Risk of HCC in Chronic HBV Patients With New Onset Diabetes

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Risk of HCC in Chronic HBV Patients With New Onset Diabetes

Abstract and Introduction


Background Diabetes increases the risk of hepatocellular carcinoma (HCC), however, the time-relationship between hepatitis B virus and diabetes for the development of HCC remains unclear.

Aim To explore the risk of HCC in chronic hepatitis B patients with newly diagnosed diabetes.

Methods We conducted a nationwide cohort study by using Taiwanese National Health Insurance Research Database, which covers over 99% of entire population. Among randomly sampled one million enrollees, 14 523 chronic hepatitis B patients were diagnosed in years 1997–2009. We defined new onset diabetes as patients who were given the diagnosis in the years 1999–2009, but not in 1997–1998. The cohorts of chronic hepatitis B with new onset diabetes (n = 2099) and 1:1 ratio age-, gender- and inception point (onset date of diabetes)- matched nondiabetes (n = 2080) were followed up from the inception point until development of HCC, withdrawal from insurance or December 2009.

Results After adjustment for competing mortality, patients with new onset diabetes had a significantly higher cumulative incidence of HCC [relative risk = 1.628, 95% confidence interval (CI) = 1.114–2.378, modified log-rank test, P = 0.012] as compared to nondiabetes patients. After adjustment for age, gender, hyperlipidaemia, chronic hepatitis B treatment, statins therapy, cirrhosis, comorbidity index and obesity, diabetes was still an independent predictor for HCC (hazard ratio = 1.798, 95% CI = 1.194–2.707, P = 0.005).

Conclusion Chronic hepatitis B patients with newly diagnosed diabetes have an increased risk of hepatocellular carcinoma over time.


Hepatitis B virus (HBV) infection is one of the major global health issues, which can cause both acute and chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Over 350 million people are chronic carriers of HBV and more than 780 000 people die of hepatitis B every year. Diabetes is also a worldwide health problem. An estimated 382 million people have diabetes worldwide. In 2012, diabetes resulted in 1.5 million deaths and it became the 8th leading cause of death. Studies had shown that diabetes increased the risk of HCC. Although several studies disclosed the association between diabetes and HCC in chronic hepatitis B patients, the time-relationship between HBV and diabetes for HCC development remains unclear.

We aimed to study the risk of HCC in chronic hepatitis B patients who developed new onset diabetes as compare to those without. To evaluate this, temporal association requires a longitudinal chronic hepatitis B cohort to enrol patients with newly diagnosed diabetes prior to the emergence of HCC. By utilising the National Health Insurance Research Database (NHIRD) in Taiwan, we investigated the risk of HCC in adult chronic hepatitis B patients who developed diabetes during long-term follow-up.

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