title: Incidence of antituberculosis-drug-induced hepatotoxicity and associated risk factors among tuberculosis patients in Dawro Zone, South Ethiopia: A cohort study.
abstract: BACKGROUND
  Antituberculosis drugs cause hepatotoxicity in some individuals leading to acute liver failure, which results in death. Such phenomena limit the clinical use of drugs, contributing to treatment failure that possibly causes drug resistance. Furthermore, associated risk factors for the development of antituberculosis-drug-induced hepatotoxicity (anti-TB-DIH) are found to be controversial among different study findings.
  
  
  METHODS
  A prospective cohort study was conducted from May 2014 to October 2014 in Dawro Zone, Tercha District Hospital Laboratory, South Ethiopia. One hundred and twenty-four new tuberculosis-positive individuals available from Tercha Hospital and five health centers during data collection were consecutively included. The sociodemographic data and anthropometric measurement were obtained. Then, 5mL of venous blood was drawn from each individual, and the alanine transaminase, aspartate transaminase, and total bilirubin were measured photometrically at baseline, and then continuously monitored by measuring these liver enzymes every 2weeks for 2months. Data were analyzed with SPSS version 20 for Windows (SPSS Inc., Chicago, IL, USA).
  
  
  RESULTS
  The incidence of anti-TB-DIH was found to be 8% (10 patients out of 124). Raised serum transaminase and bilirubin level, as well as signs and symptoms of hepatotoxicity (nausea, anorexia, vomiting, malaise, and jaundice), were observed in the cases. The onset of hepatotoxicity ranged from 13days to 58days (median, 26days) after treatment was initiated. Of the various risk factors analyzed, only high alcohol intake was associated with the incidence of anti-TB-DIH (odds ratio=9.3, 95% confidence interval 1.8-47, p<.007). Age, gender, extent of tuberculosis disease, and malnutrition were not significantly associated with anti-TB-DIH.
  
  
  CONCLUSIONS
  The incidence of anti-TB-DIH in Dawro Zone was high. The drug responsible for the hepatotoxicity was not known. However, chronic high alcohol intake was associated with the development of anti-TB-DIH.
authors.affiliation: Tercha District Hospital, Dawro Zone, Ethiopia.
authors.lastname: Wondwossen Abera
authors.affiliation: Department of Medical Laboratory Science and Pathology, Jimma University, Jimma, Ethiopia.
authors.lastname: Waqtola Cheneke
authors.affiliation: Department of Medical Laboratory Science and Pathology, Jimma University, Jimma, Ethiopia; Mycobacteriology Research Center, Institute of Biotechnology Research, Jimma University, Jimma, Ethiopia. Electronic address: gemeda.abebe@ju.edu.et.
authors.lastname: Gemeda Abebe
mesh_terms: D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000428:Alcohol Drinking / Q000009:adverse effects; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology* / Q000209:etiology* / Q000473:pathology; D002648:Child; D015331:Cohort Studies; D005002:Ethiopia / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D008099:Liver / Q000473:pathology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin
keywords: Anti-TB-DIH; Ethiopia; Incidence; Liver function test; Risk factor