The first guidelines for assessing the eligibility of patients with nonalcoholic fatty liver disease (NAFLD) steatohepatitis (NASH) for inclusion in clinical studies were published in Gastroenterology.
An accurate case definition of NASH cirrhosis is crucial for recruiting patients to clinical trials so that conclusions drawn from these studies can be both accurate and generalizable to individuals outside study populations. The liver consortium created 3 subgroups that describe the confidence of a NASH diagnosis (definite, probable, and possible) based on the clinical features of patients.
The current standard of diagnosis is based on liver biopsy, NAFLD activity score ≥4, and the clinical markers of steatosis, including inflammation and hepatocyte ballooning. However, as biopsies may be unavailable due to fear of complications and steatosis may decrease as cirrhosis progresses, a diagnosis of NASH remains dynamic.
The authors described a confirmed NASH diagnosis with 3 scenarios: patients with a current liver biopsy that shows cirrhosis with steatohepatitis; patients with a prior biopsy that showed steatohepatitis with evidence of invasive or noninvasive cirrhosis; and patients with a current biopsy that shows steatosis with at least 2 metabolic comorbidities (such as obesity or type-2 diabetes mellitus).
A probable diagnosis was described in patients who had a previous biopsy with steatosis and current evidence of cirrhosis as well as 2 metabolic comorbidities, patients with no histological data and evidence of cirrhosis and 2 metabolic comorbidities, and patients with cryptogenic cirrhosis without steatosis but with 2 comorbidities.
A possible NASH diagnosis was described as either patients with cryptogenic cirrhosis without steatosis but with 1 metabolic comorbidity, patients with previously eradicated hepatitis C virus, or those with a remote history of heavy alcohol consumption and current cirrhosis with steatohepatitis.
The guideline authors caution that NASH should only be diagnosed in the absence of excessive alcohol consumption, viral or autoimmune hepatitis, hemochromatosis, primary biliary cholangitis, primary sclerosing cholangitis, Wilson’s disease, or alph-1-antitrypsin deficiency.
The guideline authors state that subgroups of probable or possible NASH diagnosis should be incorporated into the design of clinical studies, and that researchers should assess the appropriateness of their inclusion in specific trials.
Disclosures: Some authors declared receiving consulting or funding from the pharmaceutical industry. A complete list of disclosures can be found in the original study.
Noureddin M, Chan J L, Barradas K, et al. Attribution of nonalcoholic steatohepatitis as an etiology of cirrhosis for clinical trials eligibility: recommendations from the multi-stakeholder liver forum. [available online April 27, 2020]. Gastroenterology. doi:10.1053/j.gastro.2020.04.039