Spectrum of drug-induced liver injury in a tertiary hospital in southern India.

Background Anti-tuberculosis drugs are thought to account for about 50% of drugs that cause liver injury in India. We show that the spectrum of drugs is much wider than previously reported. Methods We evaluated all patients with unexplained acute liver injury presenting during 2006-2016 using a structured proforma for drug-induced liver injury (DILI). The Roussel Uclaf Causality Assessment Method was used to assess causality. Results DILI was found in 143 of 2534 patients with acute liver injury. Nineteen patients had probable ayurvedic DILI. The other common causes of DILI were statins (16 patients) and anti-tuberculosis drugs (11 patients). Eight patients had DILI post-liver transplant. Fluconazole was the most common cause of post-liver transplant DILI. Chronic DILI (abnormal liver function test after 12 months of stopping the suspected drug) was found in 2 patients. Conclusion In otherwise unexplained acute liver injury, DILI due to ayurvedic drugs should be sought. DILI should be considered in post-liver transplant patients. Patients with DILI should be monitored for at least 12 months to exclude progression to chronic DILI.

Beyond the scope and the glue: update on evaluation and management of gastric varices.

Gastric varices are encountered less frequently than esophageal varices. Nonetheless, gastric variceal bleeding is more severe and associated with worse outcomes. Conventionally, gastric varices have been described based on the location and extent and endoscopic treatments offered based on these descriptions. With improved understanding of portal hypertension and the dynamic physiology of collateral circulation, gastric variceal classification has been refined to include inflow and outflow based hemodynamic pathways. These have led to an improvement in the management of gastric variceal disease through newer modalities of treatment such as endoscopic ultrasound-guided glue-coiling combination therapy and the emergence of highly effective endovascular treatments such as shunt and variceal complex embolization with or without transjugular intrahepatic portosystemic shunt (TIPS) placement in patients who are deemed 'difficult' to manage the traditional way. Furthermore, the decisions regarding TIPS and additional endovascular procedures in patients with gastric variceal bleeding have changed after the emergence of 'portal hypertension theories' of proximity, throughput, and recruitment. The hemodynamic classification, grounded on novel theories and its cognizance, can help in identifying patients at baseline, in whom conventional treatment could fail. In this exhaustive review, we discuss the conventional and hemodynamic diagnosis of gastric varices concerning new classifications; explore and illustrate new 'portal hypertension theories' of gastric variceal disease and corresponding management and shed light on current evidence-based treatments through a 'new' algorithmic approach, established on hemodynamic physiology of gastric varices.

Partial splenic artery embolization for severe hepatic myelopathy in cirrhosis.

Hepatic myelopathy (HM) is a devastating but rare complication of cirrhosis and portal hypertension that profoundly affects quality of life and improves only with liver transplantation. We present a case where progressive severe spastic paraparesis due to HM was substantially reversed with partial splenic artery emobilization (PSAE). (Hepatology 2018;67:1169-1171).

Complementary and alternative medicines and liver disease.

Complementary and alternative medicines (CAM) include conventional medical treatments. Patients worldwide use CAM at alarming rates; thus, reports of CAM-related DILI have been on the rise. The clinical presentations include asymptomatic liver test abnormalities, acute hepatitis with or without jaundice, acute cholestatic liver disease (bland or with hepatitis), acute liver failure, severe hepatitis with features of portal hypertension, and acute decompensation of known or unknown cirrhosis that can lead to acute-on-chronic liver failure. Acute hepatitis with or without necrosis, hepatocellular and canalicular cholestasis, herb-induced or CAM-triggered autoimmune hepatitis, granulomatous hepatitis, severe steatohepatitis, and vanishing bile duct syndrome are common liver biopsy findings in CAM-DILI. The presence of preexisting liver disease predicts severe liver injury, risk of progression to liver failure, and decreased transplant-free survival in patients with CAM-DILI. This review discusses global epidemiology and trends in CAM-DILI, clinical presentation, assessment and outcomes, commonly emerging threats in the context of hepatotoxic herbs, pragmatic assessment of "liver beneficial" herbs and health care myths, patient communication, regulatory framework, and future directions on research in CAM.

Investigating the correlation between COVID-19 and the progression of chronic liver disease.

