Shiyi Zhou, Li Ren, Xueshan Xia, Zhijiang Miao, Fen Huang, Yunlong Li, Mei Zhu, Zhenrong Xie, Yu Xu, Yuan Qian, Qiuwei Pan, Kunhua Wang

BACKGROUND & AIMS: Hepatitis E virus (HEV) infection in immunocompromised patients often results in distinct outcome, compared to the infection in general population. This study aimed to investigate the prevalence, potential risk factors and clinical features of HEV infection among HIV patients treated with antiretroviral therapy (ART) in Yunnan province, China. METHODS: A total of 770 HIV‐infected patients between May 2015 and February 2016 were enrolled in Yunnan, China. All patients received ART. All plasma samples were tested for anti‐HEV IgG, anti‐HEV IgM antibodies using ELISA kits and HEV RNA by real‐time qRT‐PCR. Association between anti‐HEV antibody positivity and demographic, clinical and laboratory measures was assessed in univariate and multivariate logistic regression models. RESULTS: Of the 770 HIV‐infected patients, 342 patients (44.42%) were anti‐HEV IgG antibody positive and 6 patients (0.78%) were anti‐HEV IgM antibody positive. None of the patients was HEV RNA positive, as tested in our assays. We found that age, gender, CD4 cell count, WHO stage, marital status and total cholesterol levels were associated with HEV infection. CONCLUSIONS: We report a high seroprevalence rate and several potential risk factors of HEV infection in a large HIV cohort from Yunnan province in China. Further research on identification of the circulating HEV strains and the clinical outcome of this patient population is required. This article is protected by copyright. All rights reserved …

Hend Ibrahim Shousha, Rasha Ahmed Abdelaziz, Sherief Musa Azab, Marwa Khairy, Shahira Ahmed Afifi, Mai Ismael Mehrez, Mohamed Ali Eshra, Ayman Yosry Abdelrahim

Background: Direct Acting Agents (DAAs) have high cure rate but still lack the knowledge of their effect on hepatic steatosis in chronic hepatitis C (CHC). Controlled Attenuation Parameter (CAP), evaluated with transient elastography, could help in assessment of steatosis grades. We aim to evaluate the effect of DAAs on BMI and steatosis in CHC using CAP. Patients and methods: This cohort study included 155 CHC Egyptian patients divided into three groups according to the DAAs regimens. All patients were subjected to pre‐treatment and 3‐months post‐treatment evaluation including BMI, laboratory workup and liver stiffness measurement with simultaneous CAP determination using the FibroScan(®) M probe. Results: Patients mean age was 45.78 ± 11.6 years, 60.6% were females, mean BMI 26.63 ± 2.75 and 18.1% were cirrhotic. Baseline assessment revealed no steatosis in 43.9%, 32.9% had mild‐moderate steatosis and 23.2% had severe steatosis. The overall sustained virological response 12 was 93.6%. Follow‐up revealed stationary steatosis in 56.7% of patients and regression in 21.3%. Mean pre‐treatment CAP were significantly lower in responders 244.9 ± 62.4dB/m vs non‐responders; 300 ± 28.4dB/m (p = 0.04). ROC curve delineated 273dB/m as best cutoff for detection of responders with an AUC of 0.801, sensitivity 68.2%, and specificity 100%. BMI significantly increased after treatment (p= 0.004) particularly in patients with worsened steatosis (p = 0.001). Steatosis significantly correlated with BMI (r = 0.3, p value = …

To the Editor: In the review article by Diehl and Day (Nov. 23 issue), about the cause, pathogenesis, and treatment of nonalcoholic steatohepatitis, the authors did not mention liraglutide (a glucagon-like peptide 1 analogue) as a therapy in Table 2. Armstrong et al. describe a phase 2 study of the……

Quercia, Romina; Perno, Carlo-Federico; Koteff, Justin; Moore, Katy; McCoig, Cynthia; St. Clair, Marty; Kuritzkes, Daniel

