Impact of hepatitis B immunoglobulin mode of administration on treatment experiences of patients after liver transplantation: Results from an online survey

BACKGROUND Hepatitis B immunoglobulin(HBIG)in combination with a potent nucleos(t)ide analog is considered the standard of care for prophylaxis against hepatitis B virus(HBV)reinfection after liver transplantation for HBV-associated disease.AIM To evaluate patients’satisfaction,preferences,and requirements for subcutaneous(SC),intramuscular(IM),and intravenous(IV)HBIG treatments.METHODS A self-completion,cross-sectional,online,22-question survey was conducted to examine perceptions and satisfaction with current HBIG treatment in adults receiving HBIG treatment following liver transplantation for HBV-associated disease in France,Italy,and Turkey.Hypothetical HBIG products with different administration modes were evaluated using target product profile assessment and a conjoint(trade-off)exercise.RESULTS Ninety patients were enrolled;32%,17%,and 51%were SC,IM,and IV HBIG users,respectively.Mean duration of treatment was 36.2 months.SC HBIG had the least negative impact on emotional well-being and social life and was perceived as the most convenient,easiest to administer,least painful,and had the highest self-rating of treatment compliance.More IM HBIG users than SC or IV HBIG users reported that administration frequency was excessive(67%,28%,and 28%,respectively).In the target product profile assessment,76%of patients were likely to use hypothetical SC HBIG.In the conjoint exercise,administration route,frequency,and duration were key drivers of treatment preferences.CONCLUSION Ease,frequency,duration,and side effects of HBIG treatment administration were key drivers of treatment preferences,and SC HBIG appeared advantageous over IM and IV HBIG for administration ease,convenience,and pain.A hypothetical SC HBIG product elicited a favorable response.Patient demographics,personal preferences,and satisfaction with HBIG treatment modalities may influence long-term treatment compliance.

Exploring the impact of hepatitis B immunoglobulin and antiviral interventions to reduce vertical transmission of hepatitis B virus

Hepatitis B virus(HBV)infection is a major public health burden.In HBV endemic regions,high prevalence is also correlated with the infections acquired in infancy through perinatal transmission or early childhood exposure to HBV,the socalled mother-to-child transmission(MTCT).Children who are infected with HBV at a young age are at higher risk of developing chronic HBV infection than those infected as adults,which may lead to worse clinical outcome.To reduce the incidence of HBV MTCT,several interventions for the infants or the mothers,or both,are already carried out.This review explores the newest information and approaches available in literature regarding HBV MTCT prevalence and its challenges,especially in high HBV endemic countries.This covers HBV screening in pregnant women,prenatal intervention,infant immunoprophylaxis,and postvaccination serological testing for children.

Immunoprophylaxis failure and vaccine response in infants born to mothers with chronic hepatitis B infection in Djibouti

BACKGROUND In endemic areas,vertical transmission of hepatitis B virus(HBV)remains a major source of the global reservoir of infected people.Eliminating mother-to-child transmission(MTCT)of HBV is at the heart of World Health Organization’s goal of reducing the incidence of HBV in children to less than 0.1%by 2030.Universal screening for hepatitis B during pregnancy and neonatal vaccination are the main preventive measures.AIM To evaluate the efficacy of HBV vaccination combined with one dose of immunoglobulin in children born to hepatitis B surface antigen(HBsAg)-positive mothers in Djibouti city.METHODS We conducted a study in a prospective cohort of HBsAg-positive pregnant women and their infants.The study ran from January 2021 to May 2022,and infants were followed up to 7 mo of age.HBV serological markers and viral load in pregnant women were measured using aVidas microparticle enzyme-linked immunosorbent assay(Biomérieux,Paris,France)and the automated Amplix platform(Biosynex,Strasbourg,France).All infants received hepatitis B immunoglobulin and were vaccinated against HBV at birth.These infants were closely monitored to assess their seroprotective response and for failure of immunoprophylaxis.Simple logistic regression was also used to identify risk factors associated with immunoprophylaxis failure and poor vaccine response.All statistical analyses were performed with version 4.0.1 of the R software.RESULTS Of the 50 pregnant women recruited,the median age was 31 years,ranging from 18 years to 41 years.The MTCT rate in this cohort was 4%(2/50)in HBsAg-positive women and 67%(2/3)in hepatitis B e antigen-positive women with a viral load>200000 IU/mL.Of the 48 infants who did not fail immunoprophylaxis,8(16%)became poor responders(anti-HB<100 mIU/mL)after HBV vaccination and hepatitis B immunoglobulin,while 40(84%)infants achieved a good level of seroprotection(anti-HB>100 mIU/mL).Factors associated with this failure of immunoprophylaxis were maternal HBV DNA levels(>200000 IU/mL)and hepatitis B e antigen-positive status(odds ratio=158,95%confidence interval:5.05-4958,P<0.01).Birth weight<2500 g was associated with a poor immune response to vaccination(odds ratio=34,95%confidence interval:3.01-383.86,P<0.01).CONCLUSION Despite a failure rate of immunoprophylaxis higher than the World Health Organization target,this study showed that the combination of immunoglobulin and HBV vaccine was effective in preventing MTCT of HBV.Therefore,further studies are needed to better understand the challenges associated with immunoprophylaxis failure in infants in Djibouti city.

