Prevalence and Risk Factors of Elevated Alanine Aminotransferase (ALT) in 2382 Treatment‐naïve HBV/HDV Co‐Infected Patients

BACKGROUND: Chronic hepatitis D (CHD) causes severe chronic hepatitis. Knowledge is limited about factors correlating with ALT in treatment-naïve patients with CHD. This study analysed the pattern and determinants of ALT elevation in a large cohort of patients with CHD, including young adults, compared to propensity score-matched (PSM) patients with chronic hepatitis B (CHB). METHODS: We identified 2382 treatment-naïve HBsAg+ adults with CHD (HDV RNA positive) and 1553 with CHB attending a liver center in Mongolia during 2015-2023. The correlation between ALT levels, virological, biochemical, and fibrosis parameters was assessed using Spearman coefficient (rho). Logistic regression analysis was used to identify determinants of elevated ALT in 1371 PSM pairs with CHD and CHB matched on age, sex, metabolic factors, and date of initial test. RESULTS: In CHD, 78.5% of patients had ALT elevation, with the highest prevalence in the 18-20 years group (n = 219, 84.5%). This age group displayed 8.2-adjusted odds ratio (aOR) for elevated ALT, 2.7-aOR for elevated GGT, and 4.5-aOR of cirrhosis than matched CHB group (all p < 0.05). In CHD, ALT correlated weakly with HDV RNA (rho = 0.23) and liver stiffness (rho = 0.37), moderately with GGT (rho = 0.48), while showed no correlation with HBV DNA or HBsAg. Independent factors for elevated ALT were age < 30 years, elevated GGT and HDV RNA levels. CONCLUSIONS: In this large cohort of Asian patients, an earlier and more severe inflammatory process could be demonstrated in CHD compared to CHB regardless of liver cirrhosis. Longitudinal studies are warranted to risk-stratify and prioritise patients for therapies.