Efficacy and safety of lamivudine or tenofovir plus intramuscular hepatitis B immunoglobulin in prevention of hepatitis B virus reinfection after liver transplant.
Mohssen Nassiri ToosiAmir KasraianfardZahra AhmadinejadHabibollah DashtiMajıd MoiniAtabak NajafiJavad SalimiAli Jafarian
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Hepatitis B immunoglobulin prophylaxis in combination with antiviral drugs is recommended for prevention of hepatitis B virus reinfection after liver transplant. However, there is no consensus on a standard prophylactic method, and controversy exists over the duration, dose, and route of administration. We conducted a prospective study to evaluate the safety and effectiveness of intramuscular hepatitis B immunoglobulin in combination with lamivudine and/or tenofovir and discontinuation of hepatitis B immunoglobulin after 1 year for prevention of hepatitis B virus reinfection.Patients with hepatitis Brelated liver cirrhosis who had undergone primary liver transplants were enrolled. The prophylactic protocol involved intraoperative intramuscular hepatitis B immunoglobulin at 10 000 IU, tapering to 5000 IU daily for the first 6 days, weekly for a month, every 2 weeks for the next month, and monthly for a year after liver transplant, in combination with antiviral drugs.From January 2002 until March 2014, two hundred sixty-eight liver transplants were performed. Forty-four patients (16.4%) who underwent liver transplants due to hepatitis B-related liver failure were enrolled. Five patients had hepatocellular carcinoma; 20 had both hepatitis D and hepatitis B virus infection. The median age was 47 years (range, 26-59 y) with a median model for end stage liver disease score of 20. Thirty-three patients were men (76%). Sixty-one percent of patients were negative for hepatitis B virus DNA at the time of transplant. The median follow-up was 13.6 months (range, 0-142 mo). Only 1 patient (2.3%) experienced hepatitis B virus reinfection (at 44.7 months posttransplant), which was successfully treated with tenofovir. Five patients died (11.4%) during the follow-up from nonhepatitis B causes.Intramuscular hepatitis B immunoglobulin in combination with lamivudine or tenofovir and discontinuation of hepatitis B immunoglobulin after 1 year posttransplant may provide safe and cost-effective protection against posttransplant hepatitis B reinfection.Keywords:
Hepatitis B
Hepatitis D virus
Liver disease
Discontinuation
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Background. Orthotopic liver transplantation (OLT) for end-stage liver disease resulting from hepatitis B virus (HBV) infection is associated with a high rate of recurrence and reduced survival. Lamivudine is effective in inhibiting HBV replication in patients with chronic hepatitis. This study evaluated the impact of lamivudine on viral suppression, liver function, and disease severity in patients awaiting OLT with HBV e-minus strain infection. Methods. Twenty-five patients received lamivudine (100 mg per day) from the day of listing for OLT. All patients were positive for serum HBV-DNA by polymerase chain reaction and all had a Child-Pugh score of 7 or higher. Results. Patients were followed for 12±9 months (mean ± SD). Eleven underwent OLT within 13 months of treatment initiation, one died after 10 months, and one dropped out after 3 months. After 3, 6, and 9 months, HBV-DNA by polymerase chain reaction was undetectable in 14 of 25, 14 of 20, and 13 of 15 patients, respectively. Two patients developed lamivudine resistance after 9 and 18 months of treatment, respectively, without liver decompensation. Comparing baseline to last visit data, a significant improvement in prothrombin activity (43±15% vs. 52±19%;P =0.0014), serum bilirubin (3.4±1.9 vs. 2.5±2.2 mg/dL;P =0.0007), serum albumin (3.3±0.3 vs. 3.6±0.5 g/dL;P =0.0278), presence of ascites (15/25 vs. 7/25;P =0.0047), and Child-Pugh score (9 vs. 8;P =0.0003) was observed. Because of liver function improvement, four patients were placed on low priority status for OLT (United Network of Organ Sharing 3) and 9 on inactive status (United Network of Organ Sharing 7). The overall probability of survival at 6 and 12 months was 100% and 90.9%, respectively. Conclusions. Lamivudine has an important role in patients with end-stage liver disease caused by HBV precore mutant strain. Not only does HBV-DNA suppression allow patients to be eligible for OLT, but the improvement of the patients' clinical status may delay the need for OLT in an era of organ shortage.
