Prophylaxis Of Recurrent Hepatitis B In Chinese Patients After Liver Transplantation Using Lamivudine Monotherapy Or Lamivudine Combined With Hepatitis B Immune Globulin

Liver Transplantation for Patients withChronic Hepatitis B in China with the Use ofLamivudine Monotherapy or LamivudineCombined with Individualized Low-doseIntramuscular Hepatitis B ImmunoglobulinObjective: The aim of this study was designed to evaluate the outcomes of liver transplant recipients with chronic hepatitis B in China receiving either lamivudine (LAM) monotherapy or LAM combined with individualized low-dose intramuscular (IM) hepatitis B immunoglobulin (HBIG) therapy.Methods: A total of 111 liver transplant recipients with chronic hepatitis B were nonrandomized devided into two groups according to the availability of HBIG before liver transplantation (LT). Thirty-two patients received LAM monotherapy (100mg qd) and 79 patients received LAM (100mg qd) combined with individualized low-dose IM HBIG according to maintaining an expected titer of antibody to hepatitis B virus (HBV) surface antigen (anti-HBs) not less than 100 IU/L post-LT, respectively. The overall patients have been followed up for a median time of 32 months (1～88 months).Results: In LAM monotherapy group: hepatitis B relapsed in 5 patients (3/5 developed YMDD mutants of HBV), with 1-, 2-, and 3-year cumulative recurrence rates and survival rates of 7.10%, 14.30%, 17.90% and 87.50%, 84.40%, 74.60%, respectively. In LAM and HBIG combination therapy group, hepatitis B relapsed in 2 patients (2/2 developed YMDD mutants of HBV), with 1-, 2-, and 3-year cumulative recurrence rates and survival rates of 0.00%, 1.80%, 5.70% (P < 0.01) and 83.50%, 80.90%, 77.60% (P > 0.05), respectively.Conclusions: Compared with LAM monotherapy, LAM combined with individualized low-dose IM HBIG can further reduce the recurrence risk of hepatitis B in liver transplant recipients with chronic hepatitis B post-LT, which could be used as a much rational strategy for prophylaxis of hepatitis B recurrence in such patients in China. The Epidemiologic Study of Hepatitis BVirus Infection after Liver TransplantationFor Patients with Hepatitis B in China—ASingle Center 7 Years ExperiencesObjective: The aim of this study was designed to evaluate the influence of related risk factors and prophylaxis strategies on hepatitis B virus (HBV) infection after liver transplantation(LT) for patients with hepatitis B in China, through an epidemiologic study of 299 patients received LT for hepatitis B in a single center from China during the past 7 years.Methods: In group A, 45 patients received the prophylaxis of LAM monotherapy (100mg,qd) post-LT. In group B, C and D, 153, 58, 43 patients received the prophylaxis of low-, moderate-, or high-dose hepatitis B immunoglobulin (HBIG) combined with LAM(100mg,qd) post-LT, respectively. The mean follow-up of the study was 22.30±18.30 months.Results: A total of 20 patients were confirmed to be infected with HBV during follow-up, including 8 cases with persistent HBV infection from liver grafts and 12 cases with hepatitis B recurrence for HBV-YMDD mutants(6/12), or HBV S-gene mutants(4/12) or compliance decrease(4/12). The 1-, 2-, 3-year cumulative HBV infection rates of group A and B was 3.00%, 12.00%, 28.00% and 1.00%, 3.00%, 9.00%, respectively, while no case developed hepatitis B recurrence in group C and D(P<0.01). Cox regression model showed that HBV-YMDD mutants, HBV S-gene mutants and compliance decrease were high risk factors for hepatitis B recurrence post-LT, respectively, while the 4 groups of prophylaxis strategy was protective fator for it.Conclusions: Under combination prophylaxis of LAM and HBIG, the recurrence risk of hepatitis B in Chinese patients received LT for hepatitis B can be reduced into a lower rate. Both HBV mutants and patients compliance decrease are high risk factors for hepatitis B recurrence post-LT. Liver grafts with HBV infection should not used except when other better alternatives unavailable. The Prevalence of Hepatitis B Virus S Mutants in Patients Infected withHepatitis B Virus after LiverTransplantation and Its ClinicalSignificanceObjective: To examine the prevalence of hepatitis B Virus (HBV) S mutants in patients infected with hepatitis B virus after liver transplantation (LT) and its clinical significance.Methods: A total of 299 patients undergoing LT for HBV realated liver diseases in a single center of China during 7 years were included in the study. After LT, 45 patients received lamivudine monotherapy, and 254 patients received combination therapy of hepatitis B immunoglobulin and lamivudine. S mutants in patients infected with HBV after LT were examined with sanger's enzymic method.Results: Twenty patients were infected with HBV after LT, including 8 cases with HBV infection from liver grafts, 12 cases with hepatitis B recurrence, and 4 cases with S mutants. The prevalence of S mutants was 1.34% (4/299), 25.00% (2/8), and 16.67% (2/12) in overall patients, patients with HBV infection from liver grafts and patients with hepatitis B recurrence, respectively. There was only one type of S mutants characterized with Thr126Ile and Gly145Ala in one patient attributed to HBV infection after LT.Conclusions: There is relatively lower rate of HBV infection after LT for patients with HBV related diseases in China. However, S mutants with variable types are moderately prevalent in patients with HBV infection after LT, and its clinical significance should be individually evaluated by considering the serology of HBV markers. Preliminary study of Clinical pathology ofrecurrent hepatitis B after livertransplantationObjective: To investigate the clinical pathology of recurrent hepatitis B after liver transplantation (LT).Methods: Clinical manifestation and hepatic pathological characteristics of 12 patients with recurrent hepatitis B after LT were examined in the study, using HE staining, immunochemical stainging of HBsAg and HBcAg, tissue in situ hybridization of HBV-DNA, and Mallory's trichrome staining.Results: Patients with recurrent hepatitis B at early stage were characterized by active HBV replication, mild-to-moderate abnormity of liver function in clinical manifestation, and mild-to-moderate viral hepatitis in pathology. Four patients without effective antivirus therapy at early stage of recurrent hepatitis B were advanced into fibrosing cholestatic hepatitis eventually, which is marked by active HBV replication, progressive jaundice and rapid deterioration of liver function in clinical manifestation, and nodular liver regeneration, cellular and canalicular cholestasis, extensive periportal fibrosis and inflammation, and ductal-type epithelium hyperplasia.Conclusions: Recurrent hepatitis B in clinical pathology is characterized by mild-to-moderate viral hepatitis at early stage and fibrosing cholestatic hepatitis at end stage. With effective viral hepatitis at early stage, recurrent hepatitis B at early stage could be reversed and prevented from advancing into fatal fibrosing cholestatic hepatitis with poor prognosis.