Hepatitis B and liver transplantation: Molecular and clinical features that influence recurrence and outcome

Abstract

Hepatitis B virus (HBV) continues to be a major cause of morbidity and mortality worldwide. It is estimated that about 350 million people throughout the world are chronically infected with HBV. Some of these people will develop hepatic cirrhosis with decompensation and/or hepatocellular carcinoma. For such patients, liver transplantation may be the only hope for cure or real improvement in quality and quantity of life. Formerly, due to rapidity of recurrence of HBV infection after liver transplantation, usually rapidly progressive, liver transplantation was considered to be contraindicated. This changed dramatically following the demonstration that hepatitis B immune globulin (HBIG), could prevent recurrent HBV infection. HBIG has been the standard of care for the past two decades or so. Recently, with the advent of highly active inhibitors of the ribose nucleic acid polymerase of HBV (entecavir, tenofovir), there has been growing evidence that HBIG needs to be given for shorter lengths of time; indeed, it may no longer be necessary at all. In this review, we describe genetic variants of HBV and past, present, and future prophylaxis of HBV infection during and after liver transplantation. We have reviewed the extant medical literature on the subject of infection with the HBV, placing particular emphasis upon the prevention and treatment of recurrent HBV during and after liver transplantation. For the review, we searched PubMed for all papers on the subject of "hepatitis B virus AND liver transplantation". We describe some of the more clinically relevant and important genetic variations in the HBV. We also describe current practices at our medical centers, provide a summary and analysis of comparative costs for alternative strategies for prevention of recurrent HBV, and pose important still unanswered questions that are in need of answers during the next decade or two. We conclude that it is now rational and cost-effective to decrease and, perhaps, cease altogether, the routine use of HBIG during and following liver transplantation for HBV infection. Here we propose an individualized prophylaxis regimen, based on an integrated approach and risk-assessment.

Mutations in the Basal Core Promoter and Precore/Core Regions of Hepatitis B Virus in Patients Co-Infected With Human Immunodeficiency Virus

“…The 1762 and 1764 mutations reduce transcription of the PC mRNA by interfering binding of transcription factors, which in turn downregulates HBeAg synthesis. Some studies have shown that genomic mutations at positions 1727G, 1741C, 1761C, 1757A /1764T /1766G, 1773T, 1773T /1775G and 1909C are associated with HCC in HBV-infected patients (15)(16)(17)(18)(19). Several studies have reported an association between CP mutations and increased risk of liver inflammation, cirrhosis (20) and HCC (21).…”

Study the Cross-talk Between Hepatitis B Virus Infection and Interferon Regulatory Factors in Liver Transplant Patients

“…Among viral hepatitis such as chronic HBV infection, the liver transplant is also considered as the final treatment method, which leads to rejection or acceptance of liver graft (3)(4)(5)(6)(7). Accordingly, activation of inflammatory signaling pathways is reported in allograft rejection.…”

“…In spite of possible determinative association between pathogenesis of chronic hepatitis B virus (HBV) infection with IRFs, limited studies were accomplished (15). Chronic HBV infection can lead to the end-stage liver diseases such as hepatocellular carcinoma and cirrhosis (3)(4)(5)(6)(25)(26)(27). Therefore, early prognosis of any change in immune factors such as IRFs molecules leads to better management of post-liver transplant outcomes and raises the possibility of graft survival.…”

Association between clinical features and YMDD mutations in patients with chronic hepatitis B following lamivudine therapy

“…Hepatitis B virus (HBV) remains a major cause of morbidity and mortality worldwide (1). It has been estimated that ~350 million individuals worldwide are chronically infected with HBV.…”

“…It has been estimated that ~350 million individuals worldwide are chronically infected with HBV. A proportion of these patients will subsequently develop hepatic cirrhosis, so therapy to control active inflammation is important (1). The key to effective treatment is to inhibit the replication of HBV and prevent it from progressing to cirrhosis, hepatic failure and hepatic cell cancer (2)(3)(4).…”