Abstract Background Infectious mononucleosis is one of the main manifestations of Epstein – Barr virus, which is characterized by fever, tonsillar-pharyngitis, lymphadenopathy and atypical lymphocytes. Although 60% of patients with IMN develop cold type antibodies, clinically significant hemolytic anemia with a high ferritin level is very rare and validity of serum ferritin as an important biomarker has not been used frequently. Case presentation 18-year-old girl presented with fever, malaise and sore throat with asymptomatic anemia, generalized lymphadenopathy, splenomegaly and mild hepatitis. Investigations revealed that she had cold type autoimmune hemolysis, significantly elevated serum ferritin, elevated serum lactate dehydrogenase level with serological evidence of recent Epstein Barr infection. She was managed conservatively and her hemoglobin and serum ferritin levels normalized without any intervention following two weeks of the acute infection. Conclusion Cold type autoimmune hemolytic anemia is a rare manifestation of infectious mononucleosis and serum ferritin is used very rarely as an important biomarker. Management of cold type anemia is mainly supportive and elevated serum ferritin indicates severe viral disease.…

Arati Mane, Jilian Sacks, Sadhya Sharma, Harpreet Singh, Alexandra Tejada-Strop, Saleem Kamili, Kartik Kacholia, Ritubhan Gautam, Madhuri Thakar, Radhey Shyam Gupta, Raman Gangakhedkar

by Arati Mane, Jilian Sacks, Sadhya Sharma, Harpreet Singh, Alexandra Tejada-Strop, Saleem Kamili, Kartik Kacholia, Ritubhan Gautam, Madhuri Thakar, Radhey Shyam Gupta, Raman Gangakhedkar Objectives Hepatitis C virus (HCV) infection is a major contributor to morbidity and mortality worldwide. Early detection and curative treatment of HCV can reduce the risk of liver-related mortality and serve to prevent transmission of new infections. India is estimated to have about six million HCV infected individuals, most of whom are unaware of their infection status. Rapid diagnostic test kits (RDTs) could help identify HCV infected persons more expeditiously and thus availability of high performing, quality-assured RDTs is essential to scale-up HCV screening efforts. The present study was thus undertaken to evaluate the performance characteristics of five anti-HCV RDTs. Methods Five anti-HCV RDTs (Alere Truline, Flaviscreen, Advanced Quality, SD Bioline and OraQuick) were evaluated using two panels of known anti-HCV positive and negative samples; one characterized from Indian patient samples (n = 360) and other obtained from the US Centers for Disease Control and Prevention (CDC), Atlanta (n = 100). Sensitivity, specificity, inter-observer agreement, test validity and operational characteristics of RDTs were assessed. Results The combined sensitivities across both panels for Alere Truline, Flaviscreen, Advanced Quality, SD Bioline and OraQuick RDTs were 99.4% (95%CI-96.6%-99.9%), 86.2% (95%CI-79.8%-91.1%), 96.2% (95%CI-91.9%-98.6%), 99.4% (95%CI-96.6%-99.9%) and 99.4% (95%CI-96.6%-99.9%) respectively. The overall specificities across both panels for all RDTs were 99.7%. The inter-observer agreement was 100% for Alere Truline, SD Bioline and OraQuick, while it was 99.5% and 98.6% with Advanced Quality and Flavicheck respectively. Discordant results were significantly associated with human immunodeficiency virus (HIV) positivity for both Advanced Quality and Flavicheck (p

