Hepatitis B Virus Endemic Areas Research Articles

Global prevalence and molecular characteristics of three clades within hepatitis B virus subgenotype C2: Predominance of the C2(3) clade in South Korea.

Hepatitis B Virus (HBV) genotypes reflect geographic, ethical or clinical traits and are currently divided into 10 genotypes (A-J). Of these, genotype C is mainly distributed in Asia, is the largest group and comprises more than seven subgenotypes (C1-C7). Subgenotype C2 is divided into three phylogenetically distinct clades, C2(1), C2(2), and C2(3), and is responsible for most genotype C infections in three East Asian nations, including China, Japan, and South Korea, which are major HBV endemic areas. However, despite the significance of subgenotype C2 with regard to clinical or epidemiologic aspects, its global distribution and molecular characteristics remain largely unknown. Here, we analyze the global prevalence and molecular characteristics between 3 clades within subgenotype C2 using 1,315 full genome sequences of HBV genotype C retrieved from public databases. Our data show that almost all HBV strains from South Korean patients infected with genotype C belong to clade C2(3) within subgenotype C2 [96.3%] but that HBV strains from Chinese or Japanese patients belong to diverse subgenotypes or clades within genotype C, suggesting clonal expansion of a specific HBV type, C2(3), among the Korean population. Our genome sequence analysis indicated a total of 21 signature sequences specific to the respective clades C2(1), C2(2), and C2(3). Of note, two types of four nonsynonymous C2(3) signature sequences, sV184A in HBsAg and xT36P in the X region, were detected in 78.9 and 82.9% of HBV C2(3) strains, respectively. In particular, HBV strains C2(3) versus C2(1) and C2(2) show a higher frequency of reverse transcriptase mutations related to nucleot(s)ide analog (NA) resistance, including rtM204I and rtL180M, suggesting an increased possibility of C2(3) infection in those with NA treatment failure. In conclusion, our data show that HBV subgenotype C2(3) is extremely prevalent in Korean patients with chronic HBV infection, which is distinct from two other East Asian nations, China and Japan, where diverse subgenotypes or clades within genotype C coexist. This epidemiologic trait might affect distinct virological and clinical traits in chronic HBV patients in Korea, where exclusively C2(3) infection is predominant.

335.2: Long-term Outcomes of Liver Transplantation Using Grafts From Donors With Active Hepatitis B virus Replication: A Multicenter Cohort Study

Background: Liver grafts from donors with hepatitis B infection contributed to expanding the donor pool under the Hepatitis B immunoglobulin (HBIG) and antiviral agents (NA: Nucleos(t)ide analogs) in the hepatitis B virus (HBV) endemic area. The purpose of this study is to describe the long-term outcome of liver transplantation (LT) using grafts from donors with active and chronic hepatitis B virus infection. Methods: Between January 2000 and April 2019, 2260 liver transplants (LTs) were performed at Seoul National University (SNU) Hospital, SNU Bundang Hospital (SNUBH), and Seoul Metropolitan Government-SNU Boramae Hospital. Twenty-six (1.2%) grafts from donors with HBsAg (+), HBeAb (+), or HBV DNA (+) were classified as active and chronic HBV hepatitis grafts and retrospectively reviewed. The demographics of donors and recipients, as well as the outcomes of transplantation, were analyzed. HBV reactivation has been defined as an increase in viral DNA in HBsAg (+) grafts and seroconversion to HBsAg positive grafts in chronic hepatitis grafts. Additionally, we used the chronic HBV infection stage to evaluate and manage recipients who received HBV-infected grafts. Results: Sixteen LT were performed on deceased donors using active HBsAg (+) grafts. Ten living donor LT were performed using inactive HBV grafts; eight patients with inactive hepatitis; HBsAg (-), HBcAb (+), and HBV DNA (+), and two patients with chronic HBV hepatitis with seroconversion; HBsAg (-), HBsAb (+), and HBeAg (+) (Figure 1). The recipients were aged 59.0 ± 10.3 years and had a MELD score of 19.9 ± 8.4. The mean duration of follow-up was 82.6 ± 60.1 months. Depending on the donor and recipient’s serology, NA and HBIG were administered during the perioperative period. Deaths (n=8) occurred between 2.0 and 47.3 months following LT. All deaths were reported in DDLT. When compared with LT using grafts without HBV, LT using HBV infected grafts did not show any significant difference in patient survival (30.8% vs. 18.6%, p=0.247) (Figure 2). The most common causes of death were infection (n=4) and HCC recurrence (n=3). All recurred HCC patients died of cancer. HBV reactivation was identified in 1 patient but resolved spontaneously without additional management. All 10 LDLT recipients survived and were in good condition during follow-up. Survivors were in inactive or resolved status for HBV infection under the HBIG and NA. No graft failure was observed. Fourteen patients followed-up more than 5 years were stable and no increase in HCC recurrence rate was observed 5 years after transplantation. Conclusion: Considering their long-term outcomes, liver grafts with active and chronic HBV infection can be safely used for LT in HBV endemic area.

