Ngo Tat Trung, Dang Chieu Duong, Hoang Van Tong, Tran Thi Thu Hien, Phan Quoc Hoan, Mai Hong Bang, Mai Thanh Binh, Thai Doan Ky, Nguyen Lam Tung, Nguyen Tien Thinh, Vu Viet Sang, Le Thi Phuong Thao, C-Thomas Bock, Thirumalaisamy P. Velavan, Christian G. Meyer, Le Huu Song, Nguyen Linh Toan

by Ngo Tat Trung, Dang Chieu Duong, Hoang Van Tong, Tran Thi Thu Hien, Phan Quoc Hoan, Mai Hong Bang, Mai Thanh Binh, Thai Doan Ky, Nguyen Lam Tung, Nguyen Tien Thinh, Vu Viet Sang, Le Thi Phuong Thao, C-Thomas Bock, Thirumalaisamy P. Velavan, Christian G. Meyer, Le Huu Song, Nguyen Linh Toan Background Circulating microRNAs (miRNA) are biomarkers for several neoplastic diseases, including hepatocellular carcinoma (HCC). We performed a literature search, followed by experimental screening and validation in order to establish a miRNA panel in combination with the assessment of alpha-fetoprotein (AFP) levels and to evaluate its performance in HCC diagnostics. Methods Expression of miRNAs was quantified by quantitative PCR (qPCR) in 406 serum samples from 118 Vietnamese patients with hepatitis B (HBV)-related HCC, 69 patients with HBV-related liver cirrhosis (LC), 100 chronic hepatitis B (CHB) patients and 119 healthy controls (HC). Results Three miRNAs (mir-21, mir-122, mir-192) were expressed differentially among the studied subgroups and positively correlated with AFP levels. The individual miRNAs mir-21, mir-122, mir192 or the triplex miRNA panel showed high diagnostic accuracy for HCC (HCC vs. CHB, AUC = 0.906; HCC vs. CHB+LC, AUC = 0.81; HCC vs. CHB+LC+HC, AUC = 0.854). When AFP levels were ≤20ng/ml, the triplex miRNA panel still was accurate in distinguishing HCC from the other conditions (CHB, AUC = 0.922; CHB+LC, AUC = 0.836; CHB+LC+HC, AUC = 0.862). When AFP levels were used in combination with the triplex miRNA panel, the diagnostic performance was significantly improved in discriminating HCC from the other groups (LC, AUC = 0.887; CHB, AUC = 0.948; CHB+LC, AUC = 0.887). Conclusions The three miRNAs mir-21, mir-122, mir-192, together with AFP, are biomarkers that may be applied to improve diagnostics of HCC in HBV patients, especially in HBV-related LC patients with normal AFP levels or HCC patients with small tumor sizes.

Colby D, Posuwan N, Kroon E, et al.

To the Editor—In response to an article by Manor et al [1], Chen et al recently reported on an outbreak of acute hepatitis A virus (HAV) in northern Taiwan that affected primarily men who have sex with men (MSM) who had human immunodeficiency virus (HIV) or other sexually transmitted infections (STIs) [2]. That outbreak started in mid-2015 and peaked with >1000 cases of acute HAV reported in 2016. By contrast,

Farzaneh Dehghani‐Dehej , Jamal Sarvari , Maryam Esghaei , Seyed Y. Hosseini , Saba Garshasbi , Saeed Kalantari , Seyed H. Monavari , Atousa Fakhim , Hossein Keyvani , Farah Bokharaei‐Salim

Due to the similar routes of transmission, individuals infected with the human immunodeficiency virus (HIV) may become infected with the hepatitis C virus (HCV) simultaneously. The aim of this study was to investigate the frequency of HCV co‐infection in Iranian individuals with HIV infection, and to genotype HCV in plasma and PBMC specimens of these patients. From September 2015 to October 2016, a total of 140 Iranian individuals with HIV infection were enrolled in this cross‐sectional study. The RNA from plasma and PBMC specimens was extracted, and genomic HCV‐RNA was amplified using RT‐nested PCR with primers that target 5′‐UTR. The HCV genotyping used the RFLP technique. To confirm HCV genotype, 10 randomly selected HCV‐positive samples were also submitted for sequencing. The mean age of patients was 35.7 ± 13.5 years (range: 1‐66). Out of 140 patients, 62 (44.3 %) were positive for anti‐HCV antibodies; among these, viral genomic RNA was detected in 34 (24.3%) and 39 (27.9%) of the plasma and PBMC specimens, respectively. The HCV genotyping showed a similar pattern of subtypes 1a (44% vs 46.2%), 3a (32.4% vs 33.3%), and 1b (17.6% vs 17.9%) in all sera and PBMC samples. It is noteworthy that the HCV genotypes in plasma and PBMC specimens of 6 HCV co‐infected patients were not the same. This study reveals that HIV/HCV co‐infection is high in Iranian patients (44.3%), especially in people who have high‐risk factors (83.9%). Also, HIV/HCV co‐infected individuals may have dissimilar HCV genotypes in their plasma and PBMC specimens.

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 …

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.

Selam Niguse , Haftamu Hailekiros , Gerezgiher Buruh , Tadese Dejene , Nega Berhe , Tsehaye Asmelash

Existing literatures from developing countries show an increased mortality and morbidity related to hepatitis E virus during pregnancy as compared to the general population. Studies focusing on pregnant women are required for policy makers to improve maternal and child health. Therefore this study is aimed at determining the prevalence and associated risk factors of hepatitis E virus infection among pregnant women attending the health facilities of Tigray region, Northern Ethiopia. In this cross sectional study 846 pregnant women were included consecutively from April 2014 to February 2016. Clinical and sociodemographic were collected using structured questionnaire and blood was collected for laboratory analysis of Hepatitis E virus using IgG and IgM HEV ELISA. The data were analyzed using SPSS software version 21.0. Association with variables with the risk factors was determined using bivariate and multivariate analysis. The overall sero‐prevalence of hepatitis E virus using anti‐HEV IgG and anti‐HEV IgM antibody among pregnant women were 367 (43.4%). From this 359 (42.4%) and 8 (0.9%) were tested positive for anti‐HEV IgG and anti‐HEV IgM antibody, respectively. Then finally age, rural residence, not washing after toilet use and lack of prevention aspects to minimize contamination were associated with HEV infection. This study shows the significant public health impact of HEV during pregnancy in low income countries.

