The Lancet

Last week, the European Centre for Disease Prevention and Control (ECDC) joined forces with the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) to release public health guidance on the prevention and control of communicable diseases in prisons. Aimed at planners and providers of health care for people over the age of 18 years in prison, the report documents the evidence behind active case finding options for the high-burden communicable diseases hepatitis B and C, HIV, other sexually transmitted infections, and tuberculosis.

The Lancet

Last week, WHO released its first Essential Diagnostics List. Designed to complement the Essential Medicines list first released over 40 years ago, the list defines an essential package of diagnostic tests for use in primary care and laboratory settings. 58 of these tests are aimed at supporting the diagnosis and monitoring of common conditions such as cardiovascular diseases, diabetes, and anaemia, and 55 tests are targeted at high priority diseases including HIV, hepatitis B and C, and malaria.

Farah Seedat, Sally Hargreaves, Laura B Nellums, Jing Ouyang, Michael Brown, Jon S Friedland

Rates of migration to Europe, and within Europe, have increased in recent years, with considerable implications for health systems. Migrants in Europe face a disproportionate burden of tuberculosis, HIV, and hepatitis B and C, yet experience a large number of barriers to accessing statutory health care on arrival. A better understanding of how to deliver effective and cost-effective screening, vaccination, and health services to this group is now crucial. We did a systematic review to document and assess the effectiveness and cost-effectiveness of approaches used for infectious diseases screening, and to explore facilitators and barriers experienced by migrants to accessing screening programmes.

Abstract Background The World Health Organization recommends all men who have sex with men (MSM) receive Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) testing. MSM in China are a high-risk group for HBV and HCV infection, but test uptake is low. Crowdsourcing invites a large group to solve a problem and then shares the solution with the public. This nationwide online randomized controlled trial will evaluate the effectiveness of a crowdsourced intervention to increase HBV and HCV testing among MSM in China. Methods Seven hundred MSM will be recruited through social media operated by MSM organizations in China. Eligible participants will be born biologically male, age 16 years or older, report previous anal sex with another man, and reside in China. After completing a baseline online survey, participants will be randomly assigned to intervention or control arms with a 1:1 allocation ratio. The intervention will include two components: (1) a multimedia component will deliver two videos and two images promoting HBV and HCV testing developed through a crowdsourcing contest in China; (2) a participatory component will invite men to submit suggestions for how to improve crowdsourced videos and images. The control arm will not view any images or videos and will not be invited to submit suggestions. All participants will be offered reimbursement for HBV and HCV testing costs. The primary outcome is HBV and HCV test uptake confirmed through electronic submission of test report photos within four weeks of enrolment. Secondary outcomes include self-reported HBV and HCV test uptake, HBV vaccination uptake, and change in stigma toward people living with HBV after four weeks. Primary and secondary outcomes will be calculated using intention to treat and as-exposed analyses and compared using two-sided 95% confidence intervals. Discussion Few previous studies have evaluated interventions to increase HBV and HCV testing in middle-income countries with a high burden of hepatitis. Delivering a crowdsourced intervention using social media is a novel approach to increasing hepatitis testing rates. HBV and HCV test uptake will be confirmed through test report photos, avoiding the limitations of self-reported testing outcomes. Trial registration NCT03482388 (29 March 2018).

Sanaka S, Kasarala G, Tillmann H.

AbstractCure of hepatitis C virus has become feasible in almost all patients. However, vigilance is needed in 3 scenarios: previous exposure to hepatitis B virus (HBV), history of organ transplantation, and history of cured hepatocellular carcinoma (HCC). The current data suggest that HBV reactivation occurs in about 10% of hepatitis B surface antigen (HBsAg)–positive patients and approximately 1% of hepatitis B core antibody–positive but HBsAg-negative patients. The risk of organ rejection is also around 1%, but can be fatal if not acted on immediately. Finally, the risk of early HCC recurrence may be increased but should not delay initiation of antiviral therapy in the setting of cured HCC; however, increased surveillance may be warranted.

Elizabeth N. da Silva, Alan Baker, Jalila Alshekaili, Krishna Karpe, Matthew C. Cook

by Elizabeth N. da Silva, Alan Baker, Jalila Alshekaili, Krishna Karpe, Matthew C. Cook Background Chronic kidney disease (CKD) is associated with an increased risk of hepatitis B infection and impaired seroconversion to hepatitis B vaccine (HBV). Studies examining augmented vaccine schedules to enhance seroconversion have so far been inconclusive. Furthermore, the defects responsible for impaired vaccine immunity in CKD have not yet been identified. Methods We studied serological and cellular responses to HBV in CKD to identify a defect in vaccine-induced cellular responses that could account for impaired seroconversion in CKD and clarify the effects of an augmented vaccine dose schedule. We compared these results with responses to seasonal influenza vaccination (Fluvax). Results We found a clear benefit in rates and magnitude of seroconversion after an augmented 40mcg HBV dose schedule in CKD. This permitted comparison of responders and non-responders. Serological non-responders with CKD exhibited reduction in CXCR3+CCR6- CXCR5+ memory T cells at baseline. Unlike Fluvax, HBV elicited a poor plasmablast (PB) response. Both vaccinations induced activation of the CXCR3+CCR6- CCR7- subset of circulating T follicular helper cells (cTFH), although this response was impaired in CKD after HBV. Conclusions CKD confers a specific T cell defect that contributes to the impaired seroconversion to HBV.

The morbidity and mortality that are associated with hepatitis B virus (HBV) infection have been overshadowed by the public health prominence of other infectious diseases, including human immunodeficiency virus (HIV) infection, tuberculosis, and malaria. There is a dawning realization that the……

This Medical Letter review compares a newly approved 2-dose hepatitis B virus vaccine that uses a synthetic oligonucleotide immunostimulatory adjuvant, and is licensed for use in adults, with other commercially available 3-dose vaccines.

Jinglan Jin MD, PhD , Hongqin Xu PhD , Ruihong Wu MM , Junqi Niu MD PhD , Shibo Li MD PhD

Abstract Purpose We aimed to study the aberrant DNA methylation profile associated with hepatitis B virus (HBV) infection and to identify key genes and pathways associated with the HBV infection stage. Methods A total of 54 antiviral treatment‐naive HBV‐infected patients and 6 healthy controls were included. Genome‐wide methylated DNA immunoprecipitation analysis was performed, as previously described, after which the chip data were preprocessed. Subsequently, Cytoscape software was used for the construction of a protein–protein interaction network, and Database for Annotation, Visualization, and Integrated Discovery software was used to conduct functional enrichment analysis. Results A total of 711,794 CpGs were obtained after data quality control, among which 152,780, 113,814, 90,747, and 175,868 CpGs showed differential methylation in acute hepatitis B (AHB) vs. Control, Total‐C vs. Control, CH1 vs. CA1, and AHB vs. Total‐C, respectively. Furthermore, RIPK3, PRDM10, JUN, and SNAI1 were at the center of the four associated networks, respectively. Differential methylated genes differentially methylated in these four comparisons were significantly enriched with olfactory transduction; positive regulation of transport; negative regulation of protein amino acid phosphorylation (e.g., JUN), phosphorylation, phosphorus metabolic process, and phosphate metabolic process; and programmed cell death, respectively. Conclusion RIPK3, PRDM10, JUN, and SNAI1 as well as olfactory transduction, positive regulation of transport, negative regulation of phosphorylation, and programmed cell death are important for the transformation associated with HBV infection stage. Moreover, JUN may be involved in HBV infection, mainly via the negative regulation of amino acid phosphorylation. This article is protected by copyright. All rights reserved.