Alternative hepatitis B virus DNA confirmatory algorithm identified occult hepatitis B virus infection in Chinese blood donors with non-discriminatory nucleic acid testing.

Multiplex viral nucleic acid testing (NAT) and a discriminatory testing algorithm have been used to detect viral infections in blood donors. Non-discriminated reactive (NDR) results may arise from low hepatitis B virus (HBV) DNA levels and are challenging for donor management by blood services. The aim of this study was to evaluate the performance and feasibility of alternative viral particle concentration methods to confirm and to characterise HBV infection status in NDR donors from Dalian, China, in order to improve routine donor management according to the potential residual risk estimate. Individual donations were tested with ULTRIO Plus, and discriminated when reactive. Virions were concentrated from 12 and 6 mL plasma samples by ultracentrifugation (UC) and polyethylene glycol (PEG) precipitation, respectively. HBV DNA was detected with four nested polymerase chain reactions (95% limit of detection: 5-25 IU/mL). Amplified products were sequenced for definitive confirmation. Anti-HBc and anti-HBs were tested. Of 77,556 donors, 79 (0.1%) were NAT NDR. After viral particle concentration by UC and PEG precipitation, HBV DNA was detected in 46 (58.2%) and 34 (43.0%) NDR donors, respectively, including 61.7% of samples that were repeatedly non-reactive with multiple NAT testing. Anti-HBc and anti-HBs (median titre: 37 mIU/mL) were detected in 87.3% and 46.8% of NDR donors, respectively. Sequencing confirmed HBV DNA in 65.8% of NDR donors, of whom 96.2% were occult HBV carriers with rare mutations in S and core proteins. A HBV DNA confirmatory procedure with limited technical constraints was implemented successfully. The majority of NDR donors had occult HBV infections with extremely low viral DNA levels, which may constitute a potential residual threat for blood safety. Only a minority of anti-HBc+ NDR donors had anti-HBs levels high enough to consider their reinstatement as donors. The data support the permanent deferral of NDR donors to ensure maximum blood safety in areas of high HBV endemicity.

Superinfection of other hepatitis viruses on top of chronic hepatitis B: The more, the worse

Superinfection of other hepatitis viruses on top of chronic hepatitis B: The more, the worse

Anti-Viral Prophylaxis for Hepatitis B Virus Is Associated with Improved Outcome in Patients with Diffuse Large B Cell Lymphoma in Taiwan - a Population-Based Study between 2011 and 2015

