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The combination of hepatitis B immunoglobulin and potent nucleos(t)ide analogs after liver transplantation is considered as the standard of care for prophylaxis against hepatitis B virus recurrence. However, the recommended doses, route of administration, and duration of HBIG administration remain unclear. Moreover, hepatitis B immunoglobulin-free prophylaxis with potent nucleos(t)ide analogs has shown promising disease outcomes in preventing hepatitis B virus recurrence. The current recommendations, produced by the Turkish Association for the Study of the Liver, Acute Liver Failure and Liver Transplantation Special Interest Group, suggest a reduced need for hepatitis B immunoglobulin administration with effective long-term suppression of hepatitis B virus replication using potent nucleos(t) ide analogs after liver transplantation.

The morbidity and mortality of hepatitis B virus-related liver disease are linked to the persistence of the hepatitis B virus replication. Viral suppression with antiviral therapy has been shown to provide clinical benefits. Several special groups of patients with hepatitis B virus infection require special attention. In this brief report, based on European Association for the Study of the Liver 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection, the current optimal management of special patient groups with hepatitis B virus infection is summarized.

Background/aims: This study aimed to analyze the knowledge and awareness of hepatitis B virus (HBV) infection in an HBV-infected Turkish population as a model for global health care practice and to evaluate potential factors associated with the disease spread and its prevention., Materials and Methods: A cross-sectional survey was conducted in Ankara University School of Medicine, Liver Disease Outpatient Clinic between August 2012 and March 2013. The survey queried sociodemographics, knowledge, and awareness of HBV infection, transmission, and consequences and common practices and behaviors., Results: A total of 181 patients were surveyed (median age=49 years); 91 (51%) had "advanced" education levels (high school, bachelor's, graduate degree), 108 (60%) had knowledge about HBV infection and transmittance, and 130 (72%) were aware of the ill consequences of HBV infection. Also, 120 (66%) had vaccinated their family members against HBV infection. Participants with knowledge of HBV infection transmittance were more likely to vaccinate their family members compared to unknowledgeable participants (p=0.015). Participants with "advanced" education levels were also more likely to vaccinate family members (p=0.047)., Conclusion: Promoting better awareness of HBV and endorsing mass educational interventions may be useful strategies to prevent the spread of HBV infection. Such strategies may be recommended as cost-effective global health care practices in HBV endemic areas.

Background: Hepatitis D virus (HDV) requires hepatitis B surface antigen (HBsAg) to propagate infection and cause disease. Entecavir is a nucleoside analog with potent antiviral efficacy, and in the woodchuck animal model it also decreased hepatitis B virus (HBV) cccDNA and woodchuck surface antigen. The aim of this study was to investigate the efficacy of entecavir in chronic hepatitis D (CHD)., Methods: This single-center study was conducted in patients with compensated liver disease. All patients had to have detectable hepatitis HDV RNA and elevated levels of alanine aminotransferase (ALT). Entecavir was given at a dosage of 1 mg/d for 1 year. The primary end point was achievement of undetectable HDV RNA at the end of treatment., Results: Thirteen consecutive patients were assessed. All patients had detectable HDV RNA, and 8 had detectable HBV DNA at baseline. At the end of treatment, HBV DNA became undetectable in all patients (P = .001). No significant decline in HDV RNA, ALT, or quantitative HBsAg levels was observed. The primary end point of undetectable HDV RNA at the end of treatment was achieved in 3 patients who had significantly lower baseline HDV RNA levels than nonresponders (2.99 log(10) copies/mL ± .70 vs 4.68 ± .97; P = .0185). In all 3 patients, ALT levels were also normal at the end of treatment., Conclusions: One year of entecavir treatment is ineffective in CHD. Any generalized beneficial effect of nucleoside/nucleotide analog treatment may necessitate prolonged treatment. Patients with CHD with HBV dominance, which is likely to occur in the later phases of CHD, may be a reasonable patient cohort in which to target nucleoside/nucleotide analog therapy.

