De novo hepatitis B infection following liver transplantation with core antibody positive grafts: The role of surface antibody status in guiding long-term prophylaxis.

Liver transplantation (LT) with hepatitis B core antibody (anti-HBc) positive grafts to hepatitis B surface-antigen (HBsAg) negative recipients is safe and has likely contributed to improvements in organ access over the years. The incidence of de novo hepatitis B infection (HBV) in these instances is low with appropriate prophylaxis and is affected by recipient immunologic status. There is debate as to whether hepatitis B surface antibody (anti-HBs) positivity may safely inform prophylaxis discontinuation post-LT. In this retrospective study of all hepatitis B surface antigen (HBsAg) negative recipients of anti-HBc positive organs at three large academic centers between January 2014 and December 2019, nine LT recipients discontinued prophylaxis after developing anti-HBs antibodies 1 year or later post-LT. Three of the nine patients (33%) developed de novo HBV, defined by positive HBsAg or hepatitis B virus (HBV) DNA, during the study period. The remaining six patients had no evidence of HBV infection after a mean follow-up of 37 months. The patients without de novo HBV had higher anti-HBs titers at the time of prophylaxis discontinuation and were less likely to have negative anti-HBs at the time of transplant or negative anti-HBc at any time point. These results suggest that quantitative anti-HBs titer thresholds rather than qualitative anti-HBs positivity at 1 year or later after LT should be used to identify patients at decreased risk of de novo infection and help guide prophylaxis duration.

A Model of Care Optimized for Marginalized Remote Population Unravels Migration Pattern in India.

BACKGROUND AND AIMS: Access to basic health needs remains a challenge for most of world's population. In this study, we developed a care model for preventive and disease-specific health care for an extremely remote and marginalized population in Arunachal Pradesh, the northeasternmost state of India. APPROACH AND RESULTS: We performed patient screenings, performed interviews, and obtained blood samples in remote villages of Arunachal Pradesh through a tablet-based data collection application, which was later synced to a cloud database for storage. Positive cases of hepatitis B virus (HBV) were confirmed and genotyped in our central laboratory. The blood tests performed included liver function tests, HBV serologies, and HBV genotyping. HBV vaccination was provided as appropriate. A total of 11,818 participants were interviewed, 11,572 samples collected, and 5,176 participants vaccinated from the 5 westernmost districts in Arunachal Pradesh. The overall hepatitis B surface antigen (HBsAg) prevalence was found to be 3.6% (n = 419). In total, 34.6% were hepatitis B e antigen positive (n = 145) and 25.5% had HBV DNA levels greater than 20,000 IU/mL (n = 107). Genotypic analysis showed that many patients were infected with HBV C/D recombinants. Certain tribes showed high seroprevalence, with rates of 9.8% and 6.3% in the Miji and Nishi tribes, respectively. The prevalence of HBsAg in individuals who reported medical injections was 3.5%, lower than the overall prevalence of HBV. CONCLUSIONS: Our unique, simplistic model of care was able to link a highly resource-limited population to screening, preventive vaccination, follow-up therapeutic care, and molecular epidemiology to define the migratory nature of the population and disease using an electronic platform. This model of care can be applied to other similar settings globally.

Effectiveness of prophylactic antiviral therapy in reducing HBV reactivation for HBsAg-positive recipients following allogeneic hematopoietic stem cell transplantation: a multi-institutional experience from an HBV endemic area.

Hepatitis B virus reactivation (HBVr) is not uncommon in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Hepatitis B surface antigen (HBsAg)-positive patients receiving allo-HSCT have a very high risk of HBVr. However, the validity of prophylactic antiviral treatment in HBsAg-positive allo-HSCT recipients has not been well studied. We aimed to add experience in dealing with HBsAg-positive patients following allo-HSCT. We conducted a cohort study that included 11 years of data of HBsAg-positive allo-HSCT patients in multiple centers. The cumulative incidence of HBVr with antiviral prophylaxis at 60 months following transplantation was 8.9%. Both lamivudine (LAM) and entecavir (ETV) effectively reduced the incidence of HBVr. Patients with absent-mild cGVHD had a lower HBVr rate than that of patients with moderate-severe cGVHD (HR = 0.201, P = 0.020). The incidence of HBsAg seroclearance at 60 months following transplantation was 34.3%. Recipients accepting from anti-HBs-negative donors were associated with a lower HBsAg seroclearance rate than that of those accepting from anti-HBs-positive donors (HR=0.255, P < 0.001). The peripheral blood stem cell (PBSC) donor source had a higher HBsAg seroclearance rates than that of the PBSC plus bone marrow stem cell source (HR = 4.700, P = 0.047). The prophylactic antiviral treatment effectively reduced HBVr in HBsAg-positive recipients receiving allo-HSCT. HBsAg-positive recipients accept anti-HBs-positive PBSC donor sources may facilitate the acquisition of HBsAg seroclearance after transplantation.

