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.

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.

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.

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…

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].

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.

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…

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…

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.

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.

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…

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.

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

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.

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 …

Abstract Background Co-infection with HIV negatively impacts the progression of chronic hepatitis B virus (HBV) infection, including causing rapid progression to liver fibrosis. Sub-Saharan Africa represents arguably the most important intersection of high endemicity of both chronic hepatitis B virus (HBV) infection and HIV infection. Methods We recruited 46 HBV/HIV-co-infected; 47 HBV-monoinfected; 39 HIV-monoinfected; and 37 HBV/HIV-uninfected patients from Tygerberg Hospital, Cape Town, South Africa. All HIV-infected patients were on antiretroviral therapy for ≥3 months. Liver stiffness measurements were assessed using the Fibroscan (Fibroscan 402, Echosens). Cell-based immunomarkers were measured by flow cytometry. Soluble serum/plasma immunomarkers were measured by Luminex technology and enzyme immunoassays. HIV (COBAS/Ampliprep TaqMan HIV-1) and HBV viral loads (in-house assay) were also performed. Results HBV/HIV co-infected patients showed significantly higher levels of immune activation %CD8+/HLA-DR+/CD38+ (median 30%, interquartile range: 17–53) and %CD8+/PD-1 (median 22%, interquartile range: 15–33), p ≤ 0.01 compared to all other study groups. Despite this, the HBV-mono-infected group had the highest proportion of patients with advanced liver fibrosis (≥13 kPa) as measured by Fibroscan (18%). HBV mono-infected patients showed highest expression of most cytokines including IL-17 and basic fibroblastic growth factor. There was significant positive correlation between detectable HIV and HBV viral replication and liver fibrosis but not immune activation or gut translocation. Discussion Highly-active antiretroviral therapy, including tenofovir, is effective against both HIV and HBV. Earlier therapy in the co-infected patients may therefore have controlled viral replication leading to better fibrosis scores when compared to HBV mono-infection in this study. On-going HBV and HIV viraemia, rather than microbial translocation or immune activation, appear to be the drivers of liver fibrosis. Moderate to advanced liver fibrosis in HBV-mono-infection may well indicate poor access to screening and treatment of HBV infection.

Piero Colombatto, Cristiana Barbera, Flavia Bortolotti, Anna M Maina, Francesco Moriconi, Daniela Cavallone, Pierluigi Calvo, Filippo Oliveri, Ferruccio Bonino, Maurizia R Brunetto

Background. Selection of HBeAg defective HBV mutants (mt) during childhood might influence infection outcome in adults. Aim of this study was to correlate the dynamics of Pre‐Core HBV mutant (Pre‐C mt) selection with virological/clinical outcomes in children followed‐up until adulthood. Methods. Eighty subjects (50‐M/30‐F), 70 HBeAg‐positive (87.5%) and 10 (12.5%) HBeAg‐negative/anti‐HBe‐positive at the admission, mostly genotype D infected (91.2%), with median age of 6.5 (range: 0.2‐17) years, were followed‐up for 14.3 years (range: 1.1‐24.5); 46 (57.5%) received IFN treatment. HBV‐DNA and q‐HBsAg were tested by commercial assays, Pre‐Core 1896 mt by direct‐sequence, oligo‐hybridization‐assay and allele‐specific‐PCR (sensitivity: 30%, 10% and 0.1% of total viremia). Results. HBeAg/anti‐HBe seroconversion (SC) occurred in 55/70 (78.6%) children. After SC, 8 (14.6%) developed HBeAg‐negative chronic hepatitis (CHB), 41 (74.5%) remain with HBeAg‐negative chronic infection, and 6 (10.9%) lost HBsAg. Baseline HBV‐DNA and HBsAg were lower in SC than in no‐SC children (median: 7.35 vs 8.95 Log IU/mL, P = 0.005 and 4.72 vs 5.04 Log IU/ml, P = 0.015). The prevalence of Pre‐C mt increased rapidly (10% to 40%) around SC. Eventually, Pre‐C mt was detected in 100% of CHB, in 33% of chronic infections without disease, and in 16% of subjects who cleared HBsAg (P …