Innovation in medicine is a dynamic, complex, and continuous process that cannot be isolated to a single moment in time. Anniversaries offer opportunities to commemorate crucial discoveries of modern medicine, such as penicillin (1928), polio vaccination (inactivated, 1955; oral, 1961), the surface antigen of the hepatitis B virus (1967), monoclonal antibodies (1975), and the first HIV antiretroviral drugs (zidovudine, 1987). The advent of antiretroviral drugs has had a profound effect on the progress of the epidemiology of HIV infection, transforming a terminal, irreversible disease that caused a global health crisis into a treatable but chronic disease. This result has been driven by the success of antiretroviral drug combinations that include nucleoside reverse transcriptase inhibitors such as lamivudine. Lamivudine, an L-enantiomeric analogue of cytosine, potently affects HIV replication by inhibiting viral reverse transcriptase enzymes at concentrations without toxicity against human polymerases. Although lamivudine was approved more than 2 decades ago, it remains a key component of first-line therapy for HIV because of its virological efficacy and ability to be partnered with other antiretroviral agents in traditional and novel combination therapies. The prominence of lamivudine in HIV therapy is highlighted by its incorporation in recent innovative treatment strategies, such as single-tablet regimens that address challenges associated with regimen complexity and treatment adherence and 2-drug regimens being developed to mitigate cumulative drug exposure and toxicities. This review summarizes how the pharmacologic and virologic properties of lamivudine have solidified its role in contemporary HIV therapy and continue to support its use in emerging therapies. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Correspondence and reprint requests to: Romina Quercia, ViiV Healthcare, CN12, 980 Great West Road, Brentford, Middlesex, UK TW8 9GS, Phone: +44 (0)20 8380 6695, Email: romina.p.quercia@viivhealthcare.com Conflicts of interest and source of funding: RQ, JK, KM, CM, MSC are employees of ViiV Healthcare and hold stock in GlaxoSmithKline. C-FP is a consultant to and has received honoraria and/or grant support from Gilead, InnoVirVax, Janssen, Merck, Bristol Myers Squibb, and ViiV Healthcare. DK is a consultant to and has received honoraria from Bionor, Gilead, GlaxoSmithKline, InnoVirVax, Janssen, Merck, and ViiV Healthcare; he has received grant support and speaking honoraria from Gilead, Merck, and ViiV Healthcare. Funding for this work was provided by ViiV Healthcare. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Ahmed Cordie, Ahmed Salama, Marwa El‐Sharkawy, Saeed M. El‐Nahaas, Marwa Khairy, Aisha Elsharkawy, Mohamed Hassany, Gamal Esmat

Background: Assessment of hepatic fibrosis in chronic hepatitis C virus patients by liver biopsy is not widely accepted despite its accuracy, being invasive, carrying complications and adding cost. This paved the way to development and use of non‐invasive markers of fibrosis in diagnosis of hepatic fibrosis. Aim: Evaluating the efficiency of Fib‐4, Egy‐score, Aspartate‐to‐platelet ratio index (APRI) and Göteborg University Cirrhosis Index (GUCI) in comparison to liver biopsy, in the assessment of hepatic fibrosis in chronic hepatitis C patients Methods: Cross sectional study including 200 chronic HCV patients were divided into two groups according to stage of fibrosis (Metavir score) into non‐significant fibrosis (0.48, Egy‐score >0.73 and GUCI >0.57 significantly predict significant fibrosis (p …

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.

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.

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 …

Mother-to-child transmission of hepatitis B virus (HBV) accounts for the majority of cases of chronic HBV infection, a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Without immunization, 30 to 42% of the infants born to HBV-infected mothers, depending on the maternal status for……

Lamoury F, Bajis S, Hajarizadeh B, et al.

AbstractPoint-of-care hepatitis C virus (HCV) RNA testing is advantageous enabling diagnosis of active infection in a single visit. This study evaluated the sensitivity and specificity of the Xpert® HCV Viral Load Fingerstick assay (Xpert HCV VL FS) for HCV RNA detection (finger-stick) and the Xpert® HCV Viral Load assay (plasma) compared with the Abbott RealTime HCV Viral Load assay by venepuncture. Plasma and finger-stick capillary whole-blood samples were collected from participants in an observational cohort in Australia. Of 223 participants enrolled, HCV RNA was detected in 40% of participants (85 of 210) with available Xpert® HCV Viral Load testing. Participants receiving HCV therapy were excluded from subsequent analyses (n=16). Sensitivity of the Xpert® HCV Viral Load assay for HCV RNA quantification in plasma collected by venepuncture was 100.0% (95% CI 96.9–100.0) and specificity was 100.0% (95% CI 94.4–100.0). Sensitivity of the Xpert® HCV VL FS assay for HCV RNA quantification in samples collected by finger-stick was 100.0% (95% CI 93.9–100.0) and specificity was 100.0% (95% CI 96.6–100.0). The Xpert® HCV VL FS test can accurately detect active infection from a finger-stick sample in one hour allowing single-visit HCV diagnosis.

