An Observational Study to Determine the Combination of Precipitating Factors Predicting 30-Day Mortality in Acute-On-Chronic Liver Failure (ACLF), With Respect to Underlying Disease Etiology and definition of ACLF

Background and Aim: Previous studies have highlighted the prognostic indicators and risk factors for mortality in ACLF, still there is sparse data on etiology-specific mortality, as well as prognosis in different underlying liver diseases, vis-a-vis acute precipitants. Methods: This was an open-labelled, hospital based, observational study. All patients admitted with a diagnosis of ACLF were enrolled. Medical history and clinical data were collected, and patients were stratified for survival analysis into groups based on combination of acute precipitants, etiologies of underlying CLD and definitions of ACLF (APASL or EASL or both). Results: In ethanol related CLD, 30-day survival was maximum in patients with combination of Severe Alcoholic Hepatitis (SAH) and Acute Viral Hepatitis (AVH). Maximum 30-day mortality in this group was seen with combination of SAH plus precipitants other than infection or AVH (HR=2.07). Amongst all etiologies of CLD, presenting with ACLF, mortality was highest with more than one acute event, compared to a single event (HR=1.56). In ethanol related ACLF, 30-day mortality was highest with upper GI bleed (UGIB) with an HR of 4.73. In viral disease related CLD with ACLF, mortality was highest with infections (HR=2.17), in AIH it was a combination of AIH flare plus infections, whereas in NASH-CLD, it was infections. On comparing APASL and EASL ACLF, there was no significant difference among 30-day mortalities, vis-s-vis acute precipitants in either APASL or EASL ACLF individually. However, in combination of APASL+EASL ACLF, 30-day mortality was highest with acute precipitant being a combination of SAH+UGIB (HR=2.45). There was no statistically significant difference among outcomes in ACLF subtypes, w.r.t etiology of underlying CLD. Conclusion: The current study has identified the combination of acute precipitants in predicting mortality in ACLF, w.r.t subtypes of ACLF and etiologies of underlying CLD. Specific preventive, diagnostic and therapeutic interventions targeting these can reduce mortality.