Liver Transplantation for Acute Liver Injury in Asians Is More Likely Due to Herbal and Dietary Supplements

Abstract

Drug‐induced liver injury (DILI) due to medications and herbal and dietary supplements (HDSs) is a major cause of acute liver injury leading to liver transplantation (LT). This study used United Network for Organ Sharing LT data to analyze severe HDS‐induced acute liver injury in the United States. By convention, patients with acute DILI are listed as “Acute Hepatic Necrosis” (AHN) under the subheading “AHN: Drug Other Specify.” All patients waitlisted from 1994 to 2020 were divided into 3 subgroups: “HDS DILI,” “Non‐HDS DILI,” and “AHN: unknown drug.” Analyses were performed to identify epidemiologic differences between patients with HDS DILI and non‐HDS DILI. A subanalysis was performed for transplanted patients, including longitudinal changes. Of 1875 patients waitlisted for LT, 736 (39.2%) underwent LT. The proportion of Asian patients in the HDS DILI group was significantly higher compared with that in the non‐HDS DILI group (17.4% versus 3.8%; P < 0.001). Excluding acetaminophen cases, the proportion of Black patients in the HDS DILI versus non‐HDS group was significantly lower (8.7% versus 25.3%; P < 0.001). Waitlisted patients with HDS DILI were significantly older (median age, 38 years for HDS DILI versus 31 years for non‐HDS DILI; P = 0.03). Lastly, the number of patients requiring LT due to HDS DILI increased significantly over time with more than 70% of cases occurring in the last 10 years (2010‐2020) compared with the prior 15 years (1994‐2009; Ptrend = 0.001). Ethnicity may help in identifying the cause of severe acute DILI, a growing problem as more patients experiment with HDS.

Secular Trends in Severe Idiosyncratic Drug-Induced Liver Injury in North America: An Update From the Acute Liver Failure Study Group Registry

“…HDS have been increasingly implicated in DILI in studies ranging from case series (29,30) to the large, multicenter DILIN registry reporting the proportion of HDS cases more than doubled over the past decade to become the second leading cause of DILI in the United States (31). In addition, recent analyses of the United Network for Organ Sharing database show significant increases in the number of patients requiring liver transplantation because of HDS DILI (32,33). Increased HDS utilization may be the major factor for rising related DILI ALF cases.…”

AKAP12 ameliorates liver injury via targeting PI3K/AKT/PCSK6 pathway

“…ALI is the initial cause of most liver diseases. Elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are established diagnostic markers of ALI [ 20 , 21 ]. ALI can cause inflammatory storms and even lead to death [ 22 , 23 ].…”

CAQ Corner

“…Antimicrobials account for half of the DILI-related ALF cases with more recent studies demonstrating an increase in cases due to herbal and dietary supplements particularly among Asians. [10][11][12] The likelihood of an individual agent causing DILI can be determined by reviewing the LiverTox database and use of electronic causality assessment methods. [13,14] A diagnosis of AIH is suggested by the presence of anti-nuclear antibody titers >1:80, anti-smooth muscle antibody titer >1:80, and an elevated immunoglobulin G (IgG) level.…”

“…Antimicrobials account for half of the DILI‐related ALF cases with more recent studies demonstrating an increase in cases due to herbal and dietary supplements particularly among Asians. [ 10 , 11 , 12 ] The likelihood of an individual agent causing DILI can be determined by reviewing the LiverTox database and use of electronic causality assessment methods. [ 13 , 14 ]…”