Current prophylactic strategies against hepatitis B virus recurrence after liver transplantation

Prophylactic strategies against hepatitis B virus(HBV) recurrence after liver transplantation(LT) are essential for patients with HBV-related disease.Before LT, lamivudine(LAM) was proposed to be down-graded from first-to second-line therapy.In contrast, adefovir dipivoxil(ADV) has been approved not only as first-line therapy but also as rescue therapy for patients with LAM resistance.Furthermore, combination of ADV and LAM may result in lower risk of ADV resistance than ADV monotherapy.Other new drugs such as entecavir, telbivudine and tenofovir, are probably candidates for the treatment of hepatitis-B-surface-antigen-positive patients awaiting LT.After LT, low-dose intramuscular hepatitis B immunoglobulin(HBIG), in combination with LAM, has been regarded as the most cost-effective regimen for the prevention of post-transplant HBV recurrence in recipients without pretransplant LAM resistance and rapidly accepted in many transplant centers.With the introduction of new antiviral drugs, new hepatitis B vaccine and its new adjuvants, post-transplant HBIG-free therapeutic regimens with new oral antiviral drug combinations or active HBV vaccination combined with adjuvants will be promising, particularly in those patients with low risk of HBV recurrence.

Clinical management of hepatitis B virus infection correlated with liver transplantation

BACKGROUND: As a radical cure for post-hepatitis B virus (HBV)-related liver cirrhosis and hepatocellular carcinoma, liver transplantation has been applied in many medical centers. Before the use of effective measures, hepatitis B recurrence and the existence of HBsAg(+) donors, patients with hepatitis B-related diseases are contraindicated for liver transplantation. Application of interferon, hepatitis B immunoglobulin (HBIG), and nucleotide analogues (e.g., lamivudine) has made great progress in the clinical care of HBV. However, there are still many shortcomings such as low viral suppression rate, rising expense, and the induction of HBV tyrosine-methionine-aspartate-aspartate (YMDD) mutation. This article systematically reviews the current evidence that immunotherapy, conventional drug combinations, and some special fields of HBV infection correlate with liver transplantation. DATA SOURCES: Studies were identified by searching MEDLINE and PubMed for articles using the keywords 'hepatitis B virus', 'hepatitis B vaccination', 'lamivudine', 'adefovir', 'entecavir', 'tenofovir', 'HBV genotype', and 'liver transplantation' up to October 2009. Additional papers were identified by a manual search of the references from the key articles. RESULTS: Hepatitis B vaccine and human monoclonal antibody have very good clinical prospects. Compared with traditional therapies, the new medical regimens have many benefits such as boosting viral suppression rate and decreasing medical expenses. The triple therapy for YMDD mutation also has an excellent therapeutic effect and a low barrier to resistance. New nucleos(t)ide analogues (entecavir and tenofovir) eliminate virus more effectively with few adverse reactions, and may replace lamivudine or HBIG in future. CONCLUSIONS: Hepatitis B vaccine needs further large-scale and rigorous randomized controlled trials to confirm its effective dose and injection frequency. Monoclonal antibody is still experimental, and the next step is to carry out the relevant animal and human studies. A consensus standard regimen for the treatment of hepatitis B should be developed.

Prevention of hepatitis B virus reinfection after orthotopic liver transplantation

