BOSTON – All phenotypes of nonalcoholic fatty liver disease (NAFLD) can progress or regress even without pharmacologic intervention, according to a prospective longitudinal study of 394 patients.
Weight loss and baseline NAFLD Activity Score predicted resolution of NAFLD, while weight gain and rising serum transaminases predicted progression to nonalcoholic steatohepatitis (NASH), Arun J. Sanyal, MD, said at the annual meeting of the American Association for the Study of Liver Diseases. Baseline and subsequent NAFLD Activity Score also was “a strong predictor of fibrosis progression or regression,” as was AST, portal inflammation, and baseline fibrosis stage, said Dr. Sanyal of Virginia Commonwealth University in Richmond, Va.
NAFLD comprises two main phenotypes, fatty liver and steatohepatitis. “The phenotype can change over time, and both phenotypes can be associated with fibrosis,” Dr. Sanyal noted. To better understand trends and clinical correlates for these phenotypes, he and his associates analyzed prospectively collected clinical and biopsy data from the NASH Clinical Research Network of the National Institutes of Diabetes and Digestive and Kidney Diseases. Each patient attended multiple clinic visits and underwent two liver biopsies at least 1 year and usually 4-5 years apart, which were interpreted by a masked central pathology review committee.
At baseline, 75 patients had fatty liver without steatohepatitis, of which only 13% resolved and 44% progressed to borderline or definite steatohepatitis. Similarly, among 74 patients with borderline steatohepatitis at baseline, only 22% regressed to fatty liver disease without steatohepatitis, while 43% progressed to definite steatohepatitis. The remaining 245 patients had definite steatohepatitis at baseline, of which 58% failed to regress at all, 20% regressed to borderline, 11% regressed to fatty liver disease without steatohepatitis, and 11% regressed to normal.
The investigators also performed a multivariable analysis of 197 patients with complete data. After the investigators controlled for serum insulin level, alkaline phosphatase level, NAS, and the presence of metabolic syndrome, each 10-U/L increase in ALT more than doubled the odds of progression from fatty liver without steatohepatitis to NASH (odds ratio, 2.2; 95% confidence interval, 1.1 to 4.1; P = .02). The association was even stronger for AST (OR, 3.5; 95% CI, 1.2 to 10.4; P = .03), and each 1-kg gain in body weight increased the odds of progression to NASH by 70% (OR, 1.7; 95% CI, 1.1 to 2.5; P = .01). In contrast, resolution of NAFLD was associated with weight loss (OR per 1 kg, 0.9; P less than .001) and lower baseline NAFLD Activity Score (OR, 0.7; P = .04).
About one in four patients had evidence of fibrosis at baseline, and 44% had at least stage 1 fibrosis at follow-up biopsy. Patients whose NAFLD progressed to a more severe phenotype were much more likely to have evidence of progressive fibrosis than were those whose NAFLD did not progress (OR, 7.2; 95% CI, 2.1 to 21.5; P less than .001), and there was no evidence that time between liver biopsies influenced this relationship. Among patients with definite NASH who had stage 0 fibrosis at baseline, 50% progressed to at least 1 fibrosis stage over the next 6.8 years, and 50% progressed to at least 2 stages over 9.6 years. Patients whose baseline NAFLD Activity Scores were between 1 and 4 were most likely to experience regression of fibrosis, while those with scores between 5 and 8 were more likely to have worsening fibrosis. Patients with severe baseline NAFLD Activity Score component scores for steatosis, lobular inflammation, and ballooning also were significantly more likely to have progressive fibrosis than were those with baseline NAFLD Activity Scores of 0 or 1. Furthermore, increasing NAFLD Activity Score over time predicted fibrosis progression.
Diabetes did not seem to affect fibrosis progression or regression, Dr. Sanyal noted. However, baseline portal inflammation predicted worsening fibrosis (P less than .01), as did baseline and subsequent elevations in AST (P less than .001), insulin (P = .03), and NAS (P less than 001), and baseline ballooning (P less than .01).
The investigators reported that the study had no sponsors. Dr. Sanyal disclosed ties to a wide number of drug companies.