An open trial of interferon alfa recombinant for hepatitis C after liver transplantation: Antiviral effects and risk of rejection

Féray, Cyrille; Samuel, Didier; Gigou, M; Paradis, Valérie; David, M.; Lemonnier, Catherine; Reynès, M; Bismuth, H

doi:10.1002/hep.1840220411

Cited by 233 publications

(151 citation statements)

References 16 publications

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“…87,88 Although properly controlled trials are limited, the general consensus is that the risk of IFN precipitating acute allograft rejection does not seem to be increased in liver transplant recipients. Although chronic rejection was increased after IFN therapy in one study, 89 the overall risk of chronic rejection in this population remains undefined.…”

Section: Toxicities Associated With Interferonmentioning

confidence: 90%

“…89,[106][107][108][109][110][111] These studies included only a limited number of patients, nearly all of whom had persistent elevations in serum liver transaminases. Although liver chemistries returned to normal in up to 42% of treated patients, only 1 patient from all of these studies achieved SVR.…”

Section: Treatment Of Established Hcv Infection In Liver Transplant Rmentioning

confidence: 99%

“…Although IFN was associated with a significant increase in chronic rejection in one study, acute rejection did not seem to be more common. 89 The combination of IFN and RBV has also been used to treat recurrent HCV in patients after liver transplantation. [111][112][113][114][115][116] Several small studies, mostly conducted at single centers, have been performed.…”

Section: Treatment Of Established Hcv Infection In Liver Transplant Rmentioning

confidence: 99%

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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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Section: Toxicities Associated With Interferonmentioning

confidence: 90%

Section: Treatment Of Established Hcv Infection In Liver Transplant Rmentioning

confidence: 99%

Section: Treatment Of Established Hcv Infection In Liver Transplant Rmentioning

confidence: 99%

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

Shiffman¹,

Vargas²,

Everson³

2003

Liver Transplantation

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“…Interferon therapy for recurrent hepatitis has had poor results-only a small percentage of patients appear to respond. 9,10 In patients with compensated hepatitis C who have not undergone transplantation, interferon is more effective when pretreatment viral levels are low. 11 In liver recipients with recurrent hepatitis C, Wright et al 9 noted that, like patients with chronic disease, patients with low pretreatment viral levels have a higher response rate to interferon.…”

Section: -838)mentioning

confidence: 99%

The efficacy of prophylactic interferon alfa-2b in preventing recurrent hepatitis C after liver transplantation

et al. 1998

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Clinical recurrence of hepatitis C after liver transplantation can lead to cirrhosis, liver failure, and death. In patients undergoing liver transplantation for hepatitis C, we assessed the efficacy of interferon alfa-2b (IFN) in preventing recurrent hepatitis. We randomized 86 patients to either an IFN group (3 MU three times a week starting within 2 weeks after transplantation and continued for 1 year) or a control (no IFN) group. Recurrence, the primary end point, was diagnosed on biopsy performed at 1 year or for abnormal biochemistries. HCV RNA levels were measured by branched-chain DNA (bcDNA) assay and arbitrarily defined as low, moderate, or high (F10 ؋ 10 5 , 10-100 ؋ 10 5 , or G100 ؋ 10 5 Eq/mL, respectively). Data on 30 IFN patients and 41 no-IFN patients who survived H3 months were reviewed. Mean follow-up was 669 ؎ 228 days for IFN patients and 594 ؎ 254 days for no-IFN patients. IFN patients were less likely to develop recurrent hepatitis (8 IFN vs. 22 no-IFN patients, P ‫؍‬ .017, log rank analysis). IFN and 1-month HCV RNA level were independent predictors of recurrence. IFN reduced the risk of recurrence by a factor of 0.4 (P ‫؍‬ .04, Cox proportional hazards model); HCV RNA level Ͼ100 ؋ 10 5 Eq/mL at 1 month after transplantation increased the risk by a factor of 3.1 (P ‫؍‬ .01). Low, moderate, and high viral levels at 1 and 3 months were associated with significantly different rates of recurrence in IFN patients (P ‫؍‬ .05 at 1 month and P ‫؍‬ .003 at 3 months) but not in untreated patients (P ‫؍‬ .28 at 1 month and P ‫؍‬ .25 at 3 months). In patients with two or more rejections, the risk of recurrence was increased by a factor of 2.17 (P ‫؍‬ .05). On 47 1-year biopsies (24 IFN; 23 no IFN), piecemeal necrosis was more common in untreated patients (P F .02). One-and 2-year patient survival, respectively, was 96% and 96% with IFN and 91.2% and 87.2% without (P ‫؍‬ NS). Prophylactic IFN reduced the incidence of recurrent hepatitis after transplant. Although IFN was most effective in patients with low HCV RNA levels, we also noted an effect in patients with moderate levels. IFN did not prevent viremia, suggesting that it may work through alternative mechanisms.(HEPATOLOGY 1998;28: 831-838.)Hepatitis C is becoming the most common indication for orthotopic liver transplantation. 1 After transplantation for this indication, however, hepatitis C viral RNA (HCV RNA) is detectable in serum in approximately 95% of patients. 2 Because the virus remains present, the new graft is at risk for recurrent disease. Clinical recurrence of hepatitis C has been reported in up to 62% of patients after orthotopic liver transplantation 2-4 and can lead to progressive liver failure, cirrhosis, and death. 5 Studies using quantitative assays for viral RNA have revealed a possible association between high serum HCV RNA levels and active hepatitis after transplantation. 6 The observation that quantitative HCV RNA levels are higher after liver and kidney transplantation than before suggests that immunosuppression may enhance...