Michael Kühl, Christian Binner, Joanna Jozwiak, Julia Fischer, Jochen Hahn, Alaeldin Addas, Boris Dinov, Jens Garbade, Gerhard Hindricks, Michael Borger

by Michael Kühl, Christian Binner, Joanna Jozwiak, Julia Fischer, Jochen Hahn, Alaeldin Addas, Boris Dinov, Jens Garbade, Gerhard Hindricks, Michael Borger Background Hypercholesterolaemia is common in patients after cardiac transplantation. Monoclonal antibodies that inhibit proprotein convertase subtilisin-kexin type 9 (PCSK9) reduce low-density lipoprotein (LDL) cholesterol levels and subsequently the risk of cardiovascular events in patients with dyslipidaemia. There are no published data on the effect of this medication class on cholesterol levels in patients after cardiac transplantation. Methods In this retrospective study we investigated patients who were treated with PCSK9 inhibitors either because of intolerance of statins or residual hypercholesterolaemia with evidence of cardiac allograft vasculopathy. We compared the data of patients prior to the start with these medications with their most recent dataset. Results Ten patients (nine men; mean age 58±6 years) underwent cardiac transplantation 8.3±4.5 (range 3–15) years ago. The treatment duration of Evolocumab or Alirocumab was on average 296±125 days and lead to a reduction of total Cholesterol (281±52 mg/dl to 197±36 mg/dl; p = 0.002) and LDL Cholesterol (170±22 mg/dl to 101±39 mg/dl; p = 0.001). No significant effects on HDL Cholesterol, BNP, Creatin Kinase or hepatic enzymes were noticed. There were no unplanned hospitalisations, episodes of rejections, change of ejection fraction or opportunistic infections. Both patients on Alirocumab developed liver pathologies: One patient died of hepatocellular carcinoma and the other developed hepatitis E. Conclusions Our study demonstrates that the PCSK9 inhibitors Evolocumab and Alirocumab lead to a significant reduction of LDL Cholesterol in heart transplantation recipients. No effect on cardiac function or episodes of rejections were noticed. Larger and long-term studies are needed to establish safety and efficacy of PCSK9 inhibitors after cardiac transplantation.…

Abstract Background After allogeneic haematopoietic stem cell transplantation (allo-HSCT), Hepatitis B virus reactivation (HBVr) can be observed in patients with previous resolved Hepatitis B virus (HBV) infections. Nephrotic syndrome (NS) is the main clinical manifestation of HBsAg-positive glomerulonephritis. However, the development of HBVr combined with NS after allo-HSCT is uncommon. Case presentation We presented a case of a 47-year-old female with acute myelogenous leukemia who underwent HLA-identical sibling allo-HSCT and achieved leukemia free survival. She had pretransplant serological markers of a resolved HBV infection (HBsAg-negative, anti-HBc and anti-HBs positive). However, she developed HBVr combined with nephrotic syndrome (NS) 16 months after HSCT. Her histological renal lesion was mesangial proliferative glomerulonephritis. IgA+, IgM+, and C1q deposits but not HBV antigens (HBsAg and HBcAg) were identified in her renal biopsy material. Long-term entecavir and immunosuppression resulted in decrease of HBV virus replication, amelioration of proteinuria and stabilisation of renal function. Conclusions Entecavir combined with immunosuppression has efficacy in the treatment of HBVr combined with NS after allo-HSCT, but long course of treatment is needed. Closely monitoring and antiviral prophylaxis might be necessary for allo-HSCT recipients to prevent reactivation of resolved HBV infection and its related complications.…

Newsum, Astrid M.; Kooij, Katherine W.; Boyd, Anders; Smit, Colette; Wit, Ferdinand W.N.M.; van der Meer, Jan T.M.; Prins, Maria; Reiss, Peter; van der Valk, Marc; on behalf of the MOSAIC study group, ATHENA observational HIV cohort and NVHB-SHM hepatitis working group

