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

Abstract

Recurrence of hepatitis C virus infection after liver transplantation is universal. A significant percentage of these patients develop progressive graft injury and cirrhosis. Those factors that modulate disease progression in liver transplant recipients with recurrent hepatitis C virus infection remain controversial and are poorly understood. Treatment of recurrent hepatitis C virus after liver transplantation with either interferon or interferon and ribavirin has yielded only limited success. Regardless of this, treatment is instituted. Peginterferon is more effective than standard interferon for treatment of chronic hepatitis C virus infection in the nontransplantation setting when used either alone or with ribavirin. The effectiveness of peginterferon, both with and without ribavirin in the posttransplantation setting, is currently being explored. In this review those factors thought to affect disease progression in patients with recurrent hepatitis C virus will be discussed, strategies that have been used to treat recurrent hepatitis C virus will be reviewed, and the impact that peginterferon may have on hepatitis C virus infection in the pretransplantation and posttransplantation setting will be explored. C irrhosis secondary to chronic infection with the hepatitis C virus (HCV) is the leading indication for liver transplantation. 1,2 Although transplantation is an effective treatment for end-stage liver disease secondary to chronic HCV infection, virus recurs in essentially all patients. 1-3 Progressive graft injury leading to cirrhosis occurs in about 25% to 33% of patients within just 5 years. [4][5][6][7][8] In addition, a limited group of patients (about 1% to 5% of recipients) develop rapidly progressive cholestatic hepatitis and liver failure within just 1 to 2 years. [8][9][10][11] Numerous studies have attempted to identify those factors that affect disease progression in these patients. Unfortunately, nearly all studies in this area have been retrospective in nature, conducted in patient populations of limited size, at single centers, utilized an array of immune suppressive medications in an uncontrolled manner, and have failed to consistently utilize protocol liver biopsy to investigate histologic progression. In addition, allograft rejection has not been either universally defined or treated and assays to measure serum HCV RNA have varied between centers and changed over time. As a result, data from many studies seem to contradict each other and the interpretation of these findings has varied widely. It is therefore not surprising how little progress has been made in our understanding of recurrent HCV over the past decade and that no universally accepted algorithm for managing these patients has emerged.Interferon (IFN) alfa with or without ribavirin (RBV) is the treatment of choice for patients with chronic HCV infection. 12,13 These medications have also been used to treat recurrent HCV after liver transplantation, but the interpretation of these data has been plagued by a similar set of limit...

Treatment of chronic hepatitis C virus genotype 1 with peginterferon, ribavirin, and epoetin alpha†

“…Approximately 10% of such patients experience a profound decline in serum hemoglobin, by 4 g or greater, within several weeks of initiating treatment and must interrupt or stop therapy. 30 Severe hemolytic anemia secondary to PEGIFN and RVN therapy is also much more common in patients with cirrhosis awaiting liver transplantation, 31 in patients with recurrent HCV following liver transplantation, 32 in patients with hemoglobinopathies, 33 and in those with chronic renal insufficiency. 34 It is unlikely that such patients could be successfully treated with PEGIFN and RVN without the use of a hematologic growth factor.…”

Liver and Intestine Transplantation in the United States, 1995–2004

“…Nearly all patients with chronic HCV develop recurrent disease (16). Recurrent HCV progresses to cirrhosis at a faster rate in liver transplant recipients compared to their nontransplant counterparts and survival in these recipients also appears to be significantly reduced (17).…”

Hepatitis C treatment before and after liver transplant

“…In addition, the immunomodulatory effect of interferon can increase the risk of acute cellular rejection, which is higher in this phase of the transplant process. Another criticism of pre-emptive treatment is that it does not distinguish patients who will actually evolve to a more significant recurrence of the disease and for whom treatment is indicated, from those who might have no need of antiviral therapy after the transplant [30,31].…”