Hepatitis A virus (HAV) infection is an uncommon indication for liver transplantation, and donor-derived or transfusion-associated HAV infection is rare. Data describing HAV recurrence or early acquisition following liver transplantation, particularly with longitudinal quantitative viral kinetics, are limited. We describe two liver transplant recipients with graft HAV infection occurring in different immunological contexts. One patient underwent emergency liver transplantation for HAV-related acute liver failure and subsequently developed recurrent HAV infection of the graft. The second patient underwent liver transplantation for paracetamol-induced acute liver failure and acquired HAV infection following peri-operative blood transfusion in the early post-transplant period. Serial qualitative and retrospective quantitative HAV ribonucleic acid (RNA) polymerase chain reaction (PCR) measurements were analysed alongside biochemical and clinical parameters. In the patient transplanted for fulminant HAV infection, serum HAV RNA declined rapidly after transplantation, consistent with removal of the infected native liver, followed by recurrent viraemia associated with graft hepatitis during the second and third post-transplant months, and with viral clearance by 4 months. In contrast, the transfusion-acquired HAV infection occurred in the setting of profound immunosuppression and absence of pre-existing immunity, resulting in a higher peak viral load, prolonged viraemia lasting over 9 months, and more severe graft hepatitis. Viral doubling times during viraemic expansion were similar in both cases but sustained high-level viraemia was observed only in the de novo infection. These cases provide novel insights into HAV viral kinetics following liver transplantation and highlight important differences between recurrent infection and newly acquired HAV infection in immunosuppressed recipients.
Direct-acting antiviral therapy can cure hepatitis C virus (HCV) infection; however, because treatment is not recommended during pregnancy, preconception treatment remains the primary strategy to prevent perinatal HCV exposure. West Virginia birth records from 2022 to 2023 were linked with statewide HCV laboratory surveillance data. This linked dataset was used to identify births to persons with active HCV infection and characterize the timing of the earliest documented positive HCV laboratory result relative to delivery. A total of 426 deliveries resulting in 433 HCV-exposed live-born infants were identified. Most pregnant persons were aged 25-34 years, White and insured by Medicaid. Overall, 38.5% had their earliest documented positive HCV laboratory result more than 5 years prior to delivery, 36.9% had their first documented positive test 1-5 years prior to delivery and 24.6% had their first documented positive test within 1 year before delivery and up to 2 weeks postpartum. These findings indicate that many pregnant persons with active HCV infection had documented longstanding infection prior to pregnancy, highlighting opportunities to strengthen linkage to care and access to curative treatment before pregnancy.
ABSTRACT Eliminating hepatitis C requires focusing efforts on people who inject drugs (PWID). The ARISTOTLE HCV‐HIV program aimed to increase HCV and HIV diagnosis and linkage to care among PWID, particularly those currently injecting and not linked to opioid agonist treatment (OAT). This study evaluated HCV diagnosis and linkage to direct‐acting antiviral (DAA) treatment before and after removal of fibrosis‐based treatment restrictions. ARISTOTLE HCV‐HIV (April 2018–February 2020) was conducted in a community setting at a fixed site in central Athens. Two respondent‐driven sampling rounds recruited PWID. Single‐visit procedures included interviews, blood collection, and liver fibrosis assessment. Reflex HCV‐RNA/HCV genotype testing was performed. Participants were linked to collaborating clinicians for DAA treatment. We estimated program reach by exploratory two‐source capture–recapture and constructed HCV care cascades. DAA initiation was assessed from the first visit documenting HCV monoinfection through 180 days after the last such visit. Among 1634 unique participants, 75.0% reported past‐30‐day injecting (exploratory model‐based reach among this population in Athens: 73.2%), 22.9% were currently receiving OAT, and 26.8% were currently homeless. Anti‐HCV prevalence was 76.9% (95% CI: 74.8–78.9), 83.3% (95% CI: 80.8–85.6) of anti‐HCV–positive individuals had viremia. Of 587 monoinfected individuals eligible for treatment, 43.4% initiated DAA. Lifting fibrosis restrictions boosted DAA utilization by 19.2 treatment courses/100 anti‐HCV–positive PWID. DAA access increased substantially after lifting liver fibrosis restrictions. Peer‐driven, community‐based interventions can achieve substantial program reach among underserved PWID and contribute to HCV elimination.
ABSTRACT Novel, well‐tolerated, short‐term therapeutics for chronic hepatitis B virus infection (cHBV) are needed. ABI‐4334 is a next‐generation capsid assembly modulator that targets the HBV core protein. The safety, tolerability, and pharmacokinetics of ABI‐4334 in healthy volunteers and participants with cHBV and antiviral effects in participants with cHBV were examined in two Phase 1 studies. Study 101 was a placebo‐controlled study of healthy volunteers that included four single‐ascending dose cohorts and two once‐daily multiple‐ascending dose cohorts randomized 6:2 (ABI‐4334:placebo), and one crossover food‐effect cohort randomized 3:3 (fed:fasted). Study 102 was a randomized, blinded, placebo‐controlled study where participants with cHBV were randomized 8:2 (ABI‐4334 [2 dose cohorts]:placebo). Overall, 54 healthy volunteers and 20 participants with cHBV were included in Studies 101 and 102, respectively. Most participants (75%) in Study 102 were hepatitis B e antigen (HBeAg) negative and generally had lower baseline HBV DNA and pregenomic RNA (pgRNA) levels. ABI‐4334 was well tolerated, with no treatment‐emergent serious adverse events (AEs) or treatment‐emergent AEs leading to study discontinuation. The mean ABI‐4334 plasma half‐life ranges were comparable across doses in both studies. Following multiple‐dose administration in participants with cHBV, the steady‐state mean plasma half‐life ranged from 17.5 to 27.5 h. HBV DNA declines were observed in both HBeAg‐positive ( n = 3) and ‐negative ( n = 13) participants across doses. Reductions in pgRNA were observed in participants with detectable pgRNA at baseline. ABI‐4334 was well tolerated, with pharmacokinetics and antiviral results supporting the continued development of ABI‐4334 as a monotherapy or component of novel combination regimens for cHBV. Trial Registration: Study 101 (NCT05569941). Study 102 (NCT06384131)
