Liver biopsy imperfect diagnostic standard Below is Dr. Giada Sebastiani’s comments on project LITMUS (funded by EU Innovative Medicines Initiatives which also has had many interactions with EMA/FDA) published yesterday, she has been and is conducting researches all related to NAFLD/NASH (many posted here previously) and some of them have been related to abdominal fat (Tesamorelin) and HIV NAFLD/NASH including the current study:
Characterization of Visceral Adiposity in HIV Mono-infected Patients With NAFLD - Full Text View - ClinicalTrials.gov She is also conducting another study evaluating ultrasound imaging in a different clinical trial for diagnosis of NASH:
“This research proposal proposes a novel approach for diagnosis of NASH and will be the first study to measure individual components of NASH (fat, inflammation and fibrosis) with quantitative ultrasound (QUS) scores. This study is timely because NASH is the second leading cause of liver transplantation in North America and is predicted to become the leading indication in the near future. ”
Quantitative Ultrasound Techniques for Diagnosis of Nonalcoholic Steatohepatitis - Full Text View - ClinicalTrials.gov The point is biopsies can be “imperfect” as it cannot detect the true ratio of the decomposed area of the liver(lesions are not evenly distributed in liver tissues) so diagnostic imagines(liver stiffness…) and blood tests(biomarkers) have been recently studied as a replacement due to less invasive nature and better accuracy. The relevance is apart from much more feasible prophylactic/therapeutic mass screening (better estimation of the true prevalence of NAFLD/NASH) noninvasive diagnosis will result in easier patient enrollment as for now all phase2b, phase3 NASH trials have to perform biopsies on the participants which causes logistical challenges and lack of compliance from the patients therefore noninvasive diagnosis of the conditions can accelerate the drug development process/approvals/commercialization and treatments for these unmet/under diagnosed and epidemic conditions with growing prevalence worldwide. The other point is to have a talented and well merited/recognized/ connected researcher like her working with the company in the past and now is absolutely very helpful resource/asset.
“Five multimarkers exceeded the 0·80 AUC threshold in detecting advanced fibrosis, but only two were superior to FIB-4, and the ADAPT score, based on age, platelets, diabetes, and N-terminal type 3 collagen propeptide. The fact that some of the biomarkers achieved the prespecified threshold for advanced liver fibrosis is noteworthy.
To the gastrohepatology community, the best balance under current epidemiological circumstances might be the availability of a pool of biomarkers that are adaptable to various clinical scenarios and that can be used according to the expertise, local resources, and clinical practice setting (eg, low disease prevalence
vs high disease prevalence).
Liver histology is also an imperfect diagnostic gold standard. Simple and cheap biomarkers, such as FIB-4, might be a balance during the pressing need for large-scale case-finding programmes, whereas more complex and expensive multimarkers might help refine the selection of people for inclusion in therapeutic trials for NASH.
GS has been a speaker for Merck, Gilead, AbbVie, Novonordisk, and Pfizer; has been an advisory board member for Pfizer, Merck, Novonordisk, Gilead, and Intercept; and has received unrestricted research funding from Theratechnologies. She is supported by a Senior Salary Award from
Fonds de Recherche du Quebec—
Sante.”
The quest for the ideal NASH biomarker - The Lancet Gastroenterology & Hepatology Biomarkers for staging fibrosis and non-alcoholic steatohepatitis in non-alcoholic fatty liver disease (the LITMUS project): a comparative diagnostic accuracy study (thelancet.com)