Outcome of liver transplantation in hepatitis C virus–infected patients who received hepatitis C virus–infected grafts

Vargas, Hugo E.; Laskus, Tomasz; Wang, Lianfu; Lee, Randall; Radkowski, Marek; Dodson, Forrest; Fung, John J.; Rakela, Jorge

doi:10.1016/s0016-5085(99)70561-5

Cited by 158 publications

(112 citation statements)

References 18 publications

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“…The authors did not comment on whether the donor age or allograft features impacted survival. This study confirmed an analysis by Vargas et al 15 that the clinical course of patients receiving a HCVϩ graft does not differ significantly from those receiving HCVϪ grafts in the short term. None of these studies, however, have evaluated the impact of donor age or histological characteristics of the donor on recipient or graft survival.…”

supporting

confidence: 91%

Impact of donor age on survival and fibrosis progression in patients with hepatitis C undergoing liver transplantation using HCV+ allografts

et al. 2006

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Studies have suggested that the use of hepatitis C virus (HCV)-positive (HCVϩ) donor allografts has no impact on survival. However, no studies have examined the effect that HCVϩ donor histology has upon recipient and graft survival. We evaluated the clinical outcome and impact of histological features in HCV patients transplanted using HCVϩ livers. We reviewed all patients transplanted for HCV at our institution from 1988 to 2004; 39 received HCVϩ allografts and 580 received HCVnegative (HCVϪ) allografts. Survival curves compared graft and patient survival. Each HCVϩ allograft was stringently matched to a control of HCVϪ graft recipients. No significant difference in survival was noted between recipients of HCVϩ livers and controls. Patients receiving HCVϩ allografts from older donors (age Ն50 yr) had higher rates of graft failure (hazard ratio, 2.74) and death rates (hazard ratio, 2.63) compared to HCVϪ allograft recipients receiving similarly-aged older donor livers. Matched case-control analysis revealed that recipients of HCVϩ allografts had more severe fibrosis post-liver transplantation than recipients of HCVϪ livers (P ϭ 0.008). More advanced fibrosis was observed in HCVϩ grafts from older donors compared to HCVϩ grafts from younger donors (P ϭ 0.012). In conclusion, recipients of HCVϩ grafts from older donors have higher rates of death and graft failure, and develop more extensive fibrosis than HCVϪ graft recipients from older donors. Recipients of HCVϩ grafts, regardless of donor age, develop more advanced liver fibrosis than recipients of HCVϪ grafts.

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confidence: 91%

Impact of donor age on survival and fibrosis progression in patients with hepatitis C undergoing liver transplantation using HCV+ allografts

et al. 2006

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“…This is similar to the finding by Vargas et al that HCV genotype 1b is dominant after liver transplantation in which both donors and recipients were HCV RNA positive. 32 Although the dominance we observed could be explained by the competitive exclusion principle of classic population theory, which predicts the final overgrowth of one virus during the course of mixed infection, it is unclear at the molecular level how this "replacement" event occurs within the liver. The HCV RNA levels are quite different in different anatomic sites within the liver.…”

Section: Discussionmentioning

confidence: 85%

Liver Transplantation With Hepatitis C Virus–Infected Graft: Interaction Between Donor and Recipient Viral Strains

Fan

Lang

et al. 2003

Hepatology

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Superinfection of different viral strains within a single host provides an opportunity for studying host-virus and virus-virus interactions, including viral interference and genetic recombination, which cannot be studied in infections with single viral strains. Hepatitis C virus (HCV) is a positive single-strand RNA virus that establishes persistent infection in as many as 85% of infected individuals. However, there are few reports regarding coinfection or superinfection of HCV. Because of the lack of tissue culture systems and small animal models supporting efficient HCV replication, we explored these issues in the setting of liver transplantation where both recipient and donor were infected with different HCV strains and therefore represent a distinct model for HCV superinfection. Serial serum samples collected at multiple time points were obtained from 6 HCV-positive liver donor/recipient pairs from the National Institute of Diabetes and Digestive and Kidney Diseases liver transplantation database. At each time point, HCV genotype was determined by both restriction fragment length polymorphism analysis and phylogenetic analysis. Furthermore, we selectively sequenced 3 full-length HCV isolates at the earliest time points after liver transplantation, including both 5 and 3 ends. Detailed genetic analyses showed that only one strain of HCV could be identified at each time point in all 6 cases. Recipient HCV strains took over in 3 cases, whereas donor HCV strains dominated after liver transplantation in the remaining 3 cases. In conclusion, in all 6 cases studied, there was no genetic recombination detected among HCV quasispecies or between donor and recipient HCV strains. (HEPATOLOGY 2003;38: 25-33.)H epatitis C virus (HCV), a single-strand, positive RNA virus, has been well documented as the major etiologic agent responsible for most posttransfusional and community-acquired hepatitis. 1 HCVrelated liver disease is now a leading cause for liver transplantation in the United States. One striking characteristic of HCV infection is its high chronicity rate; that is, it easily establishes persistent infection in up to 85% of infected individuals and causes a wide spectrum of clinical profiles. The high chronicity rate of HCV may be partially attributed to its great genetic variability, which favors its rapid adaptation to a given biological environment. HCV may be divided into at least 6 major genotypes and more than 30 subtypes according to the phylogenies of available HCV sequences. 2 Moreover, even in patients infected with a single HCV subtype, HCV circulates as a group of variants with up to 10% nucleotide sequence difference, termed quasispecies. [3][4][5][6][7] Superinfection with different viral strains within a single host is a useful model for studying host-virus and virus-virus interactions. In HCV, perhaps due to the lack of protective immunity, 8 superinfection by different HCV isolates in patients with chronic HCV is clinically observed, in particular in individuals at very high risk for infection, suc...

