Hepatitis B and C virus infection and diabetes mellitus: A cohort study

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Hepatitis B and C virus infection and diabetes mellitus: A cohort study

Hepatitis B and C virus infection and diabetes mellitus: A cohort study
Yun Soo Hong, Yoosoo Chang, Seungho Ryu, Miguel Cainzos-Achirica, Min-Jung Kwon, Yiyi Zhang, Yuni Choi, Jiin Ahn, Sanjay Rampal, Di Zhao, Roberto Pastor-Barriuso, Mariana Lazo, Hocheol Shin, Juhee Cho & Eliseo Guallar

doi:10.1038/s41598-017-04206-6

Received: 02 February 2017
Accepted: 10 May 2017
Published online:04 2017

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Abstract
The role of hepatitis virus infection in glucose homeostasis is uncertain. We examined the associations between hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the development of diabetes in a cohort (N = 439,708) of asymptomatic participants in health screening examinations. In cross-sectional analyses, the multivariable-adjusted odds ratio for prevalent diabetes comparing hepatitis B surface antigen (HBsAg) (+) to HBsAg (−) participants was 1.17 (95% CI 1.06–1.31; P = 0.003). The corresponding odds ratio comparing hepatitis C antibodies (HCV Ab) (+) to HCV Ab (−) participants was 1.43 (95% CI 1.01–2.02, P = 0.043). In prospective analyses, the multivariable-adjusted hazard ratio for incident diabetes comparing HBsAg (+) to HbsAg (−) participants was 1.23 (95% CI 1.08–1.41; P = 0.007). The number of incident cases of diabetes among HCV Ab (+) participants (10 cases) was too small to reliably estimate the prospective association between HCV infection and diabetes. In this large population at low risk of diabetes, HBV and HCV infections were associated with diabetes prevalence and HBV infection with the risk of incident diabetes. Our studies add evidence suggesting that diabetes is an additional metabolic complication of HBV and HCV infection.

Introduction
Chronic viral hepatic infections are a major threat to public health worldwide. Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) are the leading causes of cirrhosis and hepatocellular carcinoma, two conditions with increasing mortality and burden of disease especially in the developing countries1, 2. As the liver has a key role in glucose metabolism and adequate liver function is essential to maintain glucose homeostasis3, 4, diabetes may be a complication of end-stage liver disease, especially in patients with chronic HCV infection4,5,6,7. Since diabetes is another major concern in public health, it is very important to establish if chronic viral hepatitis is associated with an increased risk of diabetes prior to the development of end-stage liver disease.

The association between positive serology for hepatitis B surface antigen (HBsAg) and incident diabetes has been studied in only a few longitudinal studies5, 8, 9, that found no significant associations. Cross-sectional studies have also shown no association between positive serology for HBsAg and diabetes10, 11, although the number of participants in these studies was small and they had varying degrees of HBV-related liver disease. On the other hand, the presence of HCV antibodies (HCV Ab) appears to increase the risk of both incident and prevalent diabetes6, 7, 10,11,12,13,14, although many of these studies were not prospective6, 7, 11, 14, had small sample sizes7, 12, 13, or included cases with liver cirrhosis which, by itself, can increase the risk of diabetes14. We thus examined the prospective association between HBsAg (+) or HCV Ab (+) and incident diabetes in a large cohort of asymptomatic subjects who participated in health screening examinations. In addition to the prospective associations, we also evaluated the cross-sectional associations of hepatitis virus infection and prevalent diabetes at baseline for comparability with previous studies.

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