Background: Whether continued, accelerated liver fibrosis progression occurs following acute hepatitis C virus infection (AHCVI) in HIV-positive MSM is unknown. Design and methods: HIV-positive MSM from the AIDS Therapy Evaluation in the Netherlands and MSM Observational Study for Acute Infection with Hepatitis C-cohorts with primary AHCVI and at least one fibrosis-4 (FIB-4) measurement less than 2 years before and 1 year after estimated AHCVI were included. Mixed-effect linear models were used to evaluate (time-updated) determinants of FIB-4 levels over time. Determinants of transitioning to and from FIB-4 of 1.45 or less and more than 1.45 were examined using multistate Markov models. Results: Of 313 MSM, median FIB-4 measurements per individual was 12 (interquartile range  = 8–18) and median follow-up following AHCVI was 3.5 years (interquartile range = 1.9–5.6). FIB-4 measurements averaged at 1.00 [95% confidence interval (CI) = 0.95–1.05] before AHCVI, 1.31 (95% CI = 1.25–1.38) during the first year of AHCVI and 1.10 (95% CI = 1.05–1.15) more than 1 year after AHCVI. Mean FIB-4 more than 1 year after AHCVI was higher for chronically infected patients compared with those successfully treated (P = 0.007). Overall FIB-4 scores were significantly higher with older age, lower CD4+ cell count, longer duration from HIV-diagnosis or AHCVI, and nonresponse to HCV-treatment. At the end of follow-up, 60 (19.2%) and eight MSM (2.6%) had FIB-4 between 1.45–3.25 and at least 3.25, respectively. Older age, lower CD4+-cell count and detectable HIV-RNA were significantly associated with higher rates of progression to FIB-4 more than 1.45, whereas older age, longer duration from HIV-diagnosis and nonresponse to HCV-treatment were significantly associated with lower rates of regression to FIB-4 of 1.45 or less. Conclusion: In this population of HIV-positive MSM, FIB-4 scores were higher during the first year of AHCVI, but FIB-4 at least 3.25 was uncommon by the end of follow-up. Well controlled HIV-infection appears to attenuate FIB-4 progression. Correspondence to Astrid M. Newsum, Department of Infectious Diseases Research and Prevention, Public Health Service of Amsterdam, PO Box 2200, 1000CE Amsterdam, The Netherlands. Tel: +31 0 20 555 5436; e-mail: anewsum@ggd.amsterdam.nl Received 16 October, 2018 Revised 17 December, 2018 Accepted 18 December, 2018 Copyright © 2019 Wolters Kluwer Health, Inc.

Radwan, Daniel; Cachay, Edward; Falade-Nwulia, Oluwaseun; Moore, Richard D.; Westergaard, Ryan; Mathews, William Christopher; Aberg, Judith; Cheever, Laura; Gebo, Kelly A.; for the HIV Research Network

Background: Despite the high prevalence of Hepatitis C Virus (HCV) among persons living with HIV (PWH), the prevalence of HCV screening, treatment, and sustained virologic response (SVR) is unknown. This study aims to characterize the continuum of HCV screening and treatment among PWH in HIV care. Setting: Adult patients enrolled at 12 sites of the HIV Research Network located in three regions of the United States were included. Methods: We examined the prevalence of HCV screening, HCV coinfection, direct-acting antiretroviral (DAA) treatment, and SVR-12 between 2014-15. Multivariate logistic regression was performed to identify characteristics associated with outcomes, adjusted for site. Results: Among 29,071 PWH (age 18-87, 74.8% male, 44.4% black), 77.9% were screened for HCV antibodies; 95% of those screened had a confirmatory HCV-RNA viral load test. Among those tested, 61% were determined to have chronic HCV. We estimate that only 23.4% of those eligible for DAA were prescribed DAA, but only 17.8% of those eligible evidenced initiating DAA treatment. Those who initiated treatment achieved SVR-12 at a rate of 95.2%. Blacks and people who inject drugs (PWID) were more likely to be screened for HCV than whites or those with heterosexual risk. Persons over age 40, whites, Hispanics, and PWID (AOR 8.70 [7.74-9.78]) were more likely to be coinfected than their counterparts. When examining treatment with DAA, persons over age 50, on ART (AOR, 2.27 [1.11-4.64]), with HIV-1 RNA…

