 and CYP2E1 rs2031920 with hepatocellular carcinoma susceptibility in East Asians: a meta-analysis. World J Surg Oncol. 2020;18(1):21. https://doi.org/10.1186/s12957-020-1796-0. Koide T, Ohno T, Huang XE et al. HBV/HCV Infection, Alcohol, Tobacco and Genetic Polymorphisms for Hepatocellular Carcinoma in Nagoya, Japan. Asian Pac J Cancer Prev. 2000;1(3):237-43. Yu SZ, Huang XE, Koide T et al. Hepatitis B and C viruses infection, lifestyle and genetic polymorphisms as risk factors for hepatocellular carcinoma in Haimen, China. Jpn J Cancer Res. 2002;93(12):1287-92. https://doi.org/10.1111/j.1349-7006.2002.tb01236.x. Takeshita T, Yang X, Inoue Y et al. Relationship between alcohol drinking, ADH2 and ALDH2 genotypes, and risk for hepatocellular carcinoma in Japanese. Cancer Lett. 2000;149(1-2):69-76. https://doi.org/10.1016/s0304-3835(99)00343-2. Huang PH, Hu CC, Chien CH et al. The Defective Allele of Aldehyde Dehydrogenase 2 Gene is Associated with Favorable Postoperative Prognosis in Hepatocellular Carcinoma. J Cancer. 2019;10(23):5735-43. https://doi.org/10.7150/jca.33221. Bruix J, Sherman M, Practice Guidelines Committee AAftSoLD. Management of hepatocellular carcinoma. Hepatology. 2005;42(5):1208-36. https://doi.org/10.1002/hep.20933. Additional Declarations No competing interests reported. Supplementary Files HCCALDOP23820240603.xlsx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4506472","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":313622966,"identity":"ec1db064-3270-4714-9994-327c3803d394","order_by":0,"name":"Chih-Jan Ko","email":"","orcid":"","institution":"China Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chih-Jan","middleName":"","lastName":"Ko","suffix":""},{"id":313622967,"identity":"fb0ed317-1d46-4397-987a-0ecfe5090027","order_by":1,"name":"Wen-Lung Wang","email":"","orcid":"","institution":"I-Shou University","correspondingAuthor":false,"prefix":"","firstName":"Wen-Lung","middleName":"","lastName":"Wang","suffix":""},{"id":313622968,"identity":"cecfdc68-8a1c-4d12-9d31-507e90cc8ba0","order_by":2,"name":"Hung-Yu Lin","email":"","orcid":"","institution":"E-Da Hospital, I-Shou University","correspondingAuthor":false,"prefix":"","firstName":"Hung-Yu","middleName":"","lastName":"Lin","suffix":""},{"id":313622970,"identity":"aa9b9030-b0a3-46b0-88ab-b64cbe189310","order_by":3,"name":"Pei-Min Hsieh","email":"","orcid":"","institution":"E-Da Hospital, I-Shou University","correspondingAuthor":false,"prefix":"","firstName":"Pei-Min","middleName":"","lastName":"Hsieh","suffix":""},{"id":313622971,"identity":"9b0f889d-7b45-4a28-990b-2f52f58b3ff0","order_by":4,"name":"Szu-Ying Chen","email":"","orcid":"","institution":"E-Da Hospital, I-Shou University","correspondingAuthor":false,"prefix":"","firstName":"Szu-Ying","middleName":"","lastName":"Chen","suffix":""},{"id":313622972,"identity":"57dd11cc-9f7f-43cd-a5c4-1a35133c1d76","order_by":5,"name":"Steven Yu Lin","email":"","orcid":"","institution":"Kaohsiung American School","correspondingAuthor":false,"prefix":"","firstName":"Steven","middleName":"Yu","lastName":"Lin","suffix":""},{"id":313622973,"identity":"cbf2a647-efbd-4b65-a91b-b99a86cdddda","order_by":6,"name":"Li-Wei Chou","email":"","orcid":"","institution":"China Medical University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Li-Wei","middleName":"","lastName":"Chou","suffix":""},{"id":313622974,"identity":"16a2959d-210b-4f92-93d6-45ce44b6fa1c","order_by":7,"name":"Yaw-Sen Chen","email":"","orcid":"","institution":"E-Da Hospital, I-Shou University","correspondingAuthor":false,"prefix":"","firstName":"Yaw-Sen","middleName":"","lastName":"Chen","suffix":""},{"id":313622977,"identity":"2eeff9fc-bc68-4cc0-9198-59686d78120f","order_by":8,"name":"Yu-Wei Huang","email":"","orcid":"","institution":"E-Da Hospital, I-Shou University","correspondingAuthor":false,"prefix":"","firstName":"Yu-Wei","middleName":"","lastName":"Huang","suffix":""},{"id":313622981,"identity":"9e7630a5-0e81-4ad2-80ca-8f0a374ef04f","order_by":9,"name":"Wen-Chao Ho","email":"","orcid":"","institution":"China Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wen-Chao","middleName":"","lastName":"Ho","suffix":""},{"id":313622986,"identity":"59b2c59b-ba91-4aa6-ae8b-512a8d7463a1","order_by":10,"name":"Chih-Wen Lin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuklEQVRIiWNgGAWjYBACPmYQWWEjB6IOPCBGCxtYy5k0Y7CWBKK0gAjGlkOJDSAGcVrYeQ9+5m04kD4/7PBDoC12croNBB3GlyzNu+NO7sbbaQZALcnGZgcIauExY8498yx34+wEkJYDiduI09J2ON1wdvoH0rQkyEvnEG+LsfSfM2mGG6RzCg4kGBDhF37+M4YfZ1TYyMvPTt/84UOFnRxBLXBgAFZpQKxyEJBvIEX1KBgFo2AUjCgAAPVvQPFn1nkWAAAAAElFTkSuQmCC","orcid":"","institution":"E-Da Hospital, I-Shou University","correspondingAuthor":true,"prefix":"","firstName":"Chih-Wen","middleName":"","lastName":"Lin","suffix":""}],"badges":[],"createdAt":"2024-05-31 05:51:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4506472/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4506472/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":58760539,"identity":"02a1984e-5bbe-43f8-916b-9faf561960d0","added_by":"auto","created_at":"2024-06-20 18:50:34","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":76431,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe cumulative incidences of hepatocellular carcinoma recurrence after surgical resection.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe cumulative incidences of HCC recurrence in all patients (A). The cumulative incidences of HCC recurrence according to ALDH2 rs671 polymorphism. The pateints with GA/AA genotypes were significantly correlated with increased incidences of HCC recurrence compared with those with GG genotype (B). The patients with AST ≥ 40 IU/L were significantly correlated with increased incidences of HCC recurrence compared with those with AST \u0026lt; 40 IU/L (C).\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4506472/v1/83050f8e8bf635a3ce9b5b08.png"},{"id":58760519,"identity":"1b3b8fbf-b765-4ff7-ab04-0fd4c3ef38f2","added_by":"auto","created_at":"2024-06-20 18:50:25","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":30575,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe cumulative incidences of hepatocellular carcinoma recurrence after surgical resection after competing risk analysis.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patients with GA/AA genotypes were significantly correlated with increased incidences of HCC recurrence compared with those with GG genotype after competing risk analysis.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4506472/v1/e2494c1b7f4eb9ed22bb5186.png"},{"id":58760518,"identity":"f35afddf-e024-4883-a4e6-7a861ade7f25","added_by":"auto","created_at":"2024-06-20 18:50:25","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":73618,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe cumulative incidences of mortality after surgical resection.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe cumulative incidences of mortality in all patients (A). The cumulative incidences of mortality according to ALDH2 rs671 polymorphism. The pateints with GA/AA genotype were significantly correlated with increased incidences of mortality compared with those with GG genotype (B). The patients with age ≥ 65 years were significantly correlated with increased incidences of mortality compared with those with age \u0026lt; 65 years (C).