Impacts of metabolic syndrome diseases on long-term outcomes of chronic hepatitis B patients treated with nucleos(t)ide analogues

Clin Mol Hepatol. 2025 Jul;31(3):1003-1017. doi: 10.3350/cmh.2024.1070. Epub 2025 Mar 17.

Abstract

Background/aims: Given the increase in prevalence of metabolic diseases, we investigated their long-term impacts on the outcomes of chronic hepatitis B (CHB) patients receiving nucleos(t)ide analogue (NA) treatment.

Methods: We analyzed data from CHB patients for whom initiated NA treatment from 30 centers. We balanced patient characteristics with and without metabolic disease (diabetes, obesity, dyslipidemia, and hypertension) via propensity-score matching (PSM) to evaluate adverse outcomes.

Results: The study included 4,500 patients. PSM yielded 909 pairs of patients with balanced characteristics. When stratified by the number of metabolic diseases, only patients with ≥2 metabolic diseases had an increased cumulative incidence of cirrhosis and overall death. However, when stratified by the presence of diabetes (regardless of the presence or number of other metabolic diseases), patients with diabetes (versus those without) had a significantly higher cumulative incidence of all outcomes: cirrhosis (P=0.009), hepatocellular carcinoma (HCC, P=0.023), and overall, liver-related, and non-liver-related death (P<0.001, P=0.026 and P<0.001, respectively). Having ≥2 metabolic diseases was associated with cirrhosis, overall death, and non-liver-related death but not HCC or liver-related death, while diabetes was significantly associated with a higher risk of all outcomes: cirrhosis (hazard ratio [HR]=3.75, P=0.004), HCC (HR=2.02, P=0.020), and overall, liver-related, and non-liver-related death (HR=2.53, P<0.001; HR=2.65, P=0.016; HR=2.38, P<0.001).

Conclusion: Having two or more metabolic diseases was associated with a higher risk of cirrhosis, overall death, and non-liver-related death, but having diabetes as a single metabolic disease was significantly associated with all adverse outcomes including cirrhosis, HCC, and overall, liver-related, and non-liver-related death.

Keywords: Chronic hepatitis B; Death; Hepatocellular carcinoma; Metabolic diseases; Nucleos(t)ide analogues.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents* / therapeutic use
  • Carcinoma, Hepatocellular / complications
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / etiology
  • Diabetes Mellitus
  • Female
  • Hepatitis B, Chronic* / complications
  • Hepatitis B, Chronic* / drug therapy
  • Hepatitis B, Chronic* / mortality
  • Humans
  • Incidence
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / epidemiology
  • Liver Cirrhosis / etiology
  • Liver Neoplasms / complications
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / etiology
  • Male
  • Metabolic Syndrome* / complications
  • Middle Aged
  • Nucleosides* / therapeutic use
  • Propensity Score
  • Proportional Hazards Models
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Antiviral Agents
  • Nucleosides