Severity and outcome of acute-on-chronic liver failure is dependent on the etiology of acute hepatic insults analysis of 368 patients

Background: Acute-on-chronic liver failure (ACLF) may be precipitated by various hepatic insults. The present study evaluated the outcomes of ACLF with different acute insults. Patients and Methods: A total of 368 ACLF patients were included. Data collected included etiologies of acute hepatic insult and underlying chronic liver disease, and organ failure. Model for endstage liver disease (MELD), chronic liver failure consortium (CLIF)-C ACLF, and acute physiology and chronic health evaluation (APACHE) II scores were calculated. Predictors of survival were assessed by the Cox proportional hazard model. Results: The most frequent acute insult was active alcohol consumption [150 (40.8%) patients], followed by hepatitis B virus (HBV) [71 (19.3%) patients], hepatitis E virus (HEV) superinfection [45 (12.2%) patients], autoimmune hepatitis flare [17 (4.6%) patients], antituberculosis drugs [16 (4.3%) patients], and hepatitis A virus superinfection [2 (0.5%) patients]; 67 (18.2%) cases were cryptogenic. Alcohol-ACLF and cryptogenic-ACLF were more severe. Median CLIF-C, MELD, and APACHE II scores in alcohol-ACLF and cryptogenic-ACLF were significantly higher than those in HBV-ACLF and HEV-ACLF (CLIF-C: 47.1, 47.4 vs. 42.9, 42.0, P=0.002; MELD: 29, 29.9 vs. 28.9, 25.2, P=0.02; APACHE II: 16.5, 18.0 vs. 12, 14, P<0.001, respectively). Frequencies of kidney and brain failures were also higher in alcohol/cryptogenic-ACLF than in HBV/HEV-ACLF (kidney failure: 35.3%/34.3% vs. 23.9%/11.1%, P=0.009; brain failure: 26.0%/22.4% vs. 15.5%/4.4%, P=0.01, respectively). Mortality in the alcohol-ACLF group was the highest (64.0%), followed by that in the cryptogenic-ACLF (62.7%), HBV-ACLF (45.1%), and HEV-ACLF (17.8%) groups (P<0.001). In multivariable analysis, alcohol-ACLF had significantly higher mortality compared with HEV-ACLF (hazard ratio, 3.06; 95% confidence interval, 1.10- 8.49, P=0.03). Conclusions: Alcohol/cryptogenic-ACLF had more severe phenotypic presentation, more incidence of organ failures, and higher mortality compared with HEV/HBV-ACLF. Alcohol-ACLF had the highest mortality, whereas HEV-ACLF had the best survival.