\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4506472/v1/e5ae1e070029639e74bbecfd.png"},{"id":79336097,"identity":"33583e89-1f32-4aec-8ee9-a71d9e8e6c27","added_by":"auto","created_at":"2025-03-27 07:54:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1386274,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4506472/v1/eb9ca5de-3c66-4b8b-8076-7c25372b8355.pdf"},{"id":58760538,"identity":"bfc7f1a5-20dc-4756-ab50-924b83184bb3","added_by":"auto","created_at":"2024-06-20 18:50:34","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":78376,"visible":true,"origin":"","legend":"","description":"","filename":"HCCALDOP23820240603.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4506472/v1/043e7bafc829e02d56f149d5.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"The associated between ALDH2 rs671 polymorphism and clinical prognosis in alcohol- related hepatocellular carcinoma after curative resection","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality globally [1\u0026ndash;5]. In Taiwan, HCC often results from viral- and alcohol-related cirrhosis [6, 7]. Moreover, early-stage HCC is difficult to diagnose, resulting in elevated HCC recurrence and mortality rates after surgical resection [8\u0026ndash;13]. Despite the use of highly sensitive tumor markers to predict clinical outcomes after hepatectomy in patients with HCC, the result remains unsatisfactory [14]. Therefore, the identification of predictors for HCC recurrence and mortality could help improve the clinical prognosis of patients with HCC undergoing hepatectomy.\u003c/p\u003e \u003cp\u003eThe aldehyde dehydrogenase 2 (ALDH2) polymorphism influences the development of HCC in alcoholic patients with or without viral hepatitis [15\u0026ndash;18] and nonalcoholic patients [19, 20]. Several studies have demonstrated that the ALDH2 rs671 polymorphism is not associated with HCC in East Asians [21\u0026ndash;24]. Our previous study revealed a significant increase in the risk of HCC development and mortality in HBV-related cirrhotic patients with heavy alcohol drinking and ALDH2 rs671 polymorphism [6]. Moreover, a previous study demonstrated that the ALDH2 rs671 genotype GG correlated significantly with shorter overall survival, but not with recurrence-free survival, particularly in patients with viral-related HCC who underwent surgical resection [25]. However, the effect of ALDH2 rs671 polymorphism on HCC recurrence and mortality in patients with alcoholic liver disease (ALD)-related HCC who underwent surgical resection remains unclear. Hence, we investigated the association between ALDH2 rs671 polymorphism and HCC recurrence and mortality in patients with ALD-related HCC who underwent hepatectomy. We also explored the risk factors for HCC recurrence and mortality in this population of patients.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients and follow-up\u003c/h2\u003e \u003cp\u003eThis prospective cohort study enrolled 238 patients with ALD-related HCC who underwent surgical resection from October 2011 to December 2022 at the E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. All patients underwent liver function tests, α-fetoprotein (AFP) tests, and imaging examinations, including ultrasonography, computed tomography, and magnetic resonance imaging examinations. These clinical investigations were conducted every 3\u0026ndash;6 months or as deemed necessary for the detection of HCC. The data analyses were finalized on October 31, 2023. Patients with alcoholism were included in this study, and alcoholism was defined as consuming at least 20 g of ethanol each day for more than 5 years. However, patients with (1) hepatitis B virus infection; (2) hepatitis C virus infection; (3) alcohol intake of \u0026lt;\u0026thinsp;20 g/day and for \u0026lt;\u0026thinsp;5 years; and (4) HCC recurrence and mortality within 6 months after surgical resection were all excluded from the excluded. The presence of ALDH2 rs671 polymorphism was determined by using blood analysis. The primary endpoint was HCC recurrence whereas the secondary endpoint was overall mortality. The follow-up time was defined as the time from the date of inclusion to the date of death, the last follow-up, or the end of the study (October 31, 2023), whichever was earliest. The occurrence time was defined as the time from the date of inclusion to the date of HCC diagnosis, the date of death, the last follow-up, or the end of the study (October 31, 2023), whichever was earliest. HCC recurrence was established based on histology or at least two typical HCC imaging methods, as outlined by the HCC guidelines of the American Association for the Study of Liver Disease[26].\u003c/p\u003e \u003cp\u003eThe clinicopathological features of the patients, including demographic data and tumor characteristics, were recorded. This research was approved by the Institutional Review Board of E-DA Hospital (EMRP41111N). Additionally, the research was conducted per the guidelines of the International Conference on Harmonization for Good Clinical Practice. Notably, all participants were adults and provided written informed consent for study participation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eALDH2 rs671 polymorphism\u003c/h2\u003e \u003cp\u003eALDH2 is a major enzyme involved in the elimination of acetaldehyde from the body. The ALDH2*2 allele variant is a single point mutation (G to A) in exon 12, resulting in a change from glutamine (Glu) to lysine (Lys) at codon 487 and the inactivation of ALDH2 enzyme activity in humans, causing deficiency. The presence of a single polymorphism (Glu to Lys, G to A, or *1 to *2) was evaluated using blood samples. The ALDH2 rs671 polymorphism causes one of three genotypes: GG, AA, and GA. To evaluate ALDH2 deficiency, patients with the GA and AA genotypes were merged into a single GA/AA group.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eContinuous data are expressed as the mean and standard deviation (SD). Categorical data are described using numbers and percentages. Normally distributed continuous variables were compared using the Student\u0026rsquo;s \u003cem\u003et-\u003c/em\u003etest, and the Wilcoxon rank-sum test was applied for comparisons of two groups when continuous variables were not normally distributed. The chi-squared test was used to compare categorical variables. The cumulative HCC recurrence and mortality rates were evaluated using the Kaplan\u0026ndash;Meier method. Recognizing that patients who died were no longer at risk for HCC recurrence, competing risk analyses were conducted. These analyses aimed to evaluate the cumulative HCC recurrence, with mortality considered a competing risk. Both univariable and multivariable analyses were used to evaluate the risk predictors associated with HCC recurrence and mortality. The multivariable analyses were conducted using Cox proportional regression modes for HCC. \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicated statistical significance. All analyses were performed using the Statistical Package for Social Sciences (SPSS, version 23.0; Chicago, IL).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eBaseline demographic data\u003c/h2\u003e \u003cp\u003eThe demographic and clinicopathological features of the study participants are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Notably, 196 (82.4%) were men, and the mean (SD) age was 62.3 (10.2) years. HCC recurrence occurred in 70 patients, and 64 patients died. Additionally, one-fourth of the patients had liver cirrhosis. Regarding tumor stage, 15.5% and 14.7% of the patients were Barcelona clinic liver cancer (BCLC) stage B-C and TNM stage III-IV, respectively.