Cooper C.

HCVpoint of carenucleic acidsscreening…

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.

Strouvelle V, Braun D, Vongrad V, et al.

AbstractPegylated interferon-alpha (pIFN-α) is suggested to lower HIV-1 DNA load in antiretroviral therapy (ART) treated patients. We studied the kinetics of total HIV-1 DNA levels in 40 HIV-1/hepatitis C (HCV) coinfected patients, treated with pIFN-α for HCV and categorized into three groups according to start of ART: Chronic HIV-1 infection (n=22), acute HIV-1 infection (n=8), no-ART (n=10). Total HIV-1 DNA levels were quantified in 247 PBMC samples and remained stable before, during, and after pIFN-α treatment in all three groups. Our study-results question the benefit of pIFN-α as an immunotherapeutic agent for reducing the HIV-1 reservoir.

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……

A. Sonpar, K. Brown, J. Chen, D. Megran, M. Sabo, C. Cervera, S. Girgis, D. Kabbani

Yibeltal Assefa, Peter S Hill, Owain D Williams

Fritz M, Berger B, Schemmerer M, et al.

AbstractThere is growing evidence that hepatitis E virus (HEV) infection can present with extrahepatic manifestations including neurological disorders. Among these, neuralgic amyotrophy (NA) has been reported to occur in some industrialized countries. We investigated 35 patients with NA and a control group for markers of HEV infection. Acute HEV infection was found in NA patients only and was associated with an inflammatory response in the central nervous system. Shedding of HEV RNA into the cerebrospinal fluid and intrathecal production of anti-HEV IgM occurred in one patient suggesting that HEV is neurotropic.

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.

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.

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…

Chronic liver disease and cirrhosis are leading causes of illness and death, accounting for 38,170 deaths (1.5% of total deaths) in 2014 in the United States. The most common causes of cirrhosis are alcoholic liver disease, chronic hepatitis C, and nonalcoholic fatty liver disease. The prevalence……

Stephen A Harrison, Mary E Rinella, Manal F Abdelmalek, James F Trotter, Angelo H Paredes, Hays L Arnold, Marcelo Kugelmas, Mustafa R Bashir, Mark J Jaros, Lei Ling, Stephen J Rossi, Alex M DePaoli, Rohit Loomba

NGM282 produced rapid and significant reductions in liver fat content with an acceptable safety profile in patients with non-alcoholic steatohepatitis. Further study of NGM282 is warranted in this patient population.

Journal of Medical Virology, EarlyView.

Journal of Medical Virology, EarlyView.

Journal of Medical Virology, EarlyView.

Journal of Medical Virology, EarlyView.

Journal of Medical Virology, EarlyView.

Journal of Medical Virology, EarlyView.

Journal of Medical Virology, EarlyView.

Journal of Medical Virology, EarlyView.

Journal of Medical Virology, EarlyView.

The American Journal of Tropical Medicine and Hygiene

Authors: Campolmi I, Spinicci M, Mayaregua DR, Barahona HG, Mantella A, Lara Y, Roselli M, Strohmeyer M, Corti G, Tolari F, Pinckert JM, Dalton HR, Bartoloni A 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%...

Much has been written about the escalating crisis of opioid-overdose deaths in the United States and its mounting social and economic costs. Although political and public health leaders have begun to confront this urgent problem, hidden beneath it lies another danger: the increasing spread of……

Rivero-Juarez, Antonio; Camacho, Angela; Brieva, Teresa; Frias, Mario; Lopez-Lopez, Pedro; Risalde, María A.; Machuca, Isabel; Caston, Juan J.; Martínez Peinado, Antonio; Rivero, Antonio