Michael Owusu, Joseph Kofi Bonney, Augustina Angelina Annan, Gifty Mawuli, Kennedy Okyere, Mohamed Mutocheluh, Juliana Aryeequaye, Nicholas Kwabena Adjei, Mary Afihene, Kathryn Spangenberg, Justice Sylverken, Ellis Owusu-Dabo, Christian Drosten, Yaw Adu-Sarkodie

by Michael Owusu, Joseph Kofi Bonney, Augustina Angelina Annan, Gifty Mawuli, Kennedy Okyere, Mohamed Mutocheluh, Juliana Aryeequaye, Nicholas Kwabena Adjei, Mary Afihene, Kathryn Spangenberg, Justice Sylverken, Ellis Owusu-Dabo, Christian Drosten, Yaw Adu-Sarkodie Background Viral hepatitis continues to play significant role in causing morbidity and mortality in sub-Saharan Africa. Apart from the few population based studies available, not many have investigated the burden of these viruses in jaundiced patients. Among the few studies, hepatitis E is the least studied among jaundiced patients. This study was aimed at describing the frequency, distribution and risk of the different hepatitis viruses among jaundiced patients reporting to the second largest teaching hospital in Ghana. Methods From November, 2015 to April, 2016, a cross-sectional study was conducted among jaundiced patients attending the Komfo Anokye Teaching Hospital. Between 3–5 ml of blood was collected from each patient and screened for viral hepatitis agents using both serologic and molecular-based assays. Results In the 155 patients recruited, hepatitis B was the most prevalent [54.2% (95% CI = 46.0%–62.2%)] followed by hepatitis E [32.9% (95% CI = 25.6–40.9%)]. Most cases of hepatitis E occurred as co-infections with hepatitis B (18%), with the predominant clinical feature being hepatocellular carcinoma. Risk factor variable analysis showed middle and older aged individuals were more at risk of hepatitis B exposure whereas younger age groups (…

Hannah Evans, Sooria Balasegaram, Sam Douthwaite, Laura Hunter, Ranjababu Kulasegaram, Terry Wong, Antonio Querol-Rubiera, Gaia Nebbia

by Hannah Evans, Sooria Balasegaram, Sam Douthwaite, Laura Hunter, Ranjababu Kulasegaram, Terry Wong, Antonio Querol-Rubiera, Gaia Nebbia Therapies that halt progression of chronic hepatitis B virus (HBV) and achieve a cure for chronic hepatitis C virus (HCV) have encouraged development of innovative strategies to diagnose and link patients to care. We describe the prevalence and risk factors for HBV and HCV infections and use of an opt-out hepatitis testing and integrated linkage to care pathway in a London Emergency Department (ED). ED patients aged ≥16 years having routine blood tests from 15 February-28 March 2016 were tested for hepatitis, unless opted out. Hepatitis B surface antigen (HBsAg) and hepatitis C antibody tests (HCV-Ab, including a confirmatory hepatitis C antigen test (HCV-Ag)) were pre-selected on electronic blood test requests. Linkage to care (attending one clinic appointment) was offered to HBsAg and HCV-Ag patients (new or known-disengaged with care diagnoses). Weighted prevalence estimates and risk factors for seropositivity adjusted by demographics and survey weights were calculated using logistic regression. Hepatitis testing uptake was 56% (3,290/5,865). Overall, 26 HBsAg (10 new diagnoses) and 63 HCV-Ab patients were identified of which 32 were HCV-Ag positive (10 new diagnoses). Weighted seroprevalence of HBsAg was 0.50% (95% CI 0.3–0.8%); HCV-Ab 2.0% (95% CI 1.5–2.7%) and HCV-Ag 1.2% (95% CI 0.8–1.7%). Risk factors for infection were being male (HBsAg: aOR 4.1, 95% CI 1.5–11.3), of non-White British ethnicity (HBsAg: aOR>11) or being homeless (HCV-Ag: aOR 18.9, 95% CI 6.9–51.4). We achieved a high linkage to care uptake for HBsAg (93%) and HCV-Ag (78%) among patients who were contacted and required linkage. A pre-selected hepatitis testing ordering system facilitated a high testing uptake. New and disengaged with care diagnoses and a high HCV prevalence were identified demonstrating the potential to identify and link patients to care in this setting. Strategies connecting clinical care with community outreach services are key for improving patient linkage to care.

Daniel Mak, Chantal Babb de Villiers, Charles Chasela, Margaret I. Urban, Anna Kramvis

by Daniel Mak, Chantal Babb de Villiers, Charles Chasela, Margaret I. Urban, Anna Kramvis Objective The aims of this study were to determine the prevalence of risk factors associated with hepatocellular carcinoma (HCC) in black adult South Africans and to estimate the size of the associated risks. Methods A case-control analysis of 150 black South African patients (aged 18–75 years) with HCC—who were a subset of patients recruited for the Johannesburg Cancer Case Control Study 2000 to 2012—was undertaken. The association between this tumour and hepatitis B/C virus infections, and human immunodeficiency virus (HIV) mono- and co-infections was investigated. Odds ratios (ORs) and 95% confidence intervals (CI) adjusted for age, year of diagnosis, marital status, place of birth and selected modifiable risk factors were calculated. Results HCC was significantly associated with a rural birthplace (p2000 IU/ml (OR 8.55; CI:3.00–24.54) to ≥200,000 (OR 16.93; CI:8.65–33.13), anti-HCV (OR 8.98; CI:3.59–22.46), HBV DNA+/HIV+ co-infection (OR 5.36; CI:2.59–11.11), but not with HBV DNA-/HIV+ (OR 0.34; CI:0.14–0.85). We did not find a synergistic interaction between HBV and HIV. Modifiable risk factors (alcohol consumption, tobacco smoking, number of sexual partners, diabetes and hormonal contraceptive use) were nonsignificant. Discussion A considerable portion of the HCC burden in Johannesburg and surrounding provinces falls on rural migrants to urban areas, most of whom are men. The HBV will continue to contribute to HCC incidence in older age-groups and in others who missed vaccination. Although we did not find an increased risk for HCC in HIV positive individuals this may change as life expectancy increases due to greater access to antiretroviral therapies, necessitating the addition of hepatitis virus screening to preventive medical care.

Journal of Medical Virology, EarlyView.

