Impact of Cardiometabolic Risk Factors Control on Cardiovascular-Kidney-Metabolic Axis in Chronic Hepatitis B

The impact of cardiometabolic risk factors (CMRFs) on the cardiovascular-kidney-metabolic (CKM) axis in chronic hepatitis B (CHB) remains poorly defined.

We conducted a prospective analysis enrolling patients with CHB who were on nucleos(t)ide analogues (NUCs). CMRFs were defined as per established criteria; poorly-controlled CMRFs were defined with specific cut-offs measured across 5 years. Study outcomes include fibrosis progression (liver stiffness [LS] increase by ≥ 20%), liver-related events (LREs), chronic kidney disease (CKD) progression, major adverse cardiovascular events (MACE), and all-cause mortality.

A total of 714 NUC-treated patients (median age: 61.0 [54.5-66.7] years; 69.6% male; 90.5% undetectable HBV DNA, median NUCs duration of 14.1 [11.3-16.5] years) were followed up for 9.7 (7.2-10.2) years. LREs occurred in 112 (15.7%) patients, with annual incidence rate of 1.62 events per 100 person-years. All-cause mortality was observed in 86 (12%) patients, including 47 (6.6%) liver-related mortality. The number or types of CMRFs did not display a linear positive relationship with adverse clinical outcomes. The presence of ≥ 1 poorly controlled CMRFs is independently associated with LREs (aHR: 2.001, 95% CI: 1.350-2.965), MACE (aHR: 1.042, 95% CI: 1.030-1.081), and all-cause mortality (aHR: 2.082, 95% CI: 1.006-4.310), whereas patients having ≥ 2 and ≥ 3 poorly controlled CMRFs are independently associated with CKD progression (aOR: 1.887, 95% CI: 1.115-3.221) and fibrosis progression (aOR: 1.624, 95% CI: 1.164-2.266), respectively. The results remain robust in patients without advanced fibrosis (LS ≤ 10 kPa) at baseline.

Active optimization of CMRFs should be an integral component of CHB management in addition to NUCs therapy.