Background: Rituximab increases the possibility of reactivation of hepatitis B virus (HBV) in patients with diffuse large B cell lymphoma (DLBCL), which is the most common non-Hodgkin lymphoma worldwide. Managing HBV during the treatment for DLBCL is therefore a particularly important issue in HBV endemic area, such as Taiwan. However, there is no population-based study to investigate whether HBV status and antiviral prophylaxis influence the survival in DLBCL patients. Objective: To evaluate the impact of HBV status and antiviral prophylaxis on survival in DLBCL patients, we incorporated the data from the Taiwan Cancer Registry Database (TCRD), the National Health Insurance Research Database (NHIRD), and the National Death Registry in our study. Methods: From TCRD, we identified 6304 patients with newly diagnosed DLBCL between 2011 and 2015. Patients were excluded if they were younger than 20 years (n=52), had unknown Ann Arbor stage (n=277), had other cancers before the diagnosis of DLBCL (n=336), or did not receive any treatment for DLBCL (n=514). We also excluded patients treated with regimens other than R-CHOP, R-CVP, CHOP, or CVP (n=711), with unknown HBV (n=492) or hepatitis C virus (HCV, n=152) status, or treated with antiviral therapies but not HBV or HCV carriers (n=65). There were 3702 DLBCL patients treated by R-CHOP, R-CVP, CHOP, or CVP for survival analysis, including 781 HBV carriers. Results: According to the HBV status and the applications of antiviral prophylaxis, we stratified patients into three groups, HBsAg-negative patients (HBV-neg, n=2921), HBV carriers with antiviral prophylaxis (HBV+Tx, n=711), and HBV carriers without antiviral prophylaxis (HBV+No, n=70). The baseline characteristics were similar between the three groups, except that HBV+Tx patients were younger than others (median age: 63.7 years in HBV-neg patients, 57.0 years in HBV+Tx ones, and 62.9 years in HBV+No ones). HBV+Tx patients tended to receive R-CHOP, which was the standard frontline regimen for DLBCL patients (78.2% in HBV-neg patients, 87.5% in HBV+Tx ones, and 77.1% in HBV+No ones). The most frequent used antiviral agent was entecavir (91.0%). In survival analysis, the median overall survival (OS) of HBV-neg patients was 74.23 months, similar to that of HBV+Tx patients (median OS was not reached). However, the median OS of the HBV+No patients was only 35.61 months (P=0.0028 when compared with HBV+Tx patients), which indicated the antiviral prophylaxis improved OS in DLBCL patients with HBV infection. In the multivariate analysis of OS, we included other potential prognostic factors in DLBCL patients, such as gender difference, age, Carlson comorbidity index, Ann Arbor stage, type of frontline chemotherapies for DLBCL, radiotherapy in the frontline therapy, and the practice setting (medical centers or others). The status of HBV and antiviral prophylaxis was still an independent prognostic factor in the multivariate analysis of OS (hazard ratio and 95% confidence interval: 1 for HBV-neg, 1.01 (0.88-1.16) for HBV+Tx, and 1.70 (1.22-2.35) for HBV+No; P=0.0069). Conclusion: From our population-based study, we illustrated the importance of antiviral prophylaxis in the DLBCL patients with HBV infections. HBV carriers would have similar survival to the HBV-negative patients if they received antiviral prophylaxis for HBV infections. Figure Disclosures Tien: Daiichi Sankyo: Honoraria; Celgene: Honoraria; Pfizer: Honoraria; Abbvie: Honoraria; Johnson &Johnson: Honoraria; Novartis: Honoraria; Roche: Research Funding; Alexion: Honoraria; Celgene: Research Funding; Roche: Honoraria; BMS: Honoraria.

Cost-effectiveness of preventing hepatitis B virus reactivation in patients with lymphoma and resolved HBV infection

Hepatitis B virus (HBV) reactivation may occur in >10% of patients with lymphoma and resolved HBV infection who undergo rituximab-containing chemotherapy. Preventive strategies may have marked impact on resource allocation in HBV endemic areas. This study aims to compare the cost-effectiveness between prophylactic antiviral therapy and HBV DNA monitoring for the prevention of HBV-related complications. Data sources are studies of HBV-related events and survival for patients with lymphoma and resolved HBV infection published since 2006. Decision tree analysis was used to compare the incremental cost-effectiveness ratio (ICER) of preventing HBV-related death or liver decompensation for patients who undergo first-line rituximab-containing chemotherapy. Sensitivity analysis was performed to examine the impact of the preventive efficacy, the duration of prophylactic antiviral therapy, and the cost of different interventions. The direct medical cost was derived from the database of the NHI Administration, Taiwan. The time frame of our analysis was set to 3 years after the completion of chemotherapy. The median ICER of prophylactic antiviral therapy, according to current practice guidelines, ranged between USD 150,000 and 250,000 if we apply the guidelines generally. When a long-course (12 months after completion of chemotherapy according to clinical guidelines) prophylactic therapy was assumed, Option A was cheaper and more effective only in the anti-HBs-negative subgroup (median ICER US$149,932 vs. US$161,526, p=0.013). Identification of anti-HBs-negative subgroups is critical to improve the cost-effectiveness of prophylactic antiviral therapy in lymphoma patients with resolved HBV infection.

