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• W2000222118 abstract "Living donor liver transplantation is an alternative therapeutic option for patients with end-stage HCV cirrhosis because of the cadaveric organ shortage. Preliminary results, however, indicate that live donor grafts might be disadvantageous for HCV patients. Sixty-seven patients underwent living donor liver transplantation for HCV cirrhosis between 1996 and 2004. All the patients preemptively received antiviral therapy consisting of interferon alfa-2b and ribavirin, which was started approximately 1 month after the operation. The therapy continued for 12 months after the first negative HCV RNA test. The patients were then observed without the therapy for 6 months. The therapy was continued for at least 12 months, even when the HCV RNA test remained positive. The subjects were removed from the protocol if they could not continue the therapy for 12 months because of adverse effects or could not start the therapy because of early death. Twelve patients were removed from the protocol as a result of early death (n = 9) or cessation of the drug (n = 3). Another 16 patients are currently on the protocol. Of the remaining 39 patients, 16 patients (41%) had a sustained virologic response. The cumulative 5-year survival of the HCV-positive patients was 84%, which was comparable with that of patients negative for HCV (n = 168, 86%). The present preemptive antiviral protocol after living donor liver transplantation is safe and warrants a controlled study to confirm its benefit on graft survival. Living donor liver transplantation is an alternative therapeutic option for patients with end-stage HCV cirrhosis because of the cadaveric organ shortage. Preliminary results, however, indicate that live donor grafts might be disadvantageous for HCV patients. Sixty-seven patients underwent living donor liver transplantation for HCV cirrhosis between 1996 and 2004. All the patients preemptively received antiviral therapy consisting of interferon alfa-2b and ribavirin, which was started approximately 1 month after the operation. The therapy continued for 12 months after the first negative HCV RNA test. The patients were then observed without the therapy for 6 months. The therapy was continued for at least 12 months, even when the HCV RNA test remained positive. The subjects were removed from the protocol if they could not continue the therapy for 12 months because of adverse effects or could not start the therapy because of early death. Twelve patients were removed from the protocol as a result of early death (n = 9) or cessation of the drug (n = 3). Another 16 patients are currently on the protocol. Of the remaining 39 patients, 16 patients (41%) had a sustained virologic response. The cumulative 5-year survival of the HCV-positive patients was 84%, which was comparable with that of patients negative for HCV (n = 168, 86%). The present preemptive antiviral protocol after living donor liver transplantation is safe and warrants a controlled study to confirm its benefit on graft survival. Living donor liver transplantation (LDLT) is now a common alternative procedure to deceased donor liver transplantation (DDLT), which reduces waiting-time mortality in an era of deceased donor shortage. By June 2003, 1275 LDLT cases were recorded in the European Liver Transplantation Registry.1Data from European Liver Transplant Registry. Available at: http://www.eltr.org/publi/index_rv.php3. Accessed April 12, 2005.Google Scholar The 3-year graft survival rates were 71%, although the survival rates of HCV-positive patients are unknown. In the United States,2Data from Organ procurement and transplantation network. Available at: http://www.optn.org/latestData/advancedData.asp. Accessed April 12, 2005.Google Scholar 1526 adult LDLT cases were performed by May 2004. HCV is the most common indication for LDLT, and the number of HCV-positive patients is stable, approximately 100 per year between 2000 and 2002. According to the Japanese Liver Transplantation Society,3The Japanese Liver Transplantation SocietyLiver transplantation in Japan registry by the Japanese Liver Transplantation Society.Jpn J Transplant. 2004; 39 (in Japanese): 634-642Google Scholar 1335 adult LDLT procedures were performed in Japan by the end of 2003, and of these 297 (22%) were performed for HCV cirrhosis. A current debate in the field of liver transplantation is the possibility of increased severity of recurrent HCV infection in LDLT patients. If HCV recurs earlier and more severely after LDLT, a specific strategy for preventing the detrimental effects of HCV on living donor grafts must be developed. Preemptive interferon therapy (prophylaxis) during the early post-transplantation period might reduce the incidence and severity of HCV recurrence. In the present study, we report our results of LDLT for chronic hepatitis C and discuss the feasibility of an antiviral protocol. We performed preemptive therapy for LDLT patients with HCV infection. From 1996–2004, 67 patients underwent LDLT for HCV cirrhosis at the Tokyo University Hospital. The patients were 51 men and 16 women, and their ages ranged from 23–63 years (median, 55 years). The HCV genotype was 1b in 53 patients (79%). Forty-one patients (61%) had hepatocellular carcinoma. Our surgical technique for recipient and donor surgery is described elsewhere.4Sugawara Y. Makuuchi M. Sano K. et al.Vein reconstruction in modified right liver graft for living donor liver transplantation.Ann Surg. 2003; 237: 180-185PubMed Google Scholar All the patients received the same immunosuppressive regimens with tacrolimus (Prograf; Astellas Pharma Inc, Tokyo, Japan) and methylprednisolone as described previously.5Sugawara Y. Makuuchi M. Kaneko J. et al.Correlation between optimal tacrolimus doses and the graft weight in living donor liver transplantation.Clin Transplant. 