Prolonged incubation period of hepatitis B in a recipient of a nucleic acid amplification test-negative hepatitis B virus window donation.

BACKGROUND: The occurrence of transfusion-transmitted hepatitis B virus (HBV) infection has fallen dramatically due to continuous improvements in pre-transfusion laboratory testing. However, the characteristics of transfusion-transmitted HBV infection caused by individual donor nucleic acid amplification test (ID-NAT)-negative blood products are unclear. CASE PRESENTATION: A 76-year-old woman with acute myeloid leukemia was diagnosed with transfusion-transmitted HBV infection after receiving apheresis platelets derived from an ID-NAT-negative blood donation. This case was diagnosed definitively as transfusion-mediated because complete nucleotide homology of a 1556 bp region of the HBV Pol/preS1-preS2-S genes and a 23 bp region of the HBV core promoter/precore between the donor and recipient strains was confirmed by PCR-directed sequencing. The case is uncommon with respect to the unexpectedly prolonged HBV-DNA incubation period of nearly 5 months after transfusion (previously, the longest period observed since the recent implementation of ID-NAT pre-transfusion laboratory testing in Japan was 84 days). Slow-replicating HBV genotype A2 may contribute to the prolonged incubation period; also, the quantity of apheresis platelets delivered in a large volume of plasma, and/or the immune response of the recipient suffering from a hematological neoplasm, may have contributed to establishment of HBV infection in the recipient. This was supported by analysis of three previously documented cases of transfusion-transmitted HBV infection by blood products derived from ID-NAT-negative donations in Japan. CONCLUSION: Continuous monitoring of HBV infection for longer periods (>3 months) may be required after transfusion of blood components from an ID-NAT-negative HBV window donation.

Endoscopies, blood-borne viruses and blood donors: time to move on from precaution.

BACKGROUND AND OBJECTIVES: Based on the Council of Europe directive which dictates regulatory requirements in Australia, blood donors are currently deferred from donating for 4 months after an endoscopic procedure if either polyps were removed or a biopsy sample was taken. We aimed to assess the incidence of blood-borne viruses (BBVs) (HIV, hepatitis B and C) in blood donors who donated after an endoscopic procedure and evaluate the risk to blood safety through risk modelling. MATERIALS AND METHODS: Donors from 1/1/2013 to 31/12/2017 with an endoscopy deferral on their blood donor file with pre- and post-BBV testing were analysed to determine an incidence of BBVs using standard methods. The standard blood donor cohort was used as a comparator group. Using the incidence of endoscopies and BBV risk, the total residual risk estimate of allowing donors to return postendoscopy without restriction was calculated. RESULTS: The incidence of a BBV postendoscopy in this large cohort of 16,283 where testing has been confirmed postendoscopy was zero (95% CI 0-0·000105). The upper confidence interval of the zero events is 10·5 per 100 000 donations. Total positive donations from 2017 repeat donors were 1·87 per 100 000 (95% CI 0·0000117-0·0000277). Sensitivity analysis demonstrated that the residual risk remained negligible under realistic worst-case scenarios. CONCLUSION: A BBV endoscopy deferral is not required for blood safety in Australia. The presented data has enabled us to submit a request for an exemption to our regulator, which has been approved and the policy change subsequently implemented by Lifeblood on 4/4/2020.

Genetic polymorphisms of the HLA-DP and HLA-DQ genes could influence Hepatitis B virus infection in Yunnan population.

