Recurrent and new hepatitis C virus infection after liver transplantation

Everhart, M.P.H. James; Wei, Yue; Eng, Heather; Charlton, Michael; Persing, David H.; Wiesner, Russell H.; Germer, Jeffrey J.; Lake, John R.; Zetterman, Rowen K.; Hoofnagle, Jay H.

doi:10.1002/hep.510290412

Cited by 114 publications

(72 citation statements)

References 23 publications

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“…Six cases had been previously identified in which both the recipient and the donor were HCV RNA positive in a prospective study to evaluate recurrent HCV infection after liver transplantation. 13 Serum samples from the recipients were collected at multiple time points before and after liver transplantation. Serum samples from the donors were collected at the time of transplantation.…”

Section: Methodsmentioning

confidence: 99%

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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Section: Methodsmentioning

confidence: 99%

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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“…5,24 Although a decline in survival has not been detected within the first 5 years after transplantation of HCV-positive recipients in some studies, 1,6,25 the results from large multicenter databases such as the United Network for Organ Sharing (UNOS) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) liver transplantation database suggest that patients with HCV do have a lower 5-year survival than non-HCV liver transplant recipients. [26][27][28] What remains extremely controversial are those factors associated with fibrosis progression and if and how these could be modified. This section reviews viral, host, and immunologic factors believed to be associated with acute and chronic HCV infection, fibrosis progression, and rapidly progressive cholestatic hepatitis.…”

Section: Natural History Of Hepatitis C After Liver Transplantationmentioning

confidence: 99%

Controversies in the management of hepatitis C virus infection after liver transplantation

Shiffman¹,

Vargas²,

Everson³

2003

Liver Transplantation

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Recurrence of hepatitis C virus infection after liver transplantation is universal. A significant percentage of these patients develop progressive graft injury and cirrhosis. Those factors that modulate disease progression in liver transplant recipients with recurrent hepatitis C virus infection remain controversial and are poorly understood. Treatment of recurrent hepatitis C virus after liver transplantation with either interferon or interferon and ribavirin has yielded only limited success. Regardless of this, treatment is instituted. Peginterferon is more effective than standard interferon for treatment of chronic hepatitis C virus infection in the nontransplantation setting when used either alone or with ribavirin. The effectiveness of peginterferon, both with and without ribavirin in the posttransplantation setting, is currently being explored. In this review those factors thought to affect disease progression in patients with recurrent hepatitis C virus will be discussed, strategies that have been used to treat recurrent hepatitis C virus will be reviewed, and the impact that peginterferon may have on hepatitis C virus infection in the pretransplantation and posttransplantation setting will be explored. C irrhosis secondary to chronic infection with the hepatitis C virus (HCV) is the leading indication for liver transplantation. 1,2 Although transplantation is an effective treatment for end-stage liver disease secondary to chronic HCV infection, virus recurs in essentially all patients. 1-3 Progressive graft injury leading to cirrhosis occurs in about 25% to 33% of patients within just 5 years. [4][5][6][7][8] In addition, a limited group of patients (about 1% to 5% of recipients) develop rapidly progressive cholestatic hepatitis and liver failure within just 1 to 2 years. [8][9][10][11] Numerous studies have attempted to identify those factors that affect disease progression in these patients. Unfortunately, nearly all studies in this area have been retrospective in nature, conducted in patient populations of limited size, at single centers, utilized an array of immune suppressive medications in an uncontrolled manner, and have failed to consistently utilize protocol liver biopsy to investigate histologic progression. In addition, allograft rejection has not been either universally defined or treated and assays to measure serum HCV RNA have varied between centers and changed over time. As a result, data from many studies seem to contradict each other and the interpretation of these findings has varied widely. It is therefore not surprising how little progress has been made in our understanding of recurrent HCV over the past decade and that no universally accepted algorithm for managing these patients has emerged.Interferon (IFN) alfa with or without ribavirin (RBV) is the treatment of choice for patients with chronic HCV infection. 12,13 These medications have also been used to treat recurrent HCV after liver transplantation, but the interpretation of these data has been plagued by a similar set of limit...

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“…After liver transplantation for HCV cirrhosis, both quasispecies diversity and viremia levels are lowest immediately posttransplantation. [8][9][10][11]73 Although infection of the graft already has occurred at reperfusion, 11 antiviral prophylaxis from early posttransplantation should protect the graft from subsequent acute and chronic hepatitis. 9,74 Interferon-␣.…”

Section: Posttransplantation Prophylaxismentioning

confidence: 99%

“…1). However, a liver transplant recipient with recurrent HCV infection usually possesses multiple baseline negative predictors for both early and sustained virological responses to interferon: (1) high pretreatment viremia level: levels increase 10-to 100-fold after liver transplantation, usually exceeding 10 6 IU/mL [8][9][10] ; (2) high prevalence of HCV genotype 1 infection (Europe, 85% to 90%; United States, 80%; Fig. 2); (3) need for lifelong immunosuppression, which may inhibit the early virological response to interferon-␣ 11 ; and (4) previous nonresponse to interferon-␣ therapy before transplantation.…”

mentioning

confidence: 99%

Treatment of recurrent hepatitis C

Gane

2002

Liver Transplantation

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Key Points 1. Treatment of established recurrent hepatitis C with interferon-␣ monotherapy does not achieve sustained virologic response (SVR). 2. Treatment of established recurrent hepatitis C with combination interferon plus ribavirin achieves SVR rates of 17% to 27%, but dropout rates approach 30%. 3. Pretransplant prophylaxis against recurrent hepatitis C with combination interferon plus ribavirin is poorly tolerated in patients with decompensated hepatitis C cirrhosis. 4. Posttransplant prophylaxis with combination interferon plus ribavirin prevents both recurrent viremia and hepatitis in 15% to 20% of patients, but dropout rates approach 50%. 5. Hepatitis C virus genotype is the best predictor of response to antiviral prophylaxis and treatment of recurrent hepatitis C. 6. Interferon-␣ therapy is not associated with an increased risk of allograft rejection in liver transplant recipients. 7. Ribavirin therapy is associated with increased hemolysis in liver transplant recipients. 8. Preliminary data suggest pegylated interferon monotherapy will have similar efficacy but better tolerability than combination interferon plus ribavirin. 9. In a recent study, posttransplant immunoprophylaxis with polyclonal hepatitis C immunoglobulin had no effect on recurrent viremia or hepatitis. (Liver Transpl 2002;8: S28-S37.)

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Recurrent and new hepatitis C virus infection after liver transplantation

Cited by 114 publications

References 23 publications

Liver transplantation with hepatitis C virus-infected graft: Interaction between donor and recipient viral strains

Liver transplantation with hepatitis C virus-infected graft: Interaction between donor and recipient viral strains

Controversies in the management of hepatitis C virus infection after liver transplantation

Treatment of recurrent hepatitis C

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