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21 May 2009

Liver transplantation for hepatitis C – the special and relevant aspects from the point of own long term follow-up experience

U Ołdakowska-Jedynak

Ann Transplant 2009; 14(1): 16-16 :: ID: 880252


Hepatitis C virus (HCV) associated end-stage liver disease is an increasingly frequent indication for liver transplantation (ltx). Viral recurrence is universal, with development of histologic hepatitis in the majority of patients and accelerated fibrosis progression to cirrhosis in up to 30% after 5 years. In addition, a limited group of patients 1-5% develop rapidly progressive cholestatic hepatitis and liver failure within 1 to 2 years. Many studies have attempted to identify those factors that affect disease progression. The rate from cirrhosis to hepatic decompensation is accelerated. It remains unclear why within HCV- infected population, patients group develop progressive fibrosis and the relationship between degrees of fibrosis and immunosuppression levels The aim of this study was to describe the postransplantation history of HCV-infected patients, particularly to determine whether survival has decreased in comparison to that observed in non-HCV-infected recipients and to determine the clinical factors associated with HCV recurrence and disease severity after ltx. Donor and recipients variables have been evaluated and discussed for their influence on outcome in HCV-positive recipients population. Here I discuss the results and special, relevant aspects liver transplantation for hepatitis C from the point of view of own experiences of our HCV-positive recipients in long term follow-up At our institution, HCV disease was the primary diagnosis in 21% of cases transplanted between 1994-2004. In to this retrospective study entered 50 consecutive liver transplant recipients, who underwent ltx for HCV-related cirrhosis. The indication for ltx was either end-stage cirrhosis - 46 (92%) patients or cirrhosis with hepatocellular carcinoma (HCC) - 4 (8%) patients. Small HCC were discovered incidentally in the explanted liver in three additional cases. Increased donor age is the risk factor and important contributor for the frequency and severity of recurrent HCV liver disease. Also, several posttransplantation factors may impact on the pattern of recurrence and severity of liver disease. Donor age and cytomegalovirus infection (CMV) have been identified in our study as the risk factor for severity of HCV recurrence. Results from our study confirm previous assumption and observation from other studies. Patients who develop CMV infection after ltx present more aggressive recurrent liver disease. Donor age and CMV infection were significantly associated with more accelerated and aggressive clinical course of HCV recurrence after ltx in our observation in HCV-positive patients. Viral crosstalk or immunological interaction by proinflamatory cytokines might explain negative influence of CMVcoinfection. The current, intensified or "more potent"immunosuppression which comprised immunologic response of the recipients is also the relevant factor in the pathogenesis of HCV reinfection after ltx and important prognostic host factor of graft hepatitis..Recently used immunosuppressive protocols resulted in improving the overall outcome after ltx in HCV-negative, but not in HCV-positive liver transplanted patients. It has been suggested that the last decade was associated with higher incidence and severity of HCV recurrence after ltx. The results addressing maintenance immunosuppressive therapy are inconsistent and no specific agent has been convincingly demonstrated to be more advantageous than other in immunosuppressive therapy of HCV infected patients after ltx, especially in long term follow-up period. Many studies did not show any differences in long-term outcome of Tacrolimus and Cyclosporine A treated patients. In our own patient population, we could not determine whether a particular calcineurin ihhibitor has an advantage in patients undergoing ltx for HCV - related cirrhosis recipients group because Tacrolimus was the basic immunosuppressive agent used at our center during study period. Controversy evolves from other clinical trials regarding the corticosteroids use as a part of immunosuppressive medication of maintenance therapy, data on that are mixed and not clarified. The question about a benefit to avoiding corticosteroids in HCV-positive recipients is still open. In conclusion, appropriate donor and graft selection, if it possible, and maintain a sufficient level of immunosuppression, avoiding overall excess immunosuppression is mandatory. Sufficient and optimal immunosuppression, today hotly debated issue, however, is still difficult to translate into details concerning drugs and their therapeutic level and duration of treatment (including maintenance corticosteroids) for each patient. The frequency and more aggressive clinical course of HCV recurrence, accelerated rate of chronic hepatitic disease progression and subsequent graft failure observed in recent years in a substantial proportion of HCV-positive patients, contribute to the inferior patient and graft survival rates among the HCV infected liver recipients. This emphasizes the need for new strategies in the pre- and posttransplant therapeutic policies for HCV-positive liver transplant population to reduce or eliminate the risk factors hampering the general benefits of ltx.

Keywords: Hepatitis C, hepatitis C virus

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Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358