Challenges in PARP inhibitor therapy: A case of Olaparib-induced liver injury and successful rechallenge with Niraparib.

Olaparib, the first-in-class poly ADP-ribose polymerase (PARP) inhibitor, is approved for first line maintenance treatment in platinum-sensitive FIGO stage 3 and 4 high grade serous ovarian cancer (HGSOC) associated with a deleterious BRCA mutation. We report a case involving a 70-year-old female who experienced significant CTCAE Grade 4 hepatocellular injury after initiating first line maintenance Olaparib for Stage 3C HGSOC. Her liver injury resolved upon discontinuation of Olaparib but promptly recurred upon rechallenge. Extensive investigations, including abdominal ultrasound, computed tomography, and assessments for infectious, metabolic, and autoimmune aetiologies of liver injury, were unremarkable. Her liver enzymes returned to baseline after discontinuing Olaparib once again. Subsequently, the patient was started on Niraparib for maintenance therapy, which she tolerated well. This case represents the first instance of positive rechallenge following Olaparib-induced liver injury and highlights the absence of cross-reactive hepatotoxicity between PARP inhibitors.

Evidence related to a vegetarian diet and metabolic dysfunction-associated steatotic liver disease: protocol for a scoping review.

INTRODUCTION: Metabolic dysfunction-associated fatty liver disease (MASLD) is the hepatic manifestation of metabolic syndrome and the leading cause of chronic liver disease worldwide. Given that there is no pharmacological treatment for MASLD, it is imperative to understand whether lifestyle modifications may improve biochemical and pathological outcomes. One commonly proposed dietary modification is the Mediterranean diet; however, vegetarianism may also be a promising intervention. Vegetarianism has been shown to be associated with reduced morbidity and mortality in metabolic syndrome outcomes in coronary artery disease and diabetes; however, the relationship between vegetarian diet and MASLD is less clear. In this scoping review, we will provide a comprehensive overview of the current body of evidence related to a vegetarian diet and MASLD. METHODS AND ANALYSIS: The aim of this scoping review is to describe and summarise the current body of evidence related to MASLD and a vegetarian diet. This review will be conducted using Arksey and O'Malley's framework. The literature review will be conducted using the following databases: SCOPUS, Web of Science, CINAHL-Plus, Cochrane Library and Medline. No restriction will be made on publication date. Included studies will encompass clinical trials and observational designs that examine effects or association of vegetarian diet in adults (≥16 years) and report on the incidence, prevalence or progression of MASLD. Grey literature, non-human studies and articles focusing on changes in a specific food or nutraceutical will be excluded. Articles must have an English-language abstract available to be considered for inclusion. Screening and data extraction will be conducted by two independent reviewers. The findings will be summarised with descriptive statistics. ETHICS AND DISSEMINATION: Approval from a medical ethics committee is not required for this review. Once the review is complete, the findings will be submitted to a peer-reviewed journal.