High glycaemic burden associated with HCC development and fibrosis progression in patients with CHB + T2D

High glycaemic burden is associated with hepatocellular carcinoma (HCC) development and fibrosis progression in patients with chronic hepatitis B (CHB) and type 2 diabetes (T2D) (CHB + T2D), researchers from the University of Hong Kong (HKU) have reported.

The findings suggest that glycaemic control is a modifiable risk factor for hepatic complications in patients with CHB + T2D. “For those living with hepatitis B, good diabetes control also protects the liver,” said co-corresponding author, Professor Walter Seto of the Department of Medicine, HKU.

In this study, the researchers analyzed data from a prospective transient elastography (TE) database of Chinese adults with CHB who had HBsAg positivity for >6 months. Patients with concomitant T2D were those with fasting glucose (FG) ≥7.0 mmol/L, HbA_1c ≥6.5 percent or on antidiabetic medications. [Hepatology 2022;doi:10.1002/hep.32716]

The study cohort included 2,330 patients with CHB (mean age, 54.6 years; male, 55.5 percent; on antivirals, 57.9 percent), 671 (28.8 percent) of whom also had T2D (mean age, 61.9; male, 65.6 percent; on antiviral, 62.9 percent). Among patients with CHB + T2D, the mean duration of T2D was 7.2 years, the mean HbA_1c was 7.2 percent, and the proportion of time reaching HbA_1c target (HbA_1c-TRT) was 88 percent. Most patients with CHB + T2D (93.4 percent) received ≥1 antidiabetic medication.

At a median follow-up of 5.9 years, the overall annual incidence of HCC was 0.69 percent. In the overall cohort, T2D was independently associated with an increased risk of HCC (hazard ratio [HR], 2.080; 95 percent confidence interval [CI], 1.343–3.22; p=0.001). CHB patients with T2D had a higher cumulative HCC incidence vs those without T2D (4.92 percent vs 3.74 percent; log-rank p=0.001).

After propensity–score matching (CHB + T2D, n=637; CHB without T2D, n=1,274), multivariable analysis showed that HCC risk was predicted by T2D-specific factors, including duration of T2D (HR, 1.107; 95 percent CI, 1.023–1.198), mean HbA_1c (HR, 1.851; 95 percent CI, 1.026–3.339) and HbA_1c-TRT (HR, 0.978; 95 percent CI, 0.957–0.999).

However, in univariable analysis, there was no significant association of HCC development with HbA_1c variability (standard deviation of serial HbA_1c values [HbA_1c-SD]: HR, 1.373; 95 percent CI, 0.821–2.297; ratio of SD to mean HbA_1c: HR, 1.026; 95 percent CI, 0.983–1.071; adjusted HbA_1c-SD: HR, 1.057; 95 percent CI, 0.845–2.687), FG (HR, 1.084; 95 percent CI, 0.929–1.265) and baseline HbA_1c (HR, 1.248; 95 percent CI, 0.942–1.654).

Fibrosis progression occurred in 537 of 1,399 (38.4 percent) patients with CHB and valid 3-year TE, and 373 of 671 (55.6 percent) patients with CHB + T2D and paired TE. T2D was also an independent factor for fibrosis progression (odds ratio [OR], 4.305; 95 percent CI, 3.416–5.424, p<0.001).

Multivariable analysis revealed that duration of T2D (OR, 1.044; 95 percent CI, 1.005–1.085), mean HbA_1c (OR, 1.220; 95 percent CI, 1.005–1.481), HbA_1c-TRT (OR, 0.993; 95 percent CI, 0.988–0.999), baseline FG (OR, 1.109; 95 percent CI, 1.010–1.218) and baseline HbA_1c (OR, 1.247; 95 percent CI, 1.050–1.480) were associated with the risk of fibrosis progression at 3 years.