Hepatitis B, caused by hepatitis B virus (HBV) infection, is one of the epidemic and infectious hepatitis diseases. The sigle-nucleotide polymorphisms were identified to associate with HBV infection in East Asian population by genome-wide association study (GWAS), but no study in Yunnan HBV population was reported. We recruited 493 HBV patients and 460 general controls to genotype 7 GWAS SNPs, and then, the association study was performed between these SNPs and biochemical features of HBV patients. The results showed that genotype and allele frequencies of SNPs in the HLA-DP (rs3077, 9277535, and 3128917) and HLA-DQ (rs2856718 and 7453920) genes were associated with HBV infection. Significantly different genotyping frequencies were investigated among three HBV subgroups. Genotype AA of rs3130542 (HLA-C) showed significantly higher frequency in subgroup #1 patients than the other two subgroups (#1 vs. #2, p = .02; #1 vs. #3, p = .03). Meanwhile, genotype frequencies of rs3077, rs9277535, and 3128917 (HLA-DP) were significantly different between patients in subgroup #2 and #3. The indirect bilirubin level was significantly lower in patients with genotype CT of rs3077 than patients with genotype CC (p = .009) or TT (p = .016), and it also showed lower level in patients with genotype GT of rs3128917 than patients with genotype GG (p = .015). The direct bilirubin level was higher in patients with genotype TT of rs4821116 (UBE2L3) than patients with genotype CT (p = .010). In summary, we identified the association between GWAS SNPs and HBV infection or biochemical features in Yunnan HBV population.

Hepatitis B virus infection and its associated factors among medical waste collectors at public health facilities in eastern Ethiopia: a facility-based cross-sectional study.

BACKGROUND: The risk of hepatitis B virus infection among medical waste handlers who undergo collection, transportation, and disposal of medical wastes in the health institutions is higher due to frequent exposure to contaminated blood and other body fluids. There is limited evidence on the seroprevalence of hepatitis B among medical waste handlers in eastern Ethiopia. The study was aimed at studying the seroprevalence of Hepatitis B Virus and associated risk factors among medical waste collectors at health facilities of eastern Ethiopia. METHODS: A facility-based cross-sectional study was conducted among randomly selected medical waste collectors from public health facilities in eastern Ethiopia from March to June 2018. A pre-tested and well-structured questionnaire was used to collect data on socio-demographic characteristics and hepatitis B infection risk factors. A2.5ml venous blood was also collected, centrifuged and the serum was analyzed for hepatitis B surface antigen using the instant hepatitis B surface antigen kit. Descriptive summary measures were done. Chi-square and Fisher exact tests were used to assess the risk of association. Multivariate logistic regression was conducted with 95% CI and all value at P-value < 0.05 was declared statistically significant. RESULTS: From a total of 260 (97.38%) medical waste collectors participated, HBV was detected in 53 (20.4%) of the participants [95%CI; 15.8, 25.6]. No significant differences were observed in the detection rates of HBV with respect to socio-demographic characteristics. In both bivariate and multivariable logistic regression analysis, being unvaccinated (AOR = 6.35; 95%CI = [2.53-15.96], P = 0.001), history of blood transfusion (receiving) (AOR; 3.54; 95%CI; [1.02-12.24], P = 0.046), history of tattooing (AOR = 2.86; 95%CI = [1.12-7.27], p = 0.03), and history of multiple sexual partner (AOR = 10.28; 95%CI = [4.16-25.38], P = 0.001) remained statistically significantly associated with HBsAg positivity. CONCLUSION: This cross-sectional study identified that HBV infection is high among medical waste collectors in eastern Ethiopia. Immunization and on job health promotion and disease prevention measures should be considered in order to control the risk of HBV infection among medical waste collectors in eastern Ethiopia.

High Risk of Viral Reactivation in Hepatitis B Patients with Systemic Lupus Erythematosus.