Can Liu , Wennan Wu , Shongyan Shang , Er Huang , Zhen Xun , Jinpiao Lin , Tianbin Chen , Bin Yang , Jing Chen , Qishui Ou

Abstract The detection of HBV DNA plays a critical role in determining the level of viral replication in HBV infected patients. However, how to select appropriate HBV DNA detection method, low‐sensitivity (ls) and hypersensitivity (hs), remains unclear. In this study, HBsAg, HBeAg, ALT, AST and hs HBV DNA titers in serum of 5611 cases with suspected HBV infection were reviewed. Besides, the dynamic changes of HBV DNA and HBsAg in 85 chronic hepatitis B (CHB) patients receiving PegIFNα or entecavir (ETV) were observed. The results showed the positive rate of HBV DNA was 32.8%, of which low viral load (20~500 IU/ml) accounted for 51.8%. In the 5611 cases, when the HBsAg…

Can Liu , Wennan Wu , Shongyan Shang , Er Huang , Zhen Xun , Jinpiao Lin , Tianbin Chen , Bin Yang , Jing Chen , Qishui Ou

Abstract The detection of HBV DNA plays a critical role in determining the level of viral replication in HBV infected patients. However, how to select appropriate HBV DNA detection method, low‐sensitivity (ls) and hypersensitivity (hs), remains unclear. In this study, HBsAg, HBeAg, ALT, AST and hs HBV DNA titers in serum of 5611 cases with suspected HBV infection were reviewed. Besides, the dynamic changes of HBV DNA and HBsAg in 85 chronic hepatitis B (CHB) patients receiving PegIFNα or entecavir (ETV) were observed. The results showed the positive rate of HBV DNA was 32.8%, of which low viral load (20~500 IU/ml) accounted for 51.8%. In the 5611 cases, when the HBsAg…

A. Mazzola, M. Tran Minh, S. Jauréguiberry, D. Bernard, P. Lebray, Y. Chrétien, C. Goumard, Y. Calmus, F. Conti

Infections are common in individuals with cirrhosis, especially in patients awaiting liver transplantation (LT) [1]. The occurrence of bacterial infection is associated with the severity of the liver disease [2]. Bacterial infection increases the probability of death among patients with decompensated cirrhosis by 3.75-fold, the rate reaching 30% at 1 month and 63% at 1 year after infection [1]. Hepatitis A virus (HAV) infection may cause fulminant hepatitis, especially in patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) cirrhosis [3].

Geane Lopes Flores , Helena Medina Cruz , Juliana Custódio Miguel , Denise Vigo Potsch , José Henrique Pilotto , Lia Laura Lewis‐Ximenez , Elisabeth Lampe , Livia Melo Villar

ABSTRACT This study aims to evaluate the utility of an optimized enzyme immunoassay (EIA) to detect and quantify antibodies against hepatitis B (anti‐HBs) in dried blood spots (DBS) within the context of HIV status. Serum and DBS samples were obtained from 56 HIV‐positive and 99 HIV‐negative patients and subjected to EIA for the detection of anti‐HBs, where sample volume and cut off value were modified for DBS testing. Sensitivities of anti‐HBs detection in DBS were 79.8% and 76.8% in HIV‐ and HIV+ subjects respectively. Concordant results for anti‐HBs in serum and DBS presented high mean CD8 cell counts, HIV viral load and optical density (OD) values of anti‐HBs. Anti‐HBs titers were significantly higher in serum, whether or not anti‐HBs titers were detected in DBS. It was possible to detect anti‐HBs in DBS as low as 17.4 IU/mL and 27.3 IU/mL among HIV+ and HIV‐ subjects respectively. In conclusion, DBS can be used to detect and quantify anti‐HBs in HIV‐infected individuals, which could increase access to diagnosis and vaccination. This article is protected by copyright. All rights reserved.

Wilson P, Parr J, Jhaveri R, et al.

AbstractHepatitis B virus (HBV) is a significant public health issue that has not been adequately addressed, especially in the high-prevalence region of Africa. Despite the incorporation of HBV vaccines into the Expanded Program on Immunization (EPI), children continue to be infected with HBV through maternal-to-child transmission (MTCT). The addition of a birth dose of HBV vaccine would be a cost-effective method to reduce MTCT. Birth-dose HBV vaccine policies have been adopted in the Western Pacific region but have yet to be implemented in the African region. Even better protection against HBV MTCT can be achieved by the treatment of pregnant women with high HBV viral loads with tenofovir. Tenofovir is already widely used in prevention of HIV maternal-to-child transmission (PMTCT) programs. We suggest that existing HIV PMTCT programs could be expanded to deliver care for HBV-infected pregnant women. With appropriate adoption of birth dose vaccination policies and expansion of PMTCT programs, elimination of HBV MTCT in Africa is achievable.

Kukwah Anthony Tufon, Damian Nota Anong, Henry Dilonga Meriki, Teuwafeu Denis Georges, Mouladje Maurice, Youmbi Sylvain Kouanou, Ayah Flora Bolimo, Nyeke James Tony, Tebit Emmanuel Kwenti, Ndze Henry Wung, Theresa Nkuo-Akenji

by Kukwah Anthony Tufon, Damian Nota Anong, Henry Dilonga Meriki, Teuwafeu Denis Georges, Mouladje Maurice, Youmbi Sylvain Kouanou, Ayah Flora Bolimo, Nyeke James Tony, Tebit Emmanuel Kwenti, Ndze Henry Wung, Theresa Nkuo-Akenji Background The management of patients with chronic hepatitis B infection is quite complex because it requires an in-depth knowledge of the natural history of the disease. This study was aimed at characterizing HBV infected patients in order to determine the phase of the infection and identify the proportion eligible for treatment using 3 different guidelines. Methods HBV chronically infected patients (negative for HIV and HCV) were enrolled and the following tests were done for them: ALT, AST, HBV viral load, HBV serologic panel and Full blood count. APRI score was calculated for all patients. These patients were classified into immunotolerant, immune clearance, immune control and immune escape phases of the infection. The WHO and the 2018 AASLD criteria was also used to identify those who need treatment. Patients were clinically examined for signs and symptoms. Questionnaire was administered to all participants to ascertain their treatment status. Statistical analysis was done using SPSS version 21. Results A total of 283 participants (101 females and 182 males) with a mean age of 31.3±8.5 were enrolled. Fifty-two (18.4%) were eligible for treatment (Immune clearance and immune escape phases) and they recorded a significantly higher mean APRI score (0.71±0.51) as compared to those in the immune control and immune tolerant phase (0.43±0.20). Based on WHO and AASLD criteria, 12(4.2%) and 15 (5.3%) were eligible for treatment respectively and these were all subsets of the 52 cases mentioned above. Six (2.1%) and 29 (10.2%) of those identified under the immune control phase were on tenofovir and traditional medication respectively. Conclusion Considering treatment for patients in the immune clearance and immune escape phases of the infection can be a reliable strategy to implement in our setting as this may probably tie with considerations from other treatment guidelines. Fifty-two (18.4%) patients were eligible for treatment and none of them were among the 2.1% of patients put on Tenofovir based treatment. This calls for the need for more trained health experts to periodically assess patients, implement an adequate treatment guideline and place the right patients on treatment in Cameroon.

WeiyunZhang , JietingHuang , MinWang , DandanSong , QiaoLiao , XiaRong , TingtingLi , Jean‐PierreAllain , GuangliRen , YongshuiFu , ChengyaoLi

Abstract Myeloid‐derived suppressor cells (MDSCs) accumulate from many diseases. MDSCs are rarely explored in occult hepatitis B virus infection (OBI). The frequency of M‐MDSCs and G‐MDSCs in OBI carriers was analyzed for correlation with clinical parameters, which was no different between OBI and healthy individuals, while the frequency of M‐MDSCs but G‐MDSCs in OBI was significantly lower than that observed in chronic hepatitis B (CHB) carriers (0.4% vs. 0.7%, P=0.0004). The frequency of MDSCs was not correlated with clinical parameters and viral load of OBI, suggesting that the absence of HBsAg in OBI carriers might not induce the accumulation of MDSCs. This article is protected by copyright. All rights reserved.

