Hepatitis B Virus Infection In Recipients Research Articles

Application of nucleoside analogues to liver transplant recipients with hepatitis B.

Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donors positive for hepatitis B virus (HBV) core antibody (HBcAb) have previously been considered unsuitable for transplants. However, those who test negative for the more serious hepatitis B surface antigen can now be used as liver donors, thereby reducing organ shortages. Remarkable improvements have been made in the treatment against HBV, most notably with the development of nucleoside analogues (NAs), which markedly lessen cirrhosis and reduce post-transplantation HBV recurrence. However, HBV recurrence still occurs in many patients following liver transplantation due to the development of drug resistance and poor compliance with therapy. Optimized prophylactic treatment with appropriate NA usage is crucial prior to liver transplantation, and undetectable HBV DNA at the time of transplantation should be achieved. NA-based and hepatitis B immune globulin-based treatment regimens can differ between patients depending on the patients' condition, virus status, and presence of drug resistance. This review focuses on the current progress in applying NAs during the perioperative period of liver transplantation and the prophylactic strategies using NAs to prevent de novo HBV infection in recipients of HBcAb-positive liver grafts.

Estrategias para evitar la hepatitis B de novo postrasplante hepático (II)

Although active immunization against the hepatitis B virus (HBV) through vaccination constitutes a fundamental strategy in the prevention of infection by this virus, it is not effective in isolation for preventing de novo HBV infections in recipients of liver grafts from core antigen antibody (anti-HBc) positive donors. In this situation, the risk of developing de novo hepatitis B depends on the recipient's serological status. It has been shown that, for vaccinated patients and in the absence of prophylaxis with nucleoside/nucleotide analogues and/or hyperimmune gamma globulin, the prevalence and cumulative incidence of HBV infection after transplantation is an intermediate risk. The absence of a surface antigen antibody (anti-HBs) titer cutoff considered protective, the gradual reduction of these titers after vaccination, the presence of false positives for anti-HBs in patients undergoing infusion of blood products and escape mutations of the hepatitis B surface antigen (HBsAg) could explain this lack of efficacy. For this reason, it is recommended that vaccination protocols be implemented universally, along with the follow-up of the level of protection in patients with cirrhosis, adding prophylaxis with analogues when receiving a graft from an anti-HBc-positive donor. Clinical and serological surveillance alone can be considered for patients with anti-HBs levels greater than 200mUI/mL after vaccination.

Clinical and Virologic Courses of Hepatitis B Surface Antigen-Negative and Hepatitis B Core or Hepatitis B Surface Antibody-Positive Renal Transplant Recipients

Recent findings suggest that reactivation of hepatitis B (HB) virus (HBV) in renal transplantation recipients with a past HBV infection is an important cause of morbidity and mortality. In the present study, we reviewed the clinical and virologic courses of past HBV infections in recipients following renal transplantation. We retrospectively analyzed pretransplant HB surface antigen (HBsAg), HB core antibody (HBcAb), HB surface antibody (HBsAb), and HBV deoxyribonucleic acid (DNA) levels in 147 patients who underwent renal transplantation at our institution between September 2000 and November 2011. Thirty-four (23.1%) of the patients were diagnosed with a past HBV infection. The mean age of patients with a past HBV infection was significantly older than that of those without (48.4 vs 41.1 years, P = .002), while the duration of hemodialysis (HD) was significantly longer (138 vs 79.5 months, P = .027) and ratio of cadaveric transplantation procedures was higher (41.2% vs 21.2%, P = .035). During the follow-up period after renal transplantation, HBsAg was negative, HBV DNA was undetectable, and serum alanine aminotransferase level was normal in all patients. There were no statistically differences for graft and patient survival, and serum creatinine level between patients with and without a past HBV infection. Our results indicate that a past HBV infection is significantly associated with older age, longer duration of HD, and cadaveric transplantation. However, no HBV reactivation occurred in our previously infected patients, and the presence of HBcAb or HBsAb positivity did not influence graft or patient survival or renal function following renal transplantation.

Hepatitis B surface antigen-negative, but HBV DNA-positive patients in Bangladesh

Hepatitis B surface antigen (HBsAg) is regarded as sole marker of hepatitis B virus (HBV) infection in Bangladesh and most other developing countries. However, some HBV-negative subjects may harbor HBV DNA and transfusion of their blood may cause HBV infection in recipients. HBV DNA was checked in 20 patients with cryptogenic liver cirrhosis, 10 patients with hepatocellular carcinoma without any known etiology, and 10 apparently healthy subjects with elevated levels of serum alanine aminotransferase (ALT). HBV DNA was detected in 8 of 20 patients with cryptogenic liver cirrhosis, 1 of 10 patients with hepatocellular carcinoma, and 2 of 10 apparent healthy subjects with elevated ALT. However, all of them were negative for HBsAg in the sera. This study indicates that some additional mechanisms should be developed for detection of HBsAg-negative HBV-infected subjects for efficient control and management of HBV infection in Bangladesh.