HBV reactivation (HBVr) can occur in hepatitis B surface antigen (HBsAg)-positive and negative patients. Here, we determined the incidence of HBVr and its related hepatitis in patients with systemic lupus erythematosus (SLE). From 2000 to 2017, 3307 SLE cases were retrospectively reviewed for episodes of hepatitis. The incidence, long-term outcomes and risk factors associated with HBVr, including HBsAg reverse seroconversion (RS) were analyzed. Among them, 607 had available HBsAg status. Fifty-five (9.1%) patients were positive for HBsAg and 63 (11.4%) were HBsAg-negative/antibody to hepatitis B core antigen (anti-HBc)-positive (resolved hepatitis B infection, RHB). None of them received antiviral prophylaxis before immunosuppressive treatment. During a mean 15.4 years of follow-up, 30 (54.5%) HBsAg-positive patients developed HBVr and seven (23.3%) died of liver failure, whereas only two (3.2%) RHB cases experienced HBsAg reverse seroconversion (RS). Multivariate logistic regression analysis showed that age ≥ 40 years at diagnosis of SLE (HR 5.30, p < 0.001), receiving glucocorticoid-containing immunosuppressive therapy (HR 4.78, p = 0.003), and receiving glucocorticoid ≥ 10 mg prednisolone equivalents (HR 3.68, p = 0.003) were independent risk factors for HBVr in HBsAg-positive patients. Peak level of total bilirubin ≥ 5 mg/dL during HBVr was an independent factor of mortality (p = 0.002). In conclusion, the risk of HBVr was associated with glucocorticoid daily dose. Antiviral prophylaxis is mandatory for SLE patients diagnosed at age of ≥40 years who receive ≥ 10 mg daily dose of oral prednisone or equivalent.

Cell and Animal Models for Studying Hepatitis B Virus Infection and Drug Development.

Many cell culture and animal models have been used to study hepatitis B virus (HBV) replication and its effects in the liver; these have facilitated development of strategies to control and clear chronic HBV infection. We discuss the advantages and limitations of systems for studying HBV and developing antiviral agents, along with recent advances. New and improved model systems are needed. Cell culture systems should be convenient, support efficient HBV infection, and reproduce responses of hepatocytes in the human body. We also need animals that are fully permissive to HBV infection, convenient for study, and recapitulate human immune responses to HBV and effects in the liver. High-throughput screening technologies could facilitate drug development based on findings from cell and animal models.

Hepatitis B reactivation after kidney transplantation in hepatitis B surface antigen-negative, core antibody-positive recipients.

Nowadays, intensive immunosuppressive therapy including rituximab is commonly used prior to kidney transplantation (KT), raising concerns over hepatitis B virus (HBV) reactivation among hepatitis B surface antigen (HBsAg)-negative and anti-hepatitis B core (HBc)-positive KT recipients. Recent practice guidelines suggested watchful monitoring or antiviral prophylaxis for the first 6-12 months, the period of maximal immunosuppression. However, the actual risk for HBV reactivation, and whether short-term antiviral therapy in the early period is necessary, remains unclear. A total of 449 HBsAg-negative and anti-HBc-positive KT recipients were analysed for HBV reactivation. During a median follow-up of 6.7 (interquartile range: 4.2-9.4) years, HBV reactivation was observed in 9 patients (2.0%). The median time of HBV reactivation from KT was 2.8 years (range: 1.4-11.5 years), with cumulative incidence rates of 0%, 1% and 2% for 1, 3 and 5 years, respectively. There were no severe adverse outcomes, including liver transplantation or mortality related to HBV reactivation. The risk of HBV reactivation was not high, even in anti-HBs-negative patients (n = 60, 4% at 5 years), ABO mismatch (n = 92, 4% at 5 years), use of rituximab (n = 66, 3% at 5 years) or plasmapheresis (n = 17, 7% at 5 years), and acute rejection (n = 169, 3% at 5 years). In conclusion, the HBV reactivation risk was not high and the time of detection was not clustered in the early post-KT period. Our findings favour continued watchful monitoring over antiviral prophylaxis in the early period.

Assessment of infection in newly diagnosed multiple myeloma patients: risk factors and main characteristics.