Objective: to evaluate factors associated with increased serum cholesterol levels during Interferon-free (IFN-free) Hepatitis C virus (HCV) therapy. Design: Prospective longitudinal study Methods: HIV-infected patients who started and successfully completed IFN-free therapy for chronic HCV infection were included. Patients were treated using two different regimens, based on the clinician’s opinion: sofosbuvir and ledipasvir (SOF/LDV), or paritaprevir co-administered with ombitasvir and Dasabuvir (PrOD). Both total and LDL cholesterol were evaluated at baseline, week 1, week 2, week 4, week 8, EOT, SVR4, SVR12 and SVR24. Results: The study population therefore comprised 85 patients reaching SVR, 42 (49.4%) of whom were treated with SOF/LDV and 43 (50.6%) with PrOD. Patients using SOF/LDV was showed a higher increase on both total and LDL cholesterol during treatment period than those receiving PrOD. Analyzing the overall increase from baseline to weeks 1, 2, 4, 8 and EOT, choice of HCV regimen was associated with differential increases in total cholesterol during therapy. After end of treatment, no differences were found between SOF/LDV and PrOD with respect to total cholesterol. Conclusions: Our study suggests that the differential timing of the restoration of cholesterol metabolism in HIV/HCV genotype 1 co-infected patients achieving SVR is not mediated by HCV clearance but depends on the drug combination employed. Corresponding author: Antonio Rivero, MD PhD Avenida Menendez Pidal s/n. Hospital Univeristario Reina Sofía. Unidad de Enfermedades Infecciosas. 14004, Córdoba (Spain) e-mail: ariveror@gmail.com Tel: +34 957012421 Fax: +34 957011885, Alternative Corresponding author: Antonio Rivero-Juarez, PhD Avenida Menendez Pidal s/n. Edificio IMIBIC. Segunda Planta. Laboratorio de Investigación en Enfermedades Infecciosas (GC-03). Despacho 134. 14004, Córdoba (Spain) e-mail: arjvet@gmail.com Tel: +34 957213806 Fax: +34 957011885 Conflict of Interest: We declare no competing interests. Neither the authors nor their institutions have received payment or services at any time from a third party for any aspect of the submitted work (data monitoring board, study design, manuscript preparation, statistical analysis, and so on). Funding: This work was supported by the Ministerio de Sanidad (RD12/0017/0012) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirección General de Evaluación, the Fondo Europeo de Desarrollo Regional (FEDER), the Fundación para la Investigación en Salud (FIS) del Instituto Carlos III (PI15/01017), and the Red de Investigación en SIDA de España ISCIII-RETIC (grant number: RD16/0025/0034). M.A. Risalde is the recipient of a Sara Borrell postdoctoral perfection grant from the Instituto de Salud Carlos III (CD16/00209). Author contributions: Conceived and designed the experiments: ARJ, AC, and AR. Performed the experiments: TB, MF, ARJ, and PLL. Analyzed the results: ARJ, AC and AR. Contributed reagents/materials/analysis tool: ARJ, AC, MAR, AR. Wrote the manuscript: ARJ and AR. Critical review of the manuscript: All authors. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Abstract Background Efficient control of acute hepatitis B requires identification of current transmission routes. Countries in Central-Eastern Europe including Poland attribute an important fraction of cases to nosocomial transmission, as opposed to Western European countries. However, due to possible multiple exposures during the incubation time such assignment may be debatable. This study aimed at assessing of most affected groups and current transmission pattern of acute hepatitis B. Methods We investigated exposures reported by acute hepatitis B cases notified to routine surveillance system in Poland in 2010–2014 in comparison to data on hospitalization rates in general population. Results Hospitalization during incubation time significantly increased the risk of HBV infection (RR 3.13, 95%CI 2.58–3.80). Overall hospitalization population attributable risk (PAR%) was 25.7% (95% CI 20.3%–31.1%) as compared to 35% of acute cases assigned to hospital transmission in surveillance database. PAR% increased from 9.5% (1.12%–17.8%) in the age group 25–34 to 41.1% (28.2% - 53.9%) among those 65 +. In addition, cases …

Abstract Background Human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and Treponema pallidum (TP) infections are considered classic transfusion-transmissible infections (TTIs). Few data are available about the prevalence of TTIs in patients before blood transfusion in China. This study aimed to investigate the seroprevalence of four TTIs among patients before blood transfusion in Xiangya Hospital Central South University, China. Methods From 2011 to 2016, 442,121 hospitalized patients before possible blood transfusion were tested for hepatitis B surface antigen (HBsAg), anti-HCV, syphilis antibody (anti-TP) and anti-HIV. Results Of the 442,121 patients, the overall positivity of the four TTI serum markers was 15.35%. The positive rates of HBsAg, anti-HCV, anti-HIV and anti-TP were 10.98, 1.43, 0.16 and 2.78%, respectively. TTI serum markers showed a significant difference by gender, with positive rates of 17.98% for males and 12.79% for females. The prevalence of TTI serum markers varied significantly by age. The overall co-infection rate was 0.63%, and the top three multiple infections were HBV-TP, HBV-HCV, and HCV-TP. The co-infection rates of HBV-TP and HBV-HCV showed a significant decrease from 2011 to 2016, while the rates of other co-infections remained stable. Conclusions The prevalence of TTIs in patients before blood transfusion is much higher compared to that in blood donors in the region. The infection rates of HIV and TP increased, and the infection rate of HBsAg decreased in recent years.