De Novo Hepatitis B Virus Infection After Liver Transplantation in Hepatitis B Core-positive Recipients Using Hepatitis B Core-negative Grafts

BackgroundHepatitis B core antibody-positive (HBcAb+) graft is known as a risk for de novo hepatitis B virus (HBV) infection in recipients after liver transplantation (LT). However, little is known about the possibility or incidence of de novo HBV infections after LT in hepatitis B surface antigen-negative (HBsAg−)/HBcAb+ recipients using HBsAg−/HBcAb− grafts. The study aimed to evaluate the prevalence of de novo HBV infection in HBsAg−/HBcAb+ recipients using HBsAg−/HBcAb− grafts. A retrospective review was performed with the records of 1129 adult patients who underwent primary LT at a single institution in an HBV endemic area between January 2000 and December 2013. A total of 78 patients (6.9%) were reviewed for de novo HBV infection after LT. De novo HBV infection was developed in 1 patient (1.28%). The patient was a 65-year-old woman who underwent LT due to alcoholic liver cirrhosis. De novo HBV was not related to graft loss or death and well treated with tenofovir. In conclusion, de novo HBV infections may occur in HBsAg-/HBcAb+ recipients using HBsAg−/HBcAb− grafts, and caution is needed in these patients.

Cost-effectiveness analysis of hepatitis B vaccine booster in children born to HBsAg-positive mothers in rural China

ObjectiveIn rural areas of China with highly endemic for hepatitis B virus (HBV) infection, protective efficacy was observed in adulthood when a one-dose HBV vaccine booster was administered to high-risk children born to mothers who were positive for hepatitis B surface antigen (HBsAg). The aim of this study was to estimate the cost-effectiveness of an HBV vaccine booster in this specific group of children when given at 10 years of age. MethodsTwo potential strategies were considered: strategy 1 was a one-dose booster given if the child was negative on HBsAg screening; strategy 2 was a one-dose booster given if the child was negative on both HBsAg plus anti-HBs screening. A decision tree combined with a Markov model was developed to simulate the booster intervention process and to simulate the natural history of HBV infection in a cohort of 10-year-old children who were born to HBsAg-positive mothers. The model was calibrated based on multiple selected outcomes. Costs and quality-adjusted life years (QALYs) were measured from a societal perspective. Cost-effectiveness ratios (CERs) of the different strategies were compared in both base-case and one-way sensitivity analyses. ResultsCompared to the current practice of ‘no screening and no booster’, both strategy 1 and strategy 2 were cost-saving, with CERs estimated at US$ −6961 and US$ −6872 per QALY gained, respectively. In the one-way sensitivity analysis for strategy 1, all the CERs were found to be less than US$ −5000 per QALY gained after considering the uncertainty of all the variables, including vaccination protective efficacy, natural history, behavior, and various costs and utility weights. In a ‘worst case’ scenario (all parameter values simultaneously being at the worst), the CER of strategy 1 increased to US$ 3263 per QALY gained, which was still less than the GDP per capita of China in 2016 (US$ 8126). ConclusionsA hepatitis B vaccine booster given to children born to HBsAg-positive mothers in rural China would be cost-effective and could be considered in HBV endemic areas.

Seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) among human immunodeficiency virus (HIV)-infected patients in an HBV endemic area in Brazil.