Na Yang , Jin Feng , Taicheng Zhou , Zhuoran Li , Zhengyu Chen , Kaihua Ming , Guangtie Liang , Xiu‐xia Lei , Bang‐Lao Xu

Serum hepatitis B surface antigen (HBsAg) level has been developed as an important marker to predict treatment outcome recent years. The authors aimed to identify the correlation between quantitative HBsAg and hepatitis B virus (HBV) DNA level in chronic hepatitis B (CHB) patients and explore whether quantitative HBsAg can be used as a surrogate marker of serum HBV DNA for CHB patients. One hundred seventy‐three patients were included in this study. Patients were divided into two groups: Hepatitis B e antigen (HBeAg) positive and negative patients. There was a positive correlation between quantitative HBsAg and HBV DNA level in HBeAg positive patients (r = 0.509, P …

Kemin Liu , Mingyu Xie , Xiaomei Lu , Hui Yu , Hui Wang , Yunjian Xu , Qingqing Yang , Yongping Lin , Qiang Ma

The mechanism of the coexistence of HBsAg and anti‐HBs is still unclear. This study investigated the variations located in the major hydrophilic region (MHR) of HBV from individuals with simultaneous HBsAg and anti‐HBs in Guangzhou, southern China. Among 4455 samples analyzed, 179 (4.02%) patients were discovered with both HBsAg and anti‐HBs. Finally, 44 individuals with concurrent HBsAg and anti‐HBs (defined as group I), and 88 patients with positive HBsAg and negative anti‐HBs (defined as group II, served as control) were enrolled in the study. The number of residue changes per 100 residues within the MHR in group I was 7.1 times more frequent than group II (P …

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).

Abstract Background Information on the incubation period and period of infectiousness or shedding of infectious pathogens is critical for management and control of communicable diseases in schools and other childcare settings. Methods We performed a systematic literature review (Pubmed and Embase) to identify and critically appraise all relevant published articles using incubation, infectiousness or shedding, and exclusion period as parameters for the search. No language, time, geographical or study design restrictions were applied. Results A total of 112 articles met the eligibility criteria. A relatively large number were retrieved for gastrointestinal diseases and influenza or respiratory syncytial virus, but there were few or no studies for other diseases. Although a considerable number of publications reported the incubation and shedding periods, there was less evidence concerning the period of infectiousness. On average, five days of exclusion is considered for measles, mumps, rubella, varicella and pertussis. For other diseases, such as most cases of meningococcal disease, hepatitis A and influenza exclusion is considered as long as severe symptoms persist. However, these results are based on a diverse range of study characteristics, including age, treatment, vaccination, underlying diseases, diagnostic tools, viral load, study design and definitions, making statistical analysis difficult. Conclusions Despite inconsistent definitions for key variables and the diversity of studies reviewed, published data provide sufficient quantitative estimates to inform decision making in schools and other childcare settings. The results can be used as a reference when deciding about the exclusion of a child with a communicable disease that both prevents exposure and avoids unnecessary absenteeism.

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.

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 (

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.

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 

Irene Campolmi, Michele Spinicci, David Rojo Mayaregua, Herlan Gamboa Barahona, Antonia Mantella, Yunni Lara, Mimmo Roselli, Marianne Strohmeyer, Giampaolo Corti, Francesco Tolari, Joaquín Monasterio Pinckert, Harry R. Dalton and Alessandro Bartoloni

Abstract. In the Bolivian Chaco, south-east of Bolivia, studies conducted over the past three decades reported hepatitis A virus (HAV) and Helicobacter pylori seroprevalences above 90% and 60%, respectively. Hepatitis E virus (HEV) prevalence was previously found to be 6–7% but is probably an underestimate because of the poor sensitivity of the assays used. In November 2013, we conducted a cross-sectional study of 263 healthy volunteers from two rural communities of the Bolivian Chaco, aiming to reassess HAV, HEV, and H. pylori seroprevalence 10–20 years following the previous surveys. Hepatitis A virus seroprevalence was 95%, with universal exposure after the first decade of life; HEV seroprevalence was considerably higher (31–35%) than that previously reported; H. pylori seroprevalence was 59%, with an age-dependent distribution. The high prevalence of these infections suggests that major efforts are still needed to reduce fecal–oral transmission and to improve human health in the Bolivian Chaco.

van Bömmel F, van Bömmel A, Krauel A, et al.

AbstractBackgroundHepatitis B virus (HBV) RNA is a novel serum biomarker that has the potential to predict treatment response in patients with chronic hepatitis B. We explored whether HBV RNA serum levels can predict hepatitis B e antigen (HBeAg) seroconversion in patients treated with peginterferon alfa-2a.MethodsSerum samples from HBeAg-positive patients previously treated with peginterferon alfa-2a in two large randomized controlled trials were retrospectively analyzed. HBV RNA levels were measured using a real-time polymerase chain reaction assay. Ability of individual biomarkers to predict HBeAg seroconversion at 24 weeks post-treatment was evaluated using receiver operating characteristics (ROC) analyses.ResultsThe study included 131 subjects (70% male, 96% Asians, 35% HBV genotypes B and 61% C), 76 treated with peginterferon alfa-2a alone and 55 in combination with LAM. Median HBV RNA levels were significantly lower, at all time points, in patients achieving HBeAg seroconversion. Levels of HBV RNA at treatment weeks 12 and 24 showed good ability to predict HBeAg seroconversion (AUROC scores >0.75, p5.5 log10 copies/mL identified 30% of non-responders at week 12 (negative predictive value >90%).ConclusionSerum HBV RNA is an early predictor of HBeAg seroconversion in patients treated with peginterferon alfa-2a.