Occult hepatitis B virus infection as a cause of posttransfusion hepatitis in patients with cancers

Prevalence of hepatitis B virus (HBV) infection is increased in patients of cancer with increased mortality. Multiple transfusions of blood and blood-related products are a potential source. This study aims to assess the incidence of hepatitis B surface antigen (HBsAg) seroconversion in cancer patients receiving transfusion of blood or blood-related products and identify possible reasons for infection in these patients. Patients of cancer receiving blood products, who were HBsAg-, anti-hepatitis B core (HBc)-, and HBV DNA-negative prior to transfusion, were tested for HBsAg by ELISA at 6, 12, and 24 weeks after the last transfusion. Blood donors were screened for HBsAg by ELISA. Twenty of 3,600 (0.56 %) blood donors tested positive for HBsAg and were rejected. Nine of 150 (6 %) cancer patients became HBsAg-positive posttransfusion which included seven patients who presented with acute hepatitis B and other two patients who remained HBsAg-positive without hepatitis. In 6/9 (66.6 %) patients, HBsAg positivity was related to blood transfusion as their corresponding blood donors on retesting the stored samples were positive for anti-HBc antibody and HBV DNA. In other three patients, the cause of their HBsAg positivity could not be ascertained. Occult HBV infection in blood donors is a potential source of posttransfusion HBV infection in recipients. Anti-HBc antibody and HBV DNA should be tested in blood donors especially when blood is given to cancer patients receiving chemotherapy.

Allogeneic Hematopoietic Stem Cell Transplantation From HBsAg-Positive Donors Into HBsAg-Negative Recipients: A Safety and Practicable Regimen Under Active Prophylactic Anti-HBV Therapy

Abstract 1949 IntroductionTransmission of hepatitis B virus (HBV) may occur (de novo HBV infection) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HBsAg-positive donors into HBsAg-negative recipients. Increased HBV associated complications will cause high morbidity and mortality post-transplantation in such patients. China is an endemic area for HBV infection. The exclusion of HBsAg positive donors will greatly limit the application of HSCT. There are few published data on allo-HSCT from HBsAg-positive donors when no other alternatives can be available. Recently great advances in anti-HBV therapy and prophylaxis have been achieved. The efficacy of allo-HSCT combined with anti-HBV prophylaxis in such patients remains unknown. In the current study, we performed a retrospective analysis of the virologic and clinical outcomes of allo-HSCT from HBsAg-positive donors into HBsAg-negative recipients under active prophylactic anti-HBV therapy. Methods From 2005 to 2010, a total of 10 HBsAg-negative recipients undergoing allo-HSCT from HBsAg-positive donors in our single center were included as an observation group. We performed a matched case-controlled analysis, in which each HBsAg-positive transplantation was paired with 3 control subjects selected from among all seronegative transplantation defining as a matched control group (30 patients). Patients were matched on age, underlying disease, disease stage, conditioning regimen and donor type. All the enrolled patients underwent HLA-matched related (20% each group) and HLA-mismatched related (haploidentical, 80% each group) transplantation. For haploidentical HSCT, conditioning regimen consisted of Ara-C, busulfan (Bu), cyclophosphamide (Cy), Me-CCNU and ATG. For HLA-matched related HSCT, the conditioning regimen consisted of Bu and Cy. GVHD prophylaxis consisted of cyclosporine A, mycophenolate mofetil and short-term methotrexate. Anti-HBV therapy consisted of lamivudine or entecavir for HBsAg positive donors. Marrow harvest and HSCT were performed until donor’s serum HBV-DNA became undetectable. Hepatitis B immunoglobulin (HBIg) of 400 IU were administered to the recipients within 24 hours, 1 month and 2 months after stem cell infusion, respectively. HBsAb titers were detected once a month. If the titer was lower than 200IU/L, HBIg was injected rapidly. All the patients were followed-up weekly and HBV serology was detected once a month. Reults After transplantation, 1 and 0 patient developed HBV-related hepatitis in observation group and matched control group (P>0.05). The HBV-related hepatitis patient became positive for HBsAg 1 year post-transplantation with serum HBsAb loss. Interestingly, this patient became negative for HBsAg and positive for HBsAb after donor lymphocyte infusion due to the primary disease relapse. To date, none of the enrolled recipients in our study became positive for HBsAg. Veno-occlusive disease (VOD) is another kind of hepatic complication. One and 0 patient developed VOD in observation group and matched control group respectively (p>0.05). The presence of HBcAb in the absence of HBsAg in serum indicates past exposure to HBV. Despite the presumed resolution of the HBV infection in these patients, a minute amount of HBV DNA remains in the liver. So we analyzed HBcAb and HBsAb levels in the serum in both groups 1 year post-transplantation. Nine (90.0%) and 6 (20.0%) patients became positive for both HBcAb and HBsAb in observation group and matched control group respectively (p<0.01), suggesting possible occult HBV infection in recipients transplanted from HBsAg-positive donors. We also compared clinical outcomes between 2 groups. The incidence of aGVHD was 40.0% in obervation group and 30.0% in matched control group (p>0.05). The 1 year overall survival (OS) were 60.0% and 63.3% in observation group and matched control group respectively (p>0.05). The 1 year non-relapse mortality (NRM) were 10.0% and 13.3% in observation group and matched control group respectively (p>0.05). Conclusions Our data support that allo-HSCT from HBsAg-positive donors into HBsAg-negative recipients is a safety and practicable regimen under active prophylactic anti-HBV therapy, but these recipients are possibly complicated with occult HBV infection. A long-term prospective follow-up study on such patients is imperative currently. Disclosures:No relevant conflicts of interest to declare.

