Study of Treatment for HCV Following Recurrence of HCV After Liver Transplant

Following liver transplantation, hepatitis C usually recurs. This recurrence often leads to cirrhosis within 5 years. So, treatment of HCV is an important factor in surviving the liver transplant & doing well over a long period of time. Patients with recurring HCV after transplant were treated with standard interferon 3 MIU three times per week plus ribavirin (800-1000 mg per day). 50 partients were treated. 4 patients died (3 for HCV related causes), 3 patients had to discontinue therapy, and dose reduction was necessary in 38%. A sustained virologic response (6 months after stopping treatment) was seen in 20% of patients. For those patients who achieved viral eradication/suppression, there was no significant progression of fibrosis after 1 year of therapy. Treatment responses should improve with the availabiliy of pegylated interferon. Patients with HCV/HIV coinfection are not a high priority for liver transplants as there are a number of concerns including the status of the patient’s immune system & their ability to respond to HIV therapy. However, an experimental federally funded program to perform liver transplants in coinfected patients is being proposed for about 12 hospital based sites including in New York City. Preliminary work in liver transplants for HCV/HIV coinfected patients has been conducted. A relatively small number of such transplants have been conducted with mixed results. The best results appear to have been seen at the University of Pittsburgh transplant department where success has been seen but with a limited follow-up timewise. It appears to me that the preliminary research suggests that under the right circumstances a coinfected person can respond well to a liver transplant, but more research is needed and ongoing. For patients with HIV, it is crucial to get tested for HCV. Since HIV causes HCV to progress more quickly it is important to see a knowledgeable doctor in both HIV and HCV as soon as possible to discuss treatment strategies and to discuss a biopsy. NATAP has published a 20-page simple guide on HCV and HCV/HIV Coinfection, which is available by emailing us at info@natap.org

COMBINATION OF INTERFERON ALFA 2B AND RIBAVIRIN IN LIVER TRANSPLANT RECIPIENTS WITH HISTOLOGIC RECURRENT HEPATITIS
     C Roberto J. Firpi, David R. Nelson, Consuelo Soldevila, Manal F. Abdelmalek, Alan Reed, Alan Hemming, Richard Howard, William Van der Werk, Gregory Lauwers, Gary L. Davis, Univ of Florida, Gainesville,FL

BACKGROUND: Recurrent hepatitis C (HCV) is an important cause of progressive fibrosis and cirrhosis after liver transplantation (OLT). Histologic recurrence develops in at least 50% of patients within the first year, with progression to cirrhosis in about 20% by 5 yrs.

AIM: To assess the safety and efficacy of interferon alpha-2b plus ribavirin (Rebetron“, Schering Plough, Kenilworth, NJ) in histologic recurrent HCV after OLT.

METHODS: Since 1998, HCV post-OLT patients with significant histologic recurrence (fibrosis-3 and/or HAI-5) or a progressive cholestatic desease were treated with interferon alpha-2b (3MU SC tiw) plus ribavirin (800-1000 mg/d) for 12-18 months. Prior to therapy, immunosuppression was tapered to CyA/FK506 monotherapy. HCV RNA was assessed at entry, week 24, at the end of treatment (ETR), and 6-month after ETR. Liver biopsies were performed at inclusion, 12, and 24 months. Primary endpoint was loss of HCV RNA 6-month after the ETR, while secondary endpoint was histologic response.

RESULTS: 50 patients met criteria for treatment and have completed at least 6 months of therapy. Patients were mainly males (71% male; mean age 51 ± 5 yrs) with genotype 1 infection (65% 1a, 23% 1b, 6% 2b, 6% 3a) and high pretreatment viral load (mean HCV RNA of 43 ± 7 Meq/mL). Pretreatment histology reveals a mean fibrosis score of 3, with 16% stage 5/6 (cirrhosis). Four patients died (3 for HCV-related complications, 1 with pneumonia). Discontinuation of therapy was required in 3 other patients (cytopenias in 2 and chronic rejection in 1) and dose reduction was necessary in 38%. Intent-to-treat analysis showed that serum HCV RNA was undetectable in 16(32%), 20(40%), 10(20%) at week 24, at ETR, and at 6-month f/u, respectively. Of note, 2 eventual sustained responders had HCV RNA detectable after 6-month of therapy. Paired liver biopsies are available in 31 patients at 1-yr and 12 at 2-yr. In those who achieved viral eradication/suppression, there was no significant progression of fibrosis after 1-yr of therapy. Two-year histology data is ongoing and will be presented.

CONCLUSION: Treatment with interferon alfa-2b plus ribavirin in OLT patients with histologic recurrent HCV was effective in inducing a sustained virological response in 20% of patients. In the post-OLT setting, sustained response can still be achieved in a proportion of patients who are HCV RNA positive at 6-month. A randomized, controlled trial is needed to determine the histologic effect of viral eradication in the post-OLT setting.