Piero Colombatto , Cristiana Barbera , Flavia Bortolotti , Anna M. Maina , Francesco Moriconi , Daniela Cavallone , Pierluigi Calvo , Filippo Oliveri , Ferruccio Bonino , Maurizia R. Brunetto

Selection of HBeAg defective HBV mutants (mt) during childhood might influence infection outcome in adults. Aim of this study was to correlate the dynamics of pre‐core HBV mutant (pre‐C mt) selection with virological/clinical outcomes in children followed‐up until adulthood. Eighty subjects (50‐M/30‐F), 70 HBeAg‐positive (87.5%), and 10 (12.5%) HBeAg‐negative/anti‐HBe‐positive at the admission, mostly genotype D infected (91.2%), with median age of 6.5 (range: 0.2‐17) years, were followed‐up for 14.3 years (range: 1.1‐24.5); 46 (57.5%) received IFN treatment. HBV‐DNA and q‐HBsAg were tested by commercial assays, Pre‐Core 1896 mt by direct‐sequence, oligo‐hybridization‐assay, and allele‐specific‐PCR (sensitivity: 30%, 10%, and 0.1% of total viremia). HBeAg/anti‐HBe seroconversion (SC) occurred in 55/70 (78.6%) children. After SC, 8 (14.6%) developed HBeAg‐negative chronic hepatitis (CHB), 41 (74.5%) remain with HBeAg‐negative chronic infection, and 6 (10.9%) lost HBsAg. Baseline HBV‐DNA and HBsAg were lower in SC than in no‐SC children (median: 7.35 vs 8.95 Log IU/mL, P = 0.005, and 4.72 vs 5.04 Log IU/mL, P = 0.015). The prevalence of pre‐C mt increased rapidly (10‐40%) around SC. Eventually, pre‐C mt was detected in 100% of CHB, in 33% of chronic infections without disease, and in 16% of subjects who cleared HBsAg (P …

Wondmagegn Demsiss, Abdurahaman Seid, Temesgen Fiseha

by Wondmagegn Demsiss, Abdurahaman Seid, Temesgen Fiseha Background Health care professionals, especially medical students, are at greater risk of contracting hepatitis B and C virus infections due to their occupational exposure to percutaneous injuries and other body fluids. The aim of this study was to determine the seroprevalence of hepatitis B and C virus infections among medicine and health science students in Northeast Ethiopia and to assess their knowledge and practice towards the occupational risk of viral hepatitis. Methods A cross-sectional study was conducted among a total of 408 medicine and health science students during the period from March to September 2017. A pre-coded self-administered questionnaire was used to collect data on students’ socio- demographic characteristics, knowledge and practice of hepatitis B and C infections. Blood samples were collected and screened for hepatitis B surface antigen (HBsAg) and anti-HCV antibodies. SPSS version 20 statistical software was used for data analysis. Results The seroprevalence of HBV infection was 4.2% (95% CI 2.5 to 6.1%) and 0.7% (95% CI 0.0 to 1.7%) for HCV. Older age (AOR = 15.72, 95% CI 1.57–157.3) and exposure to needlestick injury (AOR = 3.43, 95% CI 1.10–10.73) were associated with a higher risk of HBV infection. Majority of the students (80.1%) had an adequate knowledge about hepatitis B and C infection, mode of transmission and preventive measures. Only 50.0% of students had safe practice towards occupational risk of viral hepatitis infection. Almost half (49.8%) of students experienced a needlestick injury; of which, 53.2% reported the incidence, and only 39.4% had screening test result for viral hepatitis. Conclusion A high seroprevalence but poor practice of hepatitis B and C virus infection was found in the study area despite their good knowledge towards occupational risk of viral hepatitis infection.

Kuehn BM.

Healthy infants should be vaccinated with the hepatitis B within 24 hours of birth and physicians should not delay vaccination until after discharge, according to new recommendations from the US Advisory Committee on Immunization Practices (ACIP) and the US Centers for Disease Control and Prevention (CDC). Previously, the recommendations allowed for newborn vaccination after discharge.