BACKGROUND: Hepatitis B virus reinfection is an impor-tant problem after liver transplantation. The aim of thisstudy was to discuss the prevention of hepatitis B virus rein-fection following orthotopic liver transplantation.METHODS: Sixty-eight cases of chronic fulminant hepatitisB, end-stage liver cirrhosis, and liver carcinoma complicat-ed with HBV cirrhosis were given anti-viral drugs beforeand after transplantation to prevent hepatitis B virus rein-fection. Lamivudine was administered in 2 patients, lami-vudine + hepatitis B immunoglobulin ( HBIG ) in 63, andadefovir + HBIG in 3. The measurement of serum HBV,HBV DNA, liver biopsy immunohistochemistry and clini-cal study were performed.RESULTS: In 1 of the 2 patients who developed reinfectionafter lamivudine administration, serum HBsAg, HBeAb,HBcAb, HBV DNA were positive and liver biopsy immu-nohistochemistry showed HBsAg phenotype. In 2 of 63 pa-tients who developed reinfection after use of lamivudine +HBIG, serum HBsAg, HBeAb, HBcAb were positive andliver biopsy immunohistochemistry showed HBsAg pheno-type. Serum HBV DNA was positive in one of them.Three patients developed no reinfection with HBV after useof adefovir.CONCLUSIONS: Orthotopic liver transplantation is effectivein the treatment of HBV-infected diseases. Lamivudine +HBIG or adefovir + HBIG could effectively prevent hepatitisB virus reinfection.

Management of hepatitis B virus infection after liver transplantation

Chronic hepatitis B virus(HBV) infection is responsible for up to 30% of cases of liver cirrhosis and up to 53% of cases of hepatocellular carcinoma. Liver transplantation(LT) is the best therapeutic option for patients with end-stage liver failure caused by HBV. The success of transplantation, though, depends on receiving prophylactic treatment against post-transplant viral reactivation. In the absence of prophylaxis, liver transplantation due to chronic hepatitis B(CHB) is associated with high rates of viral recurrence and poor survival. The introduction of treatment with hepatitis B immunoglobulins(HBIG) during the 1990 s and later the incorporation of oral antiviral drugs have improved the prognosis of these patients. Thus, LT for CHB is now a universally accepted option, with an estimated 5 years survival of around 85% vs the 45% survival seen prior to the introduction of HBIG. The combination of lamivudine plus HBIG has for many years been the most widely used prophylactic regimen. However, with the appearance of new more potent oral antiviral agents associated with less resistance(e.g., entecavir and tenofovir) for the treatment of CHB, new prophylactic strategies are being designed, either in combination with HBIG or alone as a monotherapy. These advances have allowed for more personalized prophylaxis based on the individual risk profile of a given patient. In addition, the small pool of donors has required the use of anti-HBc-positive donors(with the resulting possibility of transmitting HBV from these organs), which has been made possible by suitable prophylactic regimens.

A prophylactic approach for bone marrow transplantation from a hepatitis B surface antigen-positive donor

It has been accepted that bone marrow transplantation （BMT） is the only curative therapeutic option for certain hematologic malignancies. The southeast Asia region is an endemic area of hepatitis B virus （HBV） infection; thus, BMT using a hepatitis B surface antigen （HBsAg）- positive donor is occasionally unavoidable. Organ transplantation using a HBsAg-positive donor can lead to post-transplantation de novo HBV infection and severe HBV-related hepatitis if no effective prophylactic measures are taken prior to and after transplantation. In this report, a four-level approach was designed for a patient with chronic myeloid leukemia, beginning with a booster HBV vaccination before performing BMT with a HBsAg-positive donor. Prior to BMT, the HBV viral load of the donor was reduced to an undetectable level by anUviral therapy. After BMT, hepatitis B immunoglobulin was administered intramuscularly for 1 wk together with a long-term antiviral drug, lamivudine. One year after discontinuation of lamivudine, the patient is still free of HBV infection.

HBV recurrence lowered by lamivudine/HBIG combination therapy in liver transplant patients:ten-year experience

BACKGROUND: Lamivudine and hepatitis B immunoglobulin (HBIG) are widely used to treat patients with hepatitis B recurrence after liver transplantation. However, the outcomes are inconclusive. The present study was undertaken to evaluate the effect of combined therapy on patients with hepatitis B recurrence after liver transplantation. METHODS: Twenty-two patients with hepatitis B recurrence after liver transplantation from August 2000 to October 2011 were enrolled in this study. Of these patients, 16 received lamivudine plus HBIG (combination therapy group) and 6 were treated with lamivudine alone (lamivudine-treated group) The clinical features were matched in the two groups. HBV recurrence parameters, HBsAg clearance rate, patient survival rate, and survival time were compared. RESULTS: The average time of follow-up was 47.2 months (range 13-99). Significant difference was noted in the HBsAg clearance rate in the lamivudine-treated and combination therapy groups (50% vs 93.8%, P【0.05). There was no significant difference in the time of HBV recurrence, patient survival rate and survival time between lamivudine-treated and combination therapy groups (P】0.05). CONCLUSION: Compared with lamivudine monotherapy combination therapy significantly increased the HBsAg clearance rate in patients with HBV recurrence after liver transplantation.