\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\u003eBasic demographic data of all patients and correlations between ALDH2 polymorphisms and clinicopathologic features.\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=\"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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\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\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAll patients\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;238)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eALDH2 rs671 genotype\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGG (n\u0026thinsp;=\u0026thinsp;111)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGA/AA (n\u0026thinsp;=\u0026thinsp;127)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\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\u003e42 (17.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (18.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 (17.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.888\u003c/p\u003e \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\u003e196 (82.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e91 (82.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e105 (82.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62.3\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62.8\u0026thinsp;\u0026plusmn;\u0026thinsp;9.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61.9\u0026thinsp;\u0026plusmn;\u0026thinsp;11.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.510\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.078\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHTN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e103 (43.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 (46.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51 (40.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.299\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59 (24.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (27.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29 (22.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.455\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64 (26.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (34.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (20.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAST (IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48\u0026thinsp;\u0026plusmn;\u0026thinsp;32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45\u0026thinsp;\u0026plusmn;\u0026thinsp;26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50\u0026thinsp;\u0026plusmn;\u0026thinsp;37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.167\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT (IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49\u0026thinsp;\u0026plusmn;\u0026thinsp;45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50\u0026thinsp;\u0026plusmn;\u0026thinsp;53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48\u0026thinsp;\u0026plusmn;\u0026thinsp;37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.780\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal Bilirubin (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.978\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbumin (g/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.918\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.601\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet count (x10\u003csup\u003e3\u003c/sup\u003e/ml)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e188\u0026thinsp;\u0026plusmn;\u0026thinsp;70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e188\u0026thinsp;\u0026plusmn;\u0026thinsp;68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e188\u0026thinsp;\u0026plusmn;\u0026thinsp;72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.726\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eINR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.428\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAFP (ng/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3295\u0026thinsp;\u0026plusmn;\u0026thinsp;21189\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4342\u0026thinsp;\u0026plusmn;\u0026thinsp;26918\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2380\u0026thinsp;\u0026plusmn;\u0026thinsp;14497\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.477\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICG (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.8\u0026thinsp;\u0026plusmn;\u0026thinsp;6.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.732\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiver cirrhosis\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e174 (73.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e85 (76.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e89 (70.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.259\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64 (26.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (23.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38 (29.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChild-Pugh class\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eclass A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e236(99.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e109(98.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e127(100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.419\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eclass B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eOperative margin (\u0026gt;\u0026thinsp;1 cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e168(70.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78 (70.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e90 (70.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.906\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70(29.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 (29.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37 (29.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eEdmondson-Steiner Grades\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI-II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23(9.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (13.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII-IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e215(90.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e105 (94.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e110 (86.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMacrovascular invasion\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e215 (90.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e97 (87.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e118 (92.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.150\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (9.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (12.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMicrovascular invasion\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e184 (77.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83 (74.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e101 (79.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.473\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54 (22.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (25.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (20.