Chiaho Shih, Ching-Chun Yang, Gansukh Choijilsuren, Chih-Hsu Chang, An-Ting Liou

This infographic about hepatitis B virus explores its replication cycle, natural history of infection and pathogenesis, and how this can be controlled and treated.Hepatitis B virus (HBV) is a common worldwide blood-borne pathogen. Chronic hepatitis B can progress to an inactive carrier state, and then, in some patients, give rise to cirrhosis and cancer of the liver, leading to death. An HBV surface-antigen vaccine is effective, but treatments are currently not curative. HBV replicates via reverse transcription.

Abstract Background There are several epidemiological studies available on hepatitis B virus among pregnant women in Ethiopia. These individual studies revealed wide variation over time and across geographical areas. The aim of this systematic review and Meta-analysis is to estimate the overall prevalence of hepatitis B virus infection among pregnant women in Ethiopia. Methods A comprehensive search of electronic databases including PubMed, Popline, Lalicus, Ovid, MedNar, African Journal Online (AJOL) and advanced Google Scholar was conducted regardless of publication year from August 30, 2017 to September 25, 2017. The search was updated on January 02, 2018 to minimize time-lag bias. The methodological qualities of included studies were assessed using Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instruments. Results Out of 103 studies, 17 studies with a total of 5629 pregnant women were included in the Meta-analysis. The pooled prevalence of hepatitis B virus infection among pregnant women using random-effect model was 4.7%(95% CI 4.0–5.4%). The I2 statistics was I2 = 37.9%(p = 0.0575). Even though significant heterogeneity among studies was not detected, the I2 = 37.9% suggests medium heterogeneity. A subgroup Meta-analysis showed that study site, region, mean/median sample size, hepatitis B virus screening methods and methodological quality were not source of heterogeneity (p-difference > 0.05). Conclusion This review shows an intermediate level of hepatitis B virus infection among pregnant women in Ethiopia. In addition to the current practice of child vaccination, routine and universal antenatal hepatitis B virus screening program need to be implemented.

Barbara V. Lago , Francisco C. A. Mello , Tairine M. Barros , Vinicius M. Mello , Livia M. Villar , Lia L. Lewis‐Ximenez , Maria Inês M. C. Pardini , Elisabeth Lampe ,

In Brazil, the Amazon Basin is endemic for hepatitis D virus (HDV) infection; however, studies in other regions of the country are scarce. This study aims to map the seroepidemiological situation of anti‐Delta antibodies in chronic hepatitis B carriers in all five Brazilian geographic regions. Serum samples from 1240 HBsAg positive individuals (55.4% men; mean age 43.1 ± 13.4 years) from 24 of 26 Brazilian states were tested for the presence of anti‐Delta antibodies using a commercial immunoassay. Anti‐Delta antibodies were detected in 40 samples (3.2%; 52.5% female; mean age of 38.1 ± 13.8 years). Age less than 20 years was significantly associated with anti‐HDV positivity (P …

Mahale P, Aka P, Chen X, et al.

AbstractPeople who inject drugs (PWID) are commonly exposed to hepatitis B virus (HBV) and hepatitis D virus (HDV). We evaluated the prevalence of HDV viremia among hepatitis B surface antigen (HBsAg)-positive PWID (n=73) by using a new quantitative microarray antibody capture (Q-MAC) assay, HDV Western blot and HDV RNA. HDV Q-MAC performed well in this cohort: anti-HDV, 100% sensitivity and specificity; HDV viremia, 61.5% sensitivity and 100% specificity. Hepatitis D viremia was present in 35.6% of HBsAg-positive participants and was more common in those with resolved compared to chronic hepatitis C (5.1% vs. 0.6%; adjusted odds ratio, 9.80; p…

Ngongondo, McNeil; Miyahara, Sachiko; Hughes, Michael D.; Sun, Xin; Bisson, Gregory P.; Gupta, Amita; Kumwenda, Johnstone; Lavenberg, Jeffrey A.; Torres, Thiago Silva; Nyirenda, Mulinda; Kidonge, Katende Kenneth; Hosseinpour, Mina C.; for the AIDS Clinical Trials Group A5274 (REMEMBER) Study Team

