An international multicenter study found that patients with chronic hepatitis B and coexisting metabolic diseases—such as obesity, hypertension, dyslipidemia, and type 2 diabetes—were less likely to achieve optimal treatment responses with first-line nucleos(t)ide analogues compared with those without metabolic disease.
The analysis included 4,507 treatment-naïve patients with chronic hepatitis B (CHB) from 32 centers across seven countries or regions, followed for a median of about 4 years. More than half (54.8%) had at least one metabolic disease at baseline. Obesity was the most common (61.8%), followed by hypertension (38.1%), dyslipidemia (32.3%), and type 2 diabetes (21.3%).
Using propensity-score matching to balance factors such as age, sex, viral load, and liver status, researchers compared 893 matched pairs. Patients with metabolic disease had lower 5-year biochemical response (BR) rates—defined as alanine aminotransferase (ALT) normalization—than those without metabolic disease (91.3% vs 95.8%). Complete response (CR), defined as ALT normalization plus undetectable hepatitis B virus (HBV) DNA, was also lower (81.8% vs 87.4%).
Response rates declined further with increasing numbers of metabolic conditions. Patients with three or more metabolic diseases had the lowest rates—83.9% for BR and 67.0% for CR. Virologic response and hepatitis B e antigen seroconversion rates were similar between groups regardless of metabolic status.
Obesity and dyslipidemia were each linked to reduced likelihood of BR. Diabetes was associated with an increased risk of hepatocellular carcinoma (HCC).
The study also examined the relationship between delayed BR and HCC risk. Patients who failed to achieve BR within 36 months of therapy initiation had more than double the risk of developing HCC compared with those who achieved BR in that timeframe. This association persisted even in patients without metabolic disease or metabolic dysfunction–associated steatotic liver disease (MASLD).
Hepatic steatosis alone was not associated with reduced BR or CR unless metabolic diseases were also present. However, steatosis alone correlated with higher hepatitis B surface antigen loss. MASLD was associated with lower BR, CR, and virologic response rates.
"Over half of real-world CHB patients have at least one metabolic disease,” said Mindie H. Nguyen, MD, MAS, professor of medicine in the Division of Gastroenterology and Hepatology at Stanford University Medical Center, and a study author. “The presence of metabolic diseases was significantly and independently associated with lower biochemical response (BR) and complete response (CR) in a dose-dependent manner with decreasing BR and CR with an increasing number of metabolic diseases.”
The retrospective design introduces potential bias, and most participants were of Asian ethnicity, which may limit generalizability. The severity and treatment status of metabolic diseases were not evaluated, and diagnoses relied on medical records, which may have missed undiagnosed cases. Medication adherence was not assessed. In addition, the relatively small number of HCC cases limits the strength of the observed association between delayed BR and HCC, which requires further confirmation.
Full disclosures can be found in the published study.
Source: eClinical Medicine