HBV infection remains a major global health problem and continues to be a common cause of liver-related morbidity and mortality in both immunocompetent and immunosuppressed individuals. Reactivation of HBV is a serious complication of chemotherapy/immunosuppressive therapy in patients with HBV infection. In this article, we aim to describe the diagnosis, prevention and management of HBV infection in allogeneic hematopoietic stem cell transplant candidates, from the pre- to post-transplant period. The data currently available suggest that all individuals with hemato-/onco-logical malignancies who undergo chemotherapy/immunosuppressive therapy should be screened for hepatotropic viruses such as HBV and HCV. HBV surface antigen-positive individuals who receive chemotherapy/immunosuppressive therapy are at considerable risk of HBV reactivation. Antiviral prophylaxis prevents HBV reactivation, decreases reactivation-related morbidity and mortality, and prevents interruptions in chemotherapy/immunosuppressive therapy in such individuals. The optimal duration of antiviral prophylaxis remains to be elucidated. The vaccination of HBV-naive recipients and their donors against HBV infection prior to transplantation plays an important role in preventing acquired HBV infection. The presence of hepatitis B surface antigen positivity is not an absolute contraindication for allogeneic hematopoietic stem cell transplantation.

Reactivation of hepatitis B virus (HBV) is a well-recognized complication of chemo/immunosuppressive therapy in individuals who are HBV surface antigen-positive inactive carriers and in individuals with chronic HBV infection. Although it is well established that chemo/immunosuppressive therapy enhances HBV replication with a resultant increase in the viral load and disease activation, the role of prophylactic lamivudine therapy to prevent chemo/immunosuppressive therapy-induced HBV activation in HBV-positive individuals who are to receive chemo/immunosuppressive therapy remains controversial. The aims of the present article are: (i) to determine the effect of lamivudine prophylaxis in HBV carriers with haemato-oncological malignancies who require chemotherapy; (ii) to define the duration and safety of lamivudine in such individuals; and (iii) to identify the effect of lamivudine prophylaxis on the outcome of chemotherapy administered for the primary disease. The data currently available suggest that lamivudine prophylaxis prevents chemotherapy-induced HBV reactivation in HBV carriers with haemato-oncological malignancies who receive chemotherapy. Lamivudine is safe and tolerable in such individuals. The duration of lamivudine prophylaxis is not yet known; however, it would appear prudent to begin lamivudine at the time of the initiation of the chemotherapy and to continue it throughout the period of chemotherapy administration and for at least 1 and possibly 2 years following the discontinuation of the chemotherapy. Finally, the prophylactic use of lamivudine in inactive HBV carriers with haemato-oncological malignancy prevents interruptions in their treatment for primary disease as a result of HBV reactivation.

Background: The aim of this study was to determine the role of hepatitis B virus (HBV) vaccination as defined by the seroconversion to hepatitis B surface antibody (anti-HBs) positivity in peripheral blood stem cell transplants., Methods: A total of 65 recipients and their donors were enrolled in this study. Recipients were divided into four distinct groups. Group 1 consisted of individuals who were vaccinated, group 2 consisted of individuals who were naturally immunized, group 3 consisted of individuals who were HBs-Ag positive, and group 4 consisted of individuals who were HBV naïve and not vaccinated., Results: Eighty-eight percent of the HBV-vaccinated recipients (14 of 16), who had vaccinated-donors, seroconverted to anti-HBs positivity. Eighty-three percent of HBV-naïve recipients (five of six), who received stem cells from HBV-immune donors, seroconverted to anti-HBs positivity. Two of the four HBs-Ag positive recipients with HBV-immune donors seroconverted to anti-HBs positivity after transplantation. Fifty-seven percent of previously vaccinated-recipients (eight of 14) lost detectable anti-HBs antibody following transplantation. Finally, 31% of HBV-naïve recipients with HBV-naïve donors acquired a de novo HBV infection., Conclusions: (i) Hepatitis B virus immunization of recipients of allogeneic hematopoietic cell transplantation results in an effective antibody response. (ii) The HBV-immune status of the donor plays an important role in post-transplantation HBs-Ab on seroconversion. (iii) Systematic re-immunization of recipients will be necessary to maintain HBV immunity in long-term serving recipients.

