Hepatitis B Virus Reinfection Following Liver Transplantation:Clinical And Experimental Study

Part l Hepatitis B Virus Reinfection Following Liver Transplantation:A PreIiminary StudyOrthotopic liver transplantation(OLT) is the only treatTnent option for patientswith end-stage liver diseases. In China, a large majority of the liver transplantationrecipients are patients of 1iver cirrhosis or hepatocellu1ar carcinoma with HePatitis Bvirus (HBV) infection. However, the success of OLT for HBV is limited by theproblem of high frequency of recurrent HBV infection. HBV reinfection post-OLTfrequent1y causes aggressive hePatitis, and rapid progression to cirrhosis or livercancer may be observed. How to prevent HBV reinfection following livertransplantation is a key problem of successful OLT. With the deveIopment ofprophyIaxis of HBV reinfection fOllowing liver transPlantation in pro- or post-operative period, such as hepatitis B immunoglubin (HBIg) and lamivudine, the resultof HBV reinfection is promising. However, problems still remain to be solved asfollows f (l) HBIg is costly and short of supply, not aPproved for intravenous use'because of the potential risk ffr mercury toxicity. It is little Anown about the efficiencyof lamivudine monotheraPy in liver transplant recipients. (2) What will change aboutHBV serum markers when used lamivudine for prophylaxis. (3) DifficuIty of earydiagnosis of hepatitis B virus reinfection and recurrent hepatitis B following livertransplantation leads to difficulty of the further treatment of recurrent hepatitis B. (4)What effect do immunosuPpressive agents have on HBV reinfection.Patients and MethodsBforeen Jan.l999 and Mar. 200l, 40 patients with HBV-related liver diseaseunderwent liver transplantation at the First Affiliated Hospital of Medical School ofZhejiang University. A11 recipients survived Ionger than 1 month. The primarydiseases were decomPensated liver cirrhosis after hePatitis B, severe hePatitis,unresectable hepatocyte carcinoma (HCC), liver cirrhosis complicated with HCC, andincidenta1 cancer. Before trapsplantation HBsAg is positive in 40 cases (l00%),HBeAg positive in l0 cases (25%) and HBV DNA positive in l2 cases (30%).ViroIogical and Biochemical featUre were tested in due time including HBsAg,HBeAg, the corre8Ponding antibodies (ani-HBs, anti-HBe). HBcAb-IgM, serum HBVDNA, ImmunohistOchemical stUdy of HBsAg and HBcAg in Iiver biopsy SPecimen,and serum liver function. If HBV DNA tUrned to positive under lamivudine therapy,sequence ana1ysis of YMDD locus on the HBV DNA polymerase gene was done.Diagnosis of HBV reinfection after OLT was according to one of fOllows: (l) serumHBsAg positive, (2) serum HBV DNA positive, (3) serum HBcAb~IgM positive, (4)HBsAg and/br HBcAg positive in liver biopsy specimen. Diagnosis of hepatitis Brecurrence referred to common patients.The KaP1an-Meier survival method was used to estamate the cumu1ativeprobablility of HBV reinfection, a diagnosis of HBV reinfection was considered as theend point. Groups comPared univariately using the logrank test. All database ennyand statistical analysis were pefformed with SPSS version 10.0.ResultsIn All the 40 patients, Immunohistochemical stUdy showed HBsAg (--) andHBcAg (--) in Iiver biopsy hssue just after liver transplantation, All patients showedffee ofviro1ogical featUre in sera, including HBsAg (O, HBeAg (--), HBV DNA (--)and HBcAb-IgM (). Post-transP1ant fO1low-uP in these patients is 31 to 820 days(mean followup' 228 days). During this period of time, 6 cases acquired HBVreinfection and 3 cases had suffered recurrent hepahtis B. Six-month reinfechon raewas 12.2% and l2-month reinfection rate was 23.5%. HBV reinfection time was the50", 194", 62,,, 183", 80th and 47in days after trallsplantation respectively. Mutationin YMDD locus occurred in 2 patients, both G743T (M552I).The trCAnent for recurrent hePatitis B after liver transplantation includedincreasing dosage of lamiVUdine, aPplication of famciclovir, and other liverprotection m...