Negar Rezaei, Mohsen Asadi-Lari, Ali Sheidaei, Sara Khademi, Kimiya Gohari, Farnaz Delavari, Alireza Delavari, Elham Abdolhamidi, Maryam Chegini, Nazila Rezaei, Hamidreza Jamshidi, Pegah Bahrami Taghanaki, Milad Hasan, Moein Yoosefi, Farshad FarzadFar

by Negar Rezaei, Mohsen Asadi-Lari, Ali Sheidaei, Sara Khademi, Kimiya Gohari, Farnaz Delavari, Alireza Delavari, Elham Abdolhamidi, Maryam Chegini, Nazila Rezaei, Hamidreza Jamshidi, Pegah Bahrami Taghanaki, Milad Hasan, Moein Yoosefi, Farshad FarzadFar Background Liver cirrhosis mortality number has increased over the last decades. We aimed to estimate the liver cirrhosis mortality rate and its trends for the first time by sex, age, geographical distribution, and cause in Iran. Method Iranian Death Registration System, along with demographic (Complete and Summary Birth History, Maternal Age Cohort and Period methods) and statistical methods (Spatio-temporal and Gaussian process regression models) were used to address the incompleteness and misclassification and uncertainty of death registration system to estimate annual cirrhosis mortality rate. Percentages of deaths were proportionally redistributed into cirrhosis due to hepatitis B, C and alcohol use based on the data from the Global Burden of Disease (GBD) 2010 study. Results Liver cirrhosis mortality in elder patients was 12 times higher than that in younger patients at national level in 2015. Over the 26 years, liver cirrhosis mortality in males has increased more than that in females. Plus, the percentage of change in age adjusted mortality rate at provincial levels varied between decreases of 64.53% to nearly 17% increase. Mortality rate has increased until 2002 and then decreased until 2015.The province with highest mortality rate in 2015 has nearly two times greater rate compare to the lowest. More than 60% of liver cirrhosis mortality cases at national level are caused by hepatitis B and C infection. The rate of hepatitis B mortality is four times more than that from hepatitis C. Conclusion This study demonstrated an increasing and then decreasing pattern in cirrhosis mortality that could be due to national vaccination of hepatitis B program. However monitoring, early detection and treatment of risk factors of cirrhosis, mainly in high risk age groups and regions are essential. Cirrhosis mortality could be diminished by using new non-invasive methods of cirrhosis screening, hepatitis B vaccination, definite treatment of hepatitis C.…

Martyna Gassowski, Stine Nielsen, Norbert Bannert, Claus-Thomas Bock, Viviane Bremer, R.Stefan Ross, Benjamin Wenz, Ulrich Marcus, Ruth Zimmermann, DRUCK-study group

Abstract Background For patients with chronic hepatitis B and cirrhosis in less developed western regions in China, due to constraints of local economic conditions, the choice of treatment measures is often limited. However if patients recieved valid management and effective treatment, they were able to maintain their health and benign prognosis. Case presentation This study narrates the long-term treatment and careful follow-up of a patient with chronic hepatitis B and cirrhosis in a less developed western region in China, and analyzes the prognosis of the disease and countermeasures. Conclusions This would partly reflect the development of antiviral therapy for chronic hepatitis B and multidisciplinary comprehensive treatment for cirrhosis-related complications in remote region with limited resources in the past 20 years.…