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“…To prevent morbidity and mortality associated with recurrent hepatitis C, many centers have used interferon alfa (IFN-␣) and/or ribavirin (RVN) as either antiviral prophylaxis or treatment of established hepatitis C or hepatitis B. Regimens have ranged from monotherapies with RVN, [8][9][10][11][12][13][14] standard IFN-␣ , 9,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] or pegylated IFN [30][31][32] to combination therapies with a standard IFN-␣ and RVN 27,29,[33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52] or pegylated IFN-␣ and RVN. 53 H...…”

mentioning

confidence: 99%

The clinical and immunologic impact of using interferon and ribavirin in the immunosuppressed host

Braun

Vierling

2003

Liver Transplantation

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C irrhosis caused by chronic hepatitis C virus (HCV) infection is the leading indication for cadaver and living donor liver transplantation. 1 Recurrent HCV infection, which occurs within days in virtually all allografts, is associated with a 10-to 20-fold increase in serum HCV RNA levels because of enhanced replication stimulated by immunosuppression. 2,3 A majority develop acute hepatitis C 1 to 4 months post-orthotopic liver transplantation (OLT) that is characterized by lymphocytic infiltration and hepatocyte apoptosis. Progression to chronic hepatitis C is associated with: (1) decline in HCV RNA levels observed in the acute phase because of effects of HCVspecific CD4 T helper subtype 1 (T H 1) and CD8 cell responses, (2) profibrotic effects of interferon-␥ (IFN-␥), and (3) proapoptotic effects of increased hepatocyte expression of Fas. 3 Progression of chronic hepatitis C is accelerated in immunosuppressed patients post OLT, resulting in a cumulative probability of cirrhosis in 30% by 5 years. 4 In addition, a minority develop severe, usually fatal, cholestatic hepatitis C within the first 6 months after OLT that is characterized by a direct cytopathic effect of excessive intrahepatic replication of HVC, intrahepatic anti-inflammatory T H 2 cytokine expression, and absence of an HCV-specific immune response. 3 Studies of the impact of different immunosuppressive regimens on recurrent hepatitis C also have been performed in an attempt to reduce hepatitis C progression while preventing acute cellular rejection (ACR). 5 Overall, HCV infection significantly reduces graft and patient survival compared with patients who undergo OLT for non-HCV-related indications. 6 Results of re-OLT are poor, 7 and this is an increasingly unrealistic option in view of the shortage of organ donors.To prevent morbidity and mortality associated with recurrent hepatitis C, many centers have used interferon alfa (IFN-␣) and/or ribavirin (RVN) as either antiviral prophylaxis or treatment of established hepatitis C or hepatitis B. Regimens have ranged from

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An open trial of interferon alfa recombinant for hepatitis C after liver transplantation: Antiviral effects and risk of rejection

Cited by 233 publications

References 16 publications

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

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

The efficacy of prophylactic interferon alfa-2b in preventing recurrent hepatitis C after liver transplantation

The clinical and immunologic impact of using interferon and ribavirin in the immunosuppressed host

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