Hepatitis C Treatment after Liver Transplantation

By Liz Highleyman

Over time, chronic hepatitis C virus (HCV) infection can cause sever liver damage or liver cancer necessitating a liver transplant. Unfortunately, the virus usually re-infects the new liver. Interferon-based therapy can be used for post-transplant treatment, but patients often have trouble tolerating the side effects.

As reported in the October 2006 American Journal of Transplantation, researchers from Madrid conducted a study to assess the efficacy and safety of post-transplant treatment with full-dose pegylated interferon plus ribavirin.

The study included 55 patients who received standard full doses of pegylated interferon alpha-2a (Pegasys; n = 4) or pegylated interferon alpha-2b (Peg-Intron; n = 51) for 48 weeks, starting 12 months or more after receiving liver transplants.

The mean age was about 54 years, 77% of patients were men, most (90.9%) had genotype 1 HCV, and 32.7% had cirrhosis. All subjects had histologically proven HCV recurrence, and none had severe cholestasis (bile blockage). All but 5 received immunosuppressive monotherapy with tacrolimus (54.5%), cyclosporine (30.7%), or mycophenolate mofetil (5.5%).

Results

The end-of-treatment response and sustained virological response (SVR) rates were 66.7% and 43.6%, respectively.

Low baseline HCV viral load (P = 0.005) and a period of 2-4 years between liver transplantation and initiation of anti-HCV therapy (P = 0.011) were predictors of SVR.

Failure to achieve at least a 1 log decrease in HCV RNA at Week 4 and/or a 2 log decrease at Week 12 was 100% predictive of lack of SVR.

The most frequent side effects were neutropenia (76.4%), anemia (60.0%), and infectious complications (30.9%).

16 subjects (29%) discontinued pegylated interferon due to toxicity.

In 15 patients with post-treatment biopsies, histological activity index scores improved significantly (P = 0.006), but fibrosis scores did not change (P = 0.14).

3 patients died (1 each due to cholangitis, hepatic artery thrombosis, and lung cancer).

In conclusion, the authors wrote, "HCV therapy after liver transplantation was very effective, although it led to a significant rate of toxicity."

Changing Response to Therapy

In another study, reported in the August 2006 Journal of Viral Hepatology, Spanish researchers assessed whether response to interferon-based therapy was different before and after liver transplantation.

They evaluated 22 HCV positive patients who received antiviral therapy while awaiting liver transplants and who experienced HCV recurrence after transplantation; 11 underwent a renewed course of antiviral treatment. HCV sequences from hypervariable region 1 and the nonstructural 5A (NS5A) region before pre- and post-transplant treatment courses were compared.

Results

Of 11 patients, 8 (73%) showed identical early virological response (EVR) or non-response (NR) to both pre- and post-transplant courses of therapy (5 EVR/EVR, 3 NR/NR).

The response changed in 3 patients (27%): 2 previous non-responders achieved EVR after transplantation, whereas 1 with previous EVR became a non-responder.

Fixation of mutations within the NS5A region occurred preferentially in the group with differing response (100%) compared to those with similar response (37%)(P = 0.12).

However, the number of fixed mutations was not significantly different between the differing and similar response groups, suggesting that the changes in sensitivity to therapy after liver transplantation are not exclusively dependent on variations in HCV strains.

In conclusion, the authors wrote, "in HCV-infected patients undergoing liver transplantation, the pattern of response to antiviral treatment may change after transplantation, and this possibility needs to be incorporated in clinical practice."

10/13/06

References

Barcena, J M Moreno-Planas, and others. Recurrence After Liver Transplantation: Viral and Histologic Response to Full-Dose Peg-Interferon and Ribavirin. American Journal of Transplantation 6(10): 2348-2355. October 2006.

A Feliu, J A Carrion, A Massaguer, and others. Sensitivity to antiviral therapy may change after liver transplantation in patients with chronic hepatitis C virus infection. Journal of Viral Hepatitis 13(8): 544-551. August 2006.