Thiazolidinediones Use in Patients With Hepatitis B and Diabetes

Thiazolidinediones (TZDs) use was associated with a lower risk for liver-related events in patients with diabetes and chronic hepatitis B (CHB).

Thiazolidinediones (TZDs) use was associated with a lower risk for liver-related events in patients with diabetes and chronic hepatitis B (CHB), according to data published in the Journal of Viral Hepatitis.

Previous literature has demonstrated conflicting results of the link between receipt of different anti-diabetic medication and the development of hepatocellular carcinoma (HCC). The purpose of this study was to investigate the effect of TZD and glycemic control on the risks forHCC and hepatic events among patients with CHB and diabetes. To do so, researchers performed a retrospective cohort study using a territory-wide electronic healthcare database in Hong Kong.

Based on the use of any antidiabetic medication, hemoglobin A1c (HbA1c) ≥6.5%, fasting glucose ≥7 mmol/L in two measurements or ≥11.1 mmol/L in one measurement and/or diagnosis codes, 28,999 patients with CHB and diabetes were identified between 2000 and 2017. Among these patients, 3963 (13.7%) developed liver-related events at a median follow-up of 7.1 years (interquartile range, 3.7-11.8); 1153 patients received TDZ during follow-up. After adjustments for confounders were made, TZD use was associated with a reduced risk for liver-related events (adjusted hazard ratio [aHR] 0.46; 95% CI, 0.24-0.88; P = .019). Similar trends for both HCC (aHR, 0.57) and hepatic events (aHR, 0.35) were separately observed.

Compared with patients with baseline HbA1c of 6.5%, those with HbA1c ≥7% had an increased risk for liver-related events; this risk was further increased among the 5795 patients with HbA1c≥ 9% at baseline (aHR, 1.14; 95% CI, 1.04-1.26; P = .006).

The use of metformin (aHR, 0.81; 95% CI, 0.75-0.87; P< .001), statins (aHR, 0.80; 95% CI, 0.73-0.88; P< .001), aspirin/clopidogrel (aHR, 0.84; 95% CI, 0.77-0.92; P< .001), and angiotensin -converting-enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBS) (aHR, 0.86; 95% CI, 0.80-0.93; P< .001) were associated with lower risk for liver-related events, whereas the use of insulin (aHR, 1.48; 95% CI, 1.36-1.61; P< .001) and sulphonylureas (aHR, 1.19; 95% CI, 1.11-1.28; P< .001) were linked to an increased risk for liver-related events.

The study was limited by missing data and irregular intervals of laboratory measurement, which may have led to biases. Investigators noted though that these biases might be overcome by the large cohort size. Also, investigators were not able to correctly identify cirrhosis as physicians use different methods for diagnosis, which may affect diagnosing coding in computer databases. Therefore, it is possible that some patients who developed HCC might have undiagnosed cirrhosis. A composite endpoint that included HCC and hepatic events was used as the primary endpoint, which increased statistical power, but may have affected interpretations of results. Ascertainment bias might also have affected reliability of the study, due to inaccurate code entry. Investigators also had to exclude roughly 2,000 patients with HCC or hepatic events before or within the first 6 months of diabetes mellitus diagnosis and duration of diabetes mellitus was not evaluated as a risk for HCC. Finally, it is possible that other unmeasured factors such as hepatitis B virus genotype, smoking status and alcohol use may have confounded results.

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Investigators concluded that this work shows, “that TZD use is associated with a lower risk of HCC and hepatic events in diabetic patients with CHB, whereas excessively high HbA1c level is associated with an increased risk of HCC and hepatic events.” They also reported that TZD use, “showed a potentially stronger association with reduced risk of liver-related events than use of statins, aspirin/clopidogrel, and ACEIs/ARBs, and was comparable to metformin on the strength of association on reducing risk of liver-related events.”


Cheuk-Fung Yip T, Wai-Sung Wong V, Lik-Yuen Chang H, et al. Thiazolidinediones reduce the risk of hepatocellular carcinoma and hepatic events in diabetic patients with chronic hepatitis B [published online April 27 2020]. J Viral Hepat. doi:10.1111/jvh.13307