BackgroundHepatitis B virus (HBV) and hepatitis C virus (HCV) are a common cause of complications in liver disease and immunological impairment among human immunodeficiency virus (HIV)-infected patients. The aim of this study was to assess the seroprevalence of HBV and HCV and their correlation with CD4+ T-cells among HIV-infected patients in an HBV endemic area.MethodsA cross-sectional observational and retrospective study was carried out in a reference center in Southern Brazil between January 2005 and December 2016. Socio-demographic data were collected by using a structured questionnaire. Serological tests and analysis of CD4+ T-cell count levels were performed using standard procedures.ResultsThe seroprevalence of HIV-HBV, HIV-HCV, and HIV-HBV-HCV coinfections was 3.10%, 3.10%, and 0.16%, respectively. At baseline, anti-hepatitis B surface and anti-hepatitis B core antigens were detected in 46.27% and 16.74% of HIV-monoinfected patients and in 31.25% and 21.86% of the HIV-HCV coinfected patients, respectively. The median CD4+ T-cell count at baseline in the HIV-monoinfected group was higher than that in the HIV-coinfected groups, but without statistical significance. The median CD4+ T-cell count and the CD4/CD8 ratio were significantly higher in HIV-HBV and HIV-HCV groups after 24 months of combination antiretroviral therapy (cART) compared to the pre-cART values. When comparing patients with HIV-HBV and HIV-HCV on cART, CD4+ T-cell recovery was more rapid for HIV-HBV patients.ConclusionAlthough the analyzed region was endemic for HBV, the prevalence of HIV-HBV and HIV-HCV coinfection was lower than the rate found in the general population of Brazil. HBV and HCV had no significant impact on CD4+ T-cell counts among HIV-infected patients at baseline.

Knowledge regarding hepatitis B mother-to-child transmission among healthcare workers in South China.

To determine the knowledge regarding hepatitis B virus (HBV) mother-to-child transmission (MTCT) and its prevention and treatment among healthcare workers (HCWs) in Guangdong Province, China, an HBV endemic area. An HBV knowledge questionnaire was administered to 900 HCWs from the 3rd Affiliated Hospital of Sun Yat-Sen University and 2 rural hospitals in Guangdong Province. The 27 items in the questionnaire fell into 3 sections: HBV MTCT general knowledge, respondents' practices of preventing HBV MTCT and awareness of the resources of preventing HBV MTCT. The data collected were coded and analysed using SPSS software version 20. In total, 503 of 900 HCWs responded to the survey (response rate: 55.9%). Eighty-four individuals responded correctly to all of the knowledge questions: 58 were doctors, and 26 were nurses (P<.05). Doctors more often performed practices than nurses (t=3.591, P<.01). Participants from the infectious disease department demonstrated a significantly higher proportion of correct answers and resource utilization than other specialties (χ2 =14.052, 7.998, P<.01). In terms of the average knowledge score, t test or ANOVA showed that there were significant differences between the specialty groups (t=3.110, P<.01), hospital level groups (t=2.337, P<.05) and age groups (F=3.020, P<.05). Respondents' initiative increased with hospital level and age (t=2.993, 7.493, P<.01). A considerable percentage of HCWs has misconceptions about HBV MTCT. Healthcare workers, in particular nurses, those working in noninfectious disease departments or township hospitals and younger medical staff, lack systematic and comprehensive knowledge about HBV MTCT and are in urgent need of HBV-related training.

Current status and strategies for hepatitis B control in Korea.