Cost‐effectiveness of additional hepatitis B virus nucleic acid testing of individual donations or minipools of six donations in the Netherlands

To further reduce the risk of hepatitis B virus (HBV) transmission by blood transfusion, nucleic acid testing (NAT) can be employed. The aim of this study is to estimate the incremental cost-effectiveness ratio (ICER) in the Netherlands of employing a triplex NAT assay aimed at HBV nucleic acid detection in individual donations (ID-NAT) or in minipools of 6 donations (MP-6-NAT), compared to a triplex NAT assay in minipools of 24 donations (MP-24-NAT). A mathematical model was made of the whole transfusion chain from donors to recipients of blood in the Netherlands. The annual number of avoided HBV transmissions was estimated with the window-period incidence model. The natural history of a HBV infection in recipients is described by a Markov model. The ICER of adding HBV MP-6-NAT or HBV ID-NAT in the Netherlands is Euro303,218 (95% confidence interval [CI], Euro233,001-Euro408,388) and Euro518,995 (95% CI, Euro399,359-Euro699,120) per quality-adjusted life-year, respectively. The ICER strongly correlates with the age of transfusion recipients. The cost-effectiveness of additional HBV NAT is limited by the limited loss of life caused by HBV transmission. Despite a higher effectiveness, HBV ID-NAT is less cost-effective than MP-6-NAT due to higher costs. A future equivalent participation of immigrants from HBV-endemic countries in the donor base renders HBV NAT only slightly more cost-effective.

Prevention of hepatitis B virus infection from hepatitis B core antibody‐positive donor graft using hepatitis B immune globulin and lamivudine in living donor liver transplantation

Hepatic grafts from hepatitis B surface antigen-negative and anti-core antibody (HBcAb)-positive donors have been shown to transmit hepatitis B virus (HBV) infection. Recently, it has been reported that combined hepatitis B immune globulin (HBIG) and lamivudine therapy is effective in the prevention of hepatitis B recurrence after living donor liver transplantation (LDLT). In this report, we assessed the efficacy of combined HBIG and lamivudine therapy in preventing HBV transmission by graft with HBcAb-positive donors. We studied 22 patients who had undergone LDLT with allografts from HBcAb-positive living donors at Gunma University Hospital and Kyushu University Hospital. Long-term combined HBIG and lamivudine therapy were administrated to all recipients. Serum samples from the donor and recipient were tested for HBcAb, HBV DNA, and hepatitis B surface antibody. Liver biopsies from grafts were tested for HBV DNA. All recipients were HBcAb negative before LDLT. All of the donor livers were HBV DNA positive at the time of LDLT. All of the recipients had HBsAb titers greater than 300 mIU/ml 4 weeks after LDLT, and remained 100 mIU/ml thereafter. None of the recipients have become infected with HBV with a follow-up of 25-86 months. Perioperative combined HBIG and lamivudine therapy can prevent HBV infection in recipients who receive liver grafts from HBcAb-positive donors.

Use of hepatitis B core antibody-positive donors in orthotopic liver transplantation.

Hepatic allografts from donors positive for antibody to hepatitis B core antigen (anti-HBc) frequently transmit hepatitis B virus (HBV) infection to recipients. Therefore, most transplantation centers will not use these organs for orthotopic liver transplantation (OLT). Although it is expensive and not always efficacious, hepatitis B immune globulin (HBIG) has been used routinely for indefinite periods to prevent HBV infection in liver allograft recipients. We assessed the effectiveness of long-term use of a nucleoside analog, lamivudine, in preventing HBV transmission by anti-HBc-positive allografts. Retrospective study. A tertiary care center. Twelve patients received hepatic allografts from anti-HBc-positive donors at Loyola University Medical Center, Chicago, between February 23, 1998, and March 13, 2001. All patients received 10 000 U/d of intravenous HBIG for 7 days. In addition, they received 300 mg/d of lamivudine in divided doses. Their liver biopsy specimens were tested for HBV DNA, hepatitis B surface antigen (HBsAg), and hepatitis B core antibody (HBcAb). Serum samples from the donor and recipient were tested for HBcAb, HBV DNA, and hepatitis B surface antibody (HBsAb). The incidence of HBV infection in recipients who received HBcAb-positive donor livers and lamivudine prophylaxis. All recipients were anti-HBc negative before OLT. Five of the recipients had HBsAb titers greater than 150 U at the time of OLT. Three of the donor livers were HBV DNA positive and 2 were hepatitis B core antigen positive at the time of OLT. Donor serum was HBcAb positive in all 12 donors. None of the recipients have become infected with HBV with a follow-up of 2 to 38 months. Perioperative use of HBIG combined with long-term use of lamivudine can prevent HBV infection in recipients who receive hepatic allografts from HBcAb-positive donors.