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 analyzed the prevalence and determinants of ALT elevation in a large cohort of patients with CHD, including young adults, compared to propensity score-matched (PSM) HBV mono-infected patients.

Methods We identified 3,399 treatment-naïve HBsAg+ adults with CHD (HDV RNA positive) or 2,556 with HBV mono-infection attending a liver center in Mongolia during 2015-2023. The relation between ALT levels, virological, biochemical and fibrosis parameters were assessed using Spearman correlation coefficient (rho). Logistic regression analysis was used to identify factors associated with elevated ALT in the whole cohort, and in 2,231 PSM on age, sex, and date of initial test pairs with CHD and mono-HBV.

Results In CHD, 78.5% of patients had ALT elevation, with the highest prevalence in the 18-29 years group (n=340, 84%). This age group displayed 4.80-odds ratio (OR) for elevated ALT, 2.76-OR for elevated GGT, and 5.08-OR for cirrhosis, than matched mono-HBV group (all p<0.05). ALT levels 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 ≥100,000 IU/mL.

Conclusions In this large cohort of Asian patients with CHD, an early and more severe inflammatory process regardless of liver cirrhosis could be demonstrated in CHD compared to HBV-monoinfection supporting early administration of anti-HDV therapy.

The authors have declared no competing interest.

The study was funded by an ALF grant from Region Stockholm, Sweden.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethical approval was granted by the local ethics review board at the Liver center in Mongolia and by the Ethical Review Authority of Sweden.

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↵* shared first authorship

↵# share senior authorship

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