ABSTRACT
BACKGROUND: Causality assessment of suspected drug-induced liver injury (DILI) during metabolic dysfunction-associated steatohepatitis (MASH) clinical trials can be challenging, and liver biopsies are not routinely performed as part of this evaluation. While the field is moving away from liver biopsy as a diagnostic and prognostic tool, information not identified by non-invasive testing may be provided on histology. AIM: To address the appropriate utilisation of liver biopsy as part of DILI causality assessment in this setting. METHODS: From 2020 to 2022, the Liver Forum convened a series of webinars on issues pertaining to liver biopsy during MASH trials. The Histology Working Group was formed to generate a series of consensus documents addressing these challenges. This manuscript focuses on liver biopsy as part of DILI causality assessment. RESULTS: Expert opinion, guidance and recommendations on the role of liver biopsy as part of causality assessment of suspected DILI occurring during clinical trials for a drug(s) being developed for MASH are provided. Lessons learned from prior MASH programs are reviewed and gaps identified. CONCLUSIONS: Although there are no pathognomonic features, histologic evaluation of suspected DILI during MASH clinical trials may alter patient management, define the pattern and severity of injury, detect findings that favour a diagnosis of DILI versus MASH progression, identify prognostic features, characterise the clinicopathological phenotype of DILI, and/or define lesions that influence decisions about trial discontinuation and further development of the drug.
Subject(s)
Chemical and Drug Induced Liver Injury , Fatty Liver , Humans , Consensus , Liver/pathology , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/pathology , BiopsySubject(s)
Non-alcoholic Fatty Liver Disease/drug therapy , United States Food and Drug Administration , Biomarkers , Clinical Trials as Topic/standards , Drug Approval , Humans , Non-alcoholic Fatty Liver Disease/diagnosis , Treatment Outcome , United States , United States Food and Drug Administration/organization & administration , United States Food and Drug Administration/standardsSubject(s)
Clinical Trials as Topic , Drug Development , Non-alcoholic Fatty Liver Disease/drug therapy , Age Factors , Child , Humans , Liver/pathology , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/epidemiology , Patient Selection , Prevalence , Severity of Illness IndexABSTRACT
Primary sclerosing cholangitis (PSC) is a rare and chronic liver disease for which there is no effective therapy. Interest has grown in developing treatments for this condition, with several agents proposed as potential therapies. However, there is a lack of clarity about how to measure clinical benefit in trials involving patients with this complex and rare disease. This article reviews regulatory information, the available literature on natural history, as well as potential candidate clinical and surrogate endpoints for PSC. (Hepatology 2018; 00:000-000).
Subject(s)
Cholangitis, Sclerosing , Clinical Trials as Topic , HumansSubject(s)
Clinical Trials as Topic/standards , Non-alcoholic Fatty Liver Disease/therapy , Research Design/standards , Biopsy , Clinical Trials as Topic/methods , Comorbidity , Eligibility Determination , Female , Genetic Predisposition to Disease , Humans , Life Style , Liver Function Tests , Male , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/genetics , Patient Selection , Polypharmacy , Predictive Value of Tests , Risk Factors , Sex Factors , Treatment OutcomeABSTRACT
Follicular unit extraction (FUE) is an accepted method of extracting individual follicular unit grafts for hair transplant surgery. Since follicles are harvested from the back of the scalp using tiny punches resulting in minimal scarring, it has gained rapid acceptance among the patients. However, due care needs to be exercised while performing FUE. FUE should not be confused with the older plug graft extraction methods of coring out hair-bearing skin plugs. Lack of due diligence while performing such extractions can lead to subluxation of the grafts into the subdermal layer of scalp. Overtumescence of the scalp donor area, use of blunt punches and trying to "core" out the full thickness grafts can all contribute to this. The following cases illustrate some pitfalls to be avoided while performing FUE and the adverse consequences if they occur.
