PALO ALTO, CA — Chronic hepatitis B patients who have two or more metabolic diseases have a significantly higher risk of cirrhosis, overall death and non-liver-related death, but those who have diabetes as a single metabolic disease are more likely to suffer a range of adverse outcomes, including cirrhosis, hepatocellular carcinoma (HCC), overall, liver-related and non-liver-related death, according to a new study.
“Given the rise of metabolic diseases, we investigated their long-term impact in chronic hepatitis B (CHB) patients receiving nucleos(t)ide analogue (NA),” wrote the Stanford University-led international researchers, including participation from the Palo Alto, CA, Veterans Healthcare System.
For the report in Clinical & Molecular Hepatology, the study team analyzed data from CHB patients who initiated NAs from 30 centers (7 countries/regions). Patient characteristics with and without metabolic disease (diabetes, obesity, dyslipidemia, and hypertension) were balanced via propensity-score matching (PSM) to evaluate adverse liver events and mortality.
Overall, the study included 4,500 CHB patients—54.6% with one or more metabolic disease). The researchers created 909 pairs of patients with balanced characteristics.
Results indicated that, when stratified by the number of metabolic disease, only patients with two or more metabolic diseases had increased cumulative incidence of cirrhosis and overall death but not HCC or cause-specific death.
Those with diabetes, however, regardless of the presence or number of other metabolic diseases, had significantly higher cumulative incidence of all outcomes: cirrhosis (P=0.009), HCC (P=0.023), overall, liver-related and non-liver-related death (P<0.001, P=0.026 and P<0.001, respectively).
Cox regression analysis suggested that having ≥2 metabolic diseases was associated with cirrhosis, overall death and non-liver-related death but not HCC and liver-related death, while diabetes was significantly associated with higher risk of all outcomes: cirrhosis (HR=3.75, P=0.004), HCC (HR=2.02, P=0.020), 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).
“Having ≥2 metabolic diseases was associated with significantly 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, overall, liver-related and non-liver-related death,” the authors wrote.
- Huang R, Jun DW, Toyoda H, Hsu YC, et. Al. Impact of components of metabolic syndrome on long-term outcomes of CHB with nucleos(t)ide analogue treatment. Clin Mol Hepatol. 2025 Mar 17. doi: 10.3350/cmh.2024.1070. Epub ahead of print. PMID: 40091278.