BACKGROUND: Infection is a leading cause of morbidity and death in patients with multiple myeloma (MM). The increased susceptibility to infection is complicated and multifactorial. However, no studies have explored the spectrum and risk factors of infections in newly diagnosed MM patients at the first admission. This cross-sectional study aimed to provide ideas for the assessment, prevention and treatment of infection in newly diagnosed MM patients when admitted for the first time. METHODS: Retrospectively, the data from electronic medical records for 161 patients newly diagnosed with MM from May 2013 to December 2018 were analysed. All the information was collected at the time of admission, and the patients had received no antineoplastic therapy previously. Independent risk factors of infection in multiple myeloma were determined by univariate and multivariate analysis. RESULTS: Newly diagnosed patients with MM were highly susceptible to viruses (43.9%), especially Epstein-Barr virus (EBV) (24.4%) and hepatitis B virus (HBV) (17.1%). Advanced stage (ISS stage III, P = 0.040), more severe anaemia (Hb < 90 g/L, P = 0.044) and elevated CRP (> 10 mg/L, P = 0.006) were independent risk factors for infection. Moreover, infections represented a major survival threat to patients with newly diagnosed MM (P = 0.033), and the existence of risk factors for infection was significantly correlated with poor prognosis (P = 0.011), especially ISS stage III (P = 0.008) and lower haemoglobin level (P = 0.039). CONCLUSIONS: Newly diagnosed MM patients are highly susceptible to viruses. Advanced ISS stage, more severe anaemia and the elevation of CRP are independent risk factors of infection, which also have a strong impact on prognosis. Our results suggest that viral infection should be taken into account if antibacterial drugs are not effective, and the prevention of infection and improvement of prognosis should be paid more attention in newly diagnosed patents with advanced stage and more severe anaemia.

Hepatitis B, hepatitis C and HIV prevalence and related sexual and substance use risk practices among key populations who access HIV prevention, treatment and related services in South Africa: findings from a seven-city cross-sectional survey (2017).

BACKGROUND: People who use drugs including people who inject drugs (PWUD/ID), sex workers (SWs) and men who have sex with men (MSM) are at increased risk of HIV and viral hepatitis infection. Limited epidemiological data on the infections exists in key populations (KPs) in South Africa. We investigated the prevalence of hepatitis B (HBV), hepatitis C (HCV) and HIV and selected risk factors among these KPs to inform effective responses. METHODS: We used convenience sampling to recruit a targeted 3500 KPs accessing HIV-related health services across Cape Town (SWs, MSM, PWUD/ID), Durban (SWs, PWUD/ID), Pietermaritzburg (SWs), Mthatha (SWs), Port Elizabeth (SWs), Johannesburg (MSM) and Pretoria (MSM and PWUD/ID) into a cross-sectional survey. An interviewer questionnaire to assess socio-demographic characteristics, drug use and sexual risk practices, was administered. HBV surface antigen (HBsAg); HCV antibody, viral load and genotype, and HIV antibody, was tested. RESULTS: Among the 3439 people included in the study (1528 SWs, 746 MSM, 1165 PWUD/ID) the median age was 29 years, most participants were black African (60%), and 24% reported homelessness. 82% reported substance use in the last month, including alcohol (46%) and heroin (33%). 75% were sexually active in the previous month, with condom use at last sex at 74%. HIV prevalence was 37% (highest among SWs at 47%), HBsAg prevalence 4% (similar across KPs) and HCV prevalence was 16% (highest among PWUD/ID at 46%). CONCLUSIONS: HBV, HCV and HIV pose a health burden for KPs in South Africa. While HIV is key for all included KPs, HCV is of particular importance to PWUD/ID. For KPs, HBV vaccination and behavioural change interventions that support consistent condom and lubricant access and use are needed. Coverage of opioid substitution therapy and needle and syringe services, and access to HCV treatment for PWUD/ID need to be expanded.

Hepatitis B virus reactivation in kidney transplant patients with resolved hepatitis B virus infection: Risk factors and the safety and efficacy of preemptive therapy.

BACKGROUND: Hepatitis B virus (HBV) reactivation is associated with complications and adverse outcomes in patients with clinically resolved HBV infection who are seronegative for hepatitis B surface antigen (HBs Ag), and seropositive for hepatitis B core antibody (HBc Ab) and/or hepatitis B surface antibody (HBs Ab) before kidney transplantation (KT). METHODS: We retrospectively analyzed 52 patients with resolved HBV infection who were HBV-DNA negative. HBV-DNA after KT was evaluated, and the occurrence of HBV reactivation and outcomes were monitored. We defined HBV reactivation as seropositivity for HBV-DNA at or above the minimal detection level of 1.0 log IU/mL and treated preemptively (using entecavir) when the HBV-DNA level was at or above 1.3 log IU/mL, in accordance with the Japanese Guidelines for HBV treatment. RESULTS: Among the 52 patients, the mean age was 57.2 ± 10.8 years. The median HBc Ab titer was 12.8 (interquartile range, 4.6-42.6) cutoff index, and five (9.6%) cases of HBV reactivation occurred. No patients developed graft loss and died due to HBV reactivation. Statistical analysis showed that age and HBc Ab titer were significant risk factors for HBV reactivation (P = .037 and P = .042, respectively). No significant differences were found between graft survival and the presence or absence of HBV reactivation. CONCLUSION: These results suggest that HBc Ab titer and age could be significant risk factors for HBV reactivation. Resolution of HBV infection did not appear to be associated with patient or graft survival, regardless of whether HBV reactivation occurred, when following our preemptive strategy.

