Chronic Hepatitis C Virus Infection and the Risk for Diabetes

A Community-based Prospective Study

Yu-Ju Lin; Tzun-Wen G. Shaw; Hwai-I Yang; Sheng-Nan Lu; Chin-Lan Jen; Li-Yu Wang; Kang-Hsuan Wong; Soa-Yu Chan; Yong Yuan; Gilber L'Italien; Chien-Jen Chen; Mei-Hsuan Lee


Liver International. 2017;37(2):179-186. 

In This Article

Abstract and Introduction


Background: The association between hepatitis C virus (HCV) infection and the occurrence of type II diabetes remains controversial. Prospective studies are needed to assess its causal temporality.

Methods: A cohort of 21 559 adults enrolled from seven townships in Taiwan during 1991–1992 and followed till the end of 2010. Incident diabetes over a study time period from 2000 to 2010 was ascertained through computerized linkage with the National Health Insurance database and the National Death Certification profiles. Cox's proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Antibodies against HCV (anti-HCV) were tested for all participants, and serum HCV RNA levels were measured for anti-HCV seropositives.

Results: During 180 244 person-years of follow-up, there were 1917 incident diabetes cases recorded. The cumulative risk for diabetes was 10.9% for anti-HCV seronegatives and 16.7% for anti-HCV seropositives respectively. The HR for diabetes of anti-HCV seropositivity was 1.53 (95% CI: 1.29–1.81) compared with anti-HCV seronegatives after adjustment for risk predictors. The adjusted HRs were 1.63 (1.31–2.02) for anti-HCV seropositives with positive HCV RNA compared to anti-HCV seronegatives (P<.001).

Conclusion: Chronic HCV infection was associated with an increased risk for diabetes after adjustment for other risk predictors.


More than 185 million people are or have previously been infected with hepatitis C virus (HCV) worldwide.[1,2] Approximately 80% of individuals infected with HCV may progress to chronic infection, 20% of whom may develop cirrhosis within 25 years; 25% of the cirrhosis patients may subsequently progress to hepatocellular carcinoma. In addition to hepatic complications, there is accumulating evidence that patients with HCV infection have a predisposition for developing extrahepatic disorders.[3–5] The prevalence of type 2 diabetes mellitus (DM) in Asian populations has increased rapidly in recent decades, with the overall prevalence for adults of 3%–12%.[6] A large number of adults suffer from both HCV and DM and the association of these two major public health concerns has been a topic of several studies.

Most of the previous studies that examined the association between HCV infection and diabetes were hospital-based studies and enrolled clinical subjects with severe liver disease[7,8] and were vulnerable to ascertainment bias. Large population-based studies that evaluate the association between HCV infection and diabetes are rare. A well-known survey in the USA general population, National Health and Nutrition Examination Survey (NHANES), examined the relationship between HCV infection and DM in different time periods.[9–12] However, their findings were inconsistent in the different time periods. Their most recent report did not demonstrate an association of HCV infection with diabetes or with insulin resistance.[11] This well-conducted study concluded that elevated serum levels of alanine aminotransferase (ALT) and gamma glutamyl transferase were associated with diabetes or insulin resistance. The study highlighted the importance of adequately controlling for elevated liver enzymes in studies of the relationship of HCV with DM. They suggest that the HCV-infected population might also have higher rates of nonalcoholic steatohepatitis, a condition which has been shown to be associated with insulin resistance or diabetes.[13,14]

It is likely that the causal relationship between HCV infection and the development of DM cannot be elucidated clearly in cross-sectional studies.[7,9–12,15,16] This community-based follow-up study was conducted to evaluate the causation between HCV infection and the subsequent occurrence of diabetes.