Hepatitis B virus infection and fatty liver in the general population Vincent Wai-Sun Wong 1,2 , Grace Lai-Hung Wong 1,2 , Winnie Chiu-Wing Chu 1,3,⇑ , Angel Mei-Ling Chim 1,2 , Arlinking Ong 1,2,4 , David Ka-Wai Yeung 5 , Karen Kar-Lum Yiu 1,2 , Shirley Ho-Ting Chu 1,2 , Hoi-Yun Chan 1,2 , Jean Woo 2 , Francis Ka-Leung Chan 1,2 , Henry Lik-Yuen Chan 1,2,⇑ 1 Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong; 2 Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; 3 Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Hong Kong; 4 Department of Medicine, Section of Gastroenterology, University of Santo Tomas Hospital, Espana Manila, Philippines; 5 Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong Background & Aims: In animal studies, expression of hepatitis B virus (HBV) proteins causes hepatic steatosis. We aimed to study the prevalence of fatty liver in people with and without HBV infection in the general population. Methods: We performed a cross-sectional population study in Hong Kong Chinese. Intrahepatic triglyceride content (IHTG) was measured by proton-magnetic resonance spectroscopy. Results: One thousand and thirteen subjects (91 HBV patients and 922 controls) were recruited. The median IHTG was 1.3% (0.2–33.3) in HBV patients and 2.1% (0–44.2) in controls (p <0.001). Excluding subjects with significant alcohol consumption, the prevalence of nonalcoholic fatty liver disease was 13.5% (95% confidence interval [CI] 6.4%, 20.6%) in HBV patients and 28.3% (95% CI 25.3%, 31.2%) in controls (p = 0.003). The fatty liver prev- alence differed in HBV patients and controls aged 40–59 years but was similar in those aged 60 years or above. After adjusting for demographic and metabolic factors, HBV infection remained an independent factor associated with lower risk of fatty liver (adjusted odds ratio 0.42; 95% CI 0.20, 0.88; p = 0.022). HBV patients also had a lower prevalence of metabolic syndrome (11.0% vs. 20.2%; p = 0.034), but the difference was mainly attrib- uted to lower triglyceride levels. Among HBV patients, viral geno- types, HBV DNA level and hepatitis B e antigen status were not associated with fatty liver. Conclusions: HBV infection is associated with a lower prevalence of fatty liver, hypertriglyceridemia and metabolic syndrome. Viral replication may affect lipid metabolism and this warrants further studies. Ó 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. Introduction Chronic hepatitis B is estimated to affect more than 350 million people worldwide and is one of the leading causes of cirrhosis and hepatocellular carcinoma [1,2]. Nonalcoholic fatty liver dis- ease (NAFLD) is another common chronic liver disease that affects 20–40% of the general population [3,4]. NAFLD is strongly associated with obesity and metabolic syndrome [5–8], and may result in cirrhosis and hepatocellular carcinoma [9,10]. Since both chronic hepatitis B and NAFLD are common, many patients suffer from both conditions. However, the interaction between chronic hepatitis B and NAFLD is unclear. In a large cross-sectional study using transient elastography examination, chronic hepatitis B patients with metabolic syn- drome were more likely to have advanced fibrosis and cirrhosis than those without [11]. In addition, type 2 diabetes and obesity have been found to be associated with hepatocellular carcinoma development in patients with viral hepatitis [12,13]. On the other hand, several large histological series failed to demonstrate any association between hepatic steatosis and fibrosis in patients with chronic hepatitis B [14–16]. Hepatic steatosis is associated with metabolic but not viral factors such as viral load and geno- type [16–22]. Since most histological cohorts came from special- ized centers, it is uncertain if the observation may be influenced by a selection bias. For example, patients undergoing liver biop- sies are more likely to have abnormal liver function tests and radiological evidence of cirrhosis [23]. Whether hepatitis B virus infection increases the risk of fatty liver is another area of controversy. In transgenic mouse and cell line models, hepatitis B X (HBx) protein expression results in hepatic steatosis and activation of the nuclear factor kappaB Journal of Hepatology 2012 vol. 56 j 533–540 Keywords: Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Obes ity; Diabetes mellitus; Hypertriglyceridemia; Cross-sectional study. Received 27 May 2011; received in revised form 23 August 2011; accepted 21 September 2011; available online 23 October 2011 ⇑ Corresponding authors. Addresses: Department of Imaging and Interventional Radiology, Prince of Wales Hospital, 30–32 Ngan Shing Street, Shatin, Hong Kong. Tel.: +852 26322299; fax: +852 26360012 (W.C.-W. Chu), Department of Medicine and Therapeutics, Prince of Wales Hospital, 30–32 Ngan Shing Street, Shatin, Hong Kong. Tel.: +852 26323593; fax: +852 26373852 (H.L.-Y. Chan). E-mail addresses: winnie@med.cuhk.edu.hk (W.C.-W. Chu), hlychan@cuhk.edu.hk (H.L.-Y. Chan). Abbreviations: Anti-HBe, antibody against hepatitis B e antigen; CI, confidence interval; HBeAg, hepatitis B e antigen; HBV, hepatitis B virus; HBx, hepatitis B X; NAFLD, nonalcoholic fatty liver disease; 1 H-MRS, proton-magnetic resonance spectroscopy. Research Article