Risk factors of de novo hepatitis B virus infection in pediatric hepatitis B core antibody positive liver graft recipients under prophylactic therapy.

BACKGROUND AND AIM: We aim to investigate the risk factors of de novo hepatitis B virus (HBV) infection in pediatric liver transplantation recipients receiving hepatitis B core antibody positive grafts and to evaluate the efficacy of our prophylactic strategies. METHODS: One hundred thirty-nine pediatric recipients receiving hepatitis B core antibody positive grafts operated from September 2016 to September 2018 were retrospectively enrolled, and all the patients received prophylactic treatment to prevent de novo HBV infection. Donor and recipient features, operative information along with graft, and recipient outcomes were compared between recipients with or without de novo HBV infection. Univariate and multivariate analyses were applied to identify the risk factors of de novo HBV infection. RESULTS: The mean follow-up time was 23.5 ± 15.7 months, and the overall incidence of de novo HBV infection was 3.6%. Recipients with de novo HBV infection showed equal graft and recipient outcome compared with the recipients without de novo HBV infection during the follow-up time. Recipient preoperative hepatitis B surface antibody titer of < 1000 IU/L (odds ratio [OR] = 9.652, P = 0.024), graft HBV DNA of > 1000 copies (OR = 9.050, P = 0.032), and intraoperative fresh-frozen plasma transfusion of > 400 mL (OR = 10.462, P = 0.023) were identified as independent risk factors for de novo HBV infection. CONCLUSION: Hepatitis B core antibody positive grafts can safely be used in pediatric liver transplantation under rational prophylactic therapy.

High hepatitis B virus screening rate among patients receiving systemic anticancer treatment in Japan.

BACKGROUND: Patients with hepatitis B virus (HBV) infection have a risk of reactivation after chemotherapy. All patients undergoing chemotherapy should be screened for HBV infection. No large-scale studies have been conducted to examine HBV screening practice in Japan. METHODS: We analyzed health insurance claims equivalent data linked with a nationwide hospital-based cancer registry. Patients diagnosed with cancer in 2014, who were aged 20 years and older and those who underwent systemic anticancer treatment in 2014-15 were included. We assessed the HBV screening rates by the HBsAg or anti-HBc tests, HBV-DNA tests, and entecavir prescriptions. Multiple logistic regression models were used to identify factors related to the receipt of screening. RESULTS: Of 177,597 patients (mean [SD] age, 65.6 [12.2] years), 82.6% and 12.9% patients had a solid tumor and hematologic malignancy, respectively. Among them, 88.1%, 6.3%, and 5.5% received cytotoxic chemotherapy, targeted therapy, and anti-CD20 antibodies, respectively. Overall, 70.6% of patients were screened. The positive predictor of HBV screening was receiving anti-CD20 antibodies [odds ratio (OR); 2.23, 95% confidence interval (CI) 2.06-2.41, p < 0.001] and negative predictors were age ≥ 85 (OR 0.76, 95% CI 0.71-0.81), age 75-84 (OR 0.77, 95% CI 0.75-0.79) and targeted therapy (OR 0.69, 95% CI 0.67-0.72). Among the screened patients, 13.2% were tested for HBV-DNA, and 1.49% were prescribed entecavir. CONCLUSIONS: The HBV screening rate in Japan is higher than in other countries. Further improvement of the HBV screening rate is needed to prevent reactivation and avoidable deaths of patients with HBV infection.

Prevalence and associated risk factors for Hepatitis B and C viruses among refugees in Gambella, Ethiopia.