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymph node invasion\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e232 (97.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e110 (99.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e122 (96.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.136\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor number\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e218 (91.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e102 (91.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e116 (91.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.878\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (8.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (8.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor size (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.912\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor size\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt; 5 cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e145(60.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61 (55.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e84 (66.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.078\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;5 cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93 (39.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 (45.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43 (33.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTNM stage\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI-II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e201 (84.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93 (83.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e108 (85.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.791\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII-IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37 (15.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (16.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19 (15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBCLC stage\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0-A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e203 (85.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e94 (84.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e109 (85.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.804\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB-C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (14.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (15.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18 (14.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecurrence\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e168 (70.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e89 (80.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e79 (62.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70 (29.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (19.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48 (37.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecurrence time\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\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\u003eMortality\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbsent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e174 (73.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88 (79.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e86 (67.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.045\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePresent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64 (26.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (20.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41 (32.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFollow up time\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eData shown as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or number (%).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eBMI: Body mass index; HTN: Hypertension; DM: Diabetes Mellitus; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; INR: International normalized ratio; AFP: Alpha-fetoprotein; ICG: Indocyanine green; BCLC stage: Barcelona clinic liver cancer;\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eALDH2 rs671 polymorphism is associated with advanced clinicopathological features\u003c/h2\u003e \u003cp\u003eNotably, 44.6% (111) and 56.04% (127) of the 238 patients had ALDH2 rs671 genotype GG and genotype GA/AA, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The ALDH2 rs671 genotype was significantly correlated with advanced clinicopathological features, including Edmondson\u0026ndash;Steiner Grades [105 (94.6) vs. 110 (86.6), \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.038], recurrence [22 (19.8) vs. 48 (37.8), \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001], and mortality [23 (20.7) vs. 41 (32.3), \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003ePredictive factors associated with tumor recurrence in patients with HCC who underwent hepatectomy\u003c/h2\u003e \u003cp\u003eHCC recurrence was observed in 70 patients after hepatectomy, with 1-, 3-, 5-, and 10-year cumulative incidence rates of 2.6%, 12.0%, 23.8%, and 37.7%, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). The univariate analysis revealed that ALDH2 rs671 genotype GA/AA, AST\u0026thinsp;\u0026ge;\u0026thinsp;40 IU/L, and TNM stage III-IV were significantly correlated with increased HCC recurrence (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Furthermore, the multivariate Cox regression analysis revealed that the ALDH2 rs671 genotype GA/AA was significantly correlated with increased HCC recurrence (hazard ratio [HR]: 2.66, 95% confidence interval [CI]: 1.59\u0026ndash;4.43, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), followed by those with AST\u0026thinsp;\u0026ge;\u0026thinsp;40 IU/L (HR: 1.93, 95% CI: 1.18\u0026ndash;3.17, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \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\u003eUnivariate and multivariate analyses of factors associated with tumor recurrence of hepatocellular carcinoma patients who underwent curative resection.\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=\"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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\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\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUnivariate analyses\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMultivariate analyses\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP-\u003c/em\u003evalue\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender, Female vs. Male\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.43 (0.73\u0026ndash;2.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.292\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years), \u0026lt;\u0026thinsp;65 vs. \u0026ge; 65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.78 (0.48\u0026ndash;1.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.337\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody Mass Index, (kg/m2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.94 (0.59\u0026ndash;1.