Prophylaxis and treatment of hepatitis B virus reinfection following liver transplantation.
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Hepatitis B
Hepatitis D virus
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Journal Article Characterization of the Transcripts of Hepatitis D and B Viruses in Infected Human Livers Get access Pei-Jer Chen, Pei-Jer Chen Graduate Institute of Clinical Medicine, Hepatitis Research Center, and Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei Search for other works by this author on: Oxford Academic PubMed Google Scholar Pei-Ming Yang, Pei-Ming Yang Graduate Institute of Clinical Medicine, Hepatitis Research Center, and Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei Search for other works by this author on: Oxford Academic PubMed Google Scholar Chiou-Rong Chen, Chiou-Rong Chen Graduate Institute of Clinical Medicine, Hepatitis Research Center, and Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei Search for other works by this author on: Oxford Academic PubMed Google Scholar Ding-Shinn Chen Ding-Shinn Chen Graduate Institute of Clinical Medicine, Hepatitis Research Center, and Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei Please address requests for reprints to Dr. Ding-Shinn Chen, Graduate Institute of Clinical Medicine, National Taiwan University Hospital, No. 1 Chang-Te Street, Taipei, Taiwan, Republic of China 10016. Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 160, Issue 6, December 1989, Pages 944–947, https://doi.org/10.1093/infdis/160.6.944 Published: 01 December 1989 Article history Received: 27 February 1989 Accepted: 20 June 1989 Published: 01 December 1989
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Objective To prevent and early diagnose hepatitis B virus(HBV) reinfection and recurrent hepatitis B following liver transplantation.and to discuss the further treatment of recurrent hepatitis B.Methods Patients undergoing liver transplantation received lamivudine to prevent HBV reinfection.Virological and biochemical data,serum HBV-DNA,and immunohistological staining for HBsAg and HBcAg in biopsy liver tissue were tested in due time.Results Of 4 cases diagnosed as having HBV reinfection,two presented hepatitis B recurrence after liver transplantation:One developed to chronic severe hepatitis B after great efforts of treatment and one improved after a series of treatment.Conclusions HBV reinfection or recurrent hepatitis B following liver transplantation occurred mostly about 6 to 12 months after operation.It should be considered hepatitis B recurrence when liver biochemistrical data became poor during this period.The treatment for recurrent hepatitis B after liver transplantation included increasing dosage of lamivudine.application of famciclovir,and other liver protective measures.
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Liver transplantation; Hepatitis B virus; Recurrence
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Background: This study aimed to explore the prevention and treatment of new hepatitis B in children after liver transplantation with livers positive for HBcAg and to examine the treatment of new hepatitis B.Methods: A total of 22 children who received livers positive for HBcAg between January 2013 and December 2015 were retrospectively analyzed.After their operations, the children were given lamivudine for anti-hepatitis B virus (HBV) treatment, a hepatitis B vaccine or intermittent supplements of hepatitis B immunoglobulins to prevent recurrence of the infection, and entecavir for anti-hepatitis B treatment.The children were categorized into two groups: one group of children stopped taking lamivudine one year after operation (n=7) by themselves, while the other group did not (n=15).Results: Of the seven children who stopped lamivudine anti-HBV treatment, six developed hepatitis B at 24.33±13.95months after operation.Of these children, five were treated with entecavir, resulting in their HBV DNA decreasing to undetectable levels (<50 IU/mL).HBsAg turned negative in four of these patients, but in one patient it did not.The other patient with new hepatitis B continued to use lamivudine, resulting in their HBV DNA decreasing to normal levels (<50 IU/mL) but without their HBsAg turning negative.No new cases of hepatitis B were found in the 15 children who did not stop anti-HBV treatment. Conclusions:The long-term prophylactic therapy of nucleoside analogues combined with hepatitis B immunoglobulins should be used for a long time after liver transplantation with a liver positive for HBcAg.Discontinuation of nucleoside analogues is associated with a higher risk of the new onset of hepatitis B.Entecavir has a significant effect on the treatment of postoperative new hepatitis B in children.
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To study the prevention and treatment of HBV reinfection after liver transplantation.Total 19 cases of chronic fulminant hepatitis B, the end-stage of liver cirrhosis and liver carcinoma complicated with HBV cirrhosis. Were performed liver transplantation and given anti-viral drugs pre and post transplantation. Famciclovir was administered in 4 cases, lamivudine in 13 cases and lamivudine+HBIG in 2 cases. The serum HBVM and liver biopsy immunohistochemistry were performed.Four cases given famciclovir developed reinfection. Serum HBsAg, HBeAg and HBV DNA were positive in 3 cases. Liver biopsy immunohistochemistry showed HBsAg and HBeAg phenotype. Classical viral hepatitis in 1 case occurred, three cases died. In the lamivudin group 7 cases showed positive for HBsAg, 2 cases positive for HBV DNA, 4 cases HBsAg or HBcAg phenotype. One case showed positive for serum anti-HBc the other negative for HBVM, and liver biopsy immunohistochemistry was negative too.These date suggest that anti-virus prevention and treatment in pre and post liver transplantation with HBV infected correlative disease is necessary, feasible and effective.
