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Liver transplantation for hepatitis C virus (HCV) non-viremic recipients with HCV viremic donors.

ABSTRACT: In the context of organ shortage, the opioid epidemic, and effective direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV), more HCV-infected donor organs may be used for liver transplantation. Current data regarding outcomes after donor-derived HCV in previously non-viremic liver transplant recipients are limited. Clinical data for adult liver transplant recipients with donor-derived HCV infection from March 2017 to January 2018 at our institution were extracted from the medical record. Ten patients received livers from donors known to be infected with HCV based on positive nucleic acid testing. Seven had a prior diagnosis of HCV and were treated before liver transplantation. All recipients were non-viremic at the time of transplantation. All 10 recipients derived hepatitis C infection from their donor and achieved sustained virologic response at 12 weeks posttreatment with DAA-based regimens, with a median time from transplant to treatment initiation of 43 days (IQR 20-59). There have been no instances of graft loss or death, with median follow-up of 380 days (IQR 263-434) posttransplant. Transplantation of HCV-viremic livers into non-viremic recipients results in acceptable short-term outcomes. Such strategies may be used to expand the donor pool and increase access to liver transplantation.

SUBMITTER: Kwong AJ

PROVIDER: S-EPMC6663314 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Liver transplantation for hepatitis C virus (HCV) non-viremic recipients with HCV viremic donors.

Kwong Allison J AJ Wall Anji A Melcher Marc M Wang Uerica U Ahmed Aijaz A Subramanian Aruna A Kwo Paul Y PY

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 20181126 5

In the context of organ shortage, the opioid epidemic, and effective direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV), more HCV-infected donor organs may be used for liver transplantation. Current data regarding outcomes after donor-derived HCV in previously non-viremic liver transplant recipients are limited. Clinical data for adult liver transplant recipients with donor-derived HCV infection from March 2017 to January 2018 at our institution were extracted from the medical rec ...[more]

PMID: 30378723

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Project description:Introduction. While use of (hepatitis C virus) HCV-viremic kidneys may result in net benefit for the average end-stage kidney disease (ESKD) patient awaiting transplantation, patients may have different values for ESKD-related health states. Thus, the best decision for any individual may be different depending on the balance of these factors. Our objective was to explore the feasibility of sampling health utilities from hemodialysis patients in order to perform patient-specific decision analyses considering various transplantation strategies. Study Design. We assessed utilities on a convenience sample of hemodialysis patients for health states including hemodialysis, and transplantation with either an HCV-uninfected kidney or an HCV-viremic kidney. We performed patient-specific decision analyses using each patient's age, race, gender, dialysis vintage, and utilities. We used a Markov state transition model considering strategies of continuing hemodialysis, transplantation with an HCV-unexposed kidney, and transplantation with an HCV-viremic kidney and HCV treatment. We interviewed 63 ESKD patients from four dialysis centers (Dialysis Clinic Inc., DCI) in the Cincinnati metropolitan area. Results. Utilities for ESKD-related health states varied widely from patient to patient. Mean values were highest for -transplantation with an HCV-uninfected kidney (0.89, SD: 0.18), and were 0.825 (SD: 0.231) and 0.755 (SD: 0.282), respectively, for hemodialysis and transplantation with an HCV-viremic kidney. Patient-specific decision analyses indicated 37 (59%) of the 63 ESKD patients in the cohort would have a net gain in quality-adjusted life years from transplantation of an HCV-viremic kidney, while 26 would have a net loss. Conclusions. It is feasible to gather dialysis patients' health state utilities and perform personalized decision analyses. This approach could be used in the future to guide shared decision-making discussions about transplantation strategies for ESKD patients.

Project description:Acute cellular rejection (ACR) and hepatitis C virus (HCV) recurrence (HCVrec) are common complications after liver transplantation (LT) in HCV patients, who share common clinical and histological features, making a differential diagnosis difficult. Fifty-three liver allograft samples from unique HCV LT recipients were studied using microarrays, including a training set (n = 32) and a validation set (n = 19). Two no-HCV-ACR samples from LT recipients were also included. Probe set intensity values were obtained using the robust multiarray average method (RMA) method. Analysis of variance identified statistically differentially expressed genes (P ? 0.005). The limma package was used to fit the mixed-effects models using a restricted maximum likelihood procedure. The last absolute shrinkage and selection operator (LASSO) model was fit with HCVrec versus ACR as the dependent variable predicted. N-fold cross-validation was performed to provide an unbiased estimate of generalization error. A total of 179 probe sets were differentially expressed among groups, with 71 exclusive genes between HCVrec and HCV-ACR. No differences were found within ACR group (HCV-ACR vs. no-HCV-ACR). Supervised clustering analysis displayed two clearly independent groups, and no-HCV-ACR clustered within HCV-ACR. HCVrec-related genes were associated with a cytotoxic T-cell profile, and HCV-ACR-related genes were associated with the inflammatory response. The best-fitting LASSO model classifier accuracy, including 15 genes, has an accuracy of 100% in the training set. N-fold cross-validation accuracy was 78.1%, and sensitivity, specificity and positive and negative predictive values were 50.0%, 90.9%, 71.4% and 80.0%, respectively. Arginase type II (ARG2), ethylmalonic encephalopathy 1 (ETHE1), transmembrane protein 176A (TMEM176A) and TMEM176B genes were significantly confirmed in the validation set. A molecular signature capable of distinguishing HCVrec and ACR in HCV LT recipients was identified and validated.

Project description:In hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infected patients, HIV enhances HCV replication and liver damage. Several microRNAs (miRNAs), active in pro-fibrotic and inflammatory pathways, have been implicated in the pathogenesis of this phenomenon. However, these miRNAs have been tested only in explanted cirrhotic livers, when the liver damage has become chronic and irreversible. No data are available on the early phase of viral infection, such as early after liver transplantation (LT). In the present study, the expression of miR-101, miR-122, miR-155, miR-192, miR-200c, miR-338, and miR-532 was determined by quantitative real-time polymerase chain reaction in liver biopsies of HCV (n = 19) and HCV/HIV-infected (n = 20) LT recipients, as well as in a control group (n = 18) of noninfected patients, transplanted for alcoholic cirrhosis. The timing of liver biopsy was 6 months post-LT. None of the patients was treated with direct-acting anti-HCV drugs. All co-infected recipients had suppressed HIV viral load. Grading and staging were assessed according to the Ishak Classification. HCV and HIV viral load were measured in the sera. miR-101 (p = .03), miR-122 (p = .012), and miR-192 (p = .038) were significantly downregulated in HCV/HIV co-infected and HCV mono-infected recipients when compared with noninfected recipients, and such downregulation was more pronounced in co-infected ones. Moreover, in co-infected recipients but not in mono-infected ones, miR-101 inversely correlated with the peripheral HCV-RNA levels (r = .41, p = .04) and miR-122 inversely correlated with peripheral HCV-RNA levels (r = .49, p = .03) and with the histological grading (r = .51, p = .02). In conclusion, as early as 6 months after LT, the presence of HIV-HCV co-infection enhanced a significant downregulation of certain miRNAs that showed a direct correlation with HCV viral load and liver inflammation.

Dataset Information

Liver transplantation for hepatitis C virus (HCV) non-viremic recipients with HCV viremic donors.

Publications

Liver transplantation for hepatitis C virus (HCV) non-viremic recipients with HCV viremic donors.

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