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.796\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes Mellitus, Absent vs. Presence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.90 (0.51\u0026ndash;1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.715\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension, Absent vs. Presence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.86 (0.53\u0026ndash;1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.863\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking, Absent vs. Presence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.02 (0.60\u0026ndash;1.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.946\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAST (IU/L), \u0026lt;\u0026thinsp;40 vs. \u0026ge; 40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.08 (1.29\u0026ndash;3.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.93 (1.18\u0026ndash;3.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT (IU/L), \u0026lt;\u0026thinsp;40 vs. \u0026ge; 40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.39 (0.87\u0026ndash;2.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.167\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal Bilirubin (mg/dl), \u0026lt;\u0026thinsp;1.2 vs. \u0026ge; 1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.10 (0.62\u0026ndash;1.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.740\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbumin (g/dl), \u0026lt;\u0026thinsp;3.5 vs. \u0026ge; 3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.46 (1.7\u0026ndash;1.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.133\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet count (x10\u003csup\u003e3\u003c/sup\u003e/ml), \u0026lt;\u0026thinsp;100K vs. \u0026ge; 100K\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.98 (0.36\u0026ndash;2.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.960\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eINR, \u0026lt;\u0026thinsp;1.0 vs. \u0026ge; 1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.16 (0.65\u0026ndash;2.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAFP (ng/dl)\u0026thinsp;\u0026lt;\u0026thinsp;200 vs. \u0026ge; 200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.95 (0.52\u0026ndash;1.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.877\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiver cirrhosis, Absent vs. Presence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.34 (0.81\u0026ndash;2.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.250\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChild-Pugh class, A vs. B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.05 (0.01\u0026ndash;131)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.636\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOperative margin (cm), \u0026lt;\u0026thinsp;1.0 vs. \u0026ge; 1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.39 (0.84\u0026ndash;2.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.199\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor number, Single vs. Multiple\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.47 (0.70\u0026ndash;3.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.306\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor size (cm), \u0026lt;\u0026thinsp;5 vs. \u0026ge; 5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.06 (0.66\u0026ndash;1.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.806\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEdmondson-Steiner Grade I-II vs. III-IV\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMacrovascular invasion, Absent vs. Presence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.12 (0.51\u0026ndash;2.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.778\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMicrovascular invasion, Absent vs. Presence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.05 (0.58\u0026ndash;1.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.868\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymph node invasion, Absent vs. Presence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.69 (0.41\u0026ndash;6.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.464\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTNM stage, I-II vs. III-IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.89 (1.08\u0026ndash;3.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.62 (0.92\u0026ndash;2.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.098\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBCLC stage, 0-A vs. B-C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.72 (0.96\u0026ndash;3.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.070\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALDH2 rs671 genotype, GG vs. GA/AA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.63 (1.58\u0026ndash;4.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.66 (1.59\u0026ndash;4.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eAST: Aspartate aminotransferase; ALT: Alanine aminotransferase; INR: International normalized ratio; AFP: Alpha-fetoprotein; BCLC stage: Barcelona clinic liver cancer;\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe Kaplan-Meier analysis revealed that patients with ALDH2 rs671 genotype GA/AA had a significantly higher HCC recurrence rate than those with ALDH2 rs671 genotype GG. Additionally, for patients with ALDH2 rs671 genotype GA/AA, the 1-, 3-, 5- and 10-year cumulative HCC recurrence rates were 7.2%, 30.1%, 43.2%, and 59.0%, respectively. By contrast, those with genotype GG had 1-, 3-, 5- and 10-year cumulative HCC recurrence rates of 6.6%, 11.5%, 17.4%, and 23.8%, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). In addition, patients with AST\u0026thinsp;\u0026ge;\u0026thinsp;40 IU/L had a significantly higher HCC recurrence rate than those with AST\u0026thinsp;\u0026lt;\u0026thinsp;40 IU/L. For those AST\u0026thinsp;\u0026ge;\u0026thinsp;40 IU/L, the 1-, 3-, 5- and 10-year HCC recurrence rates were 8.9%, 28.9%, 39.5% and 53.2%, respectively. In contrast, those AST\u0026thinsp;\u0026lt;\u0026thinsp;40 IU/L had 1-, 3-, 5- and 10-year mortality rates of 2.5%, 14.1%, 22.3%, and 29.1%, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eC).\u003c/p\u003e \u003cp\u003eFurthermore, in the competing risk analysis, patients with ALDH2 rs671 genotype GA/AA still had a significantly higher HCC recurrence rate than those with ALDH2 rs671 genotype GG (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Additionally, for patients with ALDH2 rs671 genotype GA/AA, the 1-, 3-, 5- and 10-year cumulative HCC recurrence rates were 9.7%, 34.7%, 48%, and 62.7%, respectively. By contrast, those with genotype GG had 1-, 3-, 5- and 10-year cumulative HCC recurrence rates of 3.1%, 13%, 19.3%, and 25.7%, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003ePredictive factors associated with mortality in patients with HCC who underwent hepatectomy\u003c/h2\u003e \u003cp\u003eDuring the mean follow-up time of 5.5 years, 64 patients died. The cumulative mortality rates at 1, 3, 5, and 10 years after resection were 3.6%, 13.0%, 23.8%, and 37.7%, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). The univariate analysis revealed that the following factors were significantly correlated with increased mortality: age\u0026thinsp;\u0026ge;\u0026thinsp;65 years, ALDH2 rs671 genotype GA/AA, AST\u0026thinsp;\u0026ge;\u0026thinsp;40 IU/L, TNM stage III-IV, platelet count\u0026thinsp;\u0026lt;\u0026thinsp;100 K, multiple tumor number, Barcelona clinic liver cancer (BCLC) stage B-C, and HCC recurrence (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The multivariate Cox regression analysis revealed that patients with ALDH2 rs671 genotype GA/AA had the highest mortality rate (HR: 2.02, 95% CI: 1.17\u0026ndash;3.49, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012), followed by those with age\u0026thinsp;\u0026ge;\u0026thinsp;65 years (HR: 1.67, 95% CI: 1.01\u0026ndash;2.78, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.048) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\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\u003eUnivariate and multivariate analyses of factors associated with mortality of hepatocellular carcinoma patients who underwent curative resection.