Clinical characteristics and HLA associations of azithromycin-induced liver injury.

Background: Azithromycin (AZ) is a widely used antibiotic. The aim of this study was to characterise the clinical features, outcomes, and HLA association in patients with drug-induced liver injury (DILI) due to AZ.

Methods: The clinical characteristics of individuals with definite, highly likely, or probable AZ-DILI enrolled in the US Drug-Induced Liver Injury Network (DILIN) were reviewed.

Drug-Induced Liver Injury in Pregnancy: The U.S. Drug-Induced Liver Injury Network Experience.

There are limited data on the causative agents and characteristics of drug-induced liver injury in pregnant individuals. Data from patients with drug-induced liver injury enrolled in the ongoing multicenter Drug-Induced Liver Injury Network between 2004 and 2022 and occurring during pregnancy or 6 months postpartum were reviewed and compared with cases of drug-induced liver injury in nonpregnant women of childbearing age. Among 325 individuals of childbearing age in the Drug-Induced Liver Injury Network, 16 cases of drug-induced liver injury (5%) occurred during pregnancy or postpartum.

Value of liver biopsy in the diagnosis of drug-induced liver injury.

Background & Aims: The utility of liver biopsy in diagnosing or staging idiosyncratic drug-induced liver injury (DILI) is unclear. The aim of this study was to determine whether liver histology impacted causality assessment in suspected DILI using a novel simulation model.

Methods: Fifty patients enrolled in the DILI Network (DILIN) who had liver biopsies performed within 60 days of DILI onset were randomly selected.

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

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.

An Approach to Drug-Induced Liver Injury from the Geriatric Perspective.

Purpose Of Review: With its high variability in both presentation and severity, drug-induced liver injury (DILI) is a complex condition increasingly confronting all providers. DILI has an even more muddled presentation among the geriatric population due to age-related changes in liver physiology and biochemistry as well as polypharmacy common in the geriatric population.

Recent Findings: Most cases of DILI are idiosyncratic and unpredictable.

Liver injury associated with kratom, a popular opioid-like product: Experience from the U.S. drug induced liver injury network and a review of the literature.

Background: Kratom is a botanical product used as an opium substitute with abuse potential.

Methods: Assessment of suspected cases of kratom-induced liver injury in a prospective US cohort.

Results: Eleven cases of liver injury attributed to kratom were identified with a recent increase.

Prenatal Exposure to Gutkha, a Globally Relevant Smokeless Tobacco Product, Induces Hepatic Changes in Adult Mice.

Maternal exposures during pregnancy affect the onset and progression of adult diseases in the offspring. A prior mouse study indicated that maternal tobacco smoke exposure affects hepatic fibrosis in adult offspring. Gutkha, a broadly used smokeless tobacco (ST) product, is widely used by pregnant woman in many countries.

The Clinical Spectrum and Diagnosis of Oxaliplatin Liver Injury in the Era of Nonalcoholic Fatty Liver Disease.

Oxaliplatin is an alkylating agent given with fluorouracil and leucovorin as a mainstay adjuvant chemotherapy for stage III colorectal cancer (CRC). Liver injury from oxaliplatin ranges from mild liver enzyme increases in 42% to 57% of patients in clinical trials to rare severe injury leading to acute liver failure. Chronic injury from endothelial cell damage and architectural distortion may manifest years later with nodular regenerative hyperplasia (NRH), portal sclerosis, and noncirrhotic portal hypertension (NCPH).

Clinical Ontologies Improve Case Finding of Primary Biliary Cholangitis in UK Primary and Secondary Care.

Introduction: PBC registries in the UK focus on data from secondary care without clear coordinated contribution from primary care. The Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) receives data from > 500 primary care practices (PCPs). Notably, the Lancet commissioning group is extracting data from the RCGP RSC database to shape UK policy on liver disease.

Genetic Polymorphisms Implicated in Nonalcoholic Liver Disease or Selected Other Disorders Have No Influence on Drug-Induced Liver Injury.

With the application of genetic testing to contemporary medical diagnostics and practice, it has become apparent that the phenotypes of many disorders are modulated by host genetic factors. The aim of the current study was to determine whether selected single nucleotide polymorphisms (SNPs) unrelated to the human leukocyte antigen region or other immune pathways, including those associated with nonalcoholic fatty liver disease (NAFLD), may influence development, severity, or outcomes of drug-induced liver injury (DILI). Thirteen variants previously associated with NAFLD and/or selected other liver diseases were tested in 832 Caucasian DILI cases and 10,397 Caucasian population controls.

Correction: Cytokine profiles in acute liver injury-Results from the US Drug-Induced Liver Injury Network (DILIN) and the Acute Liver Failure Study Group.