WeiyunZhang , JietingHuang , MinWang , DandanSong , QiaoLiao , XiaRong , TingtingLi , Jean‐PierreAllain , GuangliRen , YongshuiFu , ChengyaoLi

Abstract Myeloid‐derived suppressor cells (MDSCs) accumulate from many diseases. MDSCs are rarely explored in occult hepatitis B virus infection (OBI). The frequency of M‐MDSCs and G‐MDSCs in OBI carriers was analyzed for correlation with clinical parameters, which was no different between OBI and healthy individuals, while the frequency of M‐MDSCs but G‐MDSCs in OBI was significantly lower than that observed in chronic hepatitis B (CHB) carriers (0.4% vs. 0.7%, P=0.0004). The frequency of MDSCs was not correlated with clinical parameters and viral load of OBI, suggesting that the absence of HBsAg in OBI carriers might not induce the accumulation of MDSCs. This article is protected by copyright. All rights reserved.

Tang LY, Covert E, Wilson E, et al.

This narrative review summarizes recent advances in the epidemiology, identification, natural history, diagnosis, treatment, and prognosis of chronic hepatitis B virus (HBV).

NorioAkuta , FumitakaSuzuki , MarikoKobayashi , TetsuyaHosaka , ShunichiroFujiyama , YusukeKawamura , HitomiSezaki , MasahiroKobayashi , SatoshiSaitoh , YoshiyukiSuzuki , YasujiArase , KenjiIkeda , HiromitsuKumada

Abstract It is currently unclear what impact serum microRNA‐122 (miR‐122) levels have on clearance of hepatitis B virus (HBV) surface antigen (HBsAg) in HBV‐infected patients who had not received antiviral therapy. The present study evaluated the impact of serum miR‐122 levels on HBsAg seroclearance in 367 consecutive HBV‐infected patients who had not received antiviral therapy between their initial and last visit, and investigated the predictive factors of HBsAg seroclearance. Cumulative HBsAg seroclearance rates were 13.5, 32.0, and 37.4% after 10, 20, and 30 years, respectively. The yearly incidence of HBsAg seroclearance over the investigated 30‐year period was 1.25%. A significant and strong correlation was observed between serum miR‐122 levels and HBsAg levels. Moreover, there was a significant correlation between serum miR‐122 levels and the levels of HBV DNA, HBeAg, and HBV core‐related antigen (HBcrAg). The HBsAg seroclearance rate in patients with a…

NorioAkuta , FumitakaSuzuki , MarikoKobayashi , TetsuyaHosaka , ShunichiroFujiyama , YusukeKawamura , HitomiSezaki , MasahiroKobayashi , SatoshiSaitoh , YoshiyukiSuzuki , YasujiArase , KenjiIkeda , HiromitsuKumada

It is currently unclear what impact serum microRNA‐122 (miR‐122) levels have on clearance of hepatitis B virus (HBV) surface antigen (HBsAg) in HBV‐infected patients who had not received antiviral therapy. The current study evaluated the impact of serum miR‐122 levels on HBsAg seroclearance in 367 consecutive HBV‐infected patients who had not received antiviral therapy between their initial and last visit, and investigated the predictive factors of HBsAg seroclearance. Cumulative HBsAg seroclearance rates were 13.5%, 32.0%, and 37.4% after 10, 20, and 30 years, respectively. The yearly incidence of HBsAg seroclearance over the investigated 30‐year period was 1.25%. A significant and strong correlation was observed between serum miR‐122 and HBsAg levels. Moreover, there was a significant correlation between serum miR‐122 levels and the levels of HBV DNA, hepatitis B e‐antigen, and HBV core‐related antigen. The HBsAg seroclearance rate in patients with a…

Li Liu, Di Xiao, Jin-Hong Yu, Rui Shen, Meng Wang, Qiang Li

In China, the epidemic pattern of acute hepatitis E virus (HEV) infection has changed from waterborne outbreaks to foodborne sporadic cases. However, the clinical course of sporadic acute hepatitis E has not been well defined.

Wu J, Song S, Lee C, et al.

AbstractBackgroundThis study aimed to elucidate predictors of liver fibrosis in chronic hepatitis B virus (HBV)-infected subjects.MethodsTransient elastography was performed to define liver fibrosis in 533 chronic HBV-infected patients at 30.72 ± 0.57 years of age. Protein array was performed on serum samples and lysates of Huh7 cells transfected with HBV mutants; the results were confirmed by ELISA. Single nucleotide polymorphisms in the interleukin-1β gene were examined chronic HBV-infected patients with and without liver fibrosis.ResultsMale gender, > 18 years old, and serum alpha-fetoprotein level > 3.6 ng/mL were independent predictors of a liver stiffness measurement of ≥ 7 kPa (P = 0.005, 0.019, and < 0.001, respectively). HBeAg-negative hepatitis is associated with increased liver stiffness (P…

Violaine Corbin, Pierre Frange, Florence Veber, Stéphane Blanche, Camille Runel-Belliard, Muriel Lalande, Virginie Gandemer, Marie Moukagni-Pelzer, Catherine Dollfus, Dilek Coban, Justine Prouteau, Christine Jacomet, Olivier Lesens, for the HIV adopted children study group

by Violaine Corbin, Pierre Frange, Florence Veber, Stéphane Blanche, Camille Runel-Belliard, Muriel Lalande, Virginie Gandemer, Marie Moukagni-Pelzer, Catherine Dollfus, Dilek Coban, Justine Prouteau, Christine Jacomet, Olivier Lesens, for the HIV adopted children study group Objective(s) To describe the clinical, virological and immune characteristics of internationally adopted children on arrival in France and after 6-months follow-up. Design Multicenter retrospective study. Methods 30 centers from 24 cities were asked to include, after informed consent, HIV+ children living in France and internationally adopted between 1st Jan 2005 and 1st Jan 2015. Sociodemographic, medical and biological variables collected during the first medical evaluation in France and 6 months later were analyzed. Results 41 HIV+ adoptees were included (female: 56%; median age: 3.91 years) in 14 centers. Adoptees tend to represent an increasing part of newly diagnosed HIV positive children over the years. The majority came from East-Asia. At arrival, one child was diagnosed with lymphobronchial tuberculosis and three with latent chronic hepatitis B, cleared HBV infection and chronic active hepatitis C, respectively. The mean CD4% was 32.8 ± 9% (range: 13–49%). The 34 children (83%) have been initiated on treatment from their countries of origin. Of these, 25 (74%) had an undetectable viral load (VL) on arrival. Resistance to ART was detected in five. At 6 months, 36 adoptees received ART, and the VL was undetectable in 29 children (71%), with one acquired resistance to NRTI & NNRTI. Conclusions An increasing number of HIV-infected children have been internationally adopted in France since 2005. Most of the children have been initiated on treatment from their countries of origin, had good immunity, with few opportunistic infections, and infrequently detectable VL. Low level of mutation conferring resistance was detected.