\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=\"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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\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\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUnivariate analyses\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMultivariate analyses\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHR (95% CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender, Female vs. Male\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.38 (0.68\u0026ndash;2.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.373\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years), \u0026lt;\u0026thinsp;65 vs. \u0026ge; 65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.68 (1.03\u0026ndash;2.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.037\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.67 (1.01\u0026ndash;2.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.048\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody Mass Index, (kg/m2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.63 (0.38\u0026ndash;1.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.073\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes Mellitus, Absent vs. Presence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.30 (0.76\u0026ndash;2.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.342\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension, Absent vs. Presence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.45 (0.89\u0026ndash;2.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.139\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking, Absent vs. Presence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.17 (0.69\u0026ndash;1.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.551\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAST (IU/L), \u0026lt;\u0026thinsp;40 vs. \u0026ge; 40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.84 (1.12\u0026ndash;3.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.53 (0.88\u0026ndash;2.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.135\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT (IU/L), \u0026lt;\u0026thinsp;40 vs. \u0026ge; 40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.01 (0.62\u0026ndash;1.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.959\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal Bilirubin (mg/dl), \u0026lt;\u0026thinsp;1.2 vs. \u0026ge; 1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.36 (0.77\u0026ndash;2.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.291\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbumin (g/dl), \u0026lt;\u0026thinsp;3.5 vs. \u0026ge; 3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.40 (0.14\u0026ndash;1.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.073\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet count (x10\u003csup\u003e3\u003c/sup\u003e/ml), \u0026lt;\u0026thinsp;100K vs. \u0026ge; 100K\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.40 (0.19\u0026ndash;0.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.53 (0.25\u0026ndash;1.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.103\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProthrombin time,, \u0026lt;\u0026thinsp;1.0 vs. \u0026ge; 1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.78 (0.90\u0026ndash;3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.095\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAFP (ng/dl)\u0026thinsp;\u0026lt;\u0026thinsp;200 vs. \u0026ge; 200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.17 (0.65\u0026ndash;2.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.596\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiver cirrhosis, Absent vs. Presence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.01 (0.58\u0026ndash;1.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.982\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChild-Pugh class, A vs. B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.45 (0.47\u0026ndash;25.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.223\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOperative margin (cm), \u0026lt;\u0026thinsp;1.0 vs. \u0026ge; 1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.01 (0.59\u0026ndash;1.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.971\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor number, Single vs. Multiple\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.29 (1.19\u0026ndash;4.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.70 (0.78\u0026ndash;3.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.179\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor size (cm), \u0026lt;\u0026thinsp;5 vs. \u0026ge; 5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.56 (0.96\u0026ndash;2.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.076\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEdmondson-Steiner Grade I-II vs. III-IV\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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMacrovascular invasion, Absent vs. Presence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.48 (1.35\u0026ndash;4.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.70 (0.81\u0026ndash;3.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.159\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMicrovascular invasion, Absent vs. Presence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.73 (0.99\u0026ndash;2.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.052\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTNM stage, I-II vs. III-IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.99 (1.76\u0026ndash;5.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.89 (0.87\u0026ndash;4.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.108\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBCLC stage, 0-A vs. B-C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.56 (1.48\u0026ndash;4.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.94 (0.42\u0026ndash;2.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.881\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecurrence, Absent vs. Presence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.66 (1.01\u0026ndash;2.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.30 (0.77\u0026ndash;2.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.326\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALDH2 rs671 genotype, GG vs. GA/AA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.90 (1.14\u0026ndash;3.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.02 (1.17\u0026ndash;3.