Hepatitis B virus (HBV) infection is the most common cause of chronic liver diseases in Korea. After the introduction of the universal HBV vaccination program, the prevalence of hepatitis B surface antigen was markedly reduced, and Korea is now classified as an area of intermediate endemicity for HBV. However, there are still hurdles for elimination of hepatitis B, such as immunoprophylaxis failure against vertical transmission, occurrence of acute hepatitis B among peoples who did not have vaccination at younger age, and rapid increase of immigrant populations from HBV endemic areas. To achieve the World Health Organization goal of viral hepatitis elimination by 2030 in Korea, we suggest comprehensive policies for more effective control of hepatitis B as following: i) insurance coverage for antiviral prophylaxis in mothers with high viremia, ii) screening for hepatitis B seromarkers and catch-up HBV vaccinations of susceptible persons with hepatitis B, iii) establishment of an independent 'viral hepatitis sector' in Centers for Disease Control & Prevention to organize and execute comprehensive strategy for management of viral hepatitis, iv) encourage of management of HBV infection in immigrant populations, v) national campaign to promote awareness of hepatitis B.

Hepatitis B Virus Genotypes, Epidemiological Characteristics, and Clinical Presentation of HBV Chronic Infection in Immigrant Populations Living in Southern Italy

Background: Information on hepatitis B virus (HBV) genotypes in immigrant populations living in Italy is scanty. Objectives: The current study aimed at assessing the epidemiological and clinical need to detect HBV genotypes in immigrants with HBV infection. Methods: A multicenter screening was performed in 5 first-level care facilities centers in Southern Italy to identify migrants with HBV infection. Hepatitis B surface antigen (HBsAg)-positive subjects were further investigated at a tertiary unit of infectious diseases. Results: Of the 1727 investigated immigrants, 170 (9.8%) were HBsAg-positive. These 170 subjects, prevalently males (86.5%), aged 31.0 ± 8.5 years and living in Italy for nearly 2.5 years, prevalently (80%) from sub-Saharan Africa. HBV DNA was detected in 113 (66.5%) and HBV genotypes in 109 subjects: genotype E in 69.9%, genotype A in 16.5%, genotype D in 11.9%, and genotype C in 2.7%. Genotype E was detected in 70 (83.3%) out of 84 migrants from sub-Saharan Africa and in 5 from the other areas. Of these 75, 16% were hepatitis B e antigen (HBeAg)-positive and none circulated anti-hepatitis D virus (HDV); 69.3% were inactive HBV carriers, 22.7% had chronic hepatitis and 8% cirrhosis with multifocal hepatocellular carcinoma (HCC) in 2 patients. Half of the 18 subjects with genotype A, prevalently from sub-Saharan Africa (61%), were inactive HBV carriers, 7 had chronic hepatitis, and 1 had liver cirrhosis. Of the 13 subjects with genotype D, prevalently from Eastern Europe or India-Pakistan subcontinent, 8 were HBV inactive carriers and 5 had chronic hepatitis. Conclusions: The data indicated the need to extend HBV screening and vaccination programs to all immigrants from areas of intermediate or high HBV endemicity.

Clinical characteristics and potential aetiologies of non‐B non‐C hepatocellular carcinoma in hepatitis B virus endemic area

We investigated potential aetiologies, clinical characteristics and prognosis of non-B non-C (NBNC) hepatocellular carcinoma (HCC) patients in hepatitis B virus (HBV) endemic area, according to potential causes such as previous HBV exposure, chronic alcohol intake and metabolic syndrome. Among 4690 HCC patients treated at Asan Medical Center between 2007 and 2009, 523 were newly diagnosed with NBNC HCC, and their medical records and survival data were analyzed retrospectively. Among 321 NBNC HCC patients whose hepatitis B core antibody (anti-HBc) test results were available, 81.0%, 37.1% and 15.5% had anti-HBc positivity, chronic alcohol intake and metabolic syndrome respectively. One-hundred and fifty-two patients (47.4%) had previous exposure to HBV without chronic alcohol intake or metabolic syndrome. Hepatitis B surface antibody (anti-HBs) was positive in 48.0% of the 523 NBNC HCC patients, which was much lower than that in general Korean population, and 52.3% of anti-HBc-positive NBNC HCC patients were negative for anti-HBs. Anti-HBc-negative alcoholic patients presented with more advanced cirrhosis with Child-Pugh class B/C liver function than anti-HBc-positive patients (P = 0.002). In multivariate analysis, baseline liver function, alpha-foetoprotein levels and tumour stage were significant prognostic factors and aetiology did not affect patient survival. Prior HBV infection could be a potential aetiology in over 40% of NBNC HCC patients in HBV endemic area. Positivity for anti-HBc and negativity for anti-HBs may be a serologic surrogate marker for occult HBV infection in these area. The prognosis of NBNC HCC was determined by tumour stage and underlying liver function.