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The clinical course of 10 liver transplant recipients who had hepatitis B virus (HBV) and five recipients with HBV and D (delta) infection before transplantation is described. Six patients who underwent eight transplants died. The estimated one and two year survival rates in patients with HBV only before transplantation were 74% and 67% respectively. The estimated one and two year survival in patients with HBV and HDV infection beforehand was 100%. Graft infection by HBV occurred in 8 of 10 patients infected with HBV only; and in 4 of 5 patients with previous HBV and HDV infection. There was a widely variable time from transplantation to the appearance of HBV markers in liver or serum, ranging from 6-331 days. Hepatitis D antigen (HDAg) appeared in three grafts very rapidly after transplantation at 4, 8, and 37 days respectively. Graft infection by HBV was accompanied by significant liver injury in six allografts in five recipients. In particular, there was a striking morphological appearance in five infected livers in which the hepatocytes became progressively enlarged and distorted as they accumulated huge amounts of hepatitis B surface and core antigens (HBsAg, HBcAg). These features were accompanied by pericellular fibrosis and cholestasis but little associated inflammation. This syndrome carried a poor prognosis. A gradual progression to cirrhosis occurred in one additional liver. Finally, recurrent HBV infection was a principal or a contributing factor in all deaths. The presence of HBcAg and inflammation in he native liver increased the risk of HBV induced tissue damaged in the graft whereas HDV infection in the host liver seemed to reduce the risk of significant HBV induced tissue damage in the allograft. These data suggest that post transplant HBV infection is accompanied by a variety of changes in the liver allograft, some of which are unique to the transplanted liver and may result in impaired allograft function.
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Liver transplantation in hepatitis B virus (HBV)‐infected patients is very commonly followed by recurrence of infection in the transplanted liver. Most recipients with HBV recurrence will develop chronic hepatitis that follows a more aggressive course than is seen in non‐immuno‐compromized subjects and this frequently results in graft failure. The presence of hepatitis B e antigen or significant levels of HBV‐DNA in the serum is highly predictive of recurrence and this has led to the view that patients, whose serum is positive for these conventional markers of replication, should be excluded from transplantation. The key to improving the results of transplantation in patients with HBV infection lies in the development of effective strategies to prevent reinfection. High dose anti‐HBs immunoglobulin is effective in patients who are coinfected with hepatitis D, those transplanted for fulminant hepatitis and cirrhotic patients who have very low levels of viral replication prior to transplantation. Unfortunately, immunoprophylaxis does not seem to influence the outcome in those patients with higher levels of replication. There are several new orally active nucleoside analogues that are potent inhibitors of hepatitis B replication that may be effective for both the prevention and treatment of recurrent disease. The most promising are lamivudine (2′,3′, dideoxy, 3′, thiacytidine) and famciclovir (a guanosine analogue). Both agents have been extensively evaluated in animal models of HBV and have been shown to rapidly suppress viral replication. The initial experience with these agents in liver transplant recipients has been promising and a number of studies are currently underway to determine whether these drugs, used alone or in combination with immunoprophylaxis, are able to prevent recurrence in those patients at highest risk of post‐transplant HBV recurrence.
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Patients with chronic hepatitis B virus (HBV) infection were not accepted for liver transplantation in Asia in the past because the hepatitis B immune globulin (HBIG) used to prevent post-transplantation recurrence was very expensive and it was generally believed that Asians with hepatitis B fared worse than Caucasians after liver transplantation. The availability of lamivudine has altered the indication of liver transplantation for these patients. Twenty-five Chinese patients with chronic HBV infection were given lamivudine as primary prophylaxis against HBV re-infection before transplantation. Five patients died within 40 days of transplantation. After a median follow-up period of 14 months (range, 5-39), 17 patients had lost serum HBsAg from 4 days to 27 months post transplantation, but it reappeared in three patients 4-12 months later. Antibody to HBsAg was detected periodically in the serum of 1 patients who had lost HBsAg. At the last follow-up, six patients were HBsAg-positive and HBV DNA was detected in only one of them. The indication for liver transplantation for chronic hepatitis C virus (HCV) infection is not as strict as for patients with chronic HBV infection because the long-term survival is similar to that of non-hepatitis C patients, even though re-infection by HCV in the recipients is nearly universal. The main issue in the selection of patients with HCV for liver transplantation is therefore identification of criteria that can predict re-infection and development of cirrhosis. These include factors such as multiple episodes of rejection, use of OKT3, pre-transplant viral load and genotype, but reports are not consistent and so there are no well-defined selection criteria. The selection criteria for patients with hepatocellular carcinoma are now well defined. Many studies have confirmed that a tumour > 5 cm, and showing vascular invasion, and poor differentiation adversely affects survival. In practice, only patients with a tumour < 5 cm and Child's C cirrhosis are accepted for liver transplantation. Transarterial oily chemoembolization and intralesional alcohol injection are used to control or down-stage the tumour while patients wait for a cadaveric liver graft.
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