Interferon-?? And Ribavirin for the Treatment of Recurrent Hepatitis C After Liver Transplantation1

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...

Section: Treatment Of Established Hcv Infection In Liver Transplant Rmentioning

confidence: 99%

Section: Treatment Of Established Hcv Infection In Liver Transplant Rmentioning

confidence: 99%

Section: Treatment Of Established Hcv Infection In Liver Transplant Rmentioning

confidence: 99%

See 1 more Smart Citation

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

Shiffman¹,

Vargas²,

Everson³

2003

“…4). [31][32][33][34][35][36][37][38][39] Unfortunately, between 20% and 50% 37 of patients were unable to complete treatment because of drug-related serious adverse events. …”

Section: Ribavirinmentioning

confidence: 99%

Treatment of recurrent hepatitis C

Gane

2002

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.)

“…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

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