Lean patients with nonalcoholic fatty liver disease had a higher overall mortality than did overweight or obese patients with NAFLD, according to a review of 1,090 biopsy-confirmed patients in the United States, Australia, Thailand, and Europe.
Reviewing blood and other samples taken at the time of liver biopsy, the investigators found that the 125 (11.5%) patients with a body mass index (BMI) below 25 kg/m2 (average 23 kg/m2) had less insulin resistance and less advanced fibrosis than did the 965 (88.5%) who presented with higher BMIs (average 33 kg/m2).
But among the 483 patients biopsied before 2005, 9 of the 32 (28%) lean patients died, compared with 62 of the 451 (14%) who were overweight or obese.
The cumulative survival was significantly shorter in lean patients, as well; only lean NAFLD (hazard ratio, 11.8; 95% confidence interval, 2.8-50.1; P = .001) and age (HR, 1.05; 95% CI, 1.008-1.1; P =.02) remained significant when the findings were adjusted for sex, degree of fibrosis, and other confounding factors.
Cardiovascular disease, malignancy, and liver problems were the main causes of death in both lean and overweight patients; there were no significant differences between the groups, and the reason is unclear. Perhaps lean patients have greater central fat distribution; the team plans to investigate the matter further.
"I thought patients with lean fatty liver would have lower mortality; it was exactly the opposite. The risk factors for fatty liver go beyond a person’s body weight, and signs of liver disease secondary to NAFLD in lean patients should be taken very seriously. We must not assume that patients of relatively healthy weight can’t have fatty liver disease," said senior investigator Dr. Paul Angulo, chief of hepatology at the University of Kentucky Medical Center in Lexington.
"We need to be more aggressive in patients with lean fatty liver in terms of biopsy to see how much liver injury they have, and really make a concerted effort to increase their physical activity and change their diet. They don’t need to lose weight, but they need less fat and carbohydrates and more exercise to increase insulin sensitivity, especially in the muscle mass and liver," he said at a teleconference in advance of the annual Digestive Disease Week.
Lean NAFLD patients were more likely to be men; nonwhite, especially Asian and Hispanic; and to have fewer chronic conditions, such as diabetes, hypertension, and dyslipidemia. They also had lower levels of alanine aminotransferase, fewer fatty liver deposits, and less advanced fibrosis, but more severe lobular inflammation. There was no significant difference between the two groups in age (average, 46 years), hepatocyte ballooning, or incidence of nonalcoholic steatohepatitis.
The senior investigator has no disclosures. One of the other dozen investigators is on the board of Abbott, and another advises Bristol-Myers Squibb, Gilead, Merck, Novartis, and Roche.
