Drugs-Herbs-Dietary Supplements-induced Liver Injury: A Hidden but Emerging Clinical Problem

Abstract

Background: Drug-induced liver injury (DILI) is becoming increasingly common. Additionally, there have also been worldwide increases in herbal-induced liver injury (HILI) and supplement-induced liver injury (SILI). Studies on DILI, HILI, and SILI have shown that liver injury is the result of an idiosyncratic reaction and was geographically distinct. Objective: To describe the clinical characteristics and outcomes of DILI, HILI, and SILI in a Thai population. Materials and Methods: We retrospectively included patients (both outpatients and inpatients) who were diagnosed with DILIHILI-SILI at a tertiary care university hospital setting from January 2014 to December 2019. The Roussel Uclaf Causality Assessment Method (RUCAM) score was used to assess causality in suspected cases with a cut-off score of >3. R ratio was used to identify the 3 types of liver injury: hepatocellular, cholestasis, or mixed type. Results: Seventy patients were suspected to have DILI during the study period. Twenty-three patients were excluded due to incomplete data or RUCAM score <3. The remaining 47 patients were included. Of these, 26 cases (55.3%) were due to herbs or supplements and 17 (36.2%) were admitted for a high degree of liver injury. Chinese traditional complementary (12.7%) and multi-herbal products (12.7%) were the common causes of HILI and SILI, respectively. Antimicrobial agents (19.1%) and analgesics (10.6%) were the common causes of conventional drug-induced liver damage. The liver injury patterns in DILI from conventional drugs were hepatocellular (R>5) in 47.6% and cholestatic pattern (R<2) in 33.3%, which was not significantly different (p>0.05). For the HILI and SILI groups, the liver injury patterns were hepatocellular in 46.2% and cholestatic pattern in 15.4% (p = ns). The duration of exposure to diagnosis was similar between the DILI and HILI-SILI groups (3.7 vs. 5.6 months, p = 0.42). The DILI group had longer hospital stay than the HILI and SILI groups (13.5 vs. 7 days; p = 0.63). The overall mortality rate was 2.9%, with one death in each group. Conclusion: Herbal and dietary supplements played an important role in DILI and showed a trend of shorter hospital stays. Hepatocellular liver injury pattern was the most common clinical finding in patients with DILI, HILI, and SILI. Keywords: Drug-induced liver injury, DILI-HILI-SILI, Hepatitis, R pattern