RESUMEN
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.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Hígado Graso , Humanos , Consenso , Hígado/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , BiopsiaAsunto(s)
Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , United States Food and Drug Administration , Biomarcadores , Ensayos Clínicos como Asunto/normas , Aprobación de Drogas , Humanos , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Resultado del Tratamiento , Estados Unidos , United States Food and Drug Administration/organización & administración , United States Food and Drug Administration/normasAsunto(s)
Ensayos Clínicos como Asunto , Desarrollo de Medicamentos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Factores de Edad , Niño , Humanos , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Selección de Paciente , Prevalencia , Índice de Severidad de la EnfermedadRESUMEN
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).
Asunto(s)
Colangitis Esclerosante , Ensayos Clínicos como Asunto , HumanosAsunto(s)
Ensayos Clínicos como Asunto/normas , Enfermedad del Hígado Graso no Alcohólico/terapia , Proyectos de Investigación/normas , Biopsia , Ensayos Clínicos como Asunto/métodos , Comorbilidad , Determinación de la Elegibilidad , Femenino , Predisposición Genética a la Enfermedad , Humanos , Estilo de Vida , Pruebas de Función Hepática , Masculino , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/genética , Selección de Paciente , Polifarmacia , Valor Predictivo de las Pruebas , Factores de Riesgo , Factores Sexuales , Resultado del TratamientoRESUMEN
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.