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eAST: Aspartate aminotransferase; ALT: Alanine aminotransferase; INR: International normalized ratio; AFP: Alpha-fetoprotein; BCLC stage: Barcelona clinic liver cancer;\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePatients with ALDH2 rs671 genotype GA/AA had a significantly higher mortality rate than those with ALDH2 rs671 genotype GG. For those with ALDH2 rs671 genotype GA/AA, the 1-, 3-, 5- and 10-year mortality rates were 3.2%, 17.9%, 29.8%, and 46.2%, respectively. In contrast, patients with genotype GG had 1-, 3-, 5- and 10-year mortality rates of 1.8%, 7.5%, 7.3%, and 28.7%, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB). In addition, patients with age\u0026thinsp;\u0026ge;\u0026thinsp;65 years had a significantly higher mortality rate than those with age\u0026thinsp;\u0026lt;\u0026thinsp;65 years. For those aged\u0026thinsp;\u0026ge;\u0026thinsp;65 years, the 1-, 3-, 5- and 10-year mortality rates were 6.2%, 17.2%, 18.2% and 47.9%, respectively. In contrast, those aged\u0026thinsp;\u0026lt;\u0026thinsp;65 years had 1-, 3-, 5- and 10-year mortality rates of 0%, 10%, 20.7%, and 31%, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study, involving 238 patients with ALD-related HCC who underwent curative resection, aimed to identify predictive factors for HCC recurrence and mortality. Notably, the ALDH2 rs671 genotype GA/AA exhibited a remarkable correlation with higher rates of HCC recurrence and mortality relative to ALDH2 rs671 genotype GG. In addition, the multivariable Cox regression analysis revealed the significance of the ALDH2 rs671 genotype GA/AA (HR: 2.66, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and AST\u0026thinsp;\u0026ge;\u0026thinsp;40 IU/L (HR: 1.93, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009) as risk factors for HCC recurrence. Furthermore, the study revealed risk factors for mortality, with ALDH2 rs671 genotype GA/AA (HR: 2.02, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012) and age\u0026thinsp;\u0026ge;\u0026thinsp;65 years (HR: 1.67, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.048) emerging as significant risk factors. These findings suggest that the ALDH2 rs671 genotype may serve as valuable predictors of HCC recurrence and mortality in ALD-related HCC after hepatectomy. To the best of our knowledge, this study is the first to highlight the significant association between ALDH2 rs671 polymorphisms and HCC recurrence and mortality in ALD-related HCC after hepatectomy.\u003c/p\u003e \u003cp\u003eSeveral studies have revealed that ALDH2 polymorphism impacts HCC occurrence in alcoholic liver disease [16, 18]. However, some studies have reported that ALDH2 rs671 polymorphism is not correlated with HCC development [21, 24]. Our previous study revealed that ALDH2 rs671 polymorphism, along with heavy alcohol consumption, remarkably affects the development of HCC and mortality in patients with alcohol-related cirrhosis [6]. The ALDH2*2 allele variant is a single point mutation (G to A) that results in the inactivation of ALDH2 enzyme activity in humans, causing deficiency. Notably, the ALDH2 rs671 genotype GG effectively metabolizes alcohol and is thus less likely to cause the accumulation of carcinogenic acetaldehyde [6, 25]. Our study reveals that the ALDH2 rs671 genotype GA/AA increased the risk of HCC recurrence and mortality relative to ALDH2 rs671 genotype GG in ALD-related HCC following hepatectomy. Taken together, alcoholism with ALDH2 rs671 genotype GA/AA increased the incidence of HCC development and promoted the risk of HCC recurrence after hepatectomy. Therefore, clinicians should determine the presence of ALDH2 rs671 polymorphisms to predict HCC recurrence in ALD-related HCC after resection. Previous studies have reported that the ALDH2 rs671 genotype GA/AA is not correlated with recurrence-free survival in viral- and alcohol-related HCC after resection. In that study, 96% of patients had HBV or HCV infection and only 25% had alcoholism [25]. However, the present study indicates that the ALDH2 rs671 genotype GA/AA is significantly associated with higher HCC recurrence relative to the ALDH2 rs671 genotype GG in ALD-related HCC after hepatectomy. Notably, 100% of patients drank more than 20 g of ethanol each day for at least 5 years, and we excluded those with HBV or HCV infection. The findings in our study differ from those of a previous study that suggested no correlation between the ALDH2 rs671 genotype GA/AA and recurrence-free survival [25]. This disparity may be attributed to the fact that the previous study primarily included patients with viral- and alcohol-related HCC, whereas our study included only patients who had alcoholism without viral hepatitis. Moreover, ALDH2 polymorphism is inconsistent with HCC development in viral-related HCC [6, 15, 17, 21\u0026ndash;23]. However, alcoholism with ALDH2 polymorphism increased the incidence of HCC and the risk of HCC recurrence after hepatectomy.\u003c/p\u003e \u003cp\u003eOur previous study revealed that the ALDH2 rs671 genotype GA/AA is significantly associated with higher mortality relative to the ALDH2 rs671 genotype GG in ALD-related cirrhosis [6]. In our current study, we observed a similar trend in ALD-related HCC after hepatectomy. However, previous studies have revealed that the ALDH2 rs671 genotype GA/AA is highly correlated with longer overall survival in viral- and alcohol-related HCC after surgical resection. In that study, 96% of patients had HBV or HCV infection and only 25% had alcoholism [25]. Our study shows that 100% of patients had alcohol drinking more than 20 g of ethanol each day for at least 5 years, and we excluded those with HBV or HCV infection. Our results differ from those of a previous study that suggested a significant correlation between the ALDH2 rs671 genotype GA/AA and overall survival [25]. This disparity may be because the previous study included only patients with viral-related HCC but our study included only patients who had alcoholism without viral hepatitis. In addition, alcoholism with ALDH2 polymorphism increased the incidence of mortality and promoted the risk of mortality after hepatectomy.\u003c/p\u003e \u003cp\u003eThe ALDH2 rs671 genotype GA/AA is significantly associated with higher HCC recurrence and mortality relative to the ALDH2 rs671 genotype GG in ALD-related HCC after hepatectomy. This study is the first to demonstrate that the ALDH2 rs671 genotype GA/AA is significantly associated with unfavorable clinical prognosis in ALD-related HCC after hepatectomy. Therefore, clinicians should assess ALDH2 rs671 polymorphism to determine the risk of HCC recurrence and mortality in ALD-related HCC after surgical resection.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthical statement\u003c/h2\u003e \u003cp\u003e This study was carried out in accordance with the Declara- tion of Helsinki. This research was approved by the Institutional Review Board of E-DA Hospital (EMRP41111N). All participants were adults and provided written informed consent for study participation.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eConflict of interest\u003c/h2\u003e \u003cp\u003eThe authors declare that there are no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis study was partly supported by grants from Ministry of Science and Technology (MOST 111-2314-B-214-008), E-Da Hospital (EDAHI113002, EDAHP113013, EDAHP112026, EDAHP112006, EDAHP109057, EDAHP108037, EDAHP107041, EDAHP104047, and EDAHS111040), China Medical University Hsinchu Hospital (CMUHCH-DMR-113-029), E-Da Hospital-National Taiwan University Hospital Joint Research Program (112-EDN0004), and National Health Research Institutes (NHRI-109BCCO-MF202016-03).