INTRODUCTION: The novel coronavirus disease 2019 has thrown light on various heterogeneous afflictions of newly emerging viruses on the human body. Early reports demonstrated direct effect of novel coronavirus on the liver, but subsequently, this did not stand up to validation. The SARS-CoV-2 virus affects the liver differentially; in healthy compared to those with preexisting liver disease. AREAS COVERED: This exhaustive paper reviews the current, literature on mechanisms by which COVID-19 affects the healthy liver and those with preexisting liver disease such as alcohol-related and nonalcoholic fatty liver, autoimmune liver disease, chronic liver disease and cirrhosis, hepatocellular carcinoma, viral hepatitis, and liver transplant recipients, with special mention on drug-and herb-induced liver injury with COVID-19 therapies. Search methodology: the review (Dec. 2022 - Jan. 2023) is based on PubMed (NLM) search using the keyword 'COVID' with supplementary searches using 'fibrosis;' 'liver;' 'cirrhosis;' 'CLD;' 'NAFLD;' 'NASH;' 'hepatocellular carcinoma;' 'hepatitis;' 'fatty liver;' 'alcohol;' 'viral;' 'transplant;' and 'liver failure.' EXPERT OPINION: Direct liver tropism of SARS-CoV-2 does not cause liver damage. Adverse events following infection depend on the severity of liver disease, the severity of COVID-19, and other risk factors such as metabolic syndrome and older age. Alcohol-related liver disease independently predicts adverse outcomes.

Clinical outcomes related to portal pressures before and after embolization of large portosystemic shunts in cirrhosis.

Objectives: Embolization of large portosystemic shunts effectively controls gastric variceal bleeding and prevents hepatic encephalopathy. The significance of dynamic changes in hepatic venous pressure gradient before and after embolization on clinical events and patient outcomes remains unknown. Methods: In this retrospective single-center series, 46 patients with gastric variceal bleeding, hepatic encephalopathy, or both undergoing embolization (January 2018 to October 2020) were included, and dynamic changes in portal pressures were analyzed against patient outcomes. Results: Males predominated. The most common portosystemic shunt syndrome was the lienorenal shunt. In all, 34 patients underwent embolization for hepatic encephalopathy and 11 for gastric variceal bleeding. The proportion of patients surviving at the end of 12 and 32 months was 86.96 and 54.35%, respectively. The hepatic venous pressure gradient before shunt embolization was 13.4 ± 3.2 and 16.9 ± 3.7 mm Hg after occlusion (p < 0.001). Bleeding from varices on overall follow-up was notable in five patients (10.9%), and overt hepatic encephalopathy in four (N = 42, 9.5%) patients at 6-12 months. The development of infections within 100 days and beyond the first year was associated with the risk of dying at the end of 12 and 32 months, respectively. Elevation of hepatic venous pressure gradient by >4 mm Hg from baseline and an absolute increase to >16 mm Hg immediately post-procedure significantly predicted the development of early- and late-onset ascites, respectively. Conclusion: Close monitoring for the development of infections and optimization of beta-blockers and diuretics after shunt embolization may improve clinical outcomes and help identify patients who will benefit from liver transplantation pending prospective validation.

Significant gut microbiota related to patterns of drinking and alcohol relapse in patients with alcoholic hepatitis undergoing stool transplant or corticosteroid therapy.

Alcohol-induced gut microbiota (GM) alterations are linked to alcohol use disorder (AUD) pathogenesis. Healthy donor stool transplant (fecal microbiota transplant [FMT]) reduced alcohol desire and improved clinical outcomes in small animal and human studies. Baseline and post-therapy-related GM changes in a real-world cohort with severe alcohol-related liver disease and AUD, patterns of drinking, and relapse have not been studied. We prospectively analyzed retrospective clinical data and stored samples to examine GM alterations in a cohort of severe alcohol-associated hepatitis (SAH) patients who underwent FMT or corticosteroid treatment followed for at least 12 months. The GM changes at baseline in the context of a pattern of drinking (binge vs. every day) and baseline and post-treatment alcohol relapse status (relapser vs. non-relapser). We identified 28 patients on FMT and 25 on corticosteroids who survived 1 year post-treatment. After necessary exclusions, the final cohort for various grouped GM analysis included 16 patients in the FMT arm and 14 on corticosteroids. Pedobacter and Streptophyta species at the commencement of treatment predicted alcohol relapse in steroid-ineligible patients receiving FMT and steroid-treated patients, respectively. At 6-12 months post-FMT, non-relapsers had elevated short-chain fatty acid-producing bacterial taxa linked with lower alcohol cravings. Alcohol relapse was significantly more in those on steroid therapy and was associated with the upregulation of the nucleotide metabolism pathway related to ethanol metabolism. We demonstrate pertinent baseline and post-treatment intestinal bacterial alterations that impact patterns of AUD patterns and relapse in SAH patients in the context of the therapy offered.

