Earlier liver cirrhosis onset in intrafamilial hepatitis Delta virus transmission in Moldova

Background. Hepatitis delta (HDV), a major contributor to severe liver disease, remains highly prevalent in Moldova, despite its declining incidence in Western Europe. Intrafamilial transmission plays a significant role in disease spread, yet has not been thoroughly investigated in Moldova. Understanding its impact is crucial for implementing targeted public health interventions to reduce early-onset liver cirrhosis. Aim. The study aims to assess the impact of intrafamilial HDV transmission on disease progression, particularly its role in accelerating liver cirrhosis onset. Materials and methods. In this comparative cross-sectional study, we describe the demographic, clinical and biological characteristics of 224 HDV-infected patients with chronic hepatitis or liver cirrhosis, attending care in three Moldovan centers. These patients were compared with 100 hepatitis B virus (HBV) -mono-infected subjects. Results. The age of liver cirrhosis onset was similar (48-49 years) in both HDV and HBV monoinfected patients. All delta-infected patients were anti-HBe and HBV DNA detectable much less frequently (28%) than in mono-infected ones (76-92%, P<1.0E-09). Most clinical and biological parameters were significantly worsened in the case of HDV infection. Familial transmission was much more prevalent in HDV than in HBV infection (39% vs 23%, P=0.0036). Amongst patients with HDV those with intrafamilial contamination developed liver cirrhosis significantly earlier than others (40.5±9.3years vs 46.9±8.7years, P=0.053) suggesting a direct association between familial exposure and accelerated disease progression and presented more frequently detectable HDV RNA in their plasma (98.7% vs 89.2%, P=0.0094). Patients from Southern Moldova were significantly more likely to have familial transmission than patients from other parts of the (39.2% vs 17.7%, P=0.0010). Conclusions. Hepatitis delta remains a critical public health concern in Moldova, particularly due to early cirrhosis onset in intrafamilial cases. Given these findings, early screening of HDV in HBsAg-positive individuals and preventive interventions in high-risk families should be prioritized to reduce severe liver disease burden and improve linkage to treatment.