MRI‐Proton Density Fat Fraction Treatment Response Criteria in Nonalcoholic Steatohepatitis
Year: 2020
Type: article
Abstract: NASH is one of leading causes of chronic liver disease in the United States.(1) NASH can lead to cirrhosis, end-stage liver disease, and hepatocellular carcinoma and has become one of the leading indications for liver transplant in the United States.(2) Reversal of NASH and improvement of NASH-related fibrosis is a major unmet need in the field of liver disease.Several therapies have shown promise in the treatment of NASH-related fibrosis, but there are no US Food and Drug Administration (FDA)-approved or European Medicines Agency (EMA)-approved therapies.Over the past 10 years, there has been a tremendous increase in the number of agents being evaluated for treatment of NASH-related fibrosis.Both the FDA and EMA have provided guidance regarding regulatory approval for drugs used in the treatment of NASH-related fibrosis.The acceptable endpoints for full approval include progression to cirrhosis, clinical hepatic decompensation, and a MELD score ≥15.However, because of the long natural history of NASH-related fibrosis, a subpart H pathway is provided to show improvement in liver histology as a surrogate endpoint for interim approval while data are being collected for long-term clinical outcomes.These histologic endpoints include ≥1 stage improvement in fibrosis without worsening of NASH and/or resolution of NASH without worsening of fibrosis.Histologic endpoints, although useful, pose significant limitations to clinical drug development in NASH.These limitations include the invasive nature of the liver biopsy assessment, subjective assessment of histology, low intrareader and inter-rater reliability, lack of precision and reproducibility, and long duration required to show a treatment benefit.Therefore, there is a need for a precise, reproducible, accurate biomarker for treatment response, especially in early Phase 1 and 2A trials in which histologic response assessment is impractical and may increase the risk of type 2 errors, i.e., declaring a therapy to be ineffective although it may improve NASH-related fibrosis in a larger and longer trial.(3) Over the last 10 years, many noninvasive tests, both serum and imaging-based biomarkers, have been proposed to assess treatment response in NASH.(4) Among the cadre of these noninvasive biomarkers, MRI-proton density fat fraction (MRI-PDFF) is one of the leading imaging-based biomarkers of assessing antisteatotic benefits of a drug therapy in NASH.(5)
Source: Hepatology
DOI: 10.1002/hep.31624
Author: Rohit Loomba
Institution: University of California San Diego
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,400
Funders: U.S. Department of Defense, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Center for Advancing Translational Sciences, DOD Peer Reviewed Cancer Research Program
Awards: A Cardiovascular-NASH disease nexus: Common Mechanisms and Treatments?, DETECTION AND MODELS OF TOXICANT EXPOSURE, Non-invasive screening of diabetics for advanced fibrosis due to NAFLD, G4119534169, Novel IL-23 inhibitor for the treatment of alcohol associated liver disease, G5809932816, Ancillary Studies of NAFLD and NASH in HIV infected Adults, QUS Technology for Diagnosis and Grading of Hepatic Steatosis in NAFLD, G8166743225, UC San Diego Clinical and Translational Research Institute, San Diego Digestive Diseases Research Center, Clinical Research on Nonalcoholic Fatty Liver Disease
OpenAlex ID: W3103169657