F. Elfrink et al.

C. Charre et al.

H. Wang et al.

Abstract Background A marked increase of hepatitis E cases has recently been observed in the Netherlands. Causes of the (re-)emergence of hepatitis E virus (HEV) and exact sources and routes of transmission of HEV infection are currently unknown. We aimed to identify risk factors for HEV seropositivity. Methods Using the Wantai EIA, 2100 plasma samples of blood donors from all over the Netherlands aged 18-70 years were tested for anti-HEV IgG antibodies. A questionnaire on socio-demographic characteristics, health, and potential risk factors for HEV exposure was sent to these participants. Results The overall IgG-seroprevalence was 31% (648/2100) and increased with age. Several food products were independently associated with IgG-seropositivity in a multivariate analysis adjusting for age and gender among 1562 participants who completed the questionnaire: traditional Dutch dry raw sausages called “cervelaat”, “fijnkost”, “salami” and “salametti” which are generally made from raw pork and beef (aOR 1.5; 95%CI 1.2-1.9), frequent consumption of bovine steak (aOR 1.3; 95%CI 1.0-1.7), and frequent consumption of smoked beef (aOR 1.3 95%CI 1.0-1.7). Although not frequently reported, contact with contaminated water was also a risk factor for seropositivity (aOR 2.5; 95%CI 1.5-4.4). Lower seroprevalence was associated with eating raspberries, going out for dinner, and contact with wild animals and dogs. Conclusion Several pork food products, mainly dry raw sausages, and contact with contaminated water were associated with past HEV infection in the Netherlands. Further investigation is needed into the prevalence and infectivity of HEV in these risk factor food products, as well as investigation of the production methods and possible origin of HEV-contamination within these sausages, e.g. very small amounts of pork liver, pig-derived blood products as food additive, or the pork muscle tissue.

Meng-Jie Bai, Na Zhou, Wei Dong, Guang-Xing Li, Wei Cong, Xing-Quan Zhu

Hepatitis E virus (HEV) is a single-stranded RNA virus infecting a variety of animals and humans. However, little is known of HEV infection among cancer patients in China. This study provides new epidemiological data for the prevalence of co-infection of HEV in cancer patients, indicating that HEV infection is common in this group.

To the Editor: Recent medical advances, such as targeted therapies for specific tumor genomic defects, checkpoint inhibitors for cancers, and direct-acting antiviral agents for hepatitis C, have led to increasing numbers of potentially important candidate drugs for patients with serious or……

Lin K, Hsieh S, Sheng W, et al.

AbstractWe evaluated the serologic responses to different 2-dose combinations of inactivated HAV vaccines among HIV-positive individuals during an acute hepatitis A outbreak in Taiwan. In this 16-month retrospective study, the HAVRIX®-VAQTA® and VAQTA®-VAQTA® groups achieved similar seroconversion rates at weeks 28-36 (82.3% vs 80.9%; difference, 1.3%; 95%CI, -6.3% to 3.7%) and week 48 (94.7% vs 94.4%; difference, 0.3%; 95%CI, -2.6% to 3.2%), suggesting the interchangeability of different combinations of HAV vaccines. The significantly higher seroconversion rates to the first vaccination dose with VAQTA® than with HAVRIX® (53.0% vs 32.4%) may provide potential benefits in preventing HAV infection during the outbreak.