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Adefovir
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Purpose of review This review discusses different approaches to the prevention of hepatitis B recurrence in liver recipients, including new concepts such as the withdrawal of hepatitis B immune globulin while continuing an antiviral agent or after liver transplantation antihepatitis B vaccination. Recent findings Over the past decade significant improvements in patient and graft survival have been observed after liver transplantation for hepatitis B virus-related liver disease, mostly because of efficient prophylaxis against hepatitis B recurrence. The most important factor associated with hepatitis B recurrence in the allograft is the presence of active viral replication at the time of orthotopic liver transplantation. The advent of long-term prophylaxis with hepatitis B immune globulin combined with oral antiviral agents such as lamivudine has significantly improved survival after liver transplantation and has dramatically reduced the risk of hepatitis B recurrence. Unfortunately, prolonged lamivudine therapy before liver transplantation is associated with the emergence of escape hepatitis B virus mutants and a higher risk of recurrence. New drugs, such as adefovir and tenofovir have demonstrated efficacy in suppressing lamivudine-resistant variants. Summary In patient candidates to liver transplantation, the combination of two antiviral agents without cross resistance seems to be the best therapeutic option.
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Hepatitis B virus (HBV) is DNA-based virus, member of the Hepadnaviridae family, which can cause liver disease and increased risk of hepatocellular carcinoma (HCC) in infected individuals, replicating within the hepatocytes and interacting with several cellular proteins. Chronic hepatitis B can progressively lead to liver cirrhosis, which is an independent risk factor for HCC. Complications as liver decompensation or HCC impact the survival of HBV patients and concurrent HDV infection worsens the disease. The available data provide evidence that HBV infection is associated with the risk of developing HCC with or without an underlying liver cirrhosis, due to various direct and indirect mechanisms promoting hepatocarcinogenesis. The molecular profile of HBV-HCC is extensively and continuously under study, and it is the result of altered molecular pathways, which modify the microenvironment and lead to DNA damage. HBV produces the protein HBx, which has a central role in the oncogenetic process. Furthermore, the molecular profile of HBV-HCC was recently discerned from that of HDV-HCC, despite the obligatory dependence of HDV on HBV. Proper management of the underlying HBV-related liver disease is fundamental, including HCC surveillance, viral suppression, and application of adequate predictive models. When HBV-HCC occurs, liver function and HCC characteristics guide the physician among treatment strategies but always considering the viral etiology in the treatment choice.
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Two hepatotropic viruses, hepatitis B and C viruses, are known to cause hepatocellular carcinoma in humans. Hepatocarcinogenesis is a complex, stepwise process that evolves over several to many years and precisely how hepatitis viruses contribute to malignant transformation of hepatocytes is uncertain. Hepatitis B vrus is integrated into cellular DNA in the great majority of hepatitis B virus-related hepatocellular carcinomas, whereas replicative intermediates of hepatitis C virus do not insert into chromosomal DNA, making it likely that different pathogenetic mechanisms operate with the two viruses. Indeed, evidence is mounting that both direct and indirect carcinogenic mechanisms, and often the two together, are involved in virus-induced hepatocellular carcinoma. In addition, evidence is now available that hepatitis B and C viruses interact synergistically in the pathogenesis of hepatocellular carcinoma. Animal models, — other members of the Hepadnaviridae family that cause tumors in their respecitve animal hosts, and transgenic mice into which the sequences of hepatitis B virus DNA have been inserted — are proving useful in elucidating putative mechanisms of hepatitis B virus-related hepatocarcinogenesis. Whatever the genesis of hepatitis virus-induced hepatocellular carcinoma, it is clear that hepatitis viruses do not act alone but in conjunction with other environmental carcinogens and a number of host factors.
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Co infection with hepatitis C virus and hepatitis D virus (HDV) is less common than that with HIV and HCV, although more attention has been given to HCV co infection as a result of its higher frequency of chronic disease. The present investigation was attempted to determine the exact prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) infection among liver disease patients. Hepatitis C virus and hepatitis D virus have been shown to suppress hepatitis B surface antigen (HBsAg) synthesis. Thus it is possible that HDV infection occurs despite the lack of detectable HBsAg. Serum samples from 175 liver disease patients were assayed for the presence of hepatitis B virus (HBsAg and IgM anti HBc), antibodies to HCV and antibodies to HDV using a third generation enzyme linked immunosorbent assay. 21% of the patients were positive for HBV, 2.2% were positive for both antibodies to HCV and antibodies to HDV. Most of the HCV and HDV patients had chronic liver disease. Slight variation was found in the prevalence of HBV, HCV and HDV on sex wise analysis. Individuals of the age group 51-60 years had the highest prevalence of HCV and HDV. In case of HBV it was found in the age group between 21-30 years. Among the positive subjects of hepatitis group of viruses, liver function tests were mostly abnormal particularly ALT.
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HBcAg
Famciclovir
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