Sustained Virological Response Improves Fibrosis Progression and Reduces Mortality after Liver Transplantation

By Liz Highleyman

Liver transplantation is the only effective treatment for end-stage liver disease, but in individuals with hepatitis C virus (HCV) infection, the virus typically recurs in the new organ.

However, post-transplant treatment with interferon-based therapy can improve prognosis, as described in 2 recent journal articles.

Study 1

In the first study, reported in the February 15, 2007 issue of Transplantation, German researchers assessed the rate of fibrosis progression in 28 HCV-infected liver graft recipients who achieved sustained virological response (SVR) after treatment with either conventional interferon alpha-2b (n = 8), pegylated interferon alpha-2a (Pegasys) (n=12), or pegylated interferon alpha-2b (PegIntron) (n = 8), all in combination with ribavirin.

Results

• Liver biopsies performed before treatment and at 1, 3, and 5 years after treatment showed no significant increase in mean fibrosis scores within the first 3 years.

• Mean fibrosis scores were:

- 1.8 at baseline;
- 2.0 at 1 year;
- 2.1 at 3 years.

• 5 years after cessation of therapy, the mean fibrosis score declined to 1.4 (P = 0.2).

• 6 of 28 patients (21%) showed an increase in fibrosis scores, 5 (18%) experienced a decrease, and 17 (60%) showed no change.

• The yearly fibrosis progression rate was 0.75 before antiviral treatment and 0.15 after treatment.

In conclusion, the authors wrote, "Sustained virologic response is associated with a deceleration of fibrosis progression and might therefore play a major role in prevention of graft cirrhosis in hepatitis C virus-infected liver graft recipients."

Study 2

In the second study, described in the March 2007 Journal of Hepatology, Italian investigators analyzed the efficacy and effect on survival of antiviral therapy in 61 HCV-infected liver transplant recipients.

Participants were treated with 1mcg/kg pegylated-interferon alpha-2b once weekly plus 600-800 mg/day ribavirin. The planned duration of treatment was 24 or 48 weeks, depending on HCV genotype (the standard duration is 24 weeks for genotypes 2 or 3, and 48 weeks for genotype 1). Patients who failed to respond by week 24 were considered non-responders.

Results

• In an intention-to-treat analysis, 44 patients (72%) were considered "treatment failures," including:

- 31 non-responders;
- 4 relapsers;
- 9 dropouts.

• 17 patients (28%) achieved sustained virological response.

• Factors that predicted SVR were:

- genotype 2 HCV;
- higher doses of pegylated interferon/ribavirin;
- absence of liver cirrhosis.

• During follow-up, patients who achieved SVR had a significantly lower mortality rate compared with patients who experienced treatment failure (P < 0.01).

"Response rate to antiviral therapy in HCV re-infection after liver transplantation is higher if a full dose of antiviral drugs is administered and if treatment starts before histological cirrhosis has developed," the authors concluded. "Sustained virological response improves patient survival."

02/23/07

References

M Bahra, U P Neumann, D Jacob, and others. Fibrosis progression in hepatitis C positive liver recipients after sustained virologic response to antiviral Combination Therapy (Interferon-Ribavirin Therapy). Transplantation 83(3): 351-353. February 15, 2007.

F P Picciotto, G Tritto, A G Lanza, and others. Sustained virological response to antiviral therapy reduces mortality in HCV reinfection after liver transplantation. Journal of Hepatology 46(3): 459-465. March 2007.

A Kuo and N A Terrault. Antiviral therapy in liver transplant recipients: Is SVR the only endpoint that matters? (Editorial). Journal of Hepatology 46(3): 359-361. March 2007.