Valerie J. Kinchen, Andrea L. Cox, Justin R. Bailey

While licensed vaccines elicit protective antibody responses against a variety of viral infections, an effective vaccine for hepatitis C virus (HCV) has remained elusive. The extraordinary genetic diversity of HCV and the ability of the virus to evade the immune response have hindered vaccine development efforts. However, recent studies have greatly expanded the number of well characterized broadly neutralizing human monoclonal antibodies (bNAbs) against HCV. These bNAbs target relatively conserved HCV epitopes, prevent HCV infection in animal models, and are associated with spontaneous clearance of human HCV infection.

Nevers, Q., Ruiz, I., Ahnou, N., Donati, F., Brillet, R., Softic, L., Chazal, M., Jouvenet, N., Fourati, S., Baudesson, C., Bruscella, P., Gelin, M., Guichou, J.-F., Pawlotsky, J.-M., Ahmed-Belkacem, A.

Despite Flaviviridae viruses display high incidence, morbidity and mortality rates, the development of specific antiviral drugs for each virus is unlikely. Cyclophilins, a family of host peptidyl-prolyl cis/trans isomerase (PPIase), play a pivotal role in the lifecycle of many viruses and therefore represent an attractive target for broad-spectrum antiviral development. We report here the pan-genotypic anti-hepatitis C virus (HCV) activity of a small-molecule cyclophilin inhibitor (SMCypI). Mechanistic and modeling studies revealed that SMCypI bound to cyclophilin A in competition with Cyclosporin A (CsA), inhibited its PPIase activity and disrupted the CypA/NS5A interaction. Resistance selection showed that the lead SMCypI hardly selected amino acid substitutions conferring low-level or no resistance in vitro. Interestingly, the SMCypI selected substitutions D320E and Y321H substitutions, located in the domain II of NS5A protein. These substitutions have been previously associated with low-level resistance to cyclophilin inhibitors such as Alisporivir. Finally, the SMCypI inhibited the replication of other members of the Flaviviridae family with higher EC50 values than HCV. Thus, because of its chemical plasticity and simplicity of synthesis, our new family of SMCypIs represents a promising new class of drugs with a potential for broad-spectrum anti-Flaviviridae activity, as well as an invaluable tool to explore the role of cyclophilins in viral lifecycles.

Letizia Greco , Sara C. Uceda Renteria , Davide Guarneri , Anna Orlandi , Antonella Zoccoli , Susanna Benardon , Marco Cusini , Giovanna Lunghi

Hepatitis E virus (HEV) is a feco‐orally transmitted pathogen and one of the most common cause of acute hepatitis worldwide. Recent studies in developed countries suggested that a direct human‐to‐human contact such as for sexually transmitted diseases may play a significant role in the HEV spread. The aim of this study was to investigate the seroprevalence of HEV and HAV in a group of MSM, including subjects HIV, and Treponema infected, in Milan, Italy. The overall anti HEV IgG seroprevalence in MSM was 10.2% (65/636), instead in the control group the detection rate was 5.2% (15/288) (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.

Abstract Background Hepatitis C virus (HCV) is the most common blood-borne viral infection in the United States. Previously, we used data from the National Health and Nutrition Examination Survey (NHANES) and mortality data from the National Vital Statistics System (NVSS) to estimate the prevalence of HCV antibodies (anti-HCV) and HCV RNA among all U.S. states. However, demographic differences in HCV burden at the state-level have not been systematically described. This analysis quantified the HCV burden stratified by sex and race (and associated disparities) for each U.S. state. Methods Building on our previous method, we used three publicly available data sources to estimate HCV RNA prevalence among noninstitutionalized adults stratified by sex and race group. We used a small-area estimation approach that included direct standardization of NHANES demographic data with logistic regression modeling of HCV-related mortality data as an adjustment factor to estimate the state-level prevalence and total persons with chronic HCV infection for sex and race groups in all U.S. states. Results Nationally, males had an estimated HCV RNA prevalence of 1.56% (95% CI: 1.37–1.84%) and females had a prevalence of 0.75% (95% CI: 0.63–0.96%). Stratified by race, national estimated prevalence of HCV RNA was highest among non-Hispanic black (2.43, 95% CI: 2.10–2.90%), followed by non-Hispanic white (1.05, 95% CI: 0.90–1.27%) and Hispanic/other (0.74, 95% CI: 0.59–1.04%). Males in most jurisdictions (41/51) have an HCV RNA prevalence that is between 1.5 and 2.5 times higher than their female counterparts. Conclusions HCV infection disparities by sex are mostly consistent across the country. However, race differences in HCV infection differ by state and tailored prevention and treatment efforts specific to the local HCV epidemic are needed to reduce race disparities.

