Proven bacterial infections and severe alcoholic hepatitis, alone or in combination, were identified as the major precipitating events for acute decompensation (AD) of cirrhosis and acute-on-chronic liver failure (ACLF), according to research reported in the Journal of Hepatology.
The multicenter, prospective, observational PREDICT (Predicting Acute-on-Chronic Liver Failure in Cirrhosis) study (ClinicalTrials.gov Identifier: NCT03056612) aimed to determine the precipitants leading to 2 AD phenotypes: without ACLF (AD-No ACLF) and with ACLF (AD-ACLF). The study included 1273 nonelectively hospitalized patients with AD (No-ACLF=1071; ACLF=202). The investigators obtained medical histories and clinical and laboratory data at enrollment and during the 90-day follow-up period and identified the following characteristics among the AD precipitants: induction of organ dysfunction or failure, systemic inflammation, chronology, intensity, and relationship to outcome.
The researchers found that 4 distinct clinical events — proven bacterial infection, severe alcoholic hepatitis, gastrointestinal (GI) bleeding with shock, and toxic encephalopathy —were precipitants consistently related to AD.
Among patients with precipitants in the AD-No ACLF cohort (38%) and the AD-ACLF cohort (71%), almost all (96% and 97%, respectively) had proven bacterial infection and severe alcoholic hepatitis, either alone or in combination with other events. Similar rates of survival were reported for patients with proven bacterial infections or severe alcoholic hepatitis in both cohorts. As the prevalence of suspected bacterial infections was found to be very low and similar in both groups, only proven bacterial infection was considered a precipitant of AD-ACLF. Proven bacterial infection was also found to be the most commonly occurring precipitant in both cohorts (44% in the AD-ACLF group and in 22.3% in the AD-No ACLF group [P <.0001]).
The prevalence of severe alcoholic hepatitis was found to be significantly higher among patients with AD-ACLF (43.6%) compared with the AD-No ACLF group (18.7%). The third most common precipitant was identified as severe GI bleeding associated with hypovolemic shock; however, its prevalence in patients with AD-ACLF (5.9%) and those with AD-No ACLF (1.2%) was considered low. Prevalence of toxic encephalopathy was similarly 5.9% in the AD-ACLF group and 1.2% in the AD-No ACLF group, qualifying this clinical event as a precipitant.
“The number of precipitants was associated with significantly increased 90-day mortality, and was paralleled by increasing levels of surrogates for systemic inflammation,” stated the study authors. “Importantly, adequate first-line antibiotic treatment of proven bacterial infections was associated with lower ACLF development rate and lower 90-day mortality.”
The prevalence and number of precipitants increased with severity of the AD subphenotype from stable decompensated cirrhosis/unstable decompensated cirrhosis to pre-ACLF and ACLF. The investigators found that these factors were also directly related to the severity of clinical course and short-term mortality among patients with AD.
“Our data, therefore, strongly suggest that precipitants are significantly associated with the clinical course and prognosis of patients with AD and specific preventive and therapeutic strategies for these precipitants are required to improve outcomes in decompensated cirrhosis,” the researchers concluded.
Trebicka J, Fernandez J, Papp M, et al; for the PREDICT STUDY group of the EASL-CLIF CONSORTIUM. PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis. J Hepatol. Published online November 20, 2020. doi:https://doi.org/10.1016/j.jhep.2020.11.019