Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis.

Background & Aims: It is not clear how weight loss affects histologic features of liver in patients with nonalcoholic steatohepatitis (NASH). We examined the association between the magnitude of weight loss through lifestyle modifications and changes in histologic features of NASH.

Methods: We conducted a prospective study of 293 patients with histologically proven NASH who were encouraged to adopt recommended lifestyle changes to reduce their weight over 52 weeks, from June 2009 through May 2013, at a tertiary medical center in Havana, Cuba. Liver biopsies were collected when the study began and at week 52 of the diet and were analyzed histologically.

Results: Paired liver biopsies were available from 261 patients. Among 293 patients who underwent lifestyle changes for 52 weeks, 72 (25%) achieved resolution of steatohepatitis, 138 (47%) had reductions in nonalcoholic fatty liver disease activity score (NAS), and 56 (19%) had regression of fibrosis. At week fifty-two, 88 subjects (30%) had lost ≥5% of their weight. Degree of weight loss was independently associated with improvements in all NASH-related histologic parameters (odds ratios = 1.1-2.0; P < .01). A higher proportion of subjects with ≥5% weight loss had NASH resolution (51 of 88 [58%]) and a 2-point reduction in NAS (72 of 88 [82%]) than subjects who lost <5% of their weight (P < .001). All patients who lost ≥10% of their weight had reductions NAS, 90% had resolution of NASH, and 45% had regression of fibrosis. All patients who lost 7%-10% of their weight and had few risk factors also had reduced NAS. In patients with baseline characteristics that included female sex, body mass index ≥35, fasting glucose >5.5 mmol/L, and many ballooned cells, NAS scores decreased significantly with weight reductions ≥10%.

Conclusions: A greater extent of weight loss, induced by lifestyle changes, is associated with the level of improvement in histologic features of NASH. The highest rates of NAS reduction, NASH resolution, and fibrosis regression occurred in patients with weight losses ≥10%.