Abstract Background Management of chronic hepatitis C (CHC) has significantly accelerated in the last few years. Currently, second generation direct acting antivirals (DAAs) promise clearance of infection in most of patients. Here we present the results of the first analysis carried out on data of Lazio clinical network for DAAs. Methods The study was designed as a multicenter cohort: a) to assess the evolution of treatment during the first 24 months of the activity of the Clinical Network; b) to report overall efficacy of treatments; c) to analyze potential factors associated with lack of virological response at 12 weeks after therapy (SVR12); d) to evaluate the variation of ALT at baseline and 12 weeks after therapy in those who achieved SVR12 in comparison to those who did not. Analyses of efficacy were carried out with multilevel mixed effect logistic regression model. ALT temporal variation was assessed by mixed effect model mixed models with random intercept at patient’s level and random slope at the level of the time; i.e. either before or after therapy. Results Between 30 December 2014 and 31 December 2016 5279 patients started a DAA treatment; of those, 5127 (in 14 clinical centers) had completed the 12-week follow-up. Overall proportion of SVR12 was 93.41% (N = 4780) with no heterogeneity between the 14 clinical centers. Interruption as the consequence of severe side effect was very low (only 23 patients). Unadjusted analysis indicates that proportion of SVR12 significantly changes according to patient’s baseline characteristics, however after adjusting for potential confounders only adherence to current guidelines, stage of liver diseases, gender, transplant and HIV status were independently associated with the response to therapy. Analysis of ALT temporal variation showed that ALT level normalized in most, but not, all patients who achieved SVR12. Conclusion Our study confirmed the extraordinary efficacy of DAAs outside clinical trials. The advantage of DAAs was particularly significant for those patients who were previously considered as difficult-to-treat and did not have treatment options before DAAs era. Intervention based on network of select centers and prioritization of patients according to diseases severity was successful. Further studies are needed to establish whether clearance of HCV after DAAs therapy can arrest or even revert liver fibrosis in non-cirrhotic patients and/or improve life quality and expectancy in those who achieve SVR12 with cirrhosis.

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.

Cahn, Pedro; Sax, Paul E.; Squires, Kathleen; Molina, Jean-Michel; Ratanasuwan, Winai; Rassool, Mohammed; Bloch, Mark; Xu, Xia; Zhou, Yan; Homony, Brenda; Hepler, Deborah; Teppler, Hedy; Hanna, George J.; Nguyen, Bach-Yen; Greaves, Wayne; for the ONCEMRK Study Group

Background: Raltegravir 1200mg (2x600mg tablets) once daily (QD) demonstrated non-inferior efficacy and similar safety to raltegravir 400mg BID at Week 48 of the ONCEMRK trial. Here we report the Week 96 results from this study. Methods: ONCEMRK is a phase 3, multicenter, double-blind, non-inferiority trial comparing raltegravir 1200mg QD to raltegravir 400mg BID in treatment-naïve HIV-1-infected adults. Participants were assigned (2:1) to raltegravir 2x600mg QD or 400mg BID, both with emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) for 96 weeks. Randomization was stratified by screening HIV-1 RNA and hepatitis B/C status. Efficacy was assessed as the proportion of participants with HIV-1 RNA…

Yew, W. W., Chang, K. C., Chan, D. P.

Hepatotoxicity induced by antituberculosis drugs is a serious adverse reaction with significant morbidity and even rarely mortality. This form of toxicity potentially impacts the treatment outcome of tuberculosis in some patients. Confining to first-line antituberculosis drugs, this review addresses whether and how oxidative stress, and more broadly, disturbance in redox homeostasis alongside mitochondrial dysfunction, may contribute to the hepatotoxicity induced by them. Risk factors for such toxicity that have been identified, in addition to genetic factors, principally include old age, malnutrition, alcoholism, chronic hepatitis C and chronic hepatitis B infection, HIV infection and pre-existing liver disease. Importantly, these comorbid conditions are associated with oxidative stress and beyond, per se. Thus, the shared pathogenetic mechanism(s) for liver injury might be in operation, due to disease-drug interaction. Our current ability to predict, prevent, or treat hepatotoxicity (other than removing potentially hepatotoxic drugs) remains limited. More translational research to unravel the pathogenesis, inclusive of the underlying molecular bases, regarding antituberculosis drug-induced hepatotoxicity is needed, and so is clinical research pertaining to the advances in therapy, with antioxidants and beyond. The role of pharmacogenetics in the clinical management of drug-induced hepatotoxicity also likely merits further evaluation.

Yue Feng, Yue-Mei Feng, Songmei Wang, Fang Xu, Xuehui Zhang, Chunyue Zhang, Yuanyuan Jia, Wanru Yang, Xueshan Xia, Jianzhong Yin

by Yue Feng, Yue-Mei Feng, Songmei Wang, Fang Xu, Xuehui Zhang, Chunyue Zhang, Yuanyuan Jia, Wanru Yang, Xueshan Xia, Jianzhong Yin Hepatitis E virus (HEV) infection is relatively high in the southern regions of China. Yunnan, located in southwestern China, has the highest number of ethnic groups. However, HEV infection in the ethnic population is largely unknown. Therefore, we aimed to investigate the seropositive rate, risk factor, and clinical impact of HEV infection in the ethnic groups of Yunnan. We recruited 1912 individuals from four minority groups in three prefectures of Yunnan province. Epidemiological records on potential risk factors for exposure to HEV and blood biochemical index were analyzed. All the serum samples were tested for anti-HEV IgM/IgG by enzyme-linked immunosorbent assay, and the IgM-positive samples were subjected to nested reverse transcription-PCR to detect HEV RNA. Overall, 1273 individuals (66.58%) were positive for anti-HEV IgG, 16 (0.84%) for anti-HEV IgM, and 64 (3.35%) for anti-HEV IgG and IgM both; none of them had detectable HEV RNA. Multivariate analysis revealed a strong statistical association between ethnic origin and HEV IgG seroprevalence. Anti-HEV IgG reactivity in the Hani ethnic (82.3%; 401/487) population was higher than that in the Naxi (71.9%, 340/473), Bulang (65.1%; 302/464), and Wa (60.2%; 294/488) ethnic populations (p < 0.0001). Older age and male sex were independently associated with the risk of past HEV infection. Moreover, anti-HEV IgG-positive individuals showed significantly higher levels of total and direct bilirubin and alanine amino transferase but significantly lower levels of globulin and low-density lipoprotein, than the respective levels in anti-HEV IgG-negative individuals. Thus, the seroprevalence of HEV infection is high in the ethnic populations of Yunnan, China. It is therefore necessary to increase the surveillance of specific risk groups and raise awareness about the possible infectious diseases to help limit the HEV transmission here.