Abstract Background Tuberculosis (TB) and chronic Hepatitis B virus (HBV) infection are common in China. Fist-line anti-TB medications often produce drug-induced liver injury (DILI). This study sought to investigate whether TB patients with chronic HBV co-infection are more susceptible to liver failure and poor outcomes during anti-TB treatment. Methods Eighty-four TB patients developed DILI during anti-TB treatment and were enrolled, including 58 with chronic HBV co-infection (TB-HBV group) and 26 with TB mono-infection (TB group). Clinical data and demographic characteristics were reviewed. The severity of DILI and incidences of liver failure and death were compared. Risk factors of clinical outcomes were defined. Results The patterns of DILI were similar in both groups. Compared with patients in the TB group, patients in the TB-HBV group who did not receive anti-HBV therapy before anti-TB treatment were more susceptible to Grade-4 severity of DILI (36.2% vs. 7.7%, P = 0.005), liver failure (67.2% vs. 38.5%, P = 0.013) and poor outcomes (37.9% vs. 7.7%, P = 0.005). Age > 50 years (48.1% vs. 22.6%, P = 0.049), cirrhosis (50.0% vs. 15.4%, P = 0.046) and total bilirubin > 20 mg/dl (51.6% vs. 14.8%, P = 0.005) were independent risk factors for the rate of death in the TB-HBV group, and HBV DNA > 20,000 IU/ml had borderline significance (44.1% vs. 20.8%, P = 0.081). In the TB-HBV group, nucleos(t)ide analogues as rescue therapy were not able to reduce short-term death (33.3% vs. 36.8%, P = 0.659) once liver failure had occurred. Conclusions Patients on anti-TB therapy with chronic HBV co-infection are more susceptible to developing liver failure and having poor outcomes during anti-TB treatment. Regular monitoring of liver function and HBV DNA level is mandatory. Anti-HBV treatment should be considered in those with high viral levels before anti-TB treatment.

Abstract Background Underlying coinfections may complicate infectious disease states but commonly go unnoticed because an a priori clinical suspicion is usually required so they can be detected via targeted diagnostic tools. Shotgun metagenomics is a broad diagnostic tool that can be useful for identifying multiple microbes simultaneously especially if coupled with lymph node aspirates, a clinical matrix known to house disparate pathogens. The objective of this study was to analyze the utility of this unconventional diagnostic approach (shotgun metagenomics) using clinical samples from human tularemia cases as a test model. Tularemia, caused by the bacterium Francisella tularensis, is an emerging infectious disease in Turkey. This disease commonly manifests as swelling of the lymph nodes nearest to the entry of infection. Because swollen cervical nodes are observed from many different types of human infections we used these clinical sample types to analyze the utility of shotgun metagenomics. Methods We conducted an unbiased molecular survey using shotgun metagenomics sequencing of DNA extracts from fine-needle aspirates of neck lymph nodes from eight tularemia patients who displayed protracted symptoms. The resulting metagenomics data were searched for microbial sequences (bacterial and viral). Results F. tularensis sequences were detected in all samples. In addition, we detected DNA of other known pathogens in three patients. Both Hepatitis B virus (HBV) and Human Parvovirus B-19 were detected in one individual and Human Parvovirus B-19 alone was detected in two other individuals. Subsequent PCR coupled with Sanger sequencing verified the metagenomics results. The HBV status was independently confirmed via serological diagnostics, despite evading notice during the initial assessment. Conclusion Our data highlight that shotgun metagenomics of fine-needle lymph node aspirates is a promising clinical diagnostic strategy to identify coinfections. Given the feasibility of the diagnostic approach demonstrated here, further steps to promote integration of this type of diagnostic capability into mainstream clinical practice are warranted.

Ying-Ming Chiu, Mei-Shu Lai, K. Arnold Chan

by Ying-Ming Chiu, Mei-Shu Lai, K. Arnold Chan Background and objective Potential hepatoxicity is an important clinical concern when administering immunosuppressive therapies to patients infected by hepatitis B virus (HBV). Tumor necrosis factor inhibitors (anti-TNF) increase the likelihood of hepatitis consequent to HBV reactivation, but reported risks and outcomes vary. We determined the risks of liver enzyme elevation in anti-rheumatic drug users from an HBV-endemic region with differing HBV serostatus. Methods We established retrospective cohorts with rheumatoid arthritis, ankylosing spondylitis, or psoriasis/psoriatic arthritis who: 1) received anti-TNF agents from 1 January 2004 to 30 June 2013; 2) received care from 1 June 2011 to 30 June 2013 but only ever used conventional disease-modifying anti-rheumatic drugs (DMARDs). Serology results defined three subgroups: HBV surface antigen positive (HBsAg+), HBsAg negative/HBV core antibody positive (HBsAg−/HBcAb+), or uninfected. We compared incidences of serum alanine aminotransferase (ALT) exceeding twice the upper reference limit between HBV serostatus subgroups in each treatment cohort. Results Among 783 patients treated with anti-TNF (n = 472) or DMARDs only (n = 311), HBsAg−/HBcAb+ anti-TNF users had incidence of ALT elevation commensurate with uninfected counterparts (6.1 vs. 6.0/100 person-years), compared to 19.6/100 person-years in HBsAg+ patients (standardized rate ratio 3.3, 95% CI 1.3–8.2); none effected had severe or fatal hepatitis and ALT levels in all HBsAg−/HBcAb+ patients remained stable, mostly normalizing spontaneously, or after moderating treatment. Patterns of of ALT elevation associated with differing HBV serostatus in the DMARD cohort, resembled those in anti-TNF users. Conclusions In this large HBV-endemic cohort, the absolute incidence of ALT elevation in anti-TNF users was more than three-fold higher in HBsAg+ patients than in uninfected counterparts; however, no such association was evident in patients with HBsAg−/HBcAb+ serotype, whose risk and outcomes of liver enzyme elevation were similar to uninfected patients, suggesting that anti-TNF use by HBsAg−/HBcAb+ patients is probably safe.

Ya-wen Wang, Zhong-zhou Shen, Yu Jiang

by Ya-wen Wang, Zhong-zhou Shen, Yu Jiang Background Hepatitis B virus (HBV) infection is a major public health threat in China for China has a hepatitis B prevalence of more than one million people in 2017 year. Disease incidence prediction may help hepatitis B prevention and control. This study intends to build and compare 2 forecasting models for hepatitis B incidence in China. Methods Autoregressive integrated moving average (ARIMA) model and grey model GM(1,1) were adopted to fit the monthly incidence of hepatitis B in China from March 2010 to October 2017. The fitting and forecasting performances of the 2 models were evaluated. The better one was adopted to predict the incidence from November 2017 to March 2018. Database was built by Excel 2016 and statistical analysis was completed using R 3.4.3 software. Results Descriptive analysis showed that the incidence of hepatitis B in China has seasonal variation and has shown a downward trend from 2010 to 2017. We selected the ARIMA (3,1,1) (0,1,2)12 model among all the ARIMA models for it has the lowest AIC value. Model expression of GM (1,1) was X(1) (k + 1) = 3386876.7478e0.0249k − 3289206.7428. The root mean square error (RMSE), mean absolute error (MAE) and mean absolute percentage error (MAPE) of ARIMA(3,1,1)(0,1,2)12 model were lower than GM(1,1) model on fitting part and forecasting part. According to the forecast results, the incidence may have a slight fluctuation during the following months. Conclusions The ARIMA model showed better hepatitis B fitting and forecasting performance than GM(1,1) model. It is a potential decision supportive tool for controlling hepatitis B in China before a predictive hepatitis B outbreak.

Höner zu Siederdissen C, Hui A, Sukeepaisarnjaroen W, et al.

AbstractStopping long-term nucleos(t)ide analogue therapy increases HBsAg loss rates in HBeAg-negative patients. Viral rebound may induce immune responses facilitating functional cure. We analyzed which factors are associated with timing of virological relapse in 220 Asian HBeAg-negative patients from the prospective ABX203 vaccine study. Unexpectedly, only the type of antiviral therapy was significantly associated with early virological relapse, defined as HBV DNA > 2,000 IU/ml until week 12 and occurred earlier in patients treated with tenofovir versus entecavir (median time 6 versus 24 weeks, p < 0.0001). This should be considered for future trials and monitoring of patients after treatment discontinuation.

