Optimal glycaemic control reduces risk of HCC and liver-related mortality in patients with DM

24 Oct 2024 bởiNatalia Reoutova
Optimal glycaemic control reduces risk of HCC and liver-related mortality in patients with DM

A population-based study of 146,430 Hong Kong patients with diabetes mellitus (DM) reports that optimal vs suboptimal glycaemic control is associated with reduced risk of developing hepatocellular carcinoma (HCC) and liver-related mortality.

Although DM is a well-established risk factor for HCC, the relationship between glycaemic control, liver decompensation and liver-related mortality remains poorly defined. [Hepatology 2022;76:1880-1897] The present study assessed the independent effect of optimal glycaemic control (mean HbA1c <7 percent during 3 years after DM diagnosis) on the risk of HCC development while adjusting for demographic, clinical and medical covariates.

Of 146,430 patients (mean age, 61.4 years; men, 52.2 percent; mean BMI, 26.1 kg/m2) included in the study, 91.4 percent were on antidiabetic medication, while 71.0 percent were on statins. DM-related complications (including stroke, coronary heart disease and chronic kidney disease) were present in 13.8 percent of patients, and 5.4 percent had liver-related comorbidities (including chronic hepatitis B, chronic hepatitis C and cirrhosis). During the median follow-up of 7.0 years, 0.8 percent of patients developed HCC and 0.7 percent died of liver-related causes. [Aliment Pharmacol Ther 2024;doi:10.1111/apt.18254]

Over a maximum follow-up duration of 16 years, the cumulative incidence of HCC was 1.4 vs 1.7 percent in the optimal vs suboptimal glycaemic control group. “Optimal glycaemic control was associated with a 30 percent risk reduction of HCC development compared with suboptimal glycaemic control [subdistribution hazard ratio (SHR), 0.70; 95 percent CI, 0.61–0.79; p<0.001],” highlighted the researchers.

Using the optimal glycaemic control group as reference, the researchers identified a stepwise increased trend for HCC risk (ptrend<0.001), with SHR of 1.29 (95 percent CI, 1.11–1.49) for HbA1c 7.0–<8.0 percent, 1.67 (95 percent CI, 1.38–2.01) for HbA1c 8.0–<9.0 percent, and 1.71 (95 percent CI, 1.36–2.14) for HbA1c ≥9 percent.

The 16-year cumulative incidence of liver-related mortality was also significantly lower in the optimal vs suboptimal glycaemic control group (1.3 vs 1.7 percent; p<0.001). The risk of liver-related mortality was 30 percent lower in the former group (SHR, 0.70; 95 percent CI, 0.61–0.80; p<0.001). In addition, patients with optimal glycaemic control had a lower cumulative incidence and a 24 percent lower risk of liver decompensation than those with suboptimal glycaemic control (2.3 vs 2.7 percent; SHR, 0.76; 95 percent CI, 0.68–0.85; p<0.001).

The observed associations between glycaemic control and incident HCC and liver-related mortality were validated in most subgroups, regardless of demographic, clinical and medical covariates, and were consistent across all sensitivity analyses. The researchers noted that glycaemic control was a risk factor irrespective of viral hepatitis, which was highly prevalent in this Asian cohort.

The study also found positive associations between glycaemic variability and incidence of HCC and liver-related mortality irrespective of calculation method (standard deviation [SD], coefficient of variation [CV] or average successive variability [ASV]). Lower glycaemic variability (SD, CV or ASV <25 percent quantile) was associated with a 28–31 percent reduced risk of HCC development and a 35–39 percent reduced risk of liver-related mortality vs greater glycaemic variability (SD, CV or ASV ≥25 percent quantile).

“Both glycaemic control and glycaemic variability are independent risk factors [for HCC development and liver-related mortality], and [their optimization] should be considered as oncoprotective strategy against HCC in the general DM population,” concluded the researchers.