Abstract Introduction We investigated 170 HBsAg-positive immigrants living in Italy for 1–7 years to ascertain whether they may have become infected in the host country. Methods Of 2032 adult immigrants interviewed, 1727 (85%) voluntarily adhered to a screening program for bloodborne or sexually transmitted infections. HBsAg was detected in 170 (9.8%) screened immigrants who completed the diagnostic, clinical and therapeutic process at the nearest clinic of infectious diseases. HBV molecular biology was performed applying a homemade technology. Phylogenetic signal of the datasets was obtained by a likelihood-mapping analysis using TreePuzzle. Results Of the 170 HBsAg-positive immigrants, 133 were inactive carriers, 29 had chronic hepatitis and 8 compensated cirrhosis. HBV genotype was identified in 109 of the 113 HBV-DNA-positive immigrants and HBV-genotype-E predominated (68.9%). Of these 109, 6 (5.5%) subjects showed an HBV genotype absent or extremely rare in their native country: HBV-genotype-E in three from Eastern Europe and in one from Sri Lanka, possibly acquired from other immigrants from sub-Saharan countries, HBV-genotype-D1 in one from Burkina Faso and one from Senegal, possibly acquired in Italy. Conclusion The data suggest that immigrants may acquire HBV infection in Italy and, therefore, HBV vaccination programs should be extended to all immigrants living in Italy.

Mohsen Gadallah , Sahar Kandil , Amira Mohsen

Abstract Objectives To examine the association between hepatitis C virus (HCV) infection, cardiovascular risk factors and cerebro‐cardiovascular (CCV) disease. Methods The source of data was the Egypt Health Issues Survey conducted in 2015. Participants were 11 256 individuals with complete HCV testing, age 25–59 years. Data on demographics, cardiovascular risk factors, CCV disease (myocardial infarction and/or cerebral stroke) and HCV infection were retrieved. Descriptive, bivariate, multivariable logistic regression and sensitivity analyses were performed to determine the independent association of past HCV exposure or chronic infection with diabetes, hypertension and CCV disease. Results 3.9% of participants were antibody positive/RNA negative and considered to have past HCV exposure; 7.9% had detectable HCV‐RNA and were considered to have chronic infection. Participants with negative antibodies and no history of liver disease (n = 9928) were the control group. In addition to the previously known risk factors, multivariable analyses revealed that diabetes was independently associated with past HCV exposure (OR = 1.71, 95% CI: 1.27–2.32) and HCV chronic infection (OR = 1.56, 95% CI: 1.23–1.97), whereas CCV disease was independently associated with past exposure (OR = 2.69, 95% CI: 1.62–4.46) and not with chronic infection. No evidence of an association between hypertension and either HCV status was found. Conclusion The association of both past HCV exposure and chronic infection with diabetes and that of past HCV exposure with CCV disease may suggest targeting HCV‐positive reactors for preventive and curative programmes addressing extrahepatic complications.

Abstract Background Direct-acting anti-viral agents have improved the treatment of chronic hepatitis C virus (HCV) infection, but this treatment is challenging for patients using co-medications because of potential drug–drug interactions. This study aimed to examine the comorbidities and co-medications of Japanese chronic HCV patients by age group, compared with a non-HCV patient population. Methods This was a retrospective observational study using a hospital-based medical claims database. We extracted data of patients with chronic HCV aged ≥18 years, and age-, sex-, and hospital-matched patients without HCV, for the period from January 2015 to November 2016, and then examined chronic comorbidities, long-term co-medications, and medications prescribed at least once during the study period. Results We analysed data from 128,967 chronic HCV patients and 515,868 non-HCV patients. The median age was 70 years, and 51.0% of patients were male. More chronic HCV patients than non-HCV patients (70.5% vs. 47.1%) had at least one comorbidity, and older patients had more comorbidities than younger patients. The most common comorbidities in chronic HCV patients were diseases of oesophagus, stomach and duodenum (41.7%), followed by hypertensive diseases (31.4%). Chronic HCV patients used co-medications more commonly than non-HCV patients, and older patients used more co-medications. The most common long-term co-medications in chronic HCV patients were proton pump inhibitors (14.0%), which were prescribed to 31.9% of chronic HCV patients at least once during the study period. Conclusions Patients with chronic HCV in Japan had more comorbidities than patients without chronic HCV regardless of age. Particularly older patients, who constitute the majority of the HCV patient population in Japan, commonly had multiple comorbidities and used co-medications. To optimise HCV treatment, physicians need to know the exact medication profiles of patients and take appropriate action to manage drug–drug interactions.

Lene H. Harritshøj, Zahra P. Theilgaard, Ebba Mannheimer, Sofie E. Midgley, Mercy Chiduo, Henrik Ullum, Terese L. Katzenstein

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.

Ghobad Moradi , Mohammad‐Mehdi Gouya , Fatemeh Azimizan Zavareh , Amjad Mohamadi Bolbanabad , Sonia Darvishi , Mohammad Reza Aghasadeghi , Mahmood Nabavi , Ramin Alasvand , Mehrzad Tashakorian , Bijan Nouri , Khaled Rahmani , Leila Molaei

Summary Objectives To provide more accurate estimates of the prevalence of Hepatitis B (HBV) and Hepatitis C (HCV) and their contributing factors among prisoners in Iran. Methods Cross‐sectional study of 6200 Iranian prisoners in 2015. Data were collected through questionnaires and interviews. HBV infection and HCV exposure status of the participants was determined by HBsAg and HCV antibodies blood tests using enzyme‐linked immunosorbent assay (ELISA). Data were analysed in STATA‐12. Result Prevalence of HCV exposure was 9.48% (95% CI: 8.73–10.27), and prevalence of HBV was 2.48% (95% CI: 2.07–2.89) in the general prison population. In multivariate analysis, the most important risk factor for HBV was a history of drug use in lifetime (adjusted odds ratio, AOR: 1.8, 95% CI: 1.17–3.02). The main risk factors for HCV exposure were a history of drug use in lifetime (AOR: 4.08, CI: 2.56–6.27), age over 30 (AOR: 2.68, CI: 2.01–3.56), and having tattoos (AOR = 1.67, CI: 1.35–2.07). Conclusion Although vaccination is used to control HBV among prisoners, prevalence of HCV exposure is alarming in the prison population of Iran, especially among people who inject drugs. Eliminating viral hepatitis in Iran by 2030 requires a national commitment and rapid measures for targeting this high‐risk group. Given the increased efficiency of HCV treatment in recent years, prisons provide an opportunity to access patients for treatment.

