Impact of Metabolic Diseases on Nucleos(t)ide Analogue Therapy in CHB: A Multi-centre Study

Metabolic conditions on treatment outcomes in CHB patients

• With the global burden of metabolic diseases on the rise, their influence on chronic hepatitis B (CHB) patients has become increasingly significant.

• This study investigates the impact of metabolic conditions on treatment outcomes in CHB patients receiving first-line nucleos(t)ide analogues (NAs) therapy, drawing on data from an international consortium of CHB patients.

Study Design and Propensity-Score Matched Analysis

• This study compared biochemical response (BR), virologic response (VR), and complete response (CR) between treatment-naïve chronic hepatitis B (CHB) patients with and without metabolic diseases (diabetes, obesity, dyslipidemia, and hypertension) who initiated nucleos(t)ide analogues (NAs) therapy.

• Data were collected from 32 centers across seven countries/regions (United States, Mainland China, Japan, Korea, Singapore, Argentina, and Taiwan).

• Patients with hepatocellular carcinoma (HCC), viral co-infections, or less than 6 months of follow-up were excluded.

• Propensity-score matching (PSM) was used to balance baseline characteristics, including sex, age, HBeAg status, baseline HBV DNA, platelets, albumin, total bilirubin, alanine transaminase (ALT) levels, ethnicity, alcohol intake, cirrhosis, fatty liver, and type of NA therapy (entecavir, tenofovir DF, or AF), between the groups.

Patient Characteristics and Impact of Metabolic Diseases on Outcomes

• A total of 4,507 eligible patients were analyzed, with a majority being male (62.9%) and of Asian ethnicity (97.4%), and a mean age of 50.7 years. More than half of the patients (54.8%) had at least one metabolic disease. Among those with metabolic disease, 60.8% had one metabolic condition, 27.3% had two, and 11.9% had three or more metabolic diseases.

• Patients with metabolic diseases were older on average (52.8 ± 12.6 years vs. 48.1 ± 12.7 years) and more frequently male (58.3% vs. 41.7%) compared to those without metabolic diseases, with both comparisons showing statistical significance (P < 0.001). After propensity score matching (PSM), relevant characteristics between the two groups were balanced.

• In the PSM cohort, patients with metabolic disease had significantly lower cumulative 5-year biochemical response (BR) rates (91.3% vs. 95.8%; P < 0.001) and clinical response (CR) rates (81.8% vs. 87.4%; P = 0.008) compared to patients without metabolic diseases. However, virological response (VR) rates were similar between the groups (93.5% vs. 94.1%; P = 0.647).

• Overall, patients with metabolic diseases were less likely to achieve BR (adjusted hazard ratio [aHR]: 0.73, 95% CI: 0.65–0.82, P < 0.001) and CR (aHR: 0.79, 95% CI: 0.69–0.91, P = 0.001). Among those with three or more metabolic diseases, the likelihood of achieving BR (aHR: 0.55, 95% CI: 0.41–0.73, P < 0.001) and CR (aHR: 0.53, 95% CI: 0.38–0.76, P < 0.001) was the lowest.

Key Insight

• More than half of CHB patients were found to have at least one metabolic disease, which was significantly associated with reduced biochemical and complete response rates.

• The impact was cumulative, with a greater number of metabolic conditions correlating with poorer treatment outcomes.

• These findings emphasize the critical need to account for metabolic diseases in the management and monitoring of CHB patients undergoing nucleos(t)ide analogues (NA) therapy.

By - Eeshan Aggarwal

Reference: Hepatology. Volume 80, Issue S1. Abstract Supplement for The Liver Meeting by the American Association for the Study of Liver Diseases (AASLD), November 15-19, 2024, San Diego, CA.