January 08, 2020
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Histological noninvasive tools define distinct profiles between NAFLD, NASH

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Both the fatty liver inhibition of progression algorithm and the steatosis activity and fibrosis scoring system identified distinct clinical and biological profiles of disease severity among patients with suspected nonalcoholic fatty liver disease.

“These data help better identify steatohepatitis, defined histologically, as an entity with clinical relevance: a more severe form of NAFLD, associated with a higher prevalence and degree of metabolic comorbidities and associated with an almost exclusive relationship with advanced fibrosis,” Fabio Nascimbeni, MD, PhD, of the University of Modena and Reggio Emilia, Italy, and colleagues wrote. “This complements previous data demonstrating that activity of the disease is strongly linked to fibrosis progression or regression.”

The study comprised 140 patients (cohort 1) referred for suspicion of NAFLD between January 2008 and June 2012, and a validation group of 78 patients (cohort 2) with NASH without cirrhosis, all of whom were enrolled in a multicenter randomized control trial of ASP9831, a phosphodiesterase type 4 inhibitor.

The fatty liver inhibition of progression (FLIP) algorithm categories showed a correlation between steatohepatitis and stage of fibrosis in cohort 1(r = 0.616; P < .001). Patients with NASH had more bridging fibrosis (stage 3 and stage 4) than those without NASH (48% vs. 1%; P < .001).

In contrast, none of the patients marked as having NAFLD had stage 3 or stage 4 fibrosis, and all patients without steatosis had either no or mild stage 1 fibrosis.

Researchers also observed in cohort 1 “significant fibrosis” of stage 2 or higher in 73% of patients with NASH, 14% of those with NAFLD, and 1% of those without NAFLD. In cohort 2, bridging fibrosis was present in 23% of patients.

The steatosis activity and fibrosis (SAF) score also correlated with stage of fibrosis (r = 0.655; P < .001) in cohort 1, with severe disease noted by a score of 3 or higher and fibrosis stage of 3 or higher in 57% of patients. Ten of 17 patients with an activity score of 3 or higher but a fibrosis stage of less than 3 had stage 2 fibrosis.

Additionally, the grade of steatosis correlated with histologically severe disease based on the SAF score (r = 0.34; P < .001). After pooling data from cohort 1 and cohort 2, the relationship between NASH diagnosis and activity grade, and between steatosis grade and fibrosis stage were significant.

“Defining patients to be treated by the presence of steatohepatitis and requiring resolution of steatohepatitis as an outcome for therapeutic trials is in line with the current understanding of the model of natural history of NAFLD,” the researchers wrote. “The FLIP algorithm and SAF classification are useful tools for identifying patients at risk of disease progression.” – by Talitha Bennett

Disclosures: The authors report no relevant financial disclosures.