AbstractBackground:Hepatotoxicity associated with isoniazid preventive therapy (IPT) and antiretroviral therapy (ART) has not been well studied in severely immunosuppressed people with HIV. Our objective was to determine risk factors for hepatotoxicity in severely immunosuppressed individuals taking IPT and ART.Setting:Multi-center study in resource limited settings with high burden of tuberculosis.Methods:We conducted a secondary analysis of data from one randomized arm of the REMEMBER trial. The analysis includes participants with pre-ART CD4 cell counts of 5 x upper limit of normal or symptomatic hepatitis during IPT and ART.Logistic regression was used to identify baseline risk factors for hepatotoxicity. Time to occurrence of hepatotoxicity was estimated by the Kaplan Meier method.Results:Among 426 participants (53% male, median age 35 years, median CD4 count 19 cells/µL), 31 developed hepatotoxicity (7.3%). Raised pretreatment AST/ALT (OR 3.6, 95% CI 1.7-7.7) and hepatitis B surface antigen (HBsAg) sero-positivity at baseline (OR 4.7, 95% CI 1.7-12.9) were significantly associated with an increased risk of developing hepatotoxicity. Participants with both raised AST/ALT and positive HBsAg had a higher risk (OR 19.9, 95% CI 5.3-74.3) and earlier onset of hepatotoxicity than participants who did not have these conditions at baseline.Conclusions:The incidence of hepatotoxicity during IPT and ART was high. Severely immunosuppressed individuals with raised pretreatment AST/ALT or HBsAg sero-positivity need closer monitoring for hepatotoxicity. Background: Hepatotoxicity associated with isoniazid preventive therapy (IPT) and antiretroviral therapy (ART) has not been well studied in severely immunosuppressed people with HIV. Our objective was to determine risk factors for hepatotoxicity in severely immunosuppressed individuals taking IPT and ART. Setting: Multi-center study in resource limited settings with high burden of tuberculosis. Methods: We conducted a secondary analysis of data from one randomized arm of the REMEMBER trial. The analysis includes participants with pre-ART CD4 cell counts of 5 x upper limit of normal or symptomatic hepatitis during IPT and ART. Logistic regression was used to identify baseline risk factors for hepatotoxicity. Time to occurrence of hepatotoxicity was estimated by the Kaplan Meier method. Results: Among 426 participants (53% male, median age 35 years, median CD4 count 19 cells/µL), 31 developed hepatotoxicity (7.3%). Raised pretreatment AST/ALT (OR 3.6, 95% CI 1.7-7.7) and hepatitis B surface antigen (HBsAg) sero-positivity at baseline (OR 4.7, 95% CI 1.7-12.9) were significantly associated with an increased risk of developing hepatotoxicity. Participants with both raised AST/ALT and positive HBsAg had a higher risk (OR 19.9, 95% CI 5.3-74.3) and earlier onset of hepatotoxicity than participants who did not have these conditions at baseline. Conclusions: The incidence of hepatotoxicity during IPT and ART was high. Severely immunosuppressed individuals with raised pretreatment AST/ALT or HBsAg sero-positivity need closer monitoring for hepatotoxicity. Correspondence to: McNeil Ngongondo, UNC Project, Tidziwe Centre, Lilongwe, Malawi, Phone: +265 999 782 183, Fax: +265 1 755 954, mngongondo@unclilongwe.org Conflict of Interest and Source of Funding: A5274 was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers UM1 AI068634, UM1 AI068636, and UM1 AI106701 and also supported by National Institute of Mental Health (NIMH), National Institute of Dental and Craniofacial Research (NIDCR). The primary author was supported by the ACTG-SDAC Internship program at the Center for Biostatistics AIDS Research under award number UM1 AI068634. The authors have no conflict of interest to declare. Presented at the Conference of Retroviruses and Opportunistic Infections (CROI) 2017, Seattle, 14 February 2017. Contribultors: MN did the literature search. MN, SM, XS, JAL analyzed the data and generated the figures. MN, SM, MDH, XS, JAL, TST, interpreted the data. MN, SM, MDH, MCH drafted the manuscript. MN, SM, XS, TST, JAL, MN, KK, JK, AG, GBP, MDH, MCH revised the manuscript and contributed intellectually. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Tae Hyung Kim, Eun-Ju Lee, Ji-Hye Choi, Sun Young Yim, Sunwon Lee, Jaewoo Kang, Yoo Ra Lee, Han Ah Lee, Hyuk Soon Choi, Eun Sun Kim, Bora Keum, Yeon Seok Seo, Hyung Joon Yim, Yoon Tae Jeen, Hoon Jai Chun, Hong Sik Lee, Chang Duck Kim, Hyun Goo Woo, Soon Ho Um