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“…1). 14 This suppression of one of the strains by genotype 1 strains, referred to as the overtake phenomenon, suggested to the investigators that these genotypes possess replicative advantages. Even in patients infected with the same genotype as the graft, one strain was found to overtake the other.…”

Section: Hcv ؉ Donors In Hcv ؉ Recipientsmentioning

confidence: 99%

“…11 Preliminary reports were published with short follow-ups and no differences in outcomes with the use of HCV ϩ grafts. [12][13][14] Some new studies with larger numbers of patients and longer follow-up have cleared more questions regarding virological changes and clinical outcome. [15][16][17] Virological Behavior HCV ϩ patients receiving an HCV ϩ graft create an exceptional human system to study the interaction between two different viral strains.…”

Section: Hcv ؉ Donors In Hcv ؉ Recipientsmentioning

confidence: 99%

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The use of hepatitis C-infected grafts in liver transplantation

Arenas

Vargas

Rakela

2003

Liver Transplantation

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O rthotopic liver transplantation (OLT) has become the definitive procedure for management of end-stage liver disease, with survival rates greater than 80% at 1 year. Therefore, as absolute contraindications have progressively decreased, the number of indications has proportionately increased. Unfortunately, mortality on the waiting list has increased because of the disparity between number of donors and the rapid growth in number of candidates. According to the United Network for Organ Sharing (UNOS), the number of patients on the waiting list increased from 1,527 patients in 1991 to 16,874 patients in 2000, and the number of deaths while waiting increased from 515 to 1,661 deaths in the same period. 1 Patients with hepatitis C make up the largest segment of the candidate pool, continuing to stress the ability to provide grafts to those in need. In North America, most centers report hepatitis C virus (HCV) infection in greater than 40% of their candidates.To solve the problem of donor organ availability, several approaches have been explored. One approach is the use of organs from less-than-perfect donors, also called marginal donors. These could include nonheart-beating donors, older donors (age Ͼ 65 years), donors with morbid obesity, and last, donors infected with hepatotropic viruses, specifically HCV and hepatitis B virus. This review focuses on the development of the latter practice and its virological consideration, and we suggest recommendations on how these organs should be allocated. HCV-Infected Grafts Transmission of HCV by Donor OrgansIn 1990, the first report of HCV transmission from organ donor to recipient was made, followed by several successive reports. 2,3 With more sensitive and specific techniques, Pereira et al 4 reported that virtually all organ recipients from anti-HCV-positive (HCV ؉ ) donors become infected with the virus. Another study from the United Kingdom by Wreghitt et al 5 found a transmission rate of 93%, in which 50% of recipients of HCV ϩ organs had evidence of HCV-related liver disease after OLT. HCV seroprevalence in their donor pool was 1.08%. 5 The New England Organ Bank retrospectively evaluated clinical outcomes of recipients of organs from HCV ϩ and HCV-negative (HCV ؊ ) donors. 6 Between 1986 and 1990, a total of 29 patients received organs from 13 HCV ϩ donors (determined by a first-generation enzyme-liked immunosorbent assay). They were compared with 74 recipients of grafts from 35 HCV Ϫ donors. Median posttransplantation follow-ups for the HCV ϩ and HCV Ϫ groups were 42 and 49 months, and relative risk for the development of hepatitis in the HCV ϩ group was 4.37. 6 Using the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database, Everhart et al 7 prospectively evaluated 702 liver transplant recipients and 604 donors who were tested for antibody to HCV, followed by recombinant immunoblot and HCV RNA confirmation by polymerase chain reaction. Fifteen donors were HCV ϩ by either antibody to HCV or polymerase chain reaction. Eig...

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Outcome of liver transplantation in hepatitis C virus–infected patients who received hepatitis C virus–infected grafts

Cited by 158 publications

References 18 publications

Impact of donor age on survival and fibrosis progression in patients with hepatitis C undergoing liver transplantation using HCV+ allografts

Impact of donor age on survival and fibrosis progression in patients with hepatitis C undergoing liver transplantation using HCV+ allografts

Liver Transplantation With Hepatitis C Virus–Infected Graft: Interaction Between Donor and Recipient Viral Strains

The use of hepatitis C-infected grafts in liver transplantation

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