Identification and Analysis of Gut Microbiota and Functional Metabolism in Decompensated Cirrhosis with Infection.

Background and Aims: Intestinal dysbiosis play a role in the adverse outcomes of sepsis and septic shock. However, variations in bacterial diversity and microbiota-related functional metabolic alterations within the gut microbiome in decompensated cirrhosis (DC) patients with infection remain unknown. Methods: We conducted 16-srRNA sequencing on stool samples (n=51: sepsis, 27/no sepsis, 24) collected from consecutive DC patients upon admission. Bacterial diversity, significant taxa, and respective metabolic profiling were performed based on subgroup comparisons. Conet/Cytoscape was utilized to identify significant non-random patterns of bacterial copresence and mutual exclusion for clinical events. Results: Genera associated with pathogenicity in conditions of immune exhaustion (Corynebacterium, Lautropia) were predominant in patients with sepsis. Metabolic pathways associated with oxidative stress and endotoxemia [lipopolysaccharide (LPS) synthesis and sulfur relay] were significantly upregulated in sepsis. Specific taxa were associated with sites of infection in DC patients. Protective oxidant pathways that increase glutathione were upregulated in those without sepsis. Gammaproteobacteria family of sulfur-metabolizing bacteria, exaggeration of orally predominant pathogens (Prevotella), and pathways of severe LPS-related hyperinflammatory stress were notable in those with interleukin-6 levels >1,000 pg/dL. Pathogenic genera related to an immune deficient state was significant in DC with ≥2 infection episodes. Megamonas was associated with survival during the same admission. Conclusions: Specific gut microbiota and their metabolites were associated with sepsis and related events in patients with DC. Identifying beneficial strains that reduce immune exhaustion and supplementation of favorable metabolites could improve therapeutics for DC and sepsis, for which larger prospective, well controlled population-based studies remain an unmet need.

Ashwagandha-induced liver injury-A case series from India and literature review.

BACKGROUND: Ashwagandha herb is commonly used in Ayurveda and a "fad" dietary supplement for a host of indications based on low levels of evidence. Recently, ashwagandha was implicated in multiple reports of herb-induced liver injury (HILI), mainly from the United States. We present the first, and currently largest, series of ashwagandha-HILI from multiple centers in India. METHODS: We retrospectively analyzed the respective institutional electronic medical records for ashwagandha-HILI. Patients consuming ashwagandha as part of multiherbal formulations or along with other known hepatotoxic supplements or medicines were excluded. All patients underwent a detailed diagnostic workup to exclude competing causes reasonably. Where possible, the implicated herbal formulation was retrieved and subjected to chemical analysis. RESULTS: Out of 23 patients with liver injury from ashwagandha (January 2019 to December 2022), we report 8 patients with single-ingredient formulation-related HILI. Study cohort was male predominant, and cholestatic hepatitis was the commonest presentation. Five patients had underlying chronic liver disease; 3 presented with acute-on-chronic liver failure, and all 3 died on follow-up. In others, the liver injury was prolonged, nonetheless self-limiting. Liver biopsy revealed cholestatic features predominantly with hepatocellular necrosis and lymphocyte/eosinophil predominant portal-based inflammation. One patient progressed to chronic HILI. Chemical analysis revealed only natural phytochemicals without adulteration or contamination. CONCLUSIONS: Ashwagandha-HILI presents with cholestatic hepatitis and can lead to the syndrome of acute-on-chronic liver failure with high mortality in those with pre-existing liver disease. Educating the public on avoiding the use of potentially toxic and unrecommended herbal supplements can help mitigate the avoidable liver disease burden in the community.