Background/aims: Because a more rapid and high dose vaccination schedule may be advantageous in immunosuppressed individuals to induce an earlier immunization, the aim of the present study was to assess the response to high dose, short interval hepatitis B virus vaccination in various immunosuppressed-patient populations., Methodology: A total of one hundred and thirty-eight immunosuppressed patients (86 cirrhotics, 42 dialysis patients, 10 allogeneic hematopoietic cell transplants) and 26 healthy subjects as controls were vaccinated utilizing a high dose vaccine (40 mcg) and a shortened immunization schedule., Results: Ninety-two percent of the controls responded to the high dose, short interval hepatitis B virus vaccination schedule. In contrast, only 48% of the immunosuppressed patients seroconverted to anti-HBs positivity (p < 0.001). No difference in the antibody response rate was seen between the various immunosuppressed populations studied. No significant hepatitis B virus vaccination-related adverse effects were seen in any of the groups vaccinated., Conclusions: Although a high dose, short interval hepatitis B virus vaccination schedule is safe in immunosuppressed patients, the antibody response is still significantly reduced as compared to healthy subjects and only slightly greater than that achieved with standard vaccination schedules, as reported in literature. The possibility of achieving an earlier immunization, however, may be of some advantage to protect acquired viral infection.

Objectives: The efficacy of the standard hepatitis B virus (HBV) vaccination schedule in individuals with chronic hepatitis C is reported to be reduced. Our aim was to assess the response rate to high dose, short interval HBV vaccination in such individuals., Methods: A total of 152 individuals with chronic hepatitis C were vaccinated with 40 microg of vaccine administered monthly for 3 months. Twenty-six individuals with no evidence of liver disease underwent the same vaccination schedule and were considered to be the control group. Hepatitis C virus (HCV)-positive subjects who did not seroconvert to anti-hepatitis B surface positivity after the third dose of the vaccine (nonresponder) were vaccinated with a fourth dose of vaccine (booster dose, 80 microg)., Results: One hundred nine of the 152 individuals with chronic hepatitis C (72%) seroconverted to anti-hepatitis B surface positivity (> 10 mIU/ml), as compared to 24 of the 26 controls (92%, p < 0.05). Although individuals with chronic hepatitis C responded less frequently to high dose, short interval HBV vaccination than did the controls, no differences in terms of effective immunity (>100 mIU/ml) were evident among the two groups of responders (51% vs 54%). Also, no difference in response was reported between individuals with chronic active hepatitis C and controls (92% vs 80%). The response rate was significantly lower in cirrhotics than in the noncirrhotic group (54% vs 80%, p < 0.001). Besides cirrhosis, no other demographic or bioclinical factor was found to influence the response to vaccination. After the additional booster dose, the overall response was increased to 74% of the cirrhotics and 88% of the noncirrhotics. No major HBV vaccine-related adverse effects were seen., Conclusions: A high dose, short interval HBV vaccination schedule is safe in individuals with chronic hepatitis C. From these data, it is suggested that a high dose and a short interval between HBV vaccinations may produce an effective and early antibody response in such patients.

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Background & Aims Immunohistochemical assessment of liver tissue in chronic delta hepatitis ( CDH) is underinvestigated. Aim of the study was (i) to assess variables associated with hepatitis D antigen ( HDAg), hepatitis B surface antigen ( HBsAg) and hepatitis B core antigen ( HBcAg) staining in the liver. Methods Demographic, biochemical and virologic data collected from the HIDIT 1 study were used. HBsAg, HBcAg and HDAg immunohistochemical ( IHC) staining was semiquantitatively assessed. Results Hepatitis D antigen immunohistochemical staining displayed positive correlations with age and alanine aminotransferase ( ALT) and negative correlations with serum HBsAg ( P = 0.01 for all). HBsAg IHC displayed a negative correlation with gamma glutamyl transferase and positive correlations with serum HBV DNA, serum HBsAg levels and HBeAg serology ( P < 0.001, P = 0.02 and P = 0.007 respectively). HBcAg staining was mainly nuclear and displayed negative correlations with serum HBsAg and histologic activity ( P = 0.002 and P = 0.02 respectively). Pegylated IFN based treatment led to a decline of all IHC markers, however, these markers had no impact on treatment outcome. Conclusions These data suggest an association of liver injury with HDAg expression in CDH whereas the negative correlation between HBcAg expression and liver injury and the overall nuclear localization of HBcAg suggest that HBcAg does not contribute to liver injury in CDH. HDV cases with high level of HBV replication, high serum HBsAg levels, HBeAg positivity, that are probably in the earlier stages of disease (low gamma-glutamyl transferase), had a more intense HBsAg staining profile. Overall, the data enforce the importance of HDAg and HBsAg in different phases of CDH infection. [ABSTRACT FROM AUTHOR]

