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Background: The development of modern antiviral therapy for hepatitis C virus (HCV) has allowed for the transplantation of HCV nucleic acid amplification testing-positive (NAT+) donor lungs with acceptable short-term outcomes. We sought to evaluate trends and midterm outcomes of lung transplant recipients of HCV NAT+ donor allografts.
Methods: All adults undergoing isolated lung transplantation in the United Network for Organ Sharing database from January 2016 to December 2022 were included in the study. Lung transplant recipients were stratified based on donor HCV status (HCV NAT+ vs NAT-). Propensity score matching was used to adjust for differences between groups. Several outcomes, including acute rejection by 1 year, early (30-day and in-hospital) mortality, and both 1- and 3-year survival, were compared between matched groups.
Results: A total of 16,725 patients underwent lung transplantation during the study period, with 489 (3%) receiving HCV NAT+ donor lungs. Regions 1 (18%) and 6/8 (both 0%) had the highest and lowest proportions, respectively, of HCV NAT+ donor transplants. Utilization of HCV NAT+ donors increased throughout the study period from 2 (0.1%) in 2016 to a peak of 117 (5%) in 2019. Donors who were HCV NAT+ were younger (34 vs 36 years, p < 0.001), more often female (44% vs 39%, p < 0.01), and more commonly died due to drug intoxication (56% vs 15%, p < 0.001). Recipients of HCV NAT+ donor lungs were similar in age (62 vs 62 years, p = 0.69) and female gender (43% vs 39%, p = 0.15) but had lower lung allocation scores (38 vs 41, p < 0.001) compared to others. Rates of acute rejection (13% vs 17%, p = 0.09), early mortality (30-day: 2% vs 1%, p = 0.59, in-hospital: 3% vs 4%, p = 0.38), as well as 1-year (90% vs 92%, p = 0.29) and 3-year survival (69% vs 75%, p = 0.13) were not significantly different between matched groups.
Conclusions: Lung transplant recipients of HCV NAT+ donor allografts experience similar rates of acute rejection, early mortality, and 3-year survival compared to all other lung recipients. Increased use of HCV NAT+ donor allografts may help to expand the donor pool and alleviate donor shortages.
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http://dx.doi.org/10.1016/j.healun.2023.10.014 | DOI Listing |
Nat Commun
August 2025
Department Infectious Diseases, Molecular Virology, Heidelberg University, Medical Faculty, Heidelberg, Germany.
Many positive strand RNA viruses encode helicases, but their distinct functions in viral replication cycles is poorly understood. Here, we identify a mutation in the helicase domain of HCV non-structural protein 3 (NS3h), D1467G, which specifically affects (-) strand synthesis, phenocopying mutations in the 3' untranslated region of the genome. D1467G does not impair helicase activity in vitro or the binding of NS3h to critical cis-acting RNA elements, but reduces the interaction of NS3h and NS5B polymerase, potentially contributing to defective (-) strand synthesis.
View Article and Find Full Text PDFNat Commun
August 2025
Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
An effective vaccine for the hepatitis C virus (HCV) remains an unmet medical need. There is no animal model for assessing HCV vaccines; however, rodent hepacivirus (RHV) infection in laboratory rats recapitulates the lifelong chronic hepatotropic infection and immune evasion of HCV. Here, we designed a live-attenuated vaccine (LAV) for RHV and determined its immunogenicity and efficacy for preventing chronic infection.
View Article and Find Full Text PDFAfr Health Sci
September 2024
School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
Background: Successful elimination of hepatitis as a public health threat by 2030 will partly rely on the availability and accessibility of affordable accurate disease testing platforms. In the past, testing of hepatitis C virus (HCV) in low resource settings of sub-Saharan Africa (SSA) has relied on anti-HCV testing using rapid diagnostic tests, chemiluminescent microparticle immunoassay (CMIA) and Enzyme-linked Immunosorbent Assays (ELISA) whose diagnostic accuracy has been sub-optimal. We determined the false positivity rate of a CMIA platform that is routinely used to screen donor blood for anti-HCV in Uganda.
View Article and Find Full Text PDFNat Commun
August 2025
Beijing Frontier Research Center for Biological Structure, Center for Infectious Disease Research, SXMU-Tsinghua Collaborative Innovation Center for Frontier Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
The RNA polymerase NS5B of HCV is capable of catalyzing the addition of flavin adenine dinucleotide (FAD) to its RNA as a 5' cap structure, aiding the virus in evading host immune responses. However, the exact mechanism underlying the 5'-FAD capping process of HCV RNA remains to be elucidated. Here, we determine crystal structures of the HCV NS5B de novo initiation, primed initiation and elongation complexes in presence of FAD.
View Article and Find Full Text PDFVox Sang
August 2025
School of Medicine and Health Science, Public Health Research Group, Universidad del Rosario, Bogotá, Colombia.
Background And Objectives: Colombia has a population of 52.6 million inhabitants and a blood donation rate of 26 donations per 1000 inhabitants. The 84 blood banks in the country collect approximately 1 million donations annually, which are mandatorily screened for human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), human T-lymphotropic virus (HTLV), Trypanosoma cruzi and Treponema pallidum.
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