BACKGROUND: Currently, there is an increased flow of refugees into Ethiopia from neighboring countries. However, there are no post-arrival screening mechanisms for hepatitis B and C viruses which could be an additional burden for the local population. Hence, this study aimed to determine the prevalence and associated risk factors for hepatitis B and C viruses among refugees in Gambella, Ethiopia. It also aimed to determine the knowledge, attitude, and practice concerning hepatitis B and C viruses among participants. METHODS: A cross-sectional study was conducted among 453 refugees in Gambella, Ethiopia from January until May 2018. A questionnaire was used to collect data on refugees' socio-demographic, risk factors, and KAP of hepatitis B and C infections. Five milliliters of blood sample were collected from each participant and the serum was used for HBsAg and anti-HCV antibody screening rapid tests. Positive samples were further tested by ELISA method. Data were performed using SPSS version 20, and a p-value less than 0.05 was considered statistically significant. RESULTS: The overall prevalence of HBsAg and anti-HCV among refugees was 7.3% (33/453) and 2.0% (9/453) respectively. Of these, 6.8% (25/370) and 1.4% (5/370) of females were positive for HBsAg and anti-HCV, whereas 9.6% (8/83) and 4.8% (4/83) of males were positive for HBsAg and anti-HCV. The age group of 18-29 and 30-41 years old were related to HCV infection (P = 0.003 and P = 0.020). However, proposed risk factors were not related to HBV and HCV infections. Knowledge assessment showed that 86.5% (392/453) did not know how HBV and HCV infections are transmitted, and 86.8% (393/453) had no information about the availability of HBV vaccine. CONCLUSION: This study showed intermediate prevalence of hepatitis B and hepatitis C virus in a large refugee camp in Ethiopia. The prevalence of hepatitis C virus was found to increase with age, but no other risk factor for either virus identified as significant. Refugees' understanding of hepatitis B and C was very limited. This indicates the need for screening policy to be implemented and integrated with other health services and awareness creation about the infection in all refugee camps of Gambella.

Possible Relevance of PNPLA3 and TLL1 Gene Polymorphisms to the Efficacy of PEG-IFN Therapy for HBV-Infected Patients.

Lifestyle changes have led to an increase in the number of patients with nonalcoholic fatty liver disease (NAFLD). However, the effects of NAFLD-associated single-nucleotide gene polymorphisms (SNPs) in HBV-infected patients have not been adequately investigated. Methods: We investigated the association of the NAFLD-related SNPs patatin-like phospholipase domain-containing protein 3 (PNPLA3; rs738409), transmembrane 6 superfamily member 2 (TM6SF2; rs58542926), 17-beta hydroxysteroid dehydrogenase 13 (HSD17B13; rs72613567, rs6834314 and rs62305723), membrane-bound O-acyltransferase domain containing 7 (MBOAT7; rs641738) and glucokinase regulatory protein (GCKR; rs1260326) with the presence of histologically proven hepatic steatosis (HS) in HBV-infected patients (n = 224). We also investigated tolloid-like 1 (TLL1) SNP (rs17047200), which has been reported to be involved in the disease progression in Japanese NAFLD patients, and evaluated the association of HS and various SNPs with the treatment efficacy of pegylated-interferon (PEG-IFN) monotherapy following nucleotide/nucleoside (NA) treatment (NA/PEG-IFN sequential therapy; n = 64). Among NAFLD-associated SNPs evaluated, only the PNPLA3 SNP was significantly associated with the presence of hepatic steatosis in a total of 224 HBV-infected patients (P = 1.0×10-4). Regarding the sequential therapy, PNPLA3 SNP and TLL1 SNP were related to the treatment efficacy, and patients without minor alleles of these SNPs showed favorable results with a high virologic response and significant reduction in their HBsAg titer. A multivariate analysis showed that HBeAg positivity (odds ratio 5.810, p = 0.016) and the absence of a risk allele in PNPLA3 and TLL1 SNPs (odds ratio 8.664, p = 0.0042) were significantly associated with treatment efficacy. The PNPLA3 SNP might be associated with the presence of HS, and the combination of the PNPLA3 and TLL1 SNPs might be related to the efficacy of PEG-IFN monotherapy following NA treatment.

