Drug-Induced Acute-on-Chronic Liver Failure in Asian Patients

Devarbhavi H 1 , Choudhury AK 2 , Sharma MK 2 , Maiwall R 2 , Al Mahtab M 3 , Rahman S 3 Show all authors , Chawla YK 4 , Dhiman RK 4 , Duseja A 4 , Taneja S 4 , Ning Q 5 , Jia JD 6 , Duan Z 7 , Yu C 7 , Eapen CE 8 , Goel A 8 , Tan SS 9 , Hamid SS 10 , Butt AS 10 , Jafri W 10 , Kim DJ 11 , Hu J 12 , Sood A 13 , Midha V 13 , Shukla A 14 , Ghazinian H 15 , Sahu MK 16 , Treeprasertsuk S 17 , Lee GH 18 , Lim SG 18 , Lesmana LA 19 , Lesmana CR 19 , Shah S 20 , Kalal C 20 , Abbas Z 21 , Sollano JD 2 , Prasad VGM 22 , Payawal DA 23 , Dokmeci AK 24 , Rao PN 25 , Shrestha A 26 , Lau GK 27 , Yuen MF 28 , Saraswat VA 29 , Shiha G 30 , Yokosuka O 31 , Kedarisetty CK 32 , Jain P 2 , Bhatia P 2 , Sarin SK 2 , APASL ACLF working party

Affiliations 

  • 1 Department of Gastroenterology and Hepatology, St John Medical College, Bangalore, India
  • 2 Department of Hepatology and Transplant, Institute of Liver and Biliary Sciences, New Delhi, India
  • 3 Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
  • 4 Department of Hepatology, PGIMER, Chandigarh, India
  • 5 Institute and Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • 6 Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
  • 7 Translational Hepatology Institute Capital Medical University, Beijing You'an Hospital
  • 8 Department of Hepatology, CMC, Vellore, India
  • 9 Department of Medicine, Hospital Selayang, Bata Caves, Selangor, Malaysia
  • 10 Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan
  • 11 Deparment of Internal Medicine, Hallym University College of Medicine
  • 12 Department of Medicine, 302 Millitary Hospital Beijing, China
  • 13 Department of Gastroenterology, DMC, Ludhiana, India
  • 14 Department of Hepatology, KEM Hospital and Seth GSMC
  • 15 Department of Hepatology, Nork Clinical Hospital of Infectious Disease, Armenia
  • 16 Department of Hepatology, IMS &SUM Hospital, Bhuvaneswar, Odisa, India
  • 17 Department of Medicine, Chulalongkorn University, Bangkok, Thailand
  • 18 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore
  • 19 Department of Medicine, Medistra Hospital, Jakarta, Indonesia
  • 20 Department of Hepatology, Global Hospital, Mumbai, India
  • 21 Department of Medicine, Ziauddin University Hospital, Karachi
  • 22 Department of Gastroenterology, VGM Hospital, Coimbatore, India
  • 23 Department of Medicine, Cardinal Santos Medical Center, Metro Manila, Philippines
  • 24 Department of Medicine, Ankara University School of Medicine, Turkey
  • 25 Asian Institute of Gastroenterology, Hyderabad, India
  • 26 Department of Hepatology, Foundation Nepal Sitapaila Height, Kathmandu
  • 27 Department of Medicine, Humanity and Health Medical Group, Hong Kong
  • 28 Department of Medicine, Queen Mary Hospital Hong Kong, China
  • 29 Department of Hepatology, SGPGI, Lucknow, India
  • 30 Department of Internal Medicine, Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt
  • 31 Department of Medicine, Chiba University, Japan
  • 32 Department of Hepatology, Global Hospitals, Chennai, India
Am J Gastroenterol, 2019 06;114(6):929-937.
PMID: 31021832 DOI: 10.14309/ajg.0000000000000201

Abstract

OBJECTIVES: Acute insults from viruses, infections, or alcohol are established causes of decompensation leading to acute-on-chronic liver failure (ACLF). Information regarding drugs as triggers of ACLF is lacking. We examined data regarding drugs producing ACLF and analyzed clinical features, laboratory characteristics, outcome, and predictors of mortality in patients with drug-induced ACLF.

METHODS: We identified drugs as precipitants of ACLF among prospective cohort of patients with ACLF from the Asian Pacific Association of Study of Liver (APASL) ACLF Research Consortium (AARC) database. Drugs were considered precipitants after exclusion of known causes together with a temporal association between exposure and decompensation. Outcome was defined as death from decompensation.

RESULTS: Of the 3,132 patients with ACLF, drugs were implicated as a cause in 329 (10.5%, mean age 47 years, 65% men) and other nondrug causes in 2,803 (89.5%) (group B). Complementary and alternative medications (71.7%) were the commonest insult, followed by combination antituberculosis therapy drugs (27.3%). Alcoholic liver disease (28.6%), cryptogenic liver disease (25.5%), and non-alcoholic steatohepatitis (NASH) (16.7%) were common causes of underlying liver diseases. Patients with drug-induced ACLF had jaundice (100%), ascites (88%), encephalopathy (46.5%), high Model for End-Stage Liver Disease (MELD) (30.2), and Child-Turcotte-Pugh score (12.1). The overall 90-day mortality was higher in drug-induced (46.5%) than in non-drug-induced ACLF (38.8%) (P = 0.007). The Cox regression model identified arterial lactate (P < 0.001) and total bilirubin (P = 0.008) as predictors of mortality.

DISCUSSION: Drugs are important identifiable causes of ACLF in Asia-Pacific countries, predominantly from complementary and alternative medications, followed by antituberculosis drugs. Encephalopathy, bilirubin, blood urea, lactate, and international normalized ratio (INR) predict mortality in drug-induced ACLF.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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