Non-alcoholic fatty liver disease also common in non-obese individuals
Recent findings from the Chinese University of Hong Kong (CUHK) show that one out of five non-obese individuals suffer from non-alcoholic fatty liver disease (NAFLD). Liver biopsy studies further reveal high rates of steatohepatitis and severe liver fibrosis in non-obese NAFLD patients.
Among 911 randomly selected Hong Kong citizens identified from the government census database, measurement of intrahepatic triglycerides and liver fibrosis by proton-magnetic resonance spectroscopy and transient elastography revealed NAFLD in 19.3 percent of non-obese individuals (ie, BMI <25 kg/m2; n=701) and 60.5 percent of obese individuals (ie, BMI ≥25 kg/m2; n=210). Liver biopsy from 307 patients with NAFLD showed steatohepatitis in 44 percent and severe liver fibrosis in 26 percent of non-obese individuals (n=72). [Am J Gastroenterol 2015;110:1306-1314; Hepatology 2017;65:54-64]
Among the risk factors of NAFLD identified for non-obese individuals are enlarged waist circumference, insulin resistance, higher ferritin levels, and the presence of PNPLA3 gene polymorphism.
“High ferritin levels may contribute to NAFLD through an increased generation of reactive oxygen species, which results in impaired hepatic lipid metabolism through oxidative stress and the production of pro-inflammatory factors,” explained principal investigator Professor Vincent Wong of the Division of Gastroenterology and Hepatology, Department of Medicine and Therapeutics, CUHK.
“Polymorphism of the PNPLA3 gene is an important factor for the development of fatty liver, which leads to impaired hepatic secretion of lipids,” he added.
The researchers also examined liver biopsy samples from patients with NAFLD (n=307) to further investigate histologic characteristics of NAFLD in non-obese patients. Among 72 non-obese patients, NAFLD activity scores were lower compared with obese patients (3.3 ± 1.3 vs 3.8 ± 1.2; p=0.019), mainly due to less steatosis (mean score, 1.7 ± 0.8 vs 2.0 ± 0.8; p=0.014) and lower rates of hepatocyte ballooning (60.9 vs 73.4 percent; p=0.045). Non-obese patients were also noted to have lower fibrosis stage as compared with obese patients (1.3 ± 1.5 vs 1.7 ± 1.4; p=0.004). [Hepatology 2017;65:54-64]
Multivariate analysis revealed that elevated serum triglyceride level was independently associated with higher NAFLD activity score (adjusted odds ratio [OR], 1.644; p=0.021), and elevated creatinine level was the only factor associated with advanced fibrosis (adjusted OR, 1.044; p=0.025).
“After an average follow-up of 49 months, adverse outcomes appeared to be less common in non-obese vs obese patients. These outcomes included death (0 vs 3 percent), cardiovascular events (4 vs 8 percent), liver cancer (0 vs 1 percent) and other cancers (1 vs 2 percent), but further studies should be done on the long-term prognosis of NAFLD in non-obese patients,” the researchers noted.
NAFLD is the most common chronic liver disease worldwide and affects 27 percent of the Hong Kong adult population. NAFLD is the third leading cause of liver cancer in the US. [Hepatology 2016;64:73-84]
“Our studies highlight the propensity of non-obese individuals to develop NAFLD, steatohepatitis and liver fibrosis. Proper assessment is needed for those with concurrent metabolic diseases,” said Wong.