Establishment of a Seronegative Occult Infection With an Active Hepatitis B Virus Reservoir Enriched of Vaccine Escape Mutations in a Vaccinated Infant After Liver Transplantation.

We describe the establishment of a seronegative occult hepatitis B virus (HBV) infection (OBI) in a successfully vaccinated infant who underwent liver transplantation from an donor positive for antibody to hepatitis B core antigen (anti-HBc). The use of highly sensitive droplet digital polymerase chain reaction assays revealed a not negligible and transcriptionally active intrahepatic HBV reservoir (circular covalently closed DNA, relaxed circular DNA, and pregenomic RNA: 5.6, 2.4, and 1.1 copies/1000 cells, respectively), capable to sustain ongoing viral production and initial liver damage. Next-generation sequencing revealed a peculiar enrichment of hepatitis B surface antigen vaccine-escape mutations that could have played a crucial role in OBI transmission. This clinical case highlights the pathobiological complexity and the diagnostic challenges underlying OBI.

Infection of human pegivirus 2 (HPgV-2) is associated with hepatitis C virus but not hepatitis B virus infection in people who inject drugs.

We evaluated the association between human pegivirus-2 (HPgV-2) infection and hepatitis C virus (HCV)/hepatitis B virus (HBV) co-infection in 745 plasma samples collected from HCV-positive but human immunodeficiency virus type one (HIV-1)-negative people who inject drugs in Hunan, China. The prevalence of anti-HPgV-2 was 4.43  % (33/745) and, within this, the HCV 6a genotype showed significantly higher prevalence as compared with the HCV non-6a genotypes, 6.29  % (18/286) vs. 1.69  % (4/236), respectively (P=0.009). HPgV-2 RNA was detected in 2.15  % (16/745), and was not significantly different between the HCV 6a and non-6a genotypes, 2.45  % (7/286) vs. 2.54  % (6/236), respectively (P =0.945). HBV single infection did not increase the risk of HPgV-2 infection. Compared with HCV single infection, HCV/HBV co-infection increased the risk of HPgV-2 infection by about three-fold: odds ratio (OR)=3.24 [95  % confidence interval (CI) 1.34-7.82, P=0.014] according to anti-HPgV-2 positivity or OR=3.51 (95  % CI 1.15-10.74, P=0.051) according to HPgV-2 viraemia. HPgV-2 infection did not increase the levels of liver-specific enzymes. Our study provides new findings regarding the association between HPgV-2 and HCV genotypes as well as HCV/HBV co-infection.

CCR5 deficiency enhances hepatic innate immune cell recruitment and inflammation in a murine model of acute hepatitis B infection.

Human genetic studies demonstrate a link between the 32-bp deletion that produces a nonfunctional CCR5 receptor and enhanced recovery from acute hepatitis B virus (HBV) infection. To investigate the role of CCR5 in immune responses to acute HBV, we intravenously infected Ccr5+/+ (WT) and Ccr5-/- (KO) mice with a replication-incompetent adenovirus containing the overlapping HBV1.3 construct (AdHBV), or vector control. At day 3 following AdHBV infection, analysis of intrahepatic leukocytes (IHL) showed KO mice had increased CD11b+ NK cells compared to WT (18.2% versus 7.6% of live IHL, P < 0.01). These CD11b+ NK cells were nonresident (CD49a- ) and had capacity to degranulate and produce IFN-γ following stimulation. At day 3, plasma CXCL10 was significantly increased in KO, but not WT, mice receiving AdHBV as compared to vector control, while CXCR3 expression on hepatic CD11b+ NK cells in AdHBV-treated KO mice was significantly lower than that in uninfected mice, suggesting these NK cells are recruited along the CXCL10-CXCR3 axis. At days 7 and 14, no differences between genotypes were observed in number, or HBV-specific function, of intrahepatic CD8+ T cells. Instead, at day 14, KO mice had increased intrahepatic proinflammatory monocytes compared to WT mice (17.56% versus 6.57% of live IHL, P = 0.014), corresponding with an increase in plasma alanine aminotransferase and intrahepatic IL-1ß observed in KO mice. Taken together, these findings demonstrate that loss of CCR5 signaling drives a more robust inflammatory liver microenvironment early in acute HBV infection via enrichment of hepatic innate immune cells.