by Tae Hyung Kim, Eun-Ju Lee, Ji-Hye Choi, Sun Young Yim, Sunwon Lee, Jaewoo Kang, Yoo Ra Lee, Han Ah Lee, Hyuk Soon Choi, Eun Sun Kim, Bora Keum, Yeon Seok Seo, Hyung Joon Yim, Yoon Tae Jeen, Hoon Jai Chun, Hong Sik Lee, Chang Duck Kim, Hyun Goo Woo, Soon Ho Um Background/Aims The seroclearance of hepatitis B virus (HBV) surface antigen (HBsAg) is regarded as a functional cure of chronic hepatitis B (CHB) although it occurs rarely. Recently, several genome-wide association studies (GWASs) revealed various genetic alterations related to the clinical course of HBV infection. However, all of these studies focused on the progression of HBV infection to chronicity and had limited application because of the heterogeneity of HBV genotypes. In the present study, we aimed to determine susceptibility genetic markers for seroclearance of HBsAg in CHB patients with a homogenous viral genotype. Methods One hundred patients with CHB who had experienced HBsAg seroclearance before 60 years of age and another 100 with CHB showing high serum levels of HBsAg even after 60 years of age were enrolled. Extreme-phenotype GWAS was conducted using blood samples of participants. Results We identified three single nucleotide polymorphisms, rs7944135 (P = 4.17 × 10−6, odds ratio [OR] = 4.16, 95% confidence interval [CI] = 2.27–7.63) at 11q12.1, rs171941 (P = 3.52×10−6, OR = 3.69, 95% CI = 2.13–6.42) at 5q14.1, and rs6462008 (P = 3.40×10−6, OR = 0.34, 95% CI = 0.22–0.54) at 7p15.2 as novel susceptibility loci associated with HBsAg seroclearance in patients with CHB. The flanking genes at these loci including MPEG1, DTX4, MTX3, and HOXA13 were suggested to have functional significance. In addition, through functional analysis, CXCL13 was also presumed to be related. Conclusions To the best of our knowledge, this study is the first GWAS regarding the seroclearance of HBsAg in CHB patients. We identify new susceptibility loci for cure of CHB, providing new insights into its pathophysiology.

Lee I, Yang S, Lee C, et al.

AbstractBackgroundThe long-term incidence and factors associated with HBsAg loss in HBeAg-negative chronic hepatitis B (CHB) patients receiving peginterferon is rarely reported.MethodsFrom 2004 to 2016, 233 HBeAg-negative CHB patients who completed 48 weeks of peginterferon treatment from three medical centers in Taiwan were retrospectively enrolled.ResultsDuring a median follow-up of 7.4 years, 27 cases achieved HBsAg loss. The cumulative incidences of HBsAg loss and HBsAg seroconversion at 3, 5, 10 years after peginterferon treatment were 4.7%, 9.4%, 14.2%, and 3.5%, 6.4%, 12.5%, respectively, in overall population, and 15.9%, 29.1%, 37.3%, and 13.1%, 19%, 30.6%, respectively, in patients achieving sustained off-treatment virological response (SVR). By multivariate analysis, age (