Malhotra I, LaBeaud A, Morris N, et al.

AbstractBackgroundAntenatal exposure to parasites can affect infants’ subsequent responses to vaccination. The present study investigated how maternal prenatal infections and newborns’ anti-parasite cytokine profiles relate to IgG responses to standard vaccination during infancy.Methods450 Kenyan women were tested for parasitic infections during pregnancy. Their newborns’ responses to malaria, schistosome, and filaria antigens were assessed in cord blood (CB) lymphocytes. Following standard neonatal vaccination, this infant cohort was followed biannually to age 30 months for circulating IgG levels against Haemophilus influenzae b (Hib), diphtheria toxoid (DT), hepatitis B, and tetanus.ResultsTrajectories of post-vaccination IgG levels were classified by functional principal component (PC) analysis to assess each child’s response profile. Two main components, PC1, reflecting height of response over time, and PC2, reflecting crossover from high to low or low to high, were identified. CB cytokine responses to schistosome and filarial antigens showed a significant association between augmented anti-helminth IL-10 and reduced antibody levels, particularly to DT and hepatitis B, and a more rapid post-vaccination decline in circulating IgG against Hib.ConclusionAntenatal sensitization to schistosomiasis or filariasis, and related production of anti-parasite IL-10 at birth, are associated with reduced anti-vaccine IgG levels in infancy, with possibly impaired protection.

Thomas A. Massaquoi, Rachael M. Burke, Guang Yang, Suliaman Lakoh, Stephen Sevalie, Bo Li, Hongjun Jia, Lei Huang, Gibrilla F. Deen, Fenella Beynon, Foday Sahr

by Thomas A. Massaquoi, Rachael M. Burke, Guang Yang, Suliaman Lakoh, Stephen Sevalie, Bo Li, Hongjun Jia, Lei Huang, Gibrilla F. Deen, Fenella Beynon, Foday Sahr Introduction Hepatitis B is a serious public health problem across sub-Saharan Africa. Sierra Leone has no national hepatitis B strategy plan or high quality estimates of prevalence. Healthcare workers are perceived as an at-risk group for hepatitis B. We assessed the prevalence of hepatitis B among healthcare workers at two hospital sites in Freetown, Sierra Leone. Methods In October 2017, healthcare workers were offered voluntary testing for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), hepatitis B core antibody (anti-HBc), hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) using rapid lateral flow assay for all samples, followed by Enzyme Immunosorbent Assay to confirm positive results. Participants completed a questionnaire about knowledge, attitudes and practices concerning hepatitis B. HBsAg positive participants were invited to a clinic for further assessment. Results Overall, 447 participants were tested for hepatitis B. Most (90.6%, 405/447) participants were nurses, 72.3% (323/447) were female and 71.6% (320/447) were 30 years or older. The prevalence of chronic hepatitis B (HBsAg positivity) was 8.7% (39 / 447, 95% CI 6.3–11.7%). There was no significant difference in prevalence by sex, age group, site of work or type of job. None of the 66.7% (26 / 39) of participants with chronic hepatitis B who attended the clinic met the 2015 WHO criteria to start treatment for hepatitis B on the basis of cirrhosis. Most participants (96.9% 432 / 446) stated that they were worried about their risk of hepatitis B at work. Conclusions Hepatitis B is highly prevalent among healthcare workers in Sierra Leone. It is unclear whether this reflects high community prevalence or is due to occupational risk. No participants with chronic hepatitis B needed to start treatment. In order to achieve the WHO target of elimination of viral hepatitis by 2030, introduction of birth dose vaccine for infants and catch-up vaccines for healthcare workers and healthcare students, together with a national hepatitis B screen and treat programme is advisable for Sierra Leone.

Ruth Y. Blanco, Carmen L. Loureiro, Julian A. Villalba, Yoneira F. Sulbarán, Mailis Maes, Jacobus H. de Waard, Héctor R. Rangel, Rossana C. Jaspe, Flor H. Pujol

by Ruth Y. Blanco, Carmen L. Loureiro, Julian A. Villalba, Yoneira F. Sulbarán, Mailis Maes, Jacobus H. de Waard, Héctor R. Rangel, Rossana C. Jaspe, Flor H. Pujol Prevalence and molecular epidemiology studies for hepatitis B (HBV) and C (HCV) virus are scarce in Warao Amerindians from Venezuela, where an epidemic of human immunodeficiency virus type 1 (HIV-1) has recently been documented. To carry out a molecular epidemiology analysis of hepatitis B (HBV) and C (HCV) virus in Warao individuals from the Delta Amacuro State of Venezuela. A total of 548 sera were tested for serological and molecular markers for HBV and HCV. The prevalence of active infection (presence of HBV surface antigen, HBsAg), exposure to HBV (presence of Antibody to HBV core antigen, anti-HBc) and anti-HCV, was 1.8%, 13% and 0% respectively. HBV exposure was significantly lower in men below 18 years old and also lower than rates previously reported in other Amerindian communities from Venezuela. Thirty one percent (31%, 25/80) of individuals without evidence of HBV infection exhibited anti-HBs titer ≥ 10U.I / ml, being significantly more frequent in individuals younger than 20 years. A higher HBV exposure was observed among HIV-1 positive individuals (33% vs 11%, p…

Landahl J, Bockmann J, Scheurich C, et al.

AbstractBackgroundThis study aimed to comprehensively define the breadth and specificity of the HDV-specific T-cell response in patients at different stages of chronic co-infection with hepatitis B (HBV) and delta virus (HDV).MethodsFollowing in vitro stimulation with an overlapping set of 21 HDV-specific 20mer peptides and exogenous IL-2, HDV-specific CD4+ and CD8+ T-cell response of 32 HDV-infected patients were analyzed by ELISpot and intracellular cytokine staining for interferon-γ production on a single peptide level. Additionally, HLA binding studies both in silico and in vitro were performed.ResultsWe were able to detect one or more T-cell response in more than 50% our patients. Interestingly, there was no significant difference between the breadth of response in HDV PCR+ versus PCR- patients. HDV-specific T-cell responses focused on three distinct HDV-specific epitopes that were each detected by 12-21% of patients – two HLA class II restricted (aa11-30, aa41-60) as well as one MHC class I restricted epitope (aa191-210). In in vitro HLA binding assays, the two CD4 + T-cell specificities (aa11-30, aa41-60) showed promiscuous binding to multiple HLA-DR molecules.ConclusionsThis comprehensive characterization of HDV T-cell epitopes provides important information that will facilitate further studies of HDV immunopathogenesis.

Abstract Background This study was conducted to determine the prevalence of HBV, HCV, and HDV in urban populations and Amerindians living in the state of Tocantins (Eastern Amazon). Methods A total of 948 individuals were recruited in Tocantinopolis city (Tocantins state) of whom 603 were Amerindians (from 6 tribes) and 345 were non-Amerindians (6 urban areas of Tocantinópolis city). Anti-HCV, HBsAg, anti-HBc, anti-HBs, anti-HBc IgM, anti-HBe, HBeAg, and anti-delta antibodies were determined using enzyme immunoassay. Results HBV cleared infection (both anti-HBc/anti-HBs+), chronic inactive/immune controlled HBV infection (anti-HBc + only), previous HBV vaccination (anti-HBs + only), active HBV infection (HBsAg+), individuals susceptible to HBV, and anti-HCV reactivity were found in 12.9, 1.8, 27.2, 0.5, 57.7, 1.2% in Amerindians and 12.1, 2.0, 37.1, 0.3, 55.4, 0.3% in non-Amerindians respectively. Out of 139 anti-HBc reactive individuals, 70 were anti-HBe reactive and none presented HBeAg or anti-HBc IgM. Anti-HBc prevalence was associated to older age (p 

Liu H, Li F, Zhang X, et al.