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…

Abstract Direct-acting antivirals (DAAs) for the treatment of HCV have dramatically increased the rate of sustained virological response: patients not achieving sustained virological response represent a challenge and rates of late recurrent viremia are very low. We describe here the first case of a very late HCV relapse, following an atypical kinetics (characterized by a spontaneous but transient HCV clearance after an early virological relapse), in a HIV co-infected patient treated with DAAs. Optimal adherence to the therapy was well documented and a phylogenetic analysis ruled out a possible reinfection from a different HCV strain. In conclusion, our case underlines the importance of a long follow-up (> 48 weeks) after DAAs therapies in HCV–HIV co-infected patients who might benefit the most from a very rigorous virological surveillance.

Abstract Purpose To analyse safety and efficacy of treatment based on ombitasvir/paritaprevir/ritonavir/dasabuvir plus ribavirin in the sub-group of GT1 patients older than 65 years. Methods We collected data extracted from the ABACUS compassionate-use nationwide Italian programme, in patients with cirrhosis due to hepatitis C virus (HCV) Genotype-1 (GT1) or 4 and at high risk of decompensation. GT1-HCV-infected patients received once-daily ombitasvir/paritaprevir, with the pharmacokinetic enhancer ritonavir (25/150/100 mg) and twice-daily dasabuvir (250 mg) plus Ribavirin (RBV) (OBV/PTV/r + DSV + RBV) for 12 (GT1b) or 24 (GT1a) weeks. Endpoints were to evaluate safety and efficacy, the latter defined as HCV RNA negative 12 weeks after the end of treatment (SVR12). Results Patients who suffered any adverse event (AE) were 74/240 (30.8%); 13/240 (5.4%) discontinued the treatment. A multivariate analysis found albumin

Abstract Background Prior to clinical trials of new TB drugs or therapeutic vaccines, it is necessary to develop monitoring tools to predict treatment outcomes in TB patients. Urine interferon gamma inducible protein 10 (IP-10) is a potential biomarker of treatment response in chronic hepatitis C virus infection and lung diseases, including tuberculosis. In this study, we assessed IP-10 levels in urine samples from patients with active TB at diagnosis, during treatment, and at completion, and compared these with levels in serum samples collected in parallel from matched patients to determine whether urine IP-10 can be used to monitor treatment response in patients with active TB. Methods IP-10 was measured using enzyme-linked immunosorbent assays in urine and serum samples collected concomitantly from 23 patients with active TB and 21 healthy adults (44 total individuals). The Mann-Whitney U test and Wilcoxon matched-pairs signed rank test were used for comparisons among healthy controls and patients at three time points, and LOESS regression was used for longitudinal data. Results The levels of IP-10 in urine increased significantly after 2 months of treatment (P = 0.0163), but decreased by the completion of treatment (P = 0.0035). Serum IP-10 levels exhibited a similar trend, but did not increase significantly after 2 months of treatment in patients with active TB. Conclusions Unstimulated IP-10 in urine can be used as a biomarker to monitor treatment response in patients with active pulmonary TB.

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.

Abstract A 26-year-old HIV-negative male from Ghana was treated for cervical, intrathoracic and abdominal lymph node tuberculosis (TB) and tuberculous hepatitis. Penetration of the thoracic trachea by a mediastinal lymph node had caused bronchomucosal TB. Sputum culture grew M. africanum, sensitive to all first-line antituberculous drugs. Four weeks after the beginning of directly observed treatment with isoniazid, rifampin, pyrazinamide and ethambutol, the right cervical lymph node increased in size, liquefied and caused a spontaneous fistula. A biopsy of the necrotized lymph node revealed rare acid-fast bacilli with a positive PCR for Mycobacterium tuberculosis complex. After debridement, vacuum-assisted closure therapy was performed for 6 weeks. Five months after the beginning of antituberculous therapy, a second paradoxical reaction occurred, with painful swelling of two contralateral supraclavicular lymph nodes. Extirpation of one node yielded a positive PCR for M. tuberculosis complex; the culture was negative. Antituberculous treatment was continued, and additional treatment with oral prednisolone 20 mg daily for 1 month tapering over 10 weeks was introduced, resulting in a decrease in lymphadenopathy. Antituberculous treatment was continued for a total of 9 months. The outcome was favorable, no further lymphadenopathy occurred over the following 6 months.

Abstract Purpose Sexually transmitted infections (STIs) occur frequently in risk populations. Hereby, the role of screening-programmes remains controversial. Our study aimed to determine the prevalence of STI infections in HIV-positive men-who-have-sex-with-men (MSM). Methods We enrolled asymptomatic, HIV-MSM in a prospective cross-sectional study from February to August 2016 at seven German HIV-centres. All subjects were screened for Treponema-pallidum (TP) and hepatitis-B/C-infection. HIV RNA and screening for oral, rectal and urethral colonisation by Chlamydia-trachomatis (CT) and/or Neisseria-gonorrhoeae (NG) was performed. All subjects were asked to complete a sexual-risk-behaviour-questionnaire. Results In total, 296 subjects with a median age of 43.2 (36.2–49.5) years were enrolled; 99.3% were on ART for 5.5 (2.3–11.2) years. HIV RNA was 

Abstract Purpose YKL-40 is a chitinase-like protein expressed in multiple tissues including liver and is reported as a fibrosis marker. This study aimed to determine whether YKL-40 could serve as a diagnostic marker for the assessment of liver fibrosis in chronic hepatitis B patients with normal and mildly elevated ALT. Methods Six hundred and eighty-five patients with chronic hepatitis B infection were enrolled in this study from October 2013 to March 2016. All patients underwent liver biopsy and then staged based on Ishak histological system. Serum YKL-40 levels were measured by Human Magnetic Luminex Assays. Results Among chronic hepatitis B patients with normal and mildly elevated ALT, almost more than 30% of patients have significant liver fibrosis. Serum YKL-40 levels increased significantly in parallel with the progression of fibrosis in patients with ALT less than two times the upper limit of normal range (P 

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.