Yuan-Yuei Chen, Wen-Hui Fang, Chung-Ching Wang, Tung-Wei Kao, Yaw-Wen Chang, Hui-Fang Yang, Chen-Jung Wu, Yu-Shan Sun, Wei-Liang Chen

by Yuan-Yuei Chen, Wen-Hui Fang, Chung-Ching Wang, Tung-Wei Kao, Yaw-Wen Chang, Hui-Fang Yang, Chen-Jung Wu, Yu-Shan Sun, Wei-Liang Chen Accumulated evidence has suggested associations between glucose abnormalities and insulin resistance with hepatitis C virus (HCV) and hepatitis B virus (HBV) infections. However, few studies have reported the effect of hepatitis virus infections on body composition. Our aim was to explore the association of hepatitis virus infections with percent body fat (PBF) in a cross-sectional analysis. A total of 69226 subjects obtained from the health examinations at Tri-Service General Hospital (TSGH) from 2010 to 2016 were enrolled in the study. Participants were divided into subgroups based on the presence of hepatitis B surface antigen (HBsAg) and anti-HCV. PBF was measured by bioelectrical impedance analysis (BIA). A multivariable linear regression model was applied to test the association of hepatitis virus infections with PBF and glycemic status. In male participants, hepatitis virus infections were closely associated with increased PBF, especially in those subjects with HCV/HBV coinfection. HCV/HBV coinfection was positively correlated with fasting plasma glucose and postprandial glucose while HCV and HBV mono-infection were not. The impact of hepatitis virus infection on increased PBF was observed in general population with gender difference. A further study on the treatment of hepatitis virus infection might help prevent the development of obesity-related diseases.

Zimmer C, Rinker F, Höner zu Siederdissen C, et al.

AbstractBackgroundTreatment with nucleos(t)ide analogues (NA) efficiently suppress HBV DNA but rarely leads to functional cure of chronic hepatitis B (CHB). Following NA cessation, a fraction of HBeAg-negative CHB-patients experience HBsAg loss. Cellular immune responses, including those by natural killer cells, innate lymphocytes known to respond in CHB, explaining the virological events transpiring following NA treatment cessation remain elusive.MethodsIn a single-center prospective trial, 15 HBeAg-negative CHB-patients on long-term NA treatment underwent structured NA cessation and were studied longitudinally. The NK cell compartment was assessed using high-dimensional flow cytometry and correlated with the clinical course.ResultsUnsupervised stochastic neighbor embedding analysis revealed NA treated CHB-patients to have a significantly affected NK cell compartment as compared to controls. Cessation of NA treatment resulted in only minor phenotypic alterations, but it significantly augmented NK cell natural cytotoxicity responses in the CHB-patients. This increased NK cell functionality correlated with ALT flares experienced by the patients and was particularly enhanced in patients experiencing HBsAg seroclearance at long-term follow-up.ConclusionsIncreased NK cell function associates with active hepatitis and HBsAg seroclearance following structured NA cessation. This adds to our knowledge of the immunological events that develop following cessation of NA treatment in CHB.

Abstract The introduction of BCR-ABL-tyrosine kinase inhibitors (TKI) for treatment of hematologic malignancies has made a significant impact on patient outcome. Contingent upon their targeted and off-target activity, therapy-associated infectious complications may occur. We present a case of cytomegalovirus pneumonitis and a case of adenovirus hemorrhagic cystitis in two patients with Philadelphia chromosome-positive acute lymphoblastic leukemia on BCR-ABL TKI treatment and review the literature to summarize the infectious complications based on clinical data. As life-threatening infections may occur, treating physicians should maintain a heightened awareness in patients treated with BCR-ABL TKIs. Based on the frequent reports of hepatitis B virus (HBV) reactivation under the treatment BCR-ABL TKIs, screening for and prophylactic therapy of chronic HBV infection should be considered. Similarly, patients would benefit from screening for and treatment of latent tuberculosis.

