Clinical differences between HBV and alcohol related ACLF in a WGO classification multicenter study.

Acute-on-chronic liver failure (ACLF) exhibits etiological heterogeneity across regions, with hepatitis B virus (HBV)-related ACLF predominant in China and alcohol-related ACLF dominating Western populations. This multicenter retrospective study systematically compared clinical profiles of HBV-related (n = 659) and alcohol-related ACLF (n = 296) stratified by the World Gastroenterology Organization (WGO) A/B/C classification, reflecting underlying chronic liver disease severity. Compared to HBV-related ACLF, alcohol-related ACLF showed higher systemic inflammation (leukocytosis, neutrophilia), bacterial infection (P < 0.001), extrahepatic organ failures (single-organ: renal, brain and respiratory, all P < 0.05; multi-organ: P < 0.001) and higher CLIF-C ACLF/COSSH-ACLF II scores. Conversely, HBV-related ACLF exhibited acute hepatocellular injury (elevated ALT/AST), and higher MELD/MELD-Na scores. These etiological disparities were most pronounced in type C ACLF. Despite these distinct profiles, mortality did not differ between etiologies. Type C ACLF demonstrated poorest profiles and uniformly high 90-day mortality (> 45%) regardless of etiology driven by cumulative organ failure burden. Importantly, CLIF-C ACLF and COSSH-ACLF II scores outperformed MELD and MELD-Na scores in predicting outcomes for type C patients. These findings underscore the critical influence of diverse etiologies and severity stages of underlying chronic liver diseases on ACLF profiles and outcomes, thereby necessitating stratified management approaches tailored to underlying chronic liver disease to ultimately improve patient outcomes.