Toshie Mashiba, Kouji Joko, Masayuki Kurosaki, Hironori Ochi, Yukio Osaki, Yuji Kojima, Ryo Nakata, Tohru Goto, Akahane Takehiro, Hiroyuki Kimura, Akeri Mitsuda, Chiharu Kawanami, Yasushi Uchida, Chikara Ogawa, Atsunori Kusakabe, Ryuichi Narita, Yasushi Ide, Takehiko Abe, Keiji Tsuji, Tadashi Kitamura, Kazuhiko Okada, Tetsuro Sohda, Masaya Shigeno, Takashi Satou, Namiki Izumi

by Toshie Mashiba, Kouji Joko, Masayuki Kurosaki, Hironori Ochi, Yukio Osaki, Yuji Kojima, Ryo Nakata, Tohru Goto, Akahane Takehiro, Hiroyuki Kimura, Akeri Mitsuda, Chiharu Kawanami, Yasushi Uchida, Chikara Ogawa, Atsunori Kusakabe, Ryuichi Narita, Yasushi Ide, Takehiko Abe, Keiji Tsuji, Tadashi Kitamura, Kazuhiko Okada, Tetsuro Sohda, Masaya Shigeno, Takashi Satou, Namiki Izumi Background and aim This study aimed to elucidate whether interferon (IFN)-free direct-acting antiviral (DAA) therapy for hepatitis C after curative treatment of hepatocellular carcinoma (HCC) promotes HCC recurrence in a real-world large-scale cohort. Methods This multicenter study was conducted by the Japanese Red Cross Hospital Liver Study Group. This retrospective study analyzed 516 patients who underwent antiviral treatment for hepatitis C with either IFN (n = 148) or IFN-free DAA (n = 368) after curative HCC treatment; 78 IFN-treated patients and 347 IFN-free DAA-treated patients achieved sustained virological response (SVR). The recurrence rate of HCC was compared between the antiviral therapies. Logistic analysis and Cox proportional hazards analysis identified factors associated with early recurrence of HCC within 24 weeks of antiviral therapy and recurrence throughout the observation period, respectively. Results AFP at the completion of antiviral therapy, clinical stage of HCC, and non-SVR were independent factors associated with early recurrence of HCC. Among patients who had achieved SVR, the clinical stage of HCC and the level of AFP at completion of antiviral therapy were independent factors associated with early recurrence of HCC. For recurrence throughout the observation period in SVR patients, AFP at completion of antiviral therapy, duration between last HCC treatment to antiviral therapy, and the number of treatments were independent factors. There was no significant difference in the rate of early recurrence of HCC or recurrence throughout the observation period between IFN and IFN-free DAA treated patients. Conclusions There were no differences in the early recurrence rate of HCC between patients who underwent IFN and those who underwent IFN-free DAA as antiviral therapies.

Murai, K., Shimakami, T., Welsch, C., Shirasaki, T., Liu, F., Kitabayashi, J., Tanaka, S., Funaki, M., Omura, H., Nishikawa, T., Suminyadorj, A., Honda, M., Kaneko, S.

Simeprevir is a novel NS3/4A protease inhibitor (PI) of hepatitis C virus (HCV). The baseline polymorphism NS3-Q80K is frequently observed in genotype (gt) 1a HCV and often associated with treatment failure in simeprevir-containing regimens. We aimed to elucidate mechanisms of treatment failure due to NS3-Q80K. We included a Q80R mutation in our study and generated a series of Huh-7.5 cells, each of which harbored either wild-type gt 1a H77S.3 or one of the variants, Q80K or Q80R. The cells were cultured with increasing concentrations of simeprevir, and NS3 domain sequences were determined. The mutations identified by sequence analyses were subsequently introduced into H77S.3. The sensitivity of each mutant to NS3/4A PIs simeprevir, asunaprevir, grazoprevir, and paritaprevir was analyzed. We introduced the mutations into gt 1b N.2 and compared the sensitivity to simeprevir with that in gt 1a H77S.3. While simeprevir treatment selected mutations at residue D168, such as D168A/V in the wild-type virus, an additional mutation at residue R155, R155K, was selected in Q80K/R variants at simeprevir concentrations lower than 2.5 μM. Sensitivity analyses showed that simeprevir concentrations of less than 1 μM significantly boosted the replication of Q80K/R+R155K variants. Interestingly, this boost was not observed with the other NS3/4A PIs, and not in Q80R+R155Q/G/T/W variants or gt 1b. The boosted replication of Q80K+R155K by simeprevir could be related to treatment failure in simeprevir-containing antiviral treatments in gt 1a HCV-infected patients with the NS3-Q80K polymorphism. This result provides a new insight into how resistance-associated variants can cause treatment failure.

Mani, N., Cole, A. G., Phelps, J. R., Ardzinski, A., Cobarrubias, K. D., Cuconati, A., Dorsey, B. D., Evangelista, E., Fan, K., Guo, F., Guo, H., Guo, J.-T., Harasym, T. O., Kadhim, S., Kultgen, S. G., Lee, A. C. H., Li, A. H. L., Long, Q., Majeski, S. A., Mao, R., McClintock, K. D., Reid, S. P., Rijnbrand, R., Snead, N. M., Micolochick Steuer, H. M., Stever, K., Tang, S., Wang, X., Zhao, Q., Sofia, M. J.