Simon B.Larsson , GianlucaTripodi , GiovanniRaimondo , CarloSaitta , GunnarNorkrans , TeresaPollicino , MagnusLindh

Hepatitis B virus (HBV) infection is the main risk factor for hepatocellular carcinoma (HCC) worldwide. Integration of HBV DNA into the human genome has been found in >80% of HBV‐related HCC cases. Some studies have, however, found similar integration patterns in tumorous and nontumorous tissues. Thus, the role of integrations for the development of HCC as well as the rate of integration in different stages of infection remain unclear. The aim of this study was to investigate integrations in patients without HCC, representing different stages of chronic HBV (CHB) infection. Extracted DNA in liver biopsies from 74 patients (one with 2 available biopsies) with CHB infection was analyzed by Alu‐PCR. Amplicons were further analyzed by Sanger sequencing. Integration was detected in 39 biopsies (52%) as an amplicon containing both human and HBV sequences by Alu‐PCR with one primer targeting a region in the HBV genome. Integrations were found in patients representing the different stages of CHB infection. A majority of the HBV sequences were located upstream or downstream of nucleotide position 1820, which previously has been identified as a common breakpoint in the HBV genome in integrated sequences. Approximately 60% of the HBV integrations were found in noncoding regions of the human genome. Integrations of HBV DNA into the human genome is an event frequently found in mild phases of chronic hepatitis.

Yurdaydin C, Keskin O, Kalkan Ç, et al.

AbstractBackgroundInterferon is the only treatment option in chronic delta hepatitis (CDH). A CDH database (333 patients, 161 with interferon treatment history) was analyzed for effects of treatment duration on virologic response and clinical outcomes.MethodsNinety-nine CDH patients who received at least 6 months of interferon were selected. Maintained virologic response (MVR) was defined as hepatitis D virus RNA negative for 2 years after treatment discontinuation. Cumulative median interferon treatment duration was 24 months (range 6–126 months), with a median of 2 courses (range 1–8). Post-treatment median follow-up was 55 months (24–225 months).ResultsThirty-five patients achieved MVR. Cumulative probability of MVR increased with treatment duration and reached 50% at 5 years. Patients with MVR were less likely to die from liver disease or develop complications compared to patients without MVR (P = .032, P = .006, respectively). Cirrhosis at baseline and no response to therapy (odds ratio 16.1 and 5.23, respectively) predicted an adverse endpoint. Hepatitis B surface antigen clearance occurred in 37% of patients with MVR.ConclusionViral response to interferon increases with treatment duration and favorably affects the natural course of disease. Interferon treatment duration has to be individualized with careful post-treatment assessment.

C.-H. Chen, C.-H. Hung, J.-H. Wang, S.-N. Lu, T.-H. Hu, C.-M. Lee

To investigate the long-term incidence and predictors for hepatitis B surface antigen (HBsAg) loss after nucleoside analogue therapy.

Abstract Background Infants born to hepatitis B surface antigen (HBsAg) positive mothers are at a higher risk for Hepatitis B virus (HBV) infection. Host genetic background plays an important role in determining the strength of immune response to vaccination. We conducted this study to investigate the association between Tumor necrosis factor (TNF) and Mitogen-activated protein kinase eight (MAPK8) polymorphisms and low response to hepatitis B vaccines. Methods A total of 753 infants of HBsAg positive and hepatitis Be antigen (HBeAg) negative mothers from the prevention of mother-to-infant transmission of HBV cohort were included. Five tag single nucleotide polymorphism (SNPs) (rs1799964, rs1800629, rs3093671, rs769177 and rs769178) in TNF and two tag SNPs (rs17780725 and rs3827680) in MAPK8 were genotyped using the MassARRAY platform. Results A higher percentage of breastfeeding (P = 0.013) and a higher level of Ab titers were observed in high responders (P 

Abstract Background This study evaluated cause-specific mortality trends including liver-related mortality among people with a hepatitis B virus (HBV) and hepatitis C virus (HCV) notification in New South Wales, Australia. Methods Notifications 1993-2012 were linked to cause-specific mortality records 1993-2013. Results Among 57,929 and 92,474 people with a HBV and HCV notification, 4.8% and 10.0% died since 1997. In early 2010s, 28% and 33% of HBV and HCV deaths were liver-related, 28% and 17% were cancer-related (excluding liver cancer), and 5% and 15% were drug-related, respectively. During 2002-2012, annual HBV-related liver death numbers were relatively stable (53 to 68), while HCV-related liver death numbers increased considerably (111 to 284). Age-standardised HBV-related liver mortality rates declined from 0.2 to 0.1 per 100 person-years (PY) (P