Diagnostic Considerations and Clinical End Points for Nonalcoholic Steatohepatitis
Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease seen in clinical practice. It is associated with an increased risk of liver-, cardiac-, and cancer-related mortality. Nonalcoholic steatohepatitis (NASH) is the phenotype that typically progresses to cirrhosis and is associated with increased cardiac events. The presence of NAFLD can be suspected from elevated liver enzymes without an obvious cause or from imaging studies that demonstrate the presence of hepatic steatosis. A key question in the assessment of NAFLD is to estimate the risk of development of clinically meaningful outcomes. These include an assessment of cardiovascular risk, cancer risk, and the risk of progression to cirrhosis. Elevated ALT, multiple features of the metabolic syndrome, and histological evidence of inflammation and ballooning and some degree of fibrosis are all risk factors for progression. Those who have these features should be considered for treatment. The therapeutics for NASH include both lifestyle modification to include a healthy diet, optimizing body weight via diet and exercise, and pharmacological treatment for those with aggressive NASH. Currently, a liver biopsy is the best way to assess histological response to treatment. However, there is an intense effort to evaluate response to treatment using noninvasive measures. The best end points for those with early-stage disease are histological regression of steatohepatitis, while those with advanced disease should have a decreased risk of outcomes. This chapter summarizes the diagnostic approach to NASH and the best ways to assess outcomes of treatment for NASH.
KeywordsNonalcoholic steatohepatitis Nonalcoholic fatty liver Nonalcoholic fatty liver disease Cirrhosis Model for End-Stage Liver Disease Hepatic venous pressure gradient Quantitative liver function tests Biomarkers Type 2 diabetes mellitus Metabolic syndrome
Nonalcoholic fatty liver disease
Nonalcoholic fatty liver
Hepatic venous pressure gradient
Model for End-Stage Liver Disease
Type 2 diabetes mellitus
Food and Drug Administration
American Association for the Study of Liver Disease
This work was supported in part by a grant from the National Institutes of Health to Dr. Sanyal DK 81410 and T32 DK007150.
Conflicts of Interest
Dr. Sanyal serves as a consultant to Abbvie, Bristol Myers-Squibb, Genfit, Exhalenz, Islet Pharmaceuticals, Nimbus, Nitto-Denko, and Tobira. His institution receives research funding from Gilead, Galectin, Novartis, Salix, Cumberland, and Intercept Pharmaceuticals. He has also served as a non-remunerated consultant to Immuron and Echosens.
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