ENDPOINTS AND CLINICAL TRIAL DESIGN FOR NONALCOHOLIC STEATOHEPATITIS

By Arun J. Sanyal, Elizabeth M. Brunt, David E. Kleiner, Kris V. Kowdley, N. Chalasani, J. Lavine, V. Ratziu, A. McCullough. Hepatology, 2011

738 citations recorded by the source corpus.

Nonalcoholic fatty liver disease is a common cause of chronic liver disease in the general population. Nonalcoholic steatohepatitis (NASH), the aggressive form of nonalcoholic fatty liver disease, is associated with an increased risk of liver‐related mortality and cardiovascular disease. At present, a liver biopsy is the only generally acceptable method for the diagnosis of NASH and assessment of its progression toward cirrhosis. Although several treatments have shown evidence of efficacy in clinical trials of varying design, there are no approved treatments for NASH, and published trials are often too divergent to allow meaningful comparisons. There is thus a lack of established noninvasive, point‐of‐care diagnostics and approved treatment on one hand and a substantial population burden of disease on the other. These provide the rationale for developing consensus on key endpoints and clinical trial design for NASH. Conclusion: This article summarizes the consensus arrived at a meeting of the American Association for the Study of Liver Diseases on the key endpoints and specific trial design issues that are germane for development of diagnostic biomarkers and treatment trials for NASH. (HEPATOLOGY 2011;)

Subfields: Endocrinology, Diabetes and Metabolism, Epidemiology, Hepatology

View Paper: https://www.semanticscholar.org/paper/11448a78b6ee8682edf373a0820b14cc36ca1252

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Endocrinology, Diabetes and Metabolism

1. Z. Younossi
2. M. Rinella
3. Q. Anstee
4. A. Sanyal
5. L. Adams
6. K. Cusi
7. Bart Staels
8. G. Targher

In Epidemiology

1. Z. Younossi
2. M. Rinella
3. A. Sanyal
4. Q. Anstee
5. K. Cusi
6. E. Brunt
7. J. Lavine
8. S. Harrison

In Hepatology

1. Z. Younossi
2. M. Rinella
3. A. Sanyal
4. E. Brunt
5. Q. Anstee
6. K. Cusi
7. A. Diehl
8. S. Friedman

Citations in the corpus

• Mitochondrial dynamics in health and disease: mechanisms and potential targets (2023, background): “210 Furthermore, Drp1-K38A expression lowers oxidative damage and in fl ammation within a model of NAFLD.”
• Fibrosis stage is the strongest predictor for disease‐specific mortality in NAFLD after up to 33 years of follow‐up (2015, background): “Despite the high variability of at least two of the three components of NAS, reported already in the original publication,(13) and limited data on the ability of NAS to predict disease outcome, NAS is recommended to be used to define and quantify disease activity in clinical trials of NAFLD/NASH.(14”
• Long-Term Pioglitazone Treatment for Patients With Nonalcoholic Steatohepatitis and Prediabetes or Type 2 Diabetes Mellitus (2016, neutral): “1) mg/dL 109 (33) 109 (44) Mean HDL cholesterol level (SD) mmol/L 1.”
• Elafibranor, an Agonist of the Peroxisome Proliferator-Activated Receptor-α and -δ, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening. (2016, background): “An equally important aspect when treating patients with NASH is the requirement for absence of deterioration (or at best improvement) of the cardiometabolic comorbidities that contribute to overall mortality.(25,26) In addition, insulin resistance, an almost constant feature of NASH, could be causal”
• The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases (2018, background): “A consensus meeting recommended that, for NASH clinical trials candidate eligibility purposes, significant alcohol consumption be defined as >21 standard drinks per week in men and >14 standard drinks per week in women over a 2-year period preceding baseline liver histology.((68)) According to the N”
• Histopathological algorithm and scoring system for evaluation of liver lesions in morbidly obese patients (2012, methodology): “NAFLD is defined by the presence of steatosis in >5% of hepatocytes, and NASH by the presence, in addition, of hepatocellular ballooning of any degree and lobular inflammatory infiltrates of any amount.(9) Therefore, steatosis was used as the criteria for entry into the algorithm weighted by hepatoc”
• The severity of NAFLD is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota (2016, background): “As recently recommended,((20)) NASH was defined as the presence of each of the three following conditions: steatosis grade 1; lobular”
• Liver Fibrosis, but no Other Histologic Features, Associates with Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease (2015, methodology): “Improvement in the NAS often is recommended and used as the primary end point to determine treatment efficacy in treatment trials.(20) In our study, the NAS on its own did not provide any long-term prognostic information, although some preliminary data suggested an association of NAS improvement wit”