Background and Aims The presence of the hepatitis B virus ( HBV)-eAg in patients with hepatitis B is associated with higher HBV replication and with an increased risk to develop liver-related clinical endpoints defined as liver related death, liver transplantation, development of hepatocellular carcinoma and hepatic decompensation. The aim of this study was to investigate the role of HBeAg in patients co-infected with the hepatitis D virus ( HDV). Methods We studied virological markers of HBV and HDV infection and as well as biochemical and clinical features of liver disease in a cohort of 534 anti- HDV-positive patients. In addition, we compared the clinical long-term outcome of HBeAg-positive HDV-infected patients with HBeAg-negative control patients matched for age, gender and baseline- MELD score. Results HBeAg-positive hepatitis delta was detected in 71 of 534 patients (13.3%). HBeAg positivity was associated with a higher biochemical disease activity and higher HBsAg levels in HDV co-infected patients. Sixty one per cent of the HBeAg-positive HDV-infected patients presented with HBV DNA levels below 2000 IU/ml, at least once during follow-up. Both HBeAg-positive and -negative patients showed a similar severe clinical long-term course with about half of the patients developing a liver-related clinical complication after a median follow-up period of 51 months (range: 9-193 months). Conclusions HBV DNA levels are low in both HBeAg-negative and HBeAg-positive patients suggesting suppressive effects of HDV on HBV irrespective of the phase of HBV infection. The clinical long-term outcome of HBeAg-positive patients is not different to HBeAg-negative patients infected with the HDV. [ABSTRACT FROM AUTHOR]

Background: In hepatitis B early antigen (HBeAg)-negative patients, response predictors to current treatment regimens are not well known. Hepatocyte cell cycle may influence hepatitis B virus (HBV) replication and hepatitis B core antigen (HBcAg) expression, which is a major target for antiviral immune response. The aim of the present paper was to evaluate the role of HBcAg expression in liver tissue and the rate of hepatocyte proliferation in response to antiviral treatment in chronic hepatitis B. Methods: A total of 33 chronic hepatitis B patients (nine HBeAg positive, 24 HBeAg negative) treated with either lamivudine and interferon combined or lamivudine alone were included. Liver expressions of proliferating cell nuclear antigen (PCNA) and HBcAg were immunohistochemically determined. The HBV-DNA levels were measured by a hybride capture assay. Complete response was defined as alanine aminotransferase (ALT) normalization and HBV-DNA negativity. Results: At the end of treatment, 23 patients (67.7%) were responders (12 of 23 were sustained responders), while 10 (33.3%) were non-responders. Age, sex, ALT, HBV-DNA levels, HBeAg status, histological activity, fibrosis scores and PCNA labeling index were similar in responders versus non-responders at baseline. The number of patients with positive HBcAg staining was lower in responders compared to non-responders at the end of treatment (17.4% vs 80%, respectively, P < 0.001), although a similar number of sustained responders and non-responders had positive HBcAg staining. Conclusion: Absence or a low level of HBcAg expression may predict the end of treatment response to current therapies, especially in HBeAg (–) patients. The PCNA determination does not predict treatment response. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Individuals with chronic hepatitis C who are anti-HBc positive may carry an occult hepatitis B virus (HBV) infection that can affect their response to antiviral therapy. METHODS: In this study the prevalence of anti-HBc and HBV-DNA positivity was assessed in the serum and liver of 285 HCV-RNA-positive subjects treated with interferon-α at 5 mU/day for 12 months. The response to interferon (normal ALT and undetectable serum HCV-RNA) was evaluated at three different endpoints: 1) after 6 months; 2) at the end of treatment; and 3) 6 months after interferon discontinuation. RESULTS: Ninety individuals were anti-HBc positive (32%), 2 of these were HBV-DNA positive in serum and 7 in liver (8%). None of the anti-HBc-negative individuals was HBV-DNA positive in serum or liver. The prevalence of cirrhosis was greater in the anti-HBc-positive group than in the anti-HBc- negative group (p < 0.05), whereas HCV-RNA levels were lower. Anti-HBc-positive individuals had a lower response rate to interferon at 6 months and at the end of treatment as compared to anti-HBc-negative subjects (respectively 42% vs 66%, p < 0.01; and 32% vs 57%, p < 0.01). No difference between the two groups in terms of sustained response was detected 6 months after interferon discontinuation. CONCLUSIONS: The prevalence of anti-HBc is high among HCV-positive individuals. HCV-positive individuals who are anti-HBc positive have: 1) a higher prevalence of cirrhosis; 2) lower HCV-RNA levels; and 3) an impaired ability to respond to interferon treatment. [ABSTRACT FROM AUTHOR]