AbstractBackgroundThe natural history of chronic HBV infection was divided into four phases. Patients in the inactive carrier status (IC) and immune tolerant (IT) phase had normal ALT levels but huge different viral loads. The mechanism underlying low viral replication status in IC phase is unknown.MethodsWe determined the intrahepatic transcriptomes of 83 chronic hepatitis B patients by microarray analysis of liver biopsies, and screened the effect of differentially regulated genes on HBV replication using specific siRNAs in vitro.ResultsThe gene profile distinguishing active chronic hepatitis from IT and IC was predominantly composed of immune-related genes. The liver transcriptomes between the IT and IC phase were largely similar, and 109 expressed genes were significantly different. By performing systematic screening, 5 candidate genes including EVA1A, which were expressed at relative higher level in IC phase than IT, were identified to regulate HBV replication and gene expression in cellular models.ConclusionsThe immune-related pathways were up-regulated in the active chronic hepatitis phase but not in the IT and IC phase. A number of intrahepatic genes highly expressed in the IC phase may participate in the control of HBV replication and determine the inactive status of HBV infection.

Su T, Yang H, Tseng T, et al.

AbstractBackgroundWe investigated the patterns; predictors for virological relapse (VR), clinical relapse (CR), sustained clinical response (SCR); and retreatment outcomes after nucleos(t)ide analogue (NUC) therapy discontinuation.MethodsChronic hepatitis B patients discontinuing NUC were prospectively enrolled. Viral and host predictors, including HBsAg, anti-HBc, the single nucleotide polymorphisms of NTCP (rs2296651), CTLA4 (rs231775), rs3077 (HLA-DPA1), and rs9277535 (HLA-DPB1), and post-therapy predictors were investigated. Patients’ retreatments and outcomes were recorded.ResultsOverall, 100 patients discontinuing 3-year entecavir (ETV) or tenofovir (TDF) therapy were enrolled. Patients discontinuing TDF exhibited significantly higher 3-month VR (52.9% vs. 6.1%, P…

Peiffer K, Kuhnhenn L, Jiang B, et al.

AbstractBackgroundThe hepatitis B virus (HBV) surface proteins (HBsAg) coat the viral particle and form subviral particles (SVPs). Loss of HBsAg represents a functional cure and is an important treatment goal.MethodsWe analyzed the impact of the HBV genotypes A-E and pre-S mutations on SVP expression in HBeAg negative chronic HBV infected patients. A HBV genome harboring a preS1-deletion was analyzed in hepatoma cells.ResultsWe observed a genotype-specific ratio of the three surface proteins (SHBs/MHBs/LHBs), which reflects differences in the morphology and composition of SVPs. Deletions/mutations in the preS1/preS2 domain, detected in released viral genomes, did not affect the molecular weight of MHBs and LHBs in these patients. In contrast, LHBs molecular weight was altered in vitro using a HBV genome harboring a preS1-deletion derived from one of these patients.ConclusionDifferences in composition of SVPs may result in a genotype-specific immunogenicity and pathogenesis. In the analyzed patients with preS-mutations secreted HBsAg and released viral genomes cannot be derived from the same genetic source. As viral genomes are derived from cccDNA, HBsAg is presumably derived from the integrated DNA. This important HBsAg source has to be considered for novel antiviral strategies in HBeAg negative chronic HBV infected patients.

Deping Yang , Tingting Hu , Xuan Wu , Ke Li , Qi Zhong , Weiwei Liu

Abstract This study aimed to establish a quantitative droplet digital polymerase chain reaction (ddPCR) detection system for clinical hepatitis B virus (HBV) DNA in samples from patients with HBV infection with the aim of monitoring fluctuations and planning future antiviral treatments. Primers and probes for the conserved region of HBV DNA sequence (GenBank: AB554017.1) were designed by sequence alignment with the HBV DNA sequence in GenBank. The PUC57 plasmid containing the gene fragment was then synthesized according to the fragment amplified by primer. Linear DNA templates were obtained by digestion of the PUC57 plasmid with EcoRI. Primer specificity was verified by electrophoresis and sequencing, and the plasmid was used to verify the performance of ddPCR. Serum levels of HBV DNA were then detected in 103 HBV patients by ddPCR and real‐time quantitative polymerase chain reaction (qPCR), and the consistency of the two methods were compared. The accuracy of the ddPCR assays showed good linear correlation (R2=0.9952). The ddPCR coefficient of variance (CV) for intra‐run replicates reached 2.0%, and the CV value for inter‐run replicates reached 3.6%. ddPCR could detect as little as one copy of the template, as demonstrated by continuous dilution. This assay system provided a novel and specific platform with a linear range of detection from 1–105 copies/µL. Serum samples were collected from 103 HBV patients, and HBV DNA levels quantified by ddPCR and qPCR showed good concordance based on Bland–Altman analysis. The 95% limits of agreement were (log10: 0.29 ± 0.55) copies/μL. Our findings demonstrate that ddPCR can improve the detection level of nucleic acid and absolutely quantify the nucleic acid concentration, which is suitable for the clinical detection of HBV DNA. This article is protected by copyright. All rights reserved.

Qing-Fang Xiong, Tian Xiong, Ping Huang, Yan-Dan Zhong, Hua-Li Wang, Yong-Feng Yang

by Qing-Fang Xiong, Tian Xiong, Ping Huang, Yan-Dan Zhong, Hua-Li Wang, Yong-Feng Yang Background and aims 1~4% of acute hepatitis B (AHB) cases in adults progresses to acute liver failure (ALF).The predictors of ALF and prognosis for patients with ALF are not clear. This study investigated some of predictive and prognostic factors for AHB progression to ALF. Methods A retrospective analysis was used to assess the clinical and laboratory features of 293 patients diagnosed with AHB; the patients were divided into the following two groups: ALF (n = 13) and non-ALF (n = 280). Results In total,13 of the 293 (4.43%) patients developed ALF (10 recovered、3 died). The variables of age, anti-HBc IgM titers≥10 S/CO, HBeAg negativity, and total bilirubin (TB) at admission were significantly higher in ALF patients than in non-ALF patients. Compared to non-ALF patients, ALF patients had significantly lower values for prothrombin time activity (PTA), serum albumin, and HBV DNA. At discharge, ALF patients had lower TB normalization rates and much faster clearance of HBsAg, HBeAg and HBVDNA than non-ALF patients. In multivariate analysis, TB≥5×upper limit of normal (ULN) and HBeAg negative status were independent predictors for ALF development at admission, with 84.6% sensitivity, 85.7% specificity, a likelihood ratio of 5.91 and an area under the receiver operating characteristics curve (AUROC) of 0.850.Those who died had lower levels of peak PTA (…

