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NAFLD phenotypes progress and regress over time
BOSTON — Nonalcoholic fatty liver disease phenotypes — fatty liver without steatohepatitis, borderline and definite steatohepatitis — can progress and regress over time. Changes in NAFLD Activity Score and weight gain were predictors for progression of disease, according to findings presented at The Liver Meeting.
“What we have learned over the last 5 years is phenotypes can change over time and both be associated with fibrosis. However, regression and progression remains uncertain. … Our aim was to define changes in histological phenotypes over time and rate of progression or regression of fatty liver and fibrosis,” Arun J. Sanyal, MD, FAASLD, from Virginia Commonwealth University, said during his presentation.
The researchers evaluated 394 adults with NAFLD from the NASH CRN Database. These adults previously underwent biopsy and then underwent clinical and laboratory examinations until another liver biopsy was performed. Multivariate logistic regression was used with a subset of 197 patients with complete data coinciding with available liver biopsy, to determine the risk for factors of progression and regression.
Overall, 75 patients with fatty liver without steatohepatitis, 74 with borderline steatohepatitis and 245 with definite steatohepatitis underwent two liver biopsies. In regards to changes in NAFLD phenotype, 44% with fatty liver without steatohepatitis progressed to borderline or definite, whereas 13% of patients resolved fatty liver without steatohepatitis.
“Borderline steatohepatitis is more likely to progress than regress (43% vs. 22%),” Sanyal said.
Increased alanine aminotransferase levels (P = .03), worsening NAFLD Activity Score (P = .007), and weight gain (P = .02) between the first and second liver biopsy correlated with progression to borderline or definite steatohepatitis in this cohort (P < .0001).
In addition, 43% with borderline progressed to definite steatohepatitis, whereas 23% regressed to fatty liver without steatohepatitis and 4% to non-NAFLD. Twenty-percent of patients with definite steatohepatitis regressed to borderline; 11% regressed to fatty liver; and 11% regressed to non-NAFLD.
The researchers observed changes in fibrosis among patients with fibrosis at baseline. At baseline, 25% of patients with fatty liver had some fibrosis. There were a moderate number of patients who progressed, according to Sanyal. Fibrosis worsened in 21% of patients with fatty liver, 30% in patients with borderline steatohepatitis and 29% in patients with definite steatohepatitis compared with 53%, 34% and 36% of patients in each group who regressed.
The researchers also found baseline NAFLD Activity Score is linked to both fibrosis progression and regression.
“From the first to second biopsy, you see an interesting relationship,” Sanyal said. “NAS both at baseline and its change over time, is a strong predictor of fibrosis progression or regression along with AST, portal inflammation and baseline fibrosis stage.”
Sanyal concluded: “All phenotypes of NAFLD can progress or regress without pharmacological intervention. NAFL progresses to NASH frequently and the resolution of NAFLD was linked to weight loss whereas progression to NASH from NAFL was related to weight gain.” – by Melinda Stevens
Reference:
Kleiner DE, et al. Abstract 37. Presented at: The Liver Meeting; Nov. 11-15, 2016; Boston.
Disclosures: Sanyal reports serving on the advisory committees or review panels of Abbott, Bristol Myers, Exhalenz, Gilead Sciences, Genfit and Ikaria; consulting for Echosens, Enanta, Exhalenz, Genentech, Immuron, Islet Sciences, JD Pharma, Merck, Nimbus, Salix, Takeda and Zafgen; receiving grant/research support from GalMed, Genentech, Gilead Sciences, Ikaria, Intercept, Novartis, Salix, Takeda and Tobira; and is an independent contractor for UpToDate and Elsevier.