Pilot study of the combination of interferon alfa and ribavirin as therapy of recurrent hepatitis C after liver transplantation

Abstract

End-stage liver disease caused by hepatitis C virus (HCV) units 3 times weekly) and oral ribavirin (1,200 mg/d) for a infection has become the most common indication for orduration of 6 months, followed by maintenance with ribavirin thotopic liver transplantation (OLT). The resurgence of HCV alone for an additional 6 months. Twenty-one liver transplant following transplantation is characterized early on by the recipients with recurrent hepatitis C infection (HCV-RNA-detection of HCV-RNA in serum and liver. The natural hispositive; active hepatitis without rejection on biopsy) were tory and long-term outcome of HCV recurrence following enrolled in this study. Pretreatment serum alanine transami-OLT remain uncertain. The histological consequences of nase (ALT) levels were at least two times the upper limit of HCV infection are more severe in patients after OLT than in normal. Before treatment, all patients were HCV-RNA-posi-nonimmunosuppressed subjects.1 Indeed, over 50% of liver tive and mean HCV-RNA titers were 125 million genome-transplant patients develop chronic active hepatitis after two equivalents/mL. Mean pretreatment histological score was 6.3 years; 2 subsequent progression to cirrhosis threatens graft { 2. After 6 months of combination therapy, all 21 patients function and patient survival.3 Currently, no effective prehad normal ALTs. Ten patients (48%) cleared HCV-RNA from ventive or therapeutic interventions are available to halt this their serum, as assessed by polymerase chain reaction (PCR), progressive deterioration of the graft. and HCV-RNA levels decreased significantly in the others (P The mechanisms of HCV-induced liver damage after trans-Å .0001). Improvement in histological score was seen in all plantation are poorly understood. Immunosuppression is patients after combination therapy (P Å .0013). During main-likely a major factor, because it is associated with a dramatic tenance ribavirin monotherapy, ALT remained normal in all increase of viral replication resulting in high-circulating but 1 of the 18 patients who tolerated therapy. HCV-RNA HCV-RNA levels, 16-fold higher than pretransplant values. 4 reappeared in 5 patients, but HCV-RNA levels did not return It also has been suggested that infection by genotype 1b (the to pretreament levels (P Å .0004). Comparison of pretreat-most common in this setting) has a more aggressive course ment and postribavirin monotherapy liver biopsies revealed following transplantation and that this occurs independently improvement in all but 1 of the 18 patients who tolerated of the viral burden. 5 ribavirin (P Å .0002). Side effects were restricted to anemia, Because high HCV-RNA titers and HCV 1b genotype are which necessitated cessation of ribavirin therapy in 3 patients. two of the unfavorable predictors for the lack of response to No patient experienced graft rejection during the study pe-interferon alfa (IFN-a) therapy, 6-7 it is not surprising that riod. These results are significantly better than those reported IFN-a has not been found to be effectiv...

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

“…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. Overall, SVR was achieved in 20% to 25% of treated patients.…”

“…This led to discontinuation of RBV alone or both IFN and RBV in up to half of all patients. [111][112][113][114][115][116] Of patients who remained on RBV, the mean dose that could be tolerated was only 600 mg/d. 114 Dose reduction of either IFN and/or RBV was required even in some patients administered GCSF and/or epoetin-alfa.…”

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

“…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...…”

Erratum to: Cholestatic Hepatitis C in Immunocompromised Settings

“…Because of the improved results of combination IFN and ribavirin therapy in immunocompetent HCV patients, combination interferon and ribavirin were used to treat recurrent HCV after liver transplantation, although often in the setting of mild recurrence [41]. Gopal et al [42] studied the safety and efficacy of antiviral treatment in 12 patients who developed moderate to severe HCV recurrence after transplantation.…”