Antiviral therapy in HCV-infected cirrhotic patients awaiting liver transplantation
Authors: Jose A. Carrion, Miquel Navasa, Xavier Forns
Journal: Journal of Hepatology (2009)

We would like to thank Niemczyk et al. [[1]Niemczyk M. Krawczyk M. Pączek L. Antiviral therapy preceding liver transplantation in HCV cirrhosis – Still too many doubts.J Hepatol. 2009; 51: 960Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar] for reading our manuscript [[2]Carrion J.A. Martinez-Bauer E. Crespo G. Ramirez S. Perez-Del-Pulgar S. Garcia-Valdecasas J.C. et al.Antiviral therapy increases the risk of bacterial infections in HCV-infected cirrhotic patients awaiting liver transplantation: a retrospective study.J Hepatol. 2009; 50: 719-728Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar] and taking the time to make some comments. We would like, however, to clarify some of the criticisms they made: 1. First, contrary to what was claimed we did not omit the survival endpoint in the manuscript. In fact, in the Results section of the paper [[2]Carrion J.A. Martinez-Bauer E. Crespo G. Ramirez S. Perez-Del-Pulgar S. Garcia-Valdecasas J.C. et al.Antiviral therapy increases the risk of bacterial infections in HCV-infected cirrhotic patients awaiting liver transplantation: a retrospective study.J Hepatol. 2009; 50: 719-728Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar] we clearly state that 5 patients died before LT (4 from the treated group, 1 from the control group) and that 2 from the treated group died because of a severe infection. We clearly state that “differences in survival before LT may not have reached statistical significance due to the small size of the cohort” (p. 723). Probably, the authors of the letter missed this paragraph when reading the paper. Since the number of events (deaths) is small, we cannot make a strong case on this issue. In any case mortality needs to be analyzed not only before transplantation but also after LT, particularly due to the fact that hepatitis C recurrence is the first cause of graft (and patient) loss in a significant number of liver transplant programs [3Forman L.M. Lewis J.D. Berlin J.A. Feldman H.I. Lucey M.R. The association between hepatitis C infection and survival after orthotopic liver transplantation.Gastroenterology. 2002; 122: 889-896Abstract Full Text Full Text PDF PubMed Scopus (949) Google Scholar, 4Garcia-Retortillo M. Forns X. Llovet J.M. Navasa M. Feliu A. Massaguer A. et al.Hepatitis C recurrence is more severe after living donor compared to cadaveric liver transplantation.Hepatology. 2004; 40: 699-707Crossref PubMed Scopus (168) Google Scholar]. 2. We believe that we have been very cautious when making recommendations based on our results. In fact, since severe infections occurred in patients with advanced liver failure (Child C), we stated that “antiviral treatment should not be recommended in patients with a baseline Child–Pugh >9 or MELD >18” (p. 727). 3. Exclusion of 4 patients from the treated group was not owing to death, as the authors suggest. Patients did not undergo liver transplantation due to central pontine myelinolysis (1 patient), lack of family support (1 patient) and progression of hepatocellular carcinoma (2 patients) while awaiting liver transplantation. 4. The authors state that treatment with interferon before transplantation may be detrimental and increase the severity of hepatitis C recurrence after LT. They based this statement citing an abstract (which by the way is already published as a full paper [[5]Smallwood G.A. Devine R. Fasola C. Stieber A.C. Heffron T.G. Does interferon use prior to liver transplant influence hepatitis C outcomes following transplantation?.Transplantation. 2008; 86: 1795-1798Crossref PubMed Scopus (9) Google Scholar]). If the authors read the manuscript carefully, they will realize that in the referred study, any previous exposure to interferon was considered as treatment, and thus, these were not patients treated while awaiting LT. In our experience, based on treatment of approximately 90 patients while awaiting LT, we did not observe any differences in the severity of hepatitis C recurrence between non-responders and patients who did not undergo antiviral therapy in the waiting list (unpublished data). We would like to add two more comments regarding this point: (a) there are no solid data in the literature suggesting changes in the outcome of hepatitis C recurrence in patients treated with interferon-based regimens while awaiting LT; (b) currently, most patients undergo interferon (and ribavirin) treatment at some point during the course of their disease and, with the use of more efficient treatment regimens, this proportion will increase in the future. Refraining from treating patients who have a reasonable chance to clear HCV based on unsustained observations is not acceptable. 5. It is obvious that a randomized controlled study would be the best approach to validate the results that we (and others [2Carrion J.A. Martinez-Bauer E. Crespo G. Ramirez S. Perez-Del-Pulgar S. Garcia-Valdecasas J.C. et al.Antiviral therapy increases the risk of bacterial infections in HCV-infected cirrhotic patients awaiting liver transplantation: a retrospective study.J Hepatol. 2009; 50: 719-728Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar, 6Everson G.T. Trotter J. Forman L. Kugelmas M. Halprin A. Fey B. et al.Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy.Hepatology. 2005; 42: 255-262Crossref PubMed Scopus (337) Google Scholar, 7Forns X. Garcia-Retortillo M. Serrano T. Feliu A. Suarez F. de La M.M. et al.Antiviral therapy of patients with decompensated cirrhosis to prevent recurrence of hepatitis C after liver transplantation.J Hepatol. 2003; 39: 389-396Abstract Full Text Full Text PDF PubMed Scopus (282) Google Scholar]) have published. Regretfully, the design of such a study is very difficult and should involve many experienced centers. It is possible that the use of specifically targeted therapy for HCV will soon be a choice for patients with advanced liver disease. Meanwhile, our algorithm to decide treatment of patients awaiting LT is shown above (Fig. 1).