The Evolving Profile of Idiosyncratic Drug-Induced Liver Injury.

Idiosyncratic drug-induced liver injury (DILI) is an infrequent but important cause of liver disease. Newly identified causes of DILI include the COVID vaccines, turmeric, green tea extract, and immune checkpoint inhibitors. DILI is largely a clinical diagnosis of exclusion that requires evaluation for more common causes of liver injury and a compatible temporal association with the suspect drug. Recent progress in DILI causality assessment includes the development of the semi-automated revised electronic causality assessment method (RECAM) instrument. In addition, several drug-specific HLA associations have been identified that can help with the confirmation or exclusion of DILI in individual patients. Various prognostic models can help identify the 5%-10% of patients at highest risk of death. Following suspect drug cessation, 80% of patients with DILI fully recover, whereas 10%-15% have persistently abnormal laboratory studies at 6 months of follow-up. Hospitalized patients with DILI with an elevated international normalized ratio or mental status changes should be considered for N-acetylcysteine therapy and urgent liver transplant evaluation. Selected patients with moderate to severe drug reaction with eosinophilia and systemic symptoms or autoimmune features on liver biopsy may benefit from short-term corticosteroids. However, prospective studies are needed to determine the optimal patients and dose and duration of steroids to use. LiverTox is a comprehensive, freely accessible Web site with important information regarding the hepatotoxicity profile of more than 1000 approved medications and 60 herbal and dietary supplement products. It is hoped that ongoing "omics" studies will lead to additional insight into DILI pathogenesis, improved diagnostic and prognostic biomarkers, and mechanism-based treatments.

Herb-induced Liver Injury-A Guide to Approach. Lessons from the Tinospora cordifolia (Giloy) Case Series Story.

Background: Tinospora cordifolia (TC) is being increasingly consumed in India for its health and suggested immune-enhancing benefits in preventing and countering COVID-19. We previously published our experience of hepatotoxicity with self-medication of TC in six individuals. Since herb-induced liver injury (HILI) has been described with Tinospora crispa (TCR) consumption, it was contested that our patients may have mistakenly self-medicated with TCR which is similar in appearance to TC. Methods: We collected the four plant samples and two commercial preparations that were consumed by our patients for further analysis. The six samples underwent high performance thin layer chromatography phytochemical analysis and DNA barcoding studies for the confirmation of the genus and species. The four plant part samples which included stems and leaves were also analysed by a botanist for the characteristic morphological and microscopic features. Results: Based on morphological, microscopic, phytochemical and DNA studies, the four plant part samples were identified as TC. The two commercial preparations could not be analysed on phytochemical analysis or DNA barcoding studies due to other ingredients that most likely interfered with the analysis. The herb consumed by our study subjects was confirmed to be Tinospora cordifolia. Conclusion: We have highlighted the key morphological and phytochemical differences between these two species. We propose an algorithmic approach to accurately identify the implicated herb in cases of HILI. Future studies on causality need to focus on the serological/histopathological identification of active herb/metabolites in human tissues.

Early Diagnosis and Prevention of Infections in Cirrhosis.

Strategies to prevent infection and improve outcomes in patients with cirrhosis. HAV, hepatitis A virus; HBV, hepatitis B virus; COVID-19, novel coronavirus disease 2019; NSBB, nonselective ß-blocker; PPI, proton pump inhibitors.Cirrhosis is a risk factor for infections. Majority of hospital admissions in patients with cirrhosis are due to infections. Sepsis is an immunological response to an infectious process that leads to end-organ dysfunction and death. Preventing infections may avoid the downstream complications, and early diagnosis of infections may improve the outcomes. In this review, we discuss the pathogenesis, diagnosis, and biomarkers of infection; the incremental preventive strategies for infections and sepsi; and the consequent organ failures in cirrhosis. Strategies for primary prevention include reducing gut translocation by selective intestinal decontamination, avoiding unnecessary proton pump inhibitors' use, appropriate use of ß-blockers, and vaccinations for viral diseases including novel coronavirus disease 2019. Secondary prevention includes early diagnosis and a timely and judicious use of antibiotics to prevent organ dysfunction. Organ failure support constitutes tertiary intervention in cirrhosis. In conclusion, infections in cirrhosis are potentially preventable with appropriate care strategies to then enable improved outcomes.