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eC.K.: Funding acquisition, Writing-origin draft, Writing-review and editing. W.W.: Writing-origin draft, Conceptualization, Methodology. H.L.: Writing-origin draft, Data curation, Formal analysis. P.H.: Funding acquisition, Writing-origin draft, Project administration. S.C.: Writing-origin draft, Investigation. S.L.: Writing-origin draft, Software. L.C.: Writing-origin draft, Resources. Y.C.: Funding acquisition, Writing-origin draft, Funding acquisition, Supervision. Y.H.: Funding acquisition, Writing-origin draft, Validation. W.H.: Funding acquisition, Supervision, Writing-origin draft, Writing-review and editing. C.L.: Funding acquisition, Supervision, Writing-origin draft, Writing-review and editing. All authors reviewed the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003enone\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data and materials in the current study are available from the corresponding author on reasonable request. Data is provided within supplementary information files.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLlovet JM, Kelley RK, Villanueva A et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021;7(1):6. https://doi.org/10.1038/s41572-020-00240-3.\u003c/li\u003e\n\u003cli\u003eMcGlynn KA, Petrick JL, El-Serag HB. Epidemiology of Hepatocellular Carcinoma. Hepatology. 2021;73 Suppl 1(Suppl 1):4-13. https://doi.org/10.1002/hep.31288.\u003c/li\u003e\n\u003cli\u003eMarrero JA, Kulik LM, Sirlin CB et al. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018;68(2):723-50. https://doi.org/10.1002/hep.29913.\u003c/li\u003e\n\u003cli\u003eEuropean Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. 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ALDH2 deficiency promotes alcohol-associated liver cancer by activating oncogenic pathways via oxidized DNA-enriched extracellular vesicles. J Hepatol. 2019;71(5):1000-11. https://doi.org/10.1016/j.jhep.2019.06.018.\u003c/li\u003e\n\u003cli\u003eAbe H, Aida Y, Seki N et al. Aldehyde dehydrogenase 2 polymorphism for development to hepatocellular carcinoma in East Asian alcoholic liver cirrhosis. J Gastroenterol Hepatol. 2015;30(9):1376-83. https://doi.org/10.1111/jgh.12948.\u003c/li\u003e\n\u003cli\u003eLiu J, Yang HI, Lee MH et al. Alcohol Drinking Mediates the Association between Polymorphisms of ADH1B and ALDH2 and Hepatitis B-Related Hepatocellular Carcinoma. Cancer Epidemiol Biomarkers Prev. 2016;25(4):693-9. https://doi.org/10.1158/1055-9965.EPI-15-0961.\u003c/li\u003e\n\u003cli\u003eSakamoto T, Hara M, Higaki Y et al. Influence of alcohol consumption and gene polymorphisms of ADH2 and ALDH2 on hepatocellular carcinoma in a Japanese population. 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HBV/HCV Infection, Alcohol, Tobacco and Genetic Polymorphisms for Hepatocellular Carcinoma in Nagoya, Japan. Asian Pac J Cancer Prev. 2000;1(3):237-43.\u003c/li\u003e\n\u003cli\u003eYu SZ, Huang XE, Koide T et al. Hepatitis B and C viruses infection, lifestyle and genetic polymorphisms as risk factors for hepatocellular carcinoma in Haimen, China. Jpn J Cancer Res. 2002;93(12):1287-92. https://doi.org/10.1111/j.1349-7006.2002.tb01236.x.\u003c/li\u003e\n\u003cli\u003eTakeshita T, Yang X, Inoue Y et al. Relationship between alcohol drinking, ADH2 and ALDH2 genotypes, and risk for hepatocellular carcinoma in Japanese. Cancer Lett. 2000;149(1-2):69-76. https://doi.org/10.1016/s0304-3835(99)00343-2.\u003c/li\u003e\n\u003cli\u003eHuang PH, Hu CC, Chien CH et al. The Defective Allele of Aldehyde Dehydrogenase 2 Gene is Associated with Favorable Postoperative Prognosis in Hepatocellular Carcinoma. J Cancer. 2019;10(23):5735-43. https://doi.org/10.7150/jca.33221.\u003c/li\u003e\n\u003cli\u003eBruix J, Sherman M, Practice Guidelines Committee AAftSoLD. Management of hepatocellular carcinoma. Hepatology. 2005;42(5):1208-36. https://doi.org/10.1002/hep.20933.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Hepatocellular carcinoma, ALDH2 rs671 polymorphism, predictors, recurrence, mortality, hepatectomy.","lastPublishedDoi":"10.21203/rs.3.rs-4506472/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4506472/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eWhether ALDH2 rs671 polymorphism predicts clinical prognosis in alcoholic liver disease (ALD)-related hepatocellular carcinoma (HCC) after hepatectomy remains unclear.\u003c/p\u003e\u003ch2\u003eAims\u003c/h2\u003e \u003cp\u003eThis study aims to investigate the association between ALDH2 rs671 polymorphism and HCC recurrence and mortality in patients with ALD-related HCC who underwent hepatectomy. We also explored the risk factors for HCC recurrence and mortality in this population of patients.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis prospective cohort study enrolled 238 ALD-related HCC patients underwent hepatectomy from 2011 to 2022 at the E-Da Hospital, I-Shou University. Data analyses were finalized on October, 2023. Alcoholism was defined as consuming over 20 g of ethanol each day for at least 5 years. Patients with HBsAg-positive or/and HCV-positive status were excluded. ALDH2 rs671 polymorphism was analyzed. The endpoint was HCC recurrence and overall mortality.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOf the 238 patients enrolled, 196 (82.4%) were men, and the mean (SD) age was 62.3 (10.2) years. HCC recurrence occurred in 70 patients, and 64 patients died. ALDH2 rs671 polymorphism was significantly associated with HCC recurrence and mortality. The 10-year cumulative HCC recurrence and mortality rates were significantly higher in patients with the ALDH2 rs671 genotype GA/AA relative to those with the ALDH2 rs671 genotype GG. In the Cox proportional analyses, the ALDH2 rs671 genotypes GA/AA (hazard ratio [HR]: 2.66, 95% confidence interval [CI]: 1.59\u0026ndash;4.43, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and AST\u0026thinsp;\u0026ge;\u0026thinsp;40 IU/L (HR: 1.93, 95% CI: 1.18\u0026ndash;3.17, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009) were significantly associated with increased HCC recurrence. Furthermore, the ALDH2 rs671 genotype GA/AA (HR: 2.02, 95% CI: 1.17\u0026ndash;3.49, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012) and age\u0026thinsp;\u0026ge;\u0026thinsp;65 years (HR: 1.67, 95% CI: 1.01\u0026ndash;2.78, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.048) were significantly associated with increased mortality.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe ALDH2 rs671 genotype GA/AA is significantly associated with unfavorable clinical prognosis in ALD-related HCC after hepatectomy.\u003c/p\u003e","manuscriptTitle":"The associated between ALDH2 rs671 polymorphism and clinical prognosis in alcohol- related hepatocellular carcinoma after curative resection","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-20 18:49:57","doi":"10.21203/rs.3.rs-4506472/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"92cf620d-638f-4126-b8b2-0fd85a067bf4","owner":[],"postedDate":"June 20th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-03-27T07:53:45+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-20 18:49:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4506472","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4506472","identity":"rs-4506472","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}