Ahmed Abdelbasit

American Journal of Respiratory and Critical Care Medicine, Volume 197, Issue 11, Page 1492-1496, June 1, 2018.

Patrick Miailhes, Kerstin Hartig-Lavie, Victor Virlogeux, Pierre Pradat, Mamadou Diakite, Anne-Claire Uhres, Fabien Zoulim, Marie-Nathalie Sarda

Mixed cryoglobulinemia (MC) is found in 40-60% of patients with chronic hepatitis C virus (HCV) infection. Direct-acting antiviral (DAA) regimens considerably improve clinical outcome of HCV infection with sustained virological response rates (SVR) above 90%. We aimed to evaluate the impact of DAA therapy on cryoglobulin clearance and on MC related symptoms in patients with HCV-associated MC.

Abstract Background Female gender and favorable IFNL3 genotypes are the primary independent predictors of spontaneous clearance of HCV infection. However, chronic hepatitis C infection occurs in numerous women carrying favorable IFNL3 genotypes, indicating that other host and/or virological factors contribute to the prognosis of infection. Methods A cohort of 137 anti-HCV-positive female Han Chinese cases, including 64 chronic HCV carriers and 73 HCV spontaneous resolvers, was recruited in the study. 111 SNPs in 23 genes encoding HCV co-receptors, transcription factors, Toll-like receptors, co-stimulating molecules, and cytokines were selected for SNP analysis. Results After comparison of genotypes and allelotype frequencies of 111 SNPs in 23 genes in the primary cohort, the SNPs rs9826 (P = 0.024 for CC/TT/CT; P = 0.015 for C allele/T allele) and rs1521177 (P = 0.017 for GG/TT/GT; P = 0.006 for G allele/T allele) in the RORC gene were significantly associated with spontaneous HCV clearance. In the sub-cohort carrying favorable IFNL3 genotypes (rs12979860CC, rs8099917 TT, rs12980275 AA), rs1521177 (genotype: P = 0.040; allelotype: P = 0.021) remained significantly associated with spontaneous HCV clearance. Importantly, the most common RORC haplotype rs9826-T/rs1521177-T was presented at significantly different frequencies in resolvers and carriers in both the primary cohort (P = 0.0027) and the IFNL3 favorable sub-cohort (P = 0.0117). Conclusions This study indicates that genetic polymorphisms in human Th17-related RORC gene are associated with different natural prognosis of HCV infection. The RORC haplotype, rs9826-T/rs1521177-T, was favorable for spontaneous clearance of HCV infection.

Lidofsky A, Holmes J, Feeney E, et al.

AbstractBackground & aimsCoinfection with human immunodeficiency virus (HIV) accelerates hepatitis C virus (HCV)-related liver fibrosis. Macrophages are triggered during both viral infections and are critical in liver inflammation/fibrogenesis. Liver fibrosis strongly associates with serum soluble (s)CD163 (macrophage activation marker); comprehensive evaluation in HIV/HCV coinfection is lacking.MethodsWe retrospectively analyzed sCD163 (ELISA) and hepatic CD163 (immunofluorescent CD163/CD68 costaining) in HIV/HCV, HCV or HIV, pre-/post-antiviral therapy.ResultssCD163 was significantly higher in HIV/HCV compared to either monoinfection, and decreased following successful antiviral therapy, although did not fully normalize. In HIV/HCV, sCD163 associated with necroinflammation, Ishak fibrosis scores and non-invasive fibrosis scores. We observed a novel trend whereby sCD163 levels progressively increase with increasing Ishak fibrosis score, peaking at stage 4, above which levels plateaued. Periportal CD163+ macrophage frequency was also higher with increasing fibrosis stage. When stratified by fibrosis stage, sCD163 levels were higher in HIV/HCV than HCV but only in individuals with mild-moderate fibrosis.ConclusionsIn HIV/HCV, increasing sCD163 levels accompanied periportal CD163+ macrophage enrichment in mild-moderate fibrosis, but not in established cirrhosis, suggesting that sCD163 is a dynamic biomarker of fibrogenesis rather than accumulated fibrosis. Our findings implicate HIV-related macrophage activation in accelerated fibrosis progression in HIV/HCV coinfection.

Shereen AbdelAlem , MohamedSaid , IsmailAnwar , ZeinabAbdellatif , TamerElbaz , RashaEletreby , MahmoudAbouElKhair , MagdyEl‐Serafy , SherifMogawer , MonaEl‐Amir , MostafaEl‐Shazly , AdelHosny , AymanYosry

