Higher Mortality in Lean, Not Obese, Patients With Fatty Liver Disease

Long-term mortality rates are higher in lean patients with nonalcoholic fatty liver disease (NAFLD) than in their obese NAFLD counterparts, according to Paul Angulo, MD, Section Chief of the Hepatology Division of Digestive Diseases and Nutrition at the University of Kentucky Medical Center in Lexington.

Dr Angulo reported on the findings of a multicenter, 1090-patient, retrospective study of a 20-year interval that produced results he finds “surprising” at Digestive Disease Week 2014 in Chicago.

We’re all accustomed to hearing gloomy predictions for the obese cohort, especially when they have an obesity-related comorbidity like NAFLD-and this study showed the opposite. It doesn’t address what might account for the results-lean persons with NAFLD appear to acquire the condition for completely different physiologic reasons than the obese. And because those reasons must be associated with higher risk, the investigators correctly note that much more study of this population is warranted.

In this study, lean patients with NAFLD (body mass index [BMI], lower than 25 kg/m²; mean BMI, 23 kg/m²) were compared with non-lean patients with NAFLD (BMI, 25 kg/m² or higher; mean BMI, 33 kg/m²). The mean age of the 1090 patients was 46.3±13.1 years; 125 (11.5%) were lean, and 965 (88.5%) were non-lean.

Among the 483 patients with at least 5 years of follow-up (those diagnosed in 2005 or later), the lean cohort experienced a 2-fold overall (all-cause) mortality rate during the observation period, despite maintaining a healthier weight (statistical adjustment was made for potential differences in age, sex, race, diabetes mellitus (DM), hypertension, alanine aminotransferase (ALT) level, and fibrosis stage.

Members of the lean NAFLD population were more likely to be male and non-Caucasian. They had lower rates of chronic conditions, such as DM and hypertension. The lean group had significantly less insulin resistance as well as lower ALT levels, which ordinarily would suggest less liver risk. And while lean patients had a lower degree of fatty deposits on the liver and less advanced fibrosis, these patients showed more severe inflammation of the liver.

“About 30% of the US population suffers from NAFLD, and the prevalence of this condition is increasing,” said Dr Angulo. “Although we often associate fatty liver disease with obese patients, these results suggest that possible signs of liver disease secondary to NAFLD in lean patients should be taken very seriously.”

Because this study looked at all-cause mortality, the investigators could only speculate on the likely reasons for excess mortality, suggesting cardiovascular, malignancy, or liver-related causes in this metabolically unique population. Dr Angulo and his team plan to expand on their research into this patient population by examining data beyond BMI, including fat distribution pattern and differences in cell signaling proteins, such as cytokine and adipokine profiles.