Herbal and dietary supplement induced liver injury:Highlights from the recent literature

Herbal-induced liver injury(HILI)is an important and increasingly concerning cause of liver toxicity,and this study presents recent updates to the literature.An extensive literature review was conducted encompassing September 2019 through March 2021.Studies with clinically significant findings were analyzed and included in this review.We emphasized those studies that provided a causality assessment methodology,such as Roussel Uclaf Causality Assessment Method scores.Our review includes reports of individual herbals,including Garcinia cambogia,green tea extract,kratom as well as classes such as performance enhancing supplements,Traditional Chinese medicine,Ayurvedic medicine and herbal contamination.Newly described herbals include ashwagandha,boldo,skyfruit,and‘Thermo gun’.Several studies discussing data from national registries,including the United States Drug-Induced Liver Injury(DILI)Network,Spanish DILI Registry,and Latin American DILI Network were incorporated.There has also been a continued interest in hepatoprotection,with promising use of herbals to counter hepatotoxicity from anti-tubercular medications.We also elucidated the current legal conversation surrounding use of herbals by presenting updates from the Federal Drug Administration.The highlights of the literature over the past year indicate interest in HILI that will continue as the supplement industry in the United States grows.

Characteristics of Drug-induced Liver Injury in Chronic Liver Disease:Results from the Thai Association for the Study of the Liver(THASL)DILI Registry

Background and Aims:The impact of drug-induced liver injury(DILI)on patients with chronic liver disease(CLD)is unclear.There are few reports comparing DILI in CLD and non-CLD patients.In this study,we aimed to determine the incidence and outcomes of DILI in patients with and without CLD.Methods:We collected data on eligible individuals with suspected DILI between 2018 and 2020 who were evaluated systematically for other etiologies,causes,and the severity of DILI.We compared the causative agents,clinical features,and outcomes of DILI among subjects with and without CLD who were enrolled in the Thai Association for the Study of the Liver DILI registry.Subjects with definite,or highly likely DILI were included in the analysis.Results:A total of 200 subjects diagnosed with DILI were found in the registry.Of those,41 had CLD and 159 had no evidence of CLD in their background.Complementary and alternative medicine(CAM)products were identified as the most common class of DILI agents.Approximately 59%of DILI in the CLD and 40%in non-CLD group were associated with CAM use.Individuals with pre-existing CLD had similar severity including mortality.Twelve patients(6%)developed adverse outcomes related to DILI including seven(3.5%)deaths and five(2.5%)with liver failure.Mortality was 4.88%in CLD and 3.14%in non-CLD subjects over median periods of 58(8–106)days and 22(1–65)days,respectively.Conclusions:In this liver disease registry,the causes,clinical presentation,and outcomes of DILI in subjects with CLD and without CLD patients were not different.Further study is required to confirm our findings.

Alpha-1 Anti-trypsin Exerts a Hepatoprotective Effect on Immune-mediated Hepatitis and Acetaminophen-induced Liver Injury

Background and Aims:The serine proteinase inhibitor alpha-1 anti-trypsin(AAT)protects the body against protease activity.Several functions of AAT beyond those attributed to its antiprotease activity have been described,among them immunomodulatory and anti-inflammatory properties.The present study aimed to determine the efficacy of AAT for the treatment of immune-mediated liver injury using the models of concanavalin A-induced immune-mediated hepatitis and acetaminophen-induced liver damage.Methods:AATwas administered to mice subjected to concanavalin A-induced immune-mediated hepatitis or 2 h after acetaminophen-induced liver damage.Mice were followed for changes in serum levels of liver enzymes,liver histology,and for interferon gamma serum levels.Results:Treatment with AATalleviated concanavalin A-induced immunemediated liver damage,as demonstrated by a reduction in the serum levels of liver enzymes and interferon gamma,and an improved lymphocyte infiltration into the liver on liver biopsies.Moreover,treatment with AAT was associated with alleviation of the acetaminophen-induced liver injury.Conclusions:AAT exerts an hepatoprotective effect on immune-mediated and drug-induced liver damage.The data support its potential use in patients with immune-associated liver disorders.