Highlights This retrospective cohort study analyzed the risk of hepatocellular cancer (HCC) in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (DM). Patients were evaluated with respect to antidiabetic treatments and other factors. More than 85,000 veterans were identified between 2004 and 2008 and followed until HCC diagnosis, death, or the end of 2018. Metformin use was associated with a 20% reduction in HCC risk, while insulin use in combination with other oral medications was associated with a 1.6- to 1.7-fold increase in HCC risk. . Additionally, adequate glucose control was associated with a 31% lower risk of HCC. Glycemic control can be used for HCC risk stratification in patients with NAFLD and DM. |
Background and objectives
In patients with nonalcoholic fatty liver disease (NAFLD), those with type 2 diabetes mellitus (DM) are at high risk of progression to hepatocellular cancer (HCC). However, the determinants of HCC risk in these patients remain unclear.
Results
We assembled a retrospective cohort of patients with NAFLD and DM diagnosed at 130 Veterans Administration facilities between 1/1/2004 and 12/31/2008. We followed patients from the date of NAFLD diagnosis until HCC, death, or 12/31/2018.
We used Cox proportional hazards models to determine the effects of anti-DM medications (metformin, insulin, sulfonylureas) and glycemic control (percentage of follow-up time with hemoglobin A1c < 7%) on the risk of HCC while adjusts for demographics and other metabolic traits (hypertension, obesity, dyslipidemia).
We identified 85,963 patients with NAFLD and DM. In total, 524 patients developed HCC during a mean of 10.3 years of follow-up.
The most common treatments were metformin monotherapy (19.7%), metformin-sulfonylureas (19.6%), insulin (9.3%), and sulfonylureas monotherapy (13.6%).
Compared with no medication , metformin was associated with a 20% lower risk of HCC (HR, 0.80; 95% CI, 0.93-0.98).
Insulin 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 increased risk of HCC .
Adequate glycemic control was associated with a 31% lower risk of HCC (HR, 0.69; 95% CI, 0.62-0.78).
Conclusions
- In this large cohort of patients with NAFLD and DM, metformin use was associated with a reduced risk of HCC, while use of combination therapy was associated with an increased risk .
- Glycemic control may serve as a biomarker for HCC risk stratification in patients with NAFLD and diabetes.
