Journal
HEPATOLOGY
Volume 75, Issue 6, Pages 1420-1428Publisher
WILEY
DOI: 10.1002/hep.32244
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Funding
- Cancer Prevention and Research Institute of Texas [RP150587]
- National Cancer Institute [U01 CA230997-01, R01 CA256977]
- US Department of Veterans Affairs HSR&D Center for Innovations in Quality, Effectiveness and Safety [CIN 13-413]
- Michael E. DeBakey VA Medical Center
- Center for Gastrointestinal Development, Infection and Injury [NIDDK P30 DK 56338]
- [R01DK118079]
- [P30CA016672]
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Patients with NAFLD and diabetes have a high risk of developing HCC. The study found that the use of metformin was associated with a reduced risk of developing HCC, while combination therapy was associated with an increased risk. Glycemic control can be a useful biomarker for stratifying HCC risk in these patients.
Background and Aims In patients with NAFLD, those with type 2 diabetes mellitus (DM) have a high risk of progression to HCC. However, the determinants of HCC risk in these patients remain unclear. Approach and Results We assembled a retrospective cohort of patients with NAFLD and DM diagnosed at 130 facilities in the Veterans Administration between 1/1/2004 and 12/31/2008. We followed patients from the date of NAFLD diagnosis to HCC, death, or 12/31/2018. We used landmark Cox proportional hazards models to determine the effects of anti-DM medications (metformin, insulin, sulfonylureas) and glycemic control (percent of follow-up time with hemoglobin A1c < 7%) on the risk of HCC while adjusting 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. 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 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 higher 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, use of metformin was associated with a reduced risk of HCC, whereas use of combination therapy was associated with increased risk. Glycemic control can serve as a biomarker for HCC risk stratification in patients with NAFLD and diabetes.
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