Eduardo Vilar-Gomez et al associated extent of weight loss, produced by lifestyle changes, with level of improvement in histologic features of NASH. The highest rates of NASH reduction and resolution and fibrosis regression occurred in patients with more than 10% weight loss.
With the increasing incidence of obesity and type 2 diabetes, nonalcoholic fatty liver disease (NAFLD) has become a leading cause of chronic liver disease worldwide. NAFLD encompasses a range of disorders, from fatty liver to the most aggressive form of disease, NASH, which can progress to cirrhosis.
No therapies have been approved for treatment of NASH. Comprehensive lifestyle modification, based on reduced energy intake and/or increased physical activity, has been reported to alter biochemical and metabolic features of the disease.
However, reports of the relationship between weight reduction and histologic features of NASH have been inconsistent. There have been no prospective studies of changes in NASH-related histology in subjects on weight-loss programs.
Vilar-Gomez et al performed a prospective study of the effects of diet and exercise on serologic and histologic features of NASH in 293 obese individuals in Havana, Cuba. Their mean age was 48.5 years and mean body mass index was 31.3; 59% were women.
The patients were encouraged to adopt recommended lifestyle changes to reduce their weight over 1 year. They received recommendations for a low-fat hypocaloric diet, 750 kcal/d below their daily energy need (a dietary pattern of 64% carbohydrate, 22% fat, and 14% protein). The participants recorded their daily food and beverage intake, and were encouraged to walk 200 min/week. They completed questionnaires to measure their physical activity, and attended individual behavioral sessions every 8 weeks.
Liver biopsies were collected when the study began and at week 52 of the program.
By week 52, the participants had lost an average of 4.6±3.2 kg; 30% of the subjects lost 5% or more of their weight. Vilar-Gomez et al found the degree of weight loss to be independently associated with improvements in all NASH-related histologic parameters.
Overall, steatohepatitis resolved in 25% of the participants. Fatty liver disease activity scores (a summary score of grade of steatosis, lobular inflammation, and ballooning) were reduced in 47%, and 19% had regression of fibrosis.
More than half of the subjects (58%) who lost 5% or more of their weight had NASH resolution, and 82% had a 2-point reduction in nonalcoholic fatty liver disease activity scores.
All patients who lost more than 10% of their weight had reductions in nonalcoholic fatty liver disease activity scores, 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 nonalcoholic fatty liver disease activity scores.
Fibrosis worsened over the study period in most of the patients (93%) with little or no weight reduction (less than 5%).
The study is notable because it is the first is large prospective study conducted in real-world clinical practice that explores the potential benefit of a 12-month lifestyle intervention on histologic features of NASH. It provides the important information that modest (7%−10%) and greater (≥10%) weight losses are necessary to induce significant improvements in liver histology of overweight and obese patients with NASH.
Vilar-Gomez et al admit that because fewer than 50% of patients were able to lose 7% to 10% of their body weight in this trial setting, the sustainability of this type of intervention is not clear. The participants received intense, multidisciplinary support during the program period, but implementing these modifications into every day can be difficult. The authors state that intensive lifestyle counseling must be offered to all NASH patients.
Their analyses did not examine effects of maintenance of weight loss after 12 months and its relationship to histologic changes, so additional studies are needed.
Guillaume Lassailly et al report that bariatric surgery led to the disappearance NASH from nearly 85% of patients, and reduced the pathologic features of the disease after 1 year of follow up. They found that patients had significant reductions in mean body mass index, from 49.3±8.2 to 37.4±7.0. Steatosis, which was detected in 60% of the tissue before surgery, was detected in only 10% by 1 year after the surgery. The patients’ mean nonalcoholic fatty liver disease score also reduced, from 5 before surgery to 1 afterward.
Lassailly et al state that bariatric surgery could be a therapeutic option for appropriate morbidly obese patients with NASH who do not respond to lifestyle modifications.
What happens to patients with NAFLD over the long term? In the same issue of Gastroenterology, Paul Angulo et al report the findings from a retrospective analysis of 619 patients who were diagnosed with NAFLD over a 30-year period (1975–2005) at tertiary care centers in the United States, Europe, and Asia. They found that over a median period of 12 years, 193 patients (33.2%) died or underwent liver transplantation. Fibrosis stage was independently, regardless of the presence or severity of other histologic features, associated with overall- and liver-related mortality/liver transplantation or liver-related events. This effect was seen even with the earliest stages of fibrosis (detectable by microscopic examination).