Background and aims Although coexisting alcohol-induced liver disease and hepatitis B or C virus-induced liver cirrhosis (ALD + HBV or ALD + HCV) has been the center of recent hepatology researches, numerous controversies still persist. This study aimed to showcase the influence of alcohol on the laboratory values and on the clinical outcomes of patients with hepatitis B and C virus-induced liver cirrhosis. Methods Patients diagnosed with liver cirrhosis (n = 22,287) from January 2010 to December 2019 were enrolled, and divided into five groups according to the etiology: alcohol-induced liver disease (ALD, 1652 cases), hepatitis B virus (HBV, 18,079 cases), hepatitis C virus (HCV, 682 cases), ALD + HBV (1594 cases) and ALD + HCV (280 cases). Laboratory results and proportion of different liver cirrhosis complications were contrasted between groups. Results The proportions of patients with Child Pugh grade C (28.0% vs 18.8%, P < 0.001) or MELD greater than 18 (24.1% vs 18.5%, P < 0.001) in the ALD + HBV group exceeded significantly those in the HBV group. Multivariate logistic regression revealed that the risk of hepatocellular carcinoma (HCC) and that of esophageal gastric variceal bleeding (EGVB) in the ALD + HBV group was respectively 2.01-fold and 1.74-fold that in the HBV group (HCC: OR = 2.01, 95% CI [1.58–2.55]; EGVB: OR = 1.74, 95% CI [1.30–2.33]) after adjusting for potential confounders. Furthermore, a linear-by-linear analysis test showed a decrease in the risk of HCC and EGVB with the duration of alcohol abstinence. Moreover, patients with both antiviral treatment and alcohol abstinence had the lowest risk of HCC and EGVB (HCC: OR = 0.10, 95% CI [0.05–0.20], P < 0.001; EGVB: OR = 0.17, 95% CI [0.06–0.45], P < 0.001) compared to those without any treatment, those with abstinence alone and those with antiviral therapy alone. Similar pattern was noticed while comparing the ALD + HCV group to the HCV group. Conclusion Heavy alcohol use increased the severity of liver function impairment and the prevalence of HCC and EGVB in hepatitis virus-induced liver cirrhosis patients. Remarkably, long-term alcohol abstinence coupled with antiviral treatment effectively decreased the risk of HCC and EGVB in these populations.

Aberrant immunity contributes to the pathogenesis of acute-on-chronic hepatitis B liver failure (ACHBLF), and A20 is a newly identified negative regulatory molecule of the immune response. However, no data have been reported for the role of A20 in ACHBLF. This study aimed to investigate A20 mRNA expression in ACHBLF and to determine the potential of A20 as a biomarker for the prognosis of ACHBLF. Quantitative real-time polymerase chain reaction (qPCR) was used to measure the mRNA expression of A20 in peripheral blood mononuclear cells (PBMCs) from 137 ACHBLF patients, 105 chronic hepatitis B (CHB) and 35 healthy controls (HCs). A secondary cohort with 37 ACHBLF patients was set up as validation data set. The plasma levels of interleukin (IL)-1β, IL-6 and IL-10 were determined using enzyme-linked immunosorbent assay (ELISA). Receiver-operating characteristic (ROC) curves were used to determine the predictive value of A20 for the prognosis of ACHBLF patients. A20 mRNA expression in ACHBLF was significantly higher compared with CHB and HCs. In ACHBLF patients, A20 mRNA was closely associated with total bilirubin, albumin, international normalized ratio, prothrombin time activity and model for end-stage liver disease. Furthermore, A20 mRNA was significantly correlated with IL-6 and IL-10. An optimal cut-off value of 12.32 for A20 mRNA had significant power in discriminating survival or death in ACHBLF patients. In conclusion, our results suggest that the up-regulation of the A20 gene might contribute to the severity of ACHBLF and A20 mRNA level might be a potential predictor for the prognosis of ACHBLF.

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BACKGROUND & AIM: Coexisting alcoholic liver disease and virus-induced liver cirrhosis (ALD+HBV and ALD+HCV) has not been thoroughly studied. This cross-sectional study aims to showcase the influence of alcohol on the laboratory values and on the clinical outcomes of patients with hepatitis B and C virus-induced liver cirrhosis.METHOD: Patients diagnosed with liver cirrhosis (n=22287) from January 2010 to December 2019 were collected from our hospital electronic database, and divided into five groups according to the etiology: ALD (1652 cases, 7.4%), HBV (18079 cases, 81.1%), HCV (682 cases, 3.1%), ALD+HBV (1594 cases, 7.2%) and ALD+HCV (280 cases, 1.3%). Laboratory results and proportion of different liver cirrhosis complications were contrasted between groups.RESULTS: ALD+HBV and ALD+HCV presented with higher proportions of poor prognosis patients and cirrhosis complications compared to HBV and HCV respectively. Multivariate logistic regression revealed that the risk of HCC and that of EGVB in the ALD+HBV group was respectively 2.14-fold and 1.47-fold that in the HBV group (HCC: OR=2.14, 95%CI: [1.71-2.69]; EGVB: OR=1.47, 95%CI: [1.17-1.84]) after adjusting for potential confounders. Furthermore, a decrease in the risk of HCC and EGVB with the duration of alcohol abstinence was observed. Similar pattern was noticed while comparing ALD+HCV group to HCV group.CONCLUSION: Alcohol significantly increased the severity of liver function impairment and the prevalence of liver cirrhosis complications such as HCC and EGVB in hepatitis virus-induced liver cirrhosis patients. Remarkably, long period of alcohol abstinence significantly decreased the prevalence of HCC and EGVB in these populations.