Molecular characterization of hepatitis B and hepatitis delta viruses in Mauritanian HBV chronically infected patients

Abstract Chronic hepatitis B (CHB) is highly endemic in Mauritania, and co‑infection with hepatitis delta virus (HDV) may worsen liver outcomes. We characterized circulating hepatitis B virus (HBV) and HDV strains and assessed the clinical impact of HDV co‑infection among HBsAg‑positive patients in Nouakchott. A total of 165 adults with CHB were enrolled at the National Institute of Hepato-Virology. Demographic/clinical data, serological and molecular tests, ultrasound, and fibrosis estimates (APRI, FIB-4) were collected. HBV DNA was quantified by real-time PCR; HDV RNA was measured mainly by RT-ddPCR. HBV and HDV were Sanger-sequenced. HBV DNA was detectable in 146/165 (88.5%) with median 2197.25 IU/mL; 75/165 (45.45%) exceeded 2000 IU/mL. Total anti-HDV antibodies were found in 68/112 (60.7%) tested; HDV RNA was quantified in 130/165 patients and detected in 34/130 (26.15%) with median 72,271 IU/mL, including 34/68 (50%) of anti-HDV–positive patients. HDV-RNA positivity was associated with symptoms, higher AST/ALT/AFP/APRI/FIB-4, lower HBV DNA detectability, and increased cirrhosis/HCC and treatment use ( p ≤ 0.004). HBV genotypes were D (36/65, 55.4%), including 11 isolates (16.9%) assigned to subgenotype D8, a D/E recombinant lineage first described in Niger; E (21/65, 32.3%); and A (8/65, 12.3%). HDV genotyping ( n = 21) showed mainly genotype 1 and two genotype 5 isolates. An rtA181S substitution in the polymerase reverse-transcriptase domain and a naturally occurring altered YMDD motif (rtY203N) were detected. Whole-genome analysis revealed co-circulation of HBV genotypes A (A1/A2), D (D1/D4), E, and recombinant D/E strains, with high conservation across coding regions and absence of widespread antiviral resistance in these Mauritanian patients’ samples. HDV co‑infection is frequent among Mauritanian patients with CHB and is associated with more severe liver injury. HBV genotype D predominates, with presence of inter‑genotype recombinations and HDV genotypes are mainly genotype 1. These findings support routine HDV screening, timely antiviral access, and improved HBV vaccination coverage- including the birth dose- to slow disease incidence and progression in Mauritania.