Perspectives on dual hepatitis B and C infection in Taiwan.

Dual hepatitis C virus (HCV) and hepatitis B virus (HBV) infection is not rare in HBV or HCV endemic areas, and can be found in populations at risk of parenteral viral transmission. Clinical observatory studies suggest a higher risk of liver disease progression in patients with dual HCV/HBV infection than in HBV or HCV monoinfected patients. Recent trials confirmed that combination therapy of peginterferon alfa-2a or alfa-2b and ribavirin was effective and safe in dually infected patients with positive HCV RNA. Moreover, about 30% of the dually infected patients cleared hepatitis B surface antigen within 5 years after the start of peginterferon-based therapy. The optimal treatment strategies for dually infected patients with active hepatitis B, with decompensated cirrhosis, or in other clinical situations should be explored in further studies. Finally, the advent of new direct-acting antiviral-based anti-HCV therapy may lead to the development of strategies for the treatment of dually infected patients with active hepatitis C, particularly for those not tolerating or not eligible for peginterferon-based therapy. Notably, direct-acting antivirals would not have any activity against HBV infection; simultaneous or on-demand nucleos(t)ide analogs would be needed if clinically indicated.

Hepatitis B virus infection correlates with poor prognosis of extranodal natural killer/T cell lymphoma

Studies have shown that hepatitis B virus (HBV) infection may play an important role in the lymphomagenesis of lymphoma, but no studies regarding the relationship between HBV infection and extranodal natural killer/T cell lymphoma (ENKTL) have been reported previously. One hundred and seven patients diagnosed with ENKTL were retrospectively reviewed. The hepatitis B surface antigen (HBsAg)-positive rate was 13.1%, and no significant correlation existed between HBV infection and clinical characteristics (p > 0.05). No significant difference existed in complete remission rate between HBsAg-positive and -negative groups (42.9% vs. 44.1%, p = 1.000). In a multivariate Cox regression model that included international prognostic index (IPI) score, induction chemotherapy regimen and HBsAg status, all these variables were independent prognostic factors for overall survival (OS) and progression-free survival (PFS) (p < 0.05). In conclusion, the HBsAg-positive rate in ENKTL was similar to that of the normal population in a high HBV endemic area, and HBsAg-positive status was an independent prognostic factor for OS and PFS.

Public awareness of hepatitis B infection in Turkey as a model of universal effectiveness in health care policy.

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. 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. 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). 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.

Hepatocellular carcinoma after kidney transplantation: analysis of Hong Kong Renal Registry

Kidney transplant recipients have increased risk of cancers when compared with the general population. Hepatocellular carcinoma (HCC) is extremely important in Asia where hepatitis B virus (HBV) infection is endemic. The aim is to study the epidemiological and clinical aspects of all de novo HCC in our kidney transplant recipients. Moreover, various preventive strategies which may help to optimize the outcome will also be discussed. A retrospective review of all patients who developed HCC after kidney transplantation between May 1972 and December 2011 in Hong Kong, based on the data from Hong Kong Renal Registry. After a follow-up period of 40,246 person-years, 20 patients (males 15: females 5) developed HCC. The annual incidence was 49.7/100,000 persons per year. Among them, 16 were HBV carriers, 2 were hepatitis C (HCV) carriers and 2 had HBV and HCV co-infection. Presence of HBV infection was associated with 78-fold higher risk for HCC development. Majority (85%) were asymptomatic when HCC was diagnosed by ultrasound or alpha-fetoprotein surveillance. All patients diagnosed by surveillance received active treatment while 2/3 of symptomatic patients could only receive symptomatic care and died rapidly. In conclusion, HBV infection is the major etiological factor for HCC development in kidney transplant recipients in HBV endemic areas. Regular HCC surveillance appeared to be able to detect early stage cancers which are amenable to treatment and offer the best hope of cure.