AB-423 is a sulfamoylbenzamide (SBA) class of HBV capsid inhibitor in Phase 1 clinical trials. In cell culture models AB-423 showed potent inhibition of HBV replication (EC50/EC90 = 0.08-0.27 μM/0.33-1.32 μM) with no significant cytotoxicity (CC50 >10 μM). Addition of 40% human serum resulted in a 5-fold increase in the EC50 values. AB-423 inhibited HBV genotypes A through D and nucleos/tide-resistant variants in vitro. Treatment of HepDES19 cells with AB-423 resulted in capsid particles devoid of encapsidated pgRNA and rcDNA indicating it is a class II capsid inhibitor. In a de novo infection model AB-423 prevented the conversion of encapsidated rcDNA to cccDNA presumably by interfering with the capsid uncoating process. Molecular docking of AB-423 into crystal structures of heteroaryldihydropyrimidines and an SBA and biochemical studies suggest that AB-423 likely also binds to the dimer:dimer interface of core protein. In vitro dual combination studies with AB-423 and anti-HBV agents such as nucleos/tide analogs, RNAi agents, or interferon-α resulted in additive to synergistic antiviral activity. Pharmacokinetic studies with AB-423 in CD-1 mice showed significant systemic exposures and higher liver accumulation. A 7-day BID administration of AB-423 in a hydrodynamic injection mouse model of HBV model resulted in a dose-dependent reduction in serum HBV DNA levels and combination with ETV or ARB-1467 resulted in a trend towards greater antiviral activity than either agent alone consistent with the results of the in vitro combination studies. The overall preclinical profile of AB-423 supports further evaluation for safety, pharmacokinetics and antiviral activity in CHB patients.

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.

Abstract Purpose In 2016, the number of refugees worldwide reached 65.6 million. So far, only limited data are available on the health status of refugees and asylum seekers (RAs). Especially, notifiable infectious diseases (NIDs) carry the risk of outbreaks in communal accommodations hosting RAs. Methods We conducted a monocentric retrolective cross-sectional study including 15,137 RAs treated in a special health care unit for RAs located in the major reception center in Munich from November 2014 to October 2016. Altogether 811 RAs with NIDs according to sections 6 and 7 of the German Infection Protection Act or with other infections relevant in the setting of a communal accommodation (RIDs) could be identified. Results The gender and age distribution was generally comparable to that of refugees in Germany. However, patients from East Africa and Nigeria were significantly overrepresented. NIDs/RIDs were dominated by cases of tuberculosis, hepatitis B, and vaccine-preventable and parasitic diseases. Significant risk factors included country of origin (COI) and age for hepatitis B, age for hepatitis C, gender and age for HIV, and COI, gender and age for tuberculosis and ectoparasitosis. Calculated prevalences of hepatitis B, hepatitis C, and HIV were mostly below those of the COI. Incidences of tuberculosis were mostly strongly elevated. Conclusions COI, gender, and age have an impact on the occurrence of NIDs/RIDs. Early vaccinations and improved hygiene could be effective in preventing NIDs/RIDs in communal accommodations. Screening, prompt therapy, and infection protection measures are necessary to prevent the transmission of diseases.

Abstract Purpose The aim of this study was to evaluate the effects of antiviral therapy on liver stiffness measurement (LSM). Methods Two hundred HBV patients were enrolled from four hospital centers in southern Italy; median age was 50.7 (25–75) males were 68%; 171 patients underwent to liver biopsy and 200 patients had LSM at baseline and 189 at the end of follow-up. One hundred and forty-nine patients were treated with nucleos(t)ide analogs, while 51 patients were untreated. The cutoffs of the LSM, related to the fibrosis stages, were as follows: non-advanced fibrosis ≤ 8.1 kPa and advanced fibrosis ≥ 8.2 Kpa. Results At baseline, the median value of LSM was 14.1 kPa for advanced fibrosis/cirrhosis and 6.9 kPa for non-advanced fibrosis. LSM was performed at 24 months from the start of therapy. The treated patients (68% received Entecavir and 32% Tenofovir) showed a decrease in liver stiffness measurement of 1.5 kPa (p 

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,