HOUSTON — While it is recognized that patients with nonalcoholic fatty liver disease who also have Type 2 diabetes mellitus (DM) have a high risk of progression to hepatocellular carcinoma. Exactly what causes the higher risks remain unclear, however, according to a new study.
For the report in Hepatology, researchers from the Michael E. DeBakey VAMC and Baylor College of Medicine assembled a retrospective cohort of patients with NAFLD and DM diagnosed at 130 VA facilities between Jan. 1, 2004, and Dec. 31, 2008. Patients were followed from the date of NAFLD diagnosis to HCC, death, or Dec. 31, 2018.
Researchers focused on the effects of anti-DM medications, including metformin, insulin, sulfonylureas, as well as the influence of glycemic control, defined as the percentage of follow-up time with hemoglobin A1c lower than 7%, on the risk of HCC.
Ultimately, the study team identified 85,963 patients with NAFLD and DM. Of those, 524 patients developed HCC during a mean of 10.3 years of follow-up. Most common treatments were metformin monotherapy (19.7%), metformin-sulfonylureas (19.6%), insulin (9.3%) and sulfonylureas monotherapy (13.6%).
Results indicated that, compared with no medication, metformin was associated with 20% lower risk of HCC (HR, 0.80; 95% CI, 0.93-0.98). Insulin itself had no effect on HCC risk (HR, 1.02; 95% CI, 0.85-1.22; p = 0.85). Insulin in combination with other oral medications was associated with a 1.6 to 1.7-fold higher risk of HCC, however, according to the researchers, who added that adequate glycemic control was associated with a 31% lower risk of HCC (HR, 0.69; 95% CI, 0.62-0.78).
“In this large cohort of patients with NAFLD and DM, use of metformin was associated with a reduced risk of HCC, whereas use of combination therapy was associated with increased risk,” the authors concluded. “Glycemic control can serve as a biomarker for HCC risk stratification in patients with NAFLD and diabetes.”
- Kramer JR, Natarajan Y, Dai J, Yu X, Li L, El-Serag HB, Kanwal F. Effect of diabetes medications and glycemic control on risk of hepatocellular cancer in patients with nonalcoholic fatty liver disease. Hepatology. 2021 Nov 15. doi: 10.1002/hep.32244. Epub ahead of print. PMID: 34779535.
