Drug and herbal/dietary supplements-induced liver injury:A tertiary care center experience

BACKGROUND Drug-induced liver injury(DILI)and herbal/dietary supplements(HDS)related liver injury present unique diagnostic challenges.Collaboration between the clinician and the pathologist is required for an accurate diagnosis and management.AIM To report our experience on the clinical-pathological findings of hepatic injury caused by drugs/HDS.METHODS A retrospective review of clinically proven cases of DILI/HDS who presented to our institution from January 1,2013 to December 31,2017 was performed.Slides were reviewed for histopathological patterns of injury and correlated with the causative agent.Out of 600 patients presenting with unexplained rise in liver enzymes undergoing biopsy,107 were suspected to have DILI/HDS.Of these,53 had a directly linked exposure to drug/herbal supplements.Fifteen patients were excluded for concurrent known liver disease.Thirty-eight patients with clinically proven DILI/HDS were finally included.RESULTS Thirty-eight cases of DILI/HDS with a male:female of 1:1.5 and mean age of 51±3 years were identified.DILI was identified in 84.2%cases while HDS injury in 15.8%.Acute hepatitis(42.1%)was the most common pattern of injury while granulomatous hepatitis(2.6%)was the least common.We found one case of acute-cholestasis due to rivaroxaban and two cases of cholestatic-hepatitis due to rizatriptan and trimethobenzamide-hydrochloride that,to the best of our knowledge,have not been previously reported.One case of steatohepatitis due to trimethoprim-sulfamethoxazole and three unusual cases of cholestatic-hepatitis with bile duct injury and steatosis due to dronedarone,C4-Extreme and hydroxycut,were also seen.Of our cohort,81.6%of the patients fared well with discontinuation of drug and 18.4%underwent transplant;of which 42.9%were deceased.CONCLUSION We describe the clinical findings,histopathological patterns of injury and clinical outcomes caused by drugs.In particular,we report a few previously unreported/rarely observed clinical and histopathological patterns of hepatic injury.

Non-alcoholic Fatty Liver Disease: A Review of Anti-diabetic Pharmacologic Therapies

Non-alcoholic fatty liver disease(NAFLD),the most common cause of liver disease,affects approximately 75 to 100 million Americans.Patients with concurrent NAFLD and type 2 dia-betes mellitus have a higher risk of progressing to advanced fibrosis and non-alcoholic steatohepatitis compared to non-diabetics.Lifestyle modifications,including weight loss,remain the mainstay of treatment for NAFLD,as there are no med-ications currently indicated for this disease state.Anti-diabetic pharmacologic therapies aimed at improving insulin sensitivity and decreasing insulin production have been studied to determine their potential role in slowing the progression of NAFLD.In this review,we focus on the evidence surrounding anti-diabetic medications and their ability to improve disease progression in patients with NAFLD.

Rising Rate of Liver Transplantation in the Baby Boomer Generation with Non-alcoholic Steatohepatitis in the United States

Background and Aims:Nonalcoholic steatohepatitis (NASH) is the most rapidly growing indication for liver transplantation (LT) in the United States and is on a trajectory to become the leading indication for LT in the next decade.We aimed to study the trends in NASH-related LT among persons born between 1945 and 1965,the baby boomer (BB) generation.Methods:We performed a retrospective cohort analysis using population-based data from the United Network for Organ Sharing/Organ Procurement and Transplantation Network registry from 2004-2015 to evaluate the birth cohort-specific trends in liver transplant waitlist registrations and liver transplant surgeries in patients with NASH.We stratified our study population into three birth cohorts:1) birth before 1945,2) birth between 1945 and 1965,and 3) birth after 1965.Results:The overall rates of NASH-related waitlist registrations and liver transplant surgeries steadily increased from 2004 to 2015 and were reflective of a sharp rise noted in the NASH BB sub-group.From 2004 to 2015,the proportion of BB patients with NASH added to LT waitlist demonstrated an incremental growth,60.6% in 2004 versus 83.2% in 2015 (p < 0.01).Among the liver transplant recipients with NASH,the proportion represented by the BB cohort increased from 56.3% in 2004 to 80.0% in 2015 (p < 0.01).Conclusion:We report rising rates of waitlist registration and LT for the indication of NASH.More importantly,the BB sub-cohort was mainly responsible for these alarming trends.