Abstract Purpose Hepatitis B virus (HBV) reactivation during immunosuppressive therapy is common in patients with hematological malignancies, even in case of resolved infection. Prophylaxis of HBV reactivation is universally recommended in stem cell transplant (SCT) recipients and patients treated with anti-CD20 agents (i.e., rituximab). Despite its well-established favorable safety profile, lamivudine (LAM) use in prophylaxis has been debated because of the possible emergence of resistant viral strains. The aim of this study was to investigate the efficacy of LAM in preventing HBV reactivation in allogeneic SCT recipients with a resolved HBV infection. Methods Patients who received first allogeneic SCT in years 2009–2016 were evaluated. Sixty-three patients with resolved infection received LAM prophylaxis and were included in the study. Baseline and post-SCT characteristics were recorded, including rituximab exposure, length of LAM prophylaxis, and time from transplant to the last clinical and virological follow-up. Results Overall, 39 patients (62%) were male, 39 (62%) had acute myeloid leukemia, 38 (60%) received transplant from haploidentical donor, 29 (53%) received myeloablative conditioning, and 15 (24%) received rituximab post-transplant. Median clinical follow-up was 24 months after SCT (range 0.3–97); median virological follow-up 16 months (range 0.3–78), and median length of LAM prophylaxis of 14.5 months (range 0.3–78). No patient experienced HBV reactivation while on LAM prophylaxis. One patient experienced reactivation 8 months after discontinuing prophylaxis. Conclusions In this high-risk population, LAM prophylaxis was effective in preventing HBV reactivation in patients with resolved infection. It should be considered a reasonable first-line prophylactic agent to be administered in this setting.

Qi Zhu, Xiaoping Shao, Shaoli Chen, Dingliang Li, Xiaohong Chen, Wenjin Liu, Xianghua Wu, Zengyong Jian, Rutherford Shannon, Huizhen Zheng

Abstract Background Viral hepatitis is an important public health issue in sub-Saharan Africa. Due to rising mortality from cirrhosis and hepatocellular carcinoma and limited implementation of screening and treatment programmes, it has been characterised as a neglected tropical disease. Synthesis of the existing evidence on the epidemiology of viral hepatitis B, C and D in Malawi is required to inform policy and identify research gaps. Methods We searched Pubmed, EMBASE and Scopus for studies reporting the epidemiology of viral hepatitis B, C and D in Malawi from 1990 to 2018. Articles reporting prevalence estimates were included provided they described details of participant selection, inclusion criteria and laboratory methods (detection of HBsAg, anti-HCV or anti-HDV antibody, HCV antigen or HCV RNA or HDV RNA). We assessed study quality using a prevalence assessment tool. Where appropriate, a pooled prevalence was calculated using a DerSimonian Laird random effects model. Results Searches identified 199 studies, 95 full text articles were reviewed and 19 articles were included. Hepatitis B surface antigen (HBsAg) seroprevalence was assessed in 14 general population cohorts. The pooled prevalence among adults was 8.1% (95% CI 6.1, 10.3). In 3 studies where HBsAg was stratified by HIV status, no effect of HIV on HBsAg prevalence was observed (OR 1.2 (95% CI: 0.8, 1.6, p = 0.80)). In a single study of HIV/HBV infected individuals, anti-hepatitis D antibody (anti-HDV) prevalence was low (1.5%). HCV antibody prevalence (anti-HCV) ranged from 0.7 to 18.0% among 12 cohorts in general populations. Among three studies which used PCR to confirm current infection, the pooled rate of HCV RNA confirmation among anti-HCV positive individuals was only 7.3% (95% CI: 0.0, 24.3). Conclusions Hepatitis B is highly prevalent in Malawi. There is a paucity of epidemiological data from rural areas where 85% of the population reside, and the Northern region. Priority research needs include large-scale representative community studies of HBV, HDV and HCV seroprevalence, assessment of children following introduction of the HBV vaccine in 2002, prevalence estimates of viral hepatitis among individuals with cirrhosis and HCC and data on HCV prevalence using PCR confirmation, to support a viral hepatitis strategy for Malawi.

Lucio Boglione, Giuseppe Cariti, Valeria Ghisetti, Elisa Burdino, Giovanni Di Perri

An alternative approach in the treatment of chronic hepatitis B (CHB) with pegylated (PEG)‐interferon (IFN) is the prolonged course to 96 weeks of therapy, with higher sustained response (SR) than patients treated for 48 weeks. This result was confirmed in patients with CHB and D genotype, while no data are currently available about the prolonged course of PEG‐IFN in E genotype. This retrospective analysis reported the role of different treatment duration of PEG‐IFN on the SR in patients affected by CHB and E genotype. 86 subjects with CHB and E genotype were considered in this analysis; different treatment durations were: 48 weeks (control group, 41 patients), 72 weeks (25 patients) and 96 weeks (19 patients). Treatment effectiveness was evaluated with sustained response (SR) and serological response. SR was significantly higher in patients who underwent PEG‐IFN for 96 weeks in comparison to 48 weeks: 14.6% vs 26.3% (p = 0.016). HBsAg loss rate was 5.3% in patients treated for 96 weeks and 2.4% in the control group. In the multivariate analysis only the 72 and 96 weeks of therapy (OR 2.335, 95% CI 1.550‐4.578; p = 0.020 and (OR 3.890, 95% CI 1.991‐10.961; p = 0003) were predictive of SR. The extended duration of PEG‐IFN course in patients with CHB and genotype E is a promising approach to increase the SR and HBsAg clearance. This article is protected by copyright. All rights reserved …

Journal of Medical Virology, EarlyView.

Nandhini Saranathan, Perumal Vivekanandan

G-quadruplexes (G4s) are noncanonical nucleic acid secondary structures formed by guanine-rich DNA and RNA sequences. In this review we aim to provide an overview of the biological roles of G4s in microbial genomes with emphasis on recent discoveries. G4s are enriched and conserved in the regulatory regions of microbes, including bacteria, fungi, and viruses. Importantly, G4s in hepatitis B virus (HBV) and hepatitis C virus (HCV) genomes modulate genes crucial for virus replication. Recent studies on Epstein–Barr virus (EBV) shed light on the role of G4s within the microbial transcripts as cis-acting regulatory signals that modulate translation and facilitate immune evasion.

Danping Liu, Jian Li, Wei Lu, Yanbing Wang, Xinlan Zhou, Dan Huang, Xiufen Li, Rongrong Ding, Zhanqing Zhang

To evaluate the performance of a new mathematical model gamma- glutamyl transpeptidase to cholinesterase and platelet ratio (GCPR) versus gamma- glutamyl transpeptidase to platelet ratio (GPR) in predicting significant fibrosis and cirrhosis of chronic hepatitis B (CHB).

JeroenCremer , Sanne H. I.Hofstraat , Francoisevan Heiningen , Irene K.Veldhuijzen , Birgit H. B.van Benthem , Kimberley S. M.Benschop

Genetic variation within hepatitis B surface antigen (HBsAg), in particular within the major hydrophobic region (MHR), is related to immune/vaccine and test failures and can have a significant impact on the vaccination and diagnosis of acute infection. This study shows, for the first time, variation among acute cases and compares the amino acid variation within the HBsAg between acute and chronic infections. We analyzed the virus isolated from 1231 acute and 585 chronic cases reported to an anonymized public health surveillance database between 2004 and 2014 in The Netherlands. HBsAg analysis revealed the circulation of 6 genotypes (Gt); GtA was the dominant genotype followed by GtD among both acute (68.2% and 17.4%, respectively) and chronic (34.9% and 34.2%, respectively) cases. Variation was the highest among chronic strains compared to that among acute strains. Both acute and chronic GtD showed the highest variation compared to that of other genotypes (P …