title: Acute on chronic liver failure because of acute hepatic insults: Etiologies, course, extrahepatic organ failure and predictors of mortality.
abstract: OBJECTIVE
  Acute on chronic liver failure (ACLF) because of precipitating factors (variceal bleed/infections) identifies cirrhotics at risk for high short-term mortality. Information on ACLF because of acute hepatic insults is lacking. The aim of the study was to evaluate acute hepatic insults in ACLF and their effect on the course and outcome.
  
  
  METHODS
  In a prospective study, 213 consecutive patients of ACLF because of acute hepatic insults were included. Etiology of acute hepatic insult, frequency of silent, and overt chronic liver disease (CLD), organ failure (OF), and outcomes were assessed. Prognostic models such as model for endstage liver disease (MELD), acute physiology and chronic health evaluation (APACHE II), and chronic liver failure-sequential organ failure (CLIF-SOFA) were evaluated.
  
  
  RESULTS
  Etiologies of acute hepatic insult were hepatitis virus(es)- 81 (38%; HBV-42, HEV-39), continuous alcohol consumption-77 (33.3%), antituberculosis drugs-11 (5.2%), autoimmune hepatitis flare-5(2.3%), cryptogenic-44 (20.7%). The common causes of CLD were alcohol (n = 85/40%), HBV(n = 52/24%), and cryptogenic(n = 50/20%). The MELD, APACHE II, and CLIF-SOFA scores were similar among silent and overt CLD and did not influence outcome. Predominant etiologies of ACLF were hepatitis virus(es) reactivation or superinfection in silent CLD(52/112, 46.4%) and alcohol among overt CLD(43/101, 43%). Independent predictors of mortality included hepatic-encephalopathy (early, HR: 4.01; advanced, HR: 6.10), serum creatinine ≥1.5 mg/dl (HR: 4.53), CLIF-SOFA ≥8(HR: 1.69), and etiology of acute hepatic insult (alcohol, HR: 4.08; cryptogenic, HR: 3.18). HEV-ACLF had lower mortality (12.8% vs. 33-54% in other etiologies;P < 0.001). OF was major determinant of mortality. With increasing number of OF, mortality increased linearly(P = 0.001).
  
  
  CONCLUSIONS
  Hepatitis virus(es) and continuous alcohol consumption are important causes of ACLF caused by acute hepatic insults. HEV-ACLF has lower mortality. OF is an important prognostic predictor.
authors.affiliation: Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
authors.lastname: Shalimar
authors.affiliation: Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Dharmendra
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Padmaprakash Kadavoor
authors.initials: PK
authors.lastname: Vadiraja
authors.affiliation: Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Baibaswata
authors.initials: B
authors.lastname: Nayak
authors.affiliation: Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Thakur
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Das
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Datta Gupta
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Subrat Kumar
authors.initials: SK
authors.lastname: Panda
authors.affiliation: Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Subrat Kumar
authors.initials: SK
authors.lastname: Acharya
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000209:etiology* / Q000401:mortality*; D000328:Adult; D000437:Alcoholism / Q000150:complications; D000995:Antitubercular Agents / Q000009:adverse effects; D005260:Female; D005544:Forecasting; D019693:Hepatitis, Autoimmune / Q000150:complications; D006521:Hepatitis, Chronic / Q000150:complications; D006525:Hepatitis, Viral, Human / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology*; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents
keywords: hepatitis e virus; organ failure; silent; superinfection