Preventing Vertical Transmission of Hepatitis B virus

Vertical transmission of hepatitis B virus (HBV) is the main source of chronic infection in Korea, an HBV endemic area, and chronically infected people are at high risk of developing liver cirrhosis or hepatocellular carcinoma. Thus, preventing vertical transmission is an important step in eradicating or reducing the burden of chronic HBV infection. However, despite passive-active immunoprophylaxis provided to infants, up to 10% of infants born to highly viremic mothers still become infected with HBV. Therefore, antiviral treatments or management protocols to reduce vertical transmission should be considered for highly viremic mothers and infants born to these mothers. Additionally, in-depth discussions with the mothers about the risks, benefits, and limitations of the current published data are essential. This article reviews the potential mechanisms of vertical transmission and current intervention strategies to prevent vertical transmission of HBV. (Korean J Med 2014;87:557-564)

Updates on the treatment and outcomes of dual chronic hepatitis C and B virus infection

Dual hepatitis C virus (HCV)/hepatitis B virus (HBV) infection is found in HBV or HCV endemic areas, and in specific populations exhibiting a high risk of parenteral viral transmission. Clinical observations have revealed that HCV/HBV dually infected patients demonstrate a higher risk of liver disease progression compared with HBV or HCV monoinfected patients. The viral activity responsible for liver disease progression can be determined by examining the viral loads of HCV and HBV and by conducting liver biopsy examinations. Recent trials have confirmed that the combination therapy of peginterferon alpha-2a or 2b and ribavirin for dual hepatitis patients with HCV dominance appears to be as effective and safe as it is in patients with HCV monoinfections. Strikingly, approximately 60% of dually infected patients with inactive hepatitis B before treatment develop HBV reactivation after the clearance of the HCV. The clinical significance of this HBV reactivation and the strategy to prevent and treat this event should be determined. Furthermore, approximately 30% of dually infected patients lost hepatitis B surface antigen (HBsAg) within 5 years after the start of peginterferon-based therapy, and 40% of them harbored occult HBV infection. The underlying mechanisms of their accelerating HBsAg seroclearance and the development of occult HBV await further investigations. Moreover, the optimal treatment strategies for dually infected patients who are seropositive for the hepatitis B e antigen must be explored. Finally, the advent of new direct-acting antiviral-based anti-HCV therapy may change the optimal therapies for patients with dual hepatitis in the near future, which warrants further clinical trials.

Treatment of patients with dual hepatitis C virus and hepatitis B virus infection: Resolved and unresolved issues

Dual hepatitis C virus (HCV)/hepatitis B virus (HBV) infection is not uncommon in HCV or HBV endemic areas and among subjects at risk of parenteral transmission. In patients dually infected with hepatitis C and B, the disease manifestations are usually more severe than those with either virus infection. In the past decade, the following issues have been resolved. In dually infected patients with active hepatitis C, combined pegylated interferon alfa plus ribavirin was effective, the treatment outcomes being similar to patients with HCV monoinfection. During long-term follow-up, the HCV response was sustained in around 97% of patients; and the long-term outcomes including the development of hepatocellular carcinoma and liver-related mortality were improved. However, several clinical issues remain to be resolved. First, host and viral factors influencing the long-term outcomes and treatment options in patients with dual HCV/HBV infection await further studies. Second, about 60% of dually infected patients with baseline undetectable serum HBV DNA levels develop HBV reactivation after the start of treatment. How to prevent and treat HBV reactivation should be clarified. Third, about 30% of dually infected patients lose hepatitis B surface antigen at 5 years after the end of combination therapy; the mechanisms need further investigations. Fourth, the optimal treatment strategies for dually infected patients with active hepatitis B or established cirrhosis should be explored in future clinical trials. Finally, the role of new direct-acting antiviral-based therapy for the treatment of patients with dual HCV/HBV infection also remains to be evaluated.