2002; 16: 102-106Crossref PubMed Scopus (86) Google Scholar All the patients preemptively received antiviral therapy consisting of interferon alfa-2b and ribavirin, which was started approximately 1 month after the operation. The therapy was continued for 12 months after the first negative HCV RNA test. The standard regimen included interferon alfa-2b (3 million units [MU] ×3 per week) and ribavirin (800 mg/day) for 6 months. The patients were then observed without the therapy for 6 months. The therapy was continued for at least 12 months, even if the HCV RNA test remained positive. Therapy was discontinued when there was significant leukopenia (<1500/mL), thrombocytopenia (<50,000/mL) despite application of granulocyte colony-stimulating factor (Gran; Sankyo Co Ltd, Tokyo, Japan), hemolytic anemia (hemoglobin <8 g/L), renal dysfunction (serum creatinine >2 mg/dL), depressive psychologic status, or general fatigue. The subjects were removed from the protocol if they could not continue the therapy for 12 months because of adverse effects or could not start the therapy as a result of early death. Blood counts and liver function test results were checked every 2 weeks for the first month and at 4-week intervals thereafter. Serum samples were collected once a month for quantitative HCV RNA detection. Protocol liver biopsy was not performed. The log-rank test was used to compare the survival rate of the HCV-positive patients with the HCV-negative patients who underwent transplantation during the same period (n = 168). A total of 28 patients were excluded from the analysis (Figure 1). Twelve patients were removed from the protocol because of early death (n = 9) or because of drug cessation (n = 3). Another 16 patients are currently on the protocol and were therefore excluded from the analysis. Of the remaining 39 patients, 16 (41%) obtained a sustained virologic response. The cumulative 5-year survival of the HCV-positive patients was 84%, comparable with that of patients negative for HCV (n = 168, 86%). Because interferon is more effective in patients with a lower viral load,6Yamada G. Takatani M. Kishi F. et al.Efficacy of interferon alfa therapy in chronic hepatitis C patients depends primarily on hepatitis C virus RNA level.Hepatology. 1995; 22: 1351-1354PubMed Google Scholar initiating preemptive therapy before peak viral loads are reached is a rational approach. There is, however, a theoretical risk of increasing cellular rejection, as observed in kidney and liver transplantation.7Samuel D. Hepatitis C, interferon, and risk of rejection after liver transplantation.Liver Transpl. 2004; 10: 868-871Crossref PubMed Scopus (22) Google Scholar Preemptive therapy during the early post-transplantation period with interferon in combination with ribavirin has been attempted in DDLT. In a case series by Mazzaferro et al,8Mazzaferro V. Tagger A. Schiavo M. et al.Prevention of recurrent hepatitis C after liver transplantation with early interferon and ribavirin treatment.Transplant Proc. 2001; 33: 1355-1357Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar 36 recipients were treated with interferon alfa-2b (3 MU ×3 per week) and ribavirin (10 mg · kg−1 · day−1). Treatment was started a median of 18 days after the operation and continued for 11 months. After a median follow-up of 52 months, the 5-year patient survival was 88%. Serum HCV RNA clearance was obtained in 12 patients (33%). No further antiviral treatment was required because of negative HCV RNA in serum and normal liver histology for a median of an additional 36 months. In another study,9Mazzaferro V. Schiavo M. Caccamo L. et al.Prospective randomized trial on early treatment of HCV infection after liver transplantation in HCV RNA positive patients.Liver Transpl. 2003; 9 (abstract): C-36Google Scholar 63 patients (<50% of screened cases) were randomized within 4 weeks after DDLT and treated for 48 weeks: 20 control subjects, 21 interferon alone, and 22 interferon and ribavirin. At 2 years, HCV RNA was negative in 13%, 13%, and 33%, respectively. Remarkably, there was no histologic recurrence in patients with a sustained viral response. The association between LDLT and early HCV recurrence remains to be determined,10Sugawara Y. Makuuchi M. Should living donor liver transplantation be offered to patients with hepatitis C virus cirrhosis?.J Hepatol. 2005; 42: 472-475Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar although most of the recent reports suggest that living donor graft has no effect on short-term outcome or severity of virus recurrence. Reports from New York-Presbyterian Hospital11Gaglio P.J. Malireddy S. Levitt B.S. et al.Increased risk of cholestatic hepatitis C in recipients of grafts from living versus cadaveric liver donors.Liver Transpl. 2003; 9: 1028-1035Crossref PubMed Scopus (108) Google Scholar indicate that the time to diagnosis of recurrent HCV is significantly shorter in LDLT. Other data indicate that the 5-year survival of HCV patients (n = 69) who undergo LDLT is 64%, which is comparable with that of DDLT patients (n = 202, 69%). The multicenter adult to adult LDLT cohort study (A2ALL) might soon provide answers to questions about recurrent HCV after LDLT and DDLT.12Russo M.W. Shrestha R. Is severe recurrent hepatitis C more common after adult living donor liver transplantation?.Hepatology. 2004; 40: 524-526Crossref PubMed Scopus (17) Google Scholar In areas where the cavaderic organ source is almost negligible, LDLT must be selected as a therapeutic option, regardless of any potential additional risk. The results of LDLT for HCV cirrhosis in our hospital were comparable with those for non-HCV patients. If living donor graft is associated with early HCV recurrence and consequently poorer graft survival, an aggressive antiviral protocol should be performed to improve the outcome of LDLT for HCV. The present data indicate that the protocol after LDLT is safe and warrants a controlled study to confirm its benefit for graft survival." @default.
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• W2000222118 title "Living Donor Liver Transplantation for Patients With Hepatitis C Virus Cirrhosis: Tokyo Experience" @default.
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