Hepatitis B virus (HBV) genetic variability, shaped by high mutation rates and selective pressures, complicates its management and increases the emergence of drug-resistant and immune-escape variants. This study aims to analyze immune escape mutations (IEMs) and drug resistance mutations (DRMs) in patients with HBV infection exposed to antiviral therapies and exhibiting detectable plasma HBV viremia. This monocentric retrospective real-life study was carried out at the ASST Spedali Civili di Brescia, Italy, from 2015 to 2023. A total of 102 consecutive patients with detectable serum HBV-DNA exposed to at least one NA and for whom a drug resistance assay was available were included in our study. HBV sequences were amplified, sequenced, and analyzed for mutations using Geno2pheno and Stanford University tools. Phylogenetic analysis and statistical regression were performed to confirm genotypes and identify mutation patterns and associated risk factors. Our study shows a 38.2% prevalence of DRMs, with M204I/V (95%) and L180M (64%) being the most common, and a 43% prevalence of IEMs, primarily in the major hydrophilic region. Genotype D3 exhibited a higher mutation burden than other genotypes. Significant associations were found between HBsAb presence and increased IEM burden, while HBeAg was protective against DRMs. Atypical serological profiles were observed in 18.6% of patients, including cases of HBV reactivation under immunosuppressive therapy. This study highlights the high prevalence of IEMs and DRMs in a real-world setting, particularly among HBV genotype D3 carriers. These findings underscore the importance of mutation surveillance to guide therapeutic strategies, vaccine design, and public health policies to address the challenges posed by HBV genetic variability.

Penitentiaries have a higher burden of communicable diseases compared to the general population. Prisoners should be tested for hepatitis C virus (HCV) and have direct access to treatment. We analysed the HCV cascade of care in two penitentiaries in Brescia, Northern Italy. At admission, prisoners are offered a voluntary screening for HCV, while patients with known infections are tested with an HCVRNA measurement. We performed an observational retrospective study including all the subjects admitted to the penitentiaries from 1 January 2015 to 31 October 2021. We conducted a descriptive analysis. During the study period, 5378 admissions were registered, and 2932 (54.5%) screenings were performed. Hepatitis C virus antibody positivity was found in 269 tests (9.2%). Hepatitis C virus RNA was detectable in 169 people. During the study period, 77 treatments with direct-acting antivirals (DAAs) were administered. Follow-up was available in 45 patients, and sustained virological response (SVR) was documented in 44 of them. Retention in care occurred in less than half of the prisoners after release. Our data demonstrate poor screening adherence that could benefit from educational programs. Treatment rates could be improved with test-and-treat programs. More efforts are needed to eliminate HCV as a public threat by 2030. Dedicated local networks, including infectious diseases (ID) departments, substance abuse services and prisons, could mitigate these issues.

Approved direct antiviral agent (DAA) combinations are associated with high rates of sustained virological response (SVR) and the absence of a detectable hepatitis C viral load 12–24 weeks after treatment discontinuation. However, a low percentage of individuals fail DAA therapy. Here, we report the case of a HIV/HBV/HCV co-infected patient who failed to respond to DAA pangenotypic combination therapy. The sequencing of NS5a, NS5b, NS3 and core regions evidenced a recombinant intergenotypic strain 4/1b with a recombination crossover point located inside the NS3 region. The identification of this natural recombinant virus underlines the concept that HCV recombination, even if it occurs rarely, may play a key role in the virus fitness and evolution.