[This corrects the article DOI: 10.1371/journal.pone.

A Missense Variant in PTPN22 is a Risk Factor for Drug-induced Liver Injury.

Background & Aims: We performed genetic analyses of a multiethnic cohort of patients with idiosyncratic drug-induced liver injury (DILI) to identify variants associated with susceptibility.

Methods: We performed a genome-wide association study of 2048 individuals with DILI (cases) and 12,429 individuals without (controls). Our analysis included subjects of European (1806 cases and 10,397 controls), African American (133 cases and 1,314 controls), and Hispanic (109 cases and 718 controls) ancestry.

Cytokine profiles in acute liver injury-Results from the US Drug-Induced Liver Injury Network (DILIN) and the Acute Liver Failure Study Group.

Changes in levels of cytokines and chemokines have been proposed as possible biomarkers of tissue injury, including liver injury due to drugs. Recently, in acute drug-induced liver injury (DILI), we showed that 19 of 27 immune analytes were differentially expressed and that disparate patterns of immune responses were evident. Lower values of serum albumin (< 2.

Real-world cure rates for hepatitis C virus treatments that include simeprevir and/or sofosbuvir are comparable to clinical trial results.

Aim: To assess the real-world effectiveness and cost of simeprevir (SMV), and/or sofosbuvir (SOF)-based therapy for chronic hepatitis C virus (HCV) infection.

Methods: The real-world performance of patients treated with SMV/SOF ± ribavirin (RBV), SOF/RBV, and SOF/RBV with pegylated-interferon (PEG) were analyzed in a consecutive series of 508 patients with chronic HCV infection treated at a single academic medical center. Patients with genotypes 1 through 4 were included.

Identification and Characterization of Fenofibrate-Induced Liver Injury.

Background: Fenofibrate is a commonly used hypolipidemic associated with rare instances of hepatotoxicity, and routine liver biochemistry monitoring is recommended.

Aims: The aim of this study is to describe the presenting clinical features, liver histopathology, and outcomes of 7 cases of acute liver injury associated with fenofibrate.

Methods: All cases of definite, very likely, and probable drug-induced liver injury (DILI) attributed to fenofibrate enrolled in the DILI Network study between 2004 and 2015 were reviewed.

Factors associated with success of telaprevir- and boceprevir-based triple therapy for hepatitis C virus infection.

Aim: To evaluate new therapies for hepatitis C virus (HCV), data about real-world outcomes are needed.

Methods: Outcomes of 223 patients with genotype 1 HCV who started telaprevir- or boceprevir-based triple therapy (May 2011-March 2012) at the Mount Sinai Medical Center were analyzed. Human immunodeficiency virus-positive patients and patients who received a liver transplant were excluded.

Minocycline hepatotoxicity: Clinical characterization and identification of HLA-B∗35:02 as a risk factor.

Background & Aims: Minocycline hepatotoxicity can present with prominent autoimmune features in previously healthy individuals. The aim of this study was to identify genetic determinants of minocycline drug-induced liver injury (DILI) in a well-phenotyped cohort of patients.

Methods: Caucasian patients with minocycline DILI underwent genome-wide genotyping and were compared to unexposed population controls.

Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease.

Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; ∼75% of patients have comorbid inflammatory bowel disease (IBD). We undertook the largest genome-wide association study of PSC (4,796 cases and 19,955 population controls) and identified four new genome-wide significant loci. The most associated SNP at one locus affects splicing and expression of UBASH3A, with the protective allele (C) predicted to cause nonstop-mediated mRNA decay and lower expression of UBASH3A.

Clinical presentations and outcomes of bile duct loss caused by drugs and herbal and dietary supplements.

Unlabelled: Bile duct loss during the course of drug-induced liver injury is uncommon, but can be an indication of vanishing bile duct syndrome (VBDS). In this work, we assess the frequency, causes, clinical features, and outcomes of cases of drug-induced liver injury with histologically proven bile duct loss. All cases of drug-induced liver injury enrolled into a prospective database over a 10-year period that had undergone liver biopsies (n = 363) were scored for the presence of bile duct loss and assessed for clinical and laboratory features, causes, and outcomes.

Epidemiology and Genetic Risk Factors of Drug Hepatotoxicity.

Idiosyncratic drug-induced liver injury (DILI) from prescription medications and herbal and dietary supplements has an annual incidence rate of approximately 20 cases per 100,000 per year. However, the risk of DILI varies greatly according to the drug. In the United States and Europe, antimicrobials are the commonest implicated agents, with amoxicillin/clavulanate the most common, whereas in Asian countries, herbal and dietary supplements predominate.