Progression of recurrent hepatitis C is accelerated in liver transplant (LT) recipients. Direct‐acting antivirals (DAAs) have recently emerged as a promising therapeutic regimen for the treatment of hepatitis C virus infection. Rates of sustained virological response (SVR) have drastically improved since the introduction of DAAs. The aim is to elucidate the changes in liver stiffness measurement (LSM) by transient elastography (TE) as well as acoustic radiation force impulse (ARFI) elastography and fibrosis scores after DAA treatment in LT recipients with hepatitis C virus recurrence. A single‐center, prospective study including 58 LT recipients with hepatitis C recurrence who received different sofosbuvir‐based treatment regimens. Transient elastography and ARFI elastography values were recorded as well as fibrosis 4 score (FIB‐4) and aspartate aminotransferase‐to‐platelet ratio index were calculated at baseline and SVR at week 24 (SVR24). The outcome was improvement in LSM and at least a 20% decrease in LSM at SVR24 compared with baseline. The sustained virological response was 98.1%. There was improvement of platelet counts, alanine aminotransferase, and aspartate aminotransferase, which in turn caused improvement in fibrosis scores at SVR24. LSM by TE and ARFI elastography decreased from the baseline median value of 6.3 kPa (interquartile range [IQR]; 4.6 to 8.8 kPa) and 1.28 m/s (IQR; 1.07 to 1.53 m/s) to an SVR24 median value of 6.2 kPa (IQR; 4.85 to 8.9 kPa) and 1.12 (IQR; 0.97 to 1.30 m/s), respectively. Logistic regression analysis showed that baseline viral load was the only significant predictor of improvement in LS after DAA therapy at SVR24. Sofosbuvir‐based treatment resulted in an early improvement in parameters of liver fibrosis in post‐LT patients with hepatitis C recurrence.

FangXu MD , ChongWang MD , XiaojuShi MD , JieHou MD , XiaolinGuo MD , PujunGao MD

Most cases of hepatitis B virus–associated glomerulonephritis (HBV‐GN) occur in children and present with serum HBsAg positivity. Few studies have investigated adult patients with HBV‐GN who are serum HBsAg‐negative. This study aimed to determine the clinical and pathological features of adult patients with HBV‐GN who are serum hepatitis B surface antigen (HBsAg)‐negative. Clinical, pathologic, and laboratory findings were collected and analyzed in a cohort of 27 adult patients with HBV‐GN who were serum HBsAg‐negative upon diagnosis. The study population included mostly men of middle age (40‐59 years). Clinically, patients presented with nephrotic syndrome. Serum immunoglobulin G levels were low, whereas serum immunoglobulin M, immunoglobulin A, complement C3 (C3), and complement C4 (C4) levels as well as liver and renal function tests were normal in most or all patients. Among the 27 patients, 21 tested positive for HBV antibodies. Membranous nephropathy was the dominant pathological form on kidney biopsy. In addition, only a few patients showed a “full house” staining pattern and renal immune deposit of complement C1q (C1q). Serum HBsAg‐negative HBV‐GN may represent a late stage of HBV infection. We recommend routine testing for HBV markers on renal biopsy in regions where HBV is prevalent, even when tests for serum HBV markers are negative.

DianjunCaoPhD , Yan‐YanNiPhD , MichelleWalkerMS , Yao‐WeiHuangPhD , Xiang‐JinMengMD, PhD

Hepatitis E virus (HEV), a member of the family Hepeviridae, causes both acute and chronic viral hepatitis. We have previously demonstrated that the stem‐loop structure in the junction region (JR) of HEV genome plays a critical role in HEV replication. However, the function of the sequence bordering the JR, including the 3′ terminus of open reading frame (ORF1), in HEV replication is unknown. In this study, a panel of HEV Renilla luciferase (Rluc) replicons containing various deletions at 5′ or 3′ termini of the JR was constructed to determine the effect of the deletions on HEV replication in Huh7 human liver cells. We showed that even a single nucleotide deletion at the 5′ terminus of the JR abolished HEV replication, whereas deletions at the 3′ terminus of the JR also decreased virus replication efficiency. Furthermore, we also constructed firefly luciferase and Rluc dual‐reporter HEV replicons containing the 3′ terminal ORF1 of various lengths and the JR inserted upstream of the Rluc reporter. A higher level of HEV replication was observed in cells transfected with replicons containing the 3′ terminal ORF1 than that of the JR only replicon. We also showed that the ORF3 noncoding sequence along with the JR promoted a higher level of translation activity than that promoted by JR and the ORF2 noncoding sequence.

Jean De DieuLongo , Ralph‐SydneyMboumba Bouassa , MarcelMbeko Simaleko , AndréKouabosso , Christian DiamantMossoro‐Kpinde , LemanRobin , LauraCharmant , GérardGrésenguet , LaurentBélec

Adult outpatients attending the main sexually transmitted infection clinic of Bangui, Central African Republic, were prospectively subjected to a multiplex rapid diagnostic test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). In group I (n = 208) of patients already followed for HIV, 6 (2.9%) were unexpectedly negative, thus corresponding to false positive for HIV by the national HIV algorithm; hepatitis B surface antigen and HCV positivities were high (18.7% and 4.3%, respectively). In group II (n = 71) of patients with unknown HIV status, at least 1 chronic viral disease was diagnosed in 26 (36.6%) patients, including 5 (7.1%) HIV, 17 (23.9%) HBV, and 3 (4.2%) HCV infections.

Abstract Background Blood transfusion is associated with several risks particularly exposure to blood transfusion-transmissible infections (TTI), including: Hepatitis B virus (HBV), Hepatitis C virus (HCV), Human immunodeficiency virus (HIV) and Syphilis, among others. The threat posed by these blood-borne pathogens is disproportionately high in Sub-Saharan Africa (SSA). This fact underscores the need for continuous surveillance of TTIs in the region. Therefore, the study objectives were to evaluate the prevalence of TTIs and donor characteristics associated with positivity for TTIs at the National Blood Transfusion Center (NBTC) in Asmara, Eritrea. Methods A retrospective analysis of blood donors’ records covering the period from January 2010 to December 2016 was undertaken. The records were analyzed to evaluate the annualised cumulative prevalence of TTIs. Chi-square test (χ2) or Fisher’s exact test was used to evaluate the relationship between serological positivity and particular donor characteristics. Logistic regression was fitted to identify factors associated with cumulative TTIs positivity. A P-value