Hepatitis C is the number one reason for liver transplantation in the United States.  Unfortunately, since the hepatitis C virus is in the blood the new liver will become re-infected.  In addition, the disease process can be much faster due to many factors, such as the use of immunosuppressive drugs to prevent the body’s rejection of the new liver but which also increase the rate of HCV replication and disease progression.  The faster disease progression can lead to decompensated cirrhosis and the possibility of the need for another liver transplant.  HCV treatment is urgently needed in these cases to eliminate HCV, and thereby help slow down or stop disease progression.  However, treatment success rates in people who are waiting for a transplant or have recently received a transplant are historically low.  This article will summarize a report conducted by F.D. Gordon and colleagues published in Liver Transplantation that reviewed available data on HCV treatment in post liver transplant patients with conventional interferon (with and without ribavirin) and pegylated interferon (with and without ribavirin).

The approach to treating hepatitis C after a liver transplant usually consists of two options:

Prophylactic: treat HCV immediately after transplantation to eliminate the virus before it has a chance to establish infection and damage the liver, or

Established infection: watch and wait using various screening tools and criteria to guide when and if treatment is needed

Prophylactic
One approach is to start treatment soon after receiving the liver transplant.  A review of literature found various studies using conventional (or standard) interferon (with and without ribavirin), and pegylated interferon (with and without ribavirin).  Treatment was started two to six weeks after transplantation.  In one study the sustained virological response rate (SVR – undetectable 24 weeks following treatment) was 4.5% in the patients who received conventional interferon or pegylated interferon monotherapy and 18.2% in the patients who received pegylated interferon (with and without ribavirin).  Due to the difficulty of using ribavirin in liver transplant patients the ribavirin dose was started at 600 mg/day and raised to 1000 to 1200 mg/day after 4 weeks with the goal of maintaining the ribavirin dose throughout treatment (note: only 9% were able to achieve this goal).  In another study using pegylated interferon monotherapy for 48 weeks only 8% of patients achieved an SVR.  These results are not very encouraging especially considering the high rate of side effects.  One of the reasons for the lower treatment response rates is the difficulty in maintaining the optimal dose of ribavirin since transplanted patients are already at risk for anemia.  There are also other issues that affect the lower treatment response rates such as the use of immunosuppressive drugs to prevent the body from rejecting the new liver, and the body’s need to recover from a major surgery.

Fast  Facts¹

• In 2000 there were 5000 liver transplants performed – 37% because of hepatitis C
• After transplantation: 10 to 20% of HCV patients will develop cirrhosis – the likelihood of developing decompensated cirrhosis within 12 months is 42% in those with cirrhosis
• The 3 year survival rate is considerably lower in people with hepatitis C who have received a liver transplant compared to those who had a liver transplant but who do not have hepatitis C (78.5% vs. 81.4%)
• The 5-year survival rate is 30% for those with HCV who have had a liver transplant and have progressed to cirrhosis

Established Infection
In patients treated after evidence of established infection the use of conventional interferon or pegylated interferon plus ribavirin produced SVR rates between 20% and 37%.  The authors noted that “a recent systematic review of predominantly therapeutic intervention studies also confirms that 30.2% of patients treated with pegylated interferon plus ribavirin will attain an SVR.”

Liver Transplantation Costs²

• Estimated first-year charge:  314,600
• Estimated yearly  follow-up charge:  21,900

The predictors of treatment response are more useful in this setting.  The best predictors of treatment response in the general HCV population are early virological response (EVR) which is defined as either elimination of HCV RNA or a 2 log10 drop of HCV RNA by week 12 of treatment.  Breaking it down by type of EVR appears to be even more important – in a treatment-naïve population a log drop ? 2 log10 produced a positive predictive value (PPV = the proportion of patients who are correctly predicted to achieve an SVR) of 21% compared to a PPV of 83% in the patients who were HCV RNA undetectable at week 12.  EVR and PPV have not been thoroughly studied in the post-transplant treatment population, but data from recent studies have found a PPV range of 49% to 69.2% that suggests the use of EVR is also useful in this setting.

The authors noted that identifying which patients are suitable for treatment at the pre-transplant stage, immediately following transplant stage (prophylactic) or after evidence of re-infection (established ) stage will be important to improve the SVR rates.  Two new studies – PHOENIX (Pegasys plus Copegus Administered After Liver Transplantation for Hepatitis C) and PROTECT (Pegylated Interferon Alfa-2b and Ribavirin After Orthotopic Liver Transplantation:  Efficacy and Safety in Hepatitis C Recurrence Therapy) will provide much needed information about the best strategies to improve HCV treatment outcomes in patients with post-transplant hepatitis C infection.

References
1 Liver Transplantation 15:126-136, 2009
2 Financial Matters:  Liver Transplant Cost, www.cpmc.org

Thanks to the HCV Advocate and Alan Fransiscus for this information:

http://www.hcvadvocate.org

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