Abstract: OBJECTIVE To compare the differences in clinical features, laboratory indicators and precipitating factors between patients with viral and alcoholic cirrhosis-associated hepatic encephalopathy (HE), and to screen for etiology-associated risk factors, thereby providing evidences for etiology-based risk assessment. METHODSA retrospective analysis was conducted on 287 patients with cirrhosis-associated HE hospitalized at the Fifth Medical Center of the Chinese PLA General Hospital from Feb. 2023 to Dec. 2024. They were etiologically divided into a viral cirrhosis-associated HE group (VHE group, n=164) and an alcoholic cirrhosis-associated HE group (AHE group, n=123). Univariate indicators, including clinical features, laboratory indicators and precipitating factors, were systematically compared between the two groups, and then multivariate logistic regression analysis was employed to screen for etiology-based influencing factors. RESULTSStatistically significant differences were observed between the two groups in terms of sex, smoking history, alcohol consumption history, classification of liver failure, Child-Pugh score, MELD grouping, presence of malignant tumors, splenomegaly, varices, transaminase levels and AST/ALT ratio (P<0.05). Multivariate analysis revealed that tumors, spontaneous bacterial peritonitis and post-TIPS status were associated with VHE, while smoking, hypomagnesemia and low hemoglobin level were associated with AHE (P<0.05). The recurrence rate of HE in the AHE group (56.10%) was higher than that in the VHE group (40.85%, P=0.010). CONCLUSIONS Significant differences are observed in clinical manifestations, laboratory abnormalities and precipitating factors of HE associated with cirrhosis of different etiologies. Etiology-based risk assessment helps accurately identify high-risk patients and provides a basis for stratified management and individualized intervention of HE.