Background & Aims Risk scores for hepatocellular carcinoma (HCC) developed in Asians offer poor-moderate predictability in Caucasian patients with chronic hepatitis B (CHB). This nine center cohort study aimed to develop and validate an accurate HCC risk score in Caucasian CHB patients treated with the current oral antivirals, entecavir/tenofovir. Methods We included 1815 adult Caucasians with CHB and no HCC at baseline who received entecavir/tenofovir for ⩾12 months. Using data from eight centers (derivation dataset, n = 1325), a HCC risk score was developed based on multivariable Cox models and points system for simplification. Harrell’s c-index was used as discrimination, bootstrap for internal validation and the data from the 9 th and largest center (validation dataset, n = 490) for external validation. Results The 5-year cumulative HCC incidence rates were 5.7% and 8.4% in the derivation and validation dataset, respectively. In the derivation dataset, age, gender, platelets and cirrhosis were independently associated with HCC. The PAGE-B score was developed based on age, gender and platelets (c-index = 0.82, 0.81 after bootstrap validation). The addition of cirrhosis did not substantially improve the discrimination (c-index = 0.84). The predictability of PAGE-B score was similar (c-index = 0.82) in the validation dataset. Patients with PAGE-B ⩽9, 10–17, ⩾18 had 5-year cumulative HCC incidence rates of 0%, 3%, 17% in the derivation and 0%, 4%, 16% in the validation dataset. Conclusion PAGE-B, which is based only on baseline patients’ age, gender and platelets, represents a simple and reliable score for prediction of the 5-year HCC risk in Caucasian CHB patients under entecavir/tenofovir. [ABSTRACT FROM AUTHOR]

Background & Aims The risk of hepatocellular carcinoma (HCC) in Caucasian patients with chronic hepatitis B (CHB), treated with entecavir (ETV) or tenofovir (TDF), is unclear. We evaluated the incidence and predictors of HCC and the accuracy of existing HCC risk scores in Caucasian CHB patients receiving ETV/TDF. Methods This large, multicentre, retrospective cohort study included 1666 adult Caucasian CHB patients under ETV/TDF for 39 months. CHB without cirrhosis, compensated and decompensated cirrhosis were present in 67%, 39%, and 3% of patients, respectively. The predictability of baseline parameters and three risk scores (GAG-HCC, CU-HCC, and REACH-B), developed in Asian patients, was assessed. Results The cumulative probability of HCC was 1.3%, 3.4%, and 8.7% at year-1, year-3, and year-5 after ETV/TDF onset. Older age and lower platelets were strong independent HCC predictors in the total population and in the subgroups of cirrhotic and non-cirrhotic patients, while liver disease severity was an independent HCC predictor in the total population and in the cirrhotics. GAG-HCC, CU-HCC, and REACH-B risk scores were associated with HCC development only in the univariable but not in the multivariable analyses and offered poor to modest predictability. Conclusions HCC can still develop in Caucasian CHB patients treated with ETV/TDF. Besides the well-known predictors of HCC, such as older age, male gender and more advanced liver disease, lower platelets represent an independent factor of higher HCC risk. The applicability and predictability of HCC risk scores developed in Asian patients are poor or modest in Caucasian CHB patients, for whom different risk scores are required. [ABSTRACT FROM AUTHOR]