Risk of HCC in Chronic HCV Patients With New Onset Diabetes

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Risk of HCC in Chronic HCV Patients With New Onset Diabetes

Abstract and Introduction

Abstract


Background The impact of diabetes for hepatocellular carcinoma (HCC) development in chronic hepatitis C (CHC) patients remains controversial.

Aim To investigate the risk of HCC in CHC patients who develop new onset diabetes.

Methods We conducted a nation-wide cohort study by using Taiwanese National Health Insurance Research Database, which comprised of data from >99% of entire population. Among randomly sampled one million enrollees, 6251 adult CHC patients were identified from 1997 to 2009. Diabetes was defined as new onset in the patient who was given the diagnosis in the years 1999–2009 but not in 1997–1998. The cohorts of CHC with new onset diabetes (n = 1100) and 1:1 ratio age-, gender-, and inception point (onset date of diabetes) matched nondiabetes (n = 1087) were followed up from the inception point until the 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 = 1.544, 95% CI = 1.000–2.387, modified log-rank test, P = 0.047) as compared to those without. After adjustment for age, gender, cirrhosis, hyperlipidaemia, CHC treatment, diabetes treatment, comorbidity index, obesity and statins therapy by Cox proportional hazard model, diabetes was still an independent predictor for HCC (hazard ratio (HR) = 1.906, 95% CI = 1.102–3.295, P = 0.021). The risk for HCC was increased in those who were 40–59 years old, independent of other variables (HR = 3.086, 95% CI = 1.045–9.112, P = 0.041), and after adjustment for competing mortality (modified log-rank test, P = 0.009).

Conclusion Chronic hepatitis C patients who develop diabetes are at an increased risk of hepatocellular carcinoma over time.

Introduction


Hepatitis C virus (HCV) infection is a global health problem, which infects about 170 million people in the world. The infection leads to chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Diabetes has been proposed as a risk factor for HCC in chronic hepatitis C (CHC) patients with or without cirrhosis and after eradication of HCV. Other studies disclose the nonsignificant risk of diabetes on HCC development in patients with CHC. Thus, the impact of diabetes for HCC development in CHC patients remains controversial. Furthermore, HCV infection causes insulin resistance (IR) and accelerates the development of diabetes in pre-disposed individuals. The temporal relationship between newly developed diabetes and HCC occurrence in CHC patients is far from clear.

We aimed to study the risk of HCC in CHC patients who develop diabetes as compare to those without diabetes. To evaluate the temporal association between diabetes and HCC requires a longitudinal CHC cohort to enroll patients with new onset diabetes prior to the emergence of HCC. In this large population-based cohort study, we utilised the National Health Insurance Research Database (NHIRD) in Taiwan to study the risk of HCC in adult CHC patients who develop diabetes during long-term follow-up.

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