Nonalcoholic Fatty Liver Disease for the Incidence of Drug-Induced Liver Injury

Abstract

We read with a great interest the recent article reporting a high risk for drug-induced liver injury (DILI) in patients with suspected nonalcoholic fatty liver disease (NAFLD).1Lammert C. et al.Clin Gastroenterol Hepatol. 2019; 17: 2814-2815Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar The authors studied European-American and African-American subjects, but most of the study subjects (87.1%) were European. The ethnic difference is considered important in DILI, where African-Americans have greater morbidity and mortality compared with Whites.2Chalasani N. et al.Am J Gastroenterol. 2017; 112: 1382-1388Crossref PubMed Scopus (35) Google Scholar Therefore, we would like to examine this hypothesis in another population (East Asians) to assess the increased susceptibility of NAFLD patients to DILI. In the study by Lammert et al,1Lammert C. et al.Clin Gastroenterol Hepatol. 2019; 17: 2814-2815Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar 3 cohorts were classified by a serum alanine aminotransferase level: (1) control group 1 (≤45 U/L), (2) control group 2 (≤31 U/L in male and ≤19 U/L in female), and (3) suspected NAFLD group (>45 U/L). Therefore, NAFLD diagnosis was not clear and the case-control study design has limitations because of the various unknown confounding factors in DILI including genetic variation. We examined DILI in patients with NAFLD, where both conditions were diagnosed by a clinician as part of routine care. The risk of developing DILI among patients with NAFLD was estimated by the incidence rate ratios (IRRs) using the baseline period as the reference (>90 days before NAFLD diagnosis).3Takeuchi Y. et al.BMC Med Res Methodol. 2018; 18: 4Crossref PubMed Scopus (13) Google Scholar In South Korea, the National Health Insurance Service (NHIS) constructed a representative sample database called the NHIS-National Sample Cohort (NHIS-NSC), which constitutes approximately 1 million participants.4Lee J. et al.Int J Epidemiol. 2017; 46: e15PubMed Google Scholar The NHIS-NSC was constructed retrospectively for 4 years (2002–2005) and prospectively for 10 years (2006–2015). Therefore, we selected patients with an episode of DILI diagnosed by a clinician (K71) and NAFLD (K76.0) according to the International Classification of Diseases-10 diagnosis recorded within the prospective observation period of NHIS-NSC (2006–2015). After excluding other liver diseases including viral hepatitis and congenital malformations of the gallbladder, bile ducts, and liver, a total of 4255 patients (1669 females and 2586 males) were analyzed. The average age of patients was 53.76 ± 14.96 years at the time of DILI diagnosis. Our analysis showed strong evidence of an increase in the risk of DILI associated with NAFLD. The risk was high within 90 days before the diagnosis of NAFLD (IRR, 3.81; P < .001), the highest within 7–28 days after the diagnosis (IRR, 7.74; P < .001), and decreased thereafter (IRR, 1.81; P < .001). Next, we excluded the effect of alcohol consumption on DILI in our analysis.5Schmidt L.E. et al.Hepatology. 2002; 35: 876-882Crossref PubMed Scopus (156) Google Scholar Thus, the patients were excluded according to self-report regarding alcohol consumption or medical diagnosis of the following alcohol-related diseases: alcoholic liver disease (K70), alcoholic polyneuropathy (G62.1), alcoholic myopathy (G72.1), alcoholic cardiomyopathy (I42.6), and alcoholic gastritis (K29.2). A total of 1180 patients (844 females and 336 males) were evaluated, without substantial change in the results (1–90 days before NAFLD diagnosis: IRR, 3.65 [P < .001]; 7–28 days after NAFLD diagnosis: IRR, 4.42 [P < .001]; and 28 days after NAFLD diagnosis: IRR, 1.79 [P < 0.001]). Our observation in this East Asian cohort not only supports the previous hypothesis that NAFLD patients have the increased susceptibility to DILI but we also agree that further study is needed to identify risk factors of developing DILI. Patients With Chronic Liver Disease Suggestive of Nonalcoholic Fatty Liver Disease May Be at Higher Risk for Drug-Induced Liver InjuryClinical Gastroenterology and HepatologyVol. 17Issue 13PreviewTo date, there have been no studies that systematically examined if individuals with nonalcoholic fatty liver disease (NAFLD) have an increased risk of drug-induced liver injury (DILI). We conducted a study to test if the frequency of suspected DILI from prescription agents is higher in individuals with chronic liver disease (CLD) suggestive of NAFLD. Full-Text PDF