Qingsong Lei, Lin Li, Wenxiang Huang, Bo Qin, Shujun Zhang

ABSTRACTS Hepatitis E virus could induce chronic hepatitis and liver failure with high mortality through unknown mechanisms. Previous study showed that HEV ORF3 could inhibit macrophages inflammatory response. Impaired macrophages phagocytosis was also found in patients infected with HEV and its nucleic acids could be detected in macrophages. To elucidate the role of HEV ORF3 on phagocytosis, the phagocytosis activation was measured by phagocytosis test, flow cytometry and phalloidin staining. Meanwhile, the expression of key phagocytic receptors and the activation of transduction pathway were investigated by using RT‐qPCR and western blot. Results of phagocytosis test showed that HEV ORF3 could significantly impair the absorption capacity of latex beads. Furthermore, results of RT‐qPCR and western blot showed that the expression of CD14 and CD64 decreased. Afterwards, the present study showed that the activation of JAK1/STAT1 signaling pathway was inhibited by HEV ORF3 and downregulation of CD14 and CD64 could be reversed by interferon gamma (IFNγ), one activator of JAK1/STAT1 signaling pathway. In conclusion, HEV ORF3 could significantly impaired the phagocytosis of macrophage by down‐regulating expression of CD14 and CD64, which may functioned by inhibiting the activation of JAK1/STAT1 signaling pathway. This article is protected by copyright. All rights reserved.

Andonov A, Robbins M, Borlang J, et al.

AbstractHepatitis E virus (HEV) is a major public health concern in developing countries where the primary transmission is via contaminated water. Zoonotic HEV cases have been increasingly described in Europe, Japan and the United States with pigs representing the main animal reservoir of infection. We report an unusual acute hepatitis infection in a previously healthy man caused by a rat hepatitis E virus with a considerably divergent genomic sequence compared to other rat HEV strains. It is possible that rat HEV is an under recognized cause of hepatitis infection and further studies are necessary to elucidate its potential risk and mode of transmission.

Xiao‐bo Zhu, Ling‐yun Zhuo, Ming Yue, Mei Liu, Feng Zang, Hao‐zhi Fan, Jing‐jing Wu, Xue‐shan Xia, A‐mei Zhang, Rong‐bin Yu, Peng Huang

Abstract Aims To investigate the association between two RIG‐I like receptors gene polymorphisms and HCV infection in Chinese Han population. Methods The current study genotyped two selected SNPs (IFIH1 rs3747517 and DDX58 rs9695310) using TaqMan allelic discrimination assay to assess their association with the susceptibility and clinical outcome of HCV infection among 3065 participants (1545 non‐HCV infection individuals, 568 spontaneous HCV clearance cases and 952 persistent infection patients). Results IFIH1 rs3747517 (dominant model: adjusted OR = 1.34, 95% CI = 1.07‐1.68, P = 0.009) and DDX58 rs9695310 (dominant model: adjusted OR = 1.43, 95% CI = 1.15‐1.78, P = 0.001) were associated with chronic hepatitis C (CHC). And the risk of CHC increased when people were carrying more unfavorable rs3747517‐GA/AA and rs9695310‐GC/CC genotypes from zero to two with the chronic rates of 56.72%, 59.38% and 69.01%, respectively (P trend < 0.001). Conclusion Genetic variations at IFIH1 rs3747517 and DDX58 rs9695310 were independent predictor of chronic hepatitis C in Chinese Han population. This article is protected by copyright. All rights reserved.

Stephanie Popping, Sebastiaan J. Hullegie, Anne Boerekamps, Bart J. A. Rijnders, Robert J. de Knegt, Jürgen K. Rockstroh, Annelies Verbon, Charles A. B. Boucher, Brooke E. Nichols, David A. M. C. van de Vijver

by Stephanie Popping, Sebastiaan J. Hullegie, Anne Boerekamps, Bart J. A. Rijnders, Robert J. de Knegt, Jürgen K. Rockstroh, Annelies Verbon, Charles A. B. Boucher, Brooke E. Nichols, David A. M. C. van de Vijver Background Treatment of hepatitis C virus infections (HCV) with direct acting antivirals (DAA) can prevent new infections since cured individuals cannot transmit HCV. However, as DAAs are expensive, many countries defer treatment to advances stages of fibrosis, which results in ongoing transmission. We assessed the epidemiological impact and cost-effectiveness of treatment initiation in different stages of infection in the Netherlands where the epidemic is mainly concentrated among HIV-infected MSMs. Methods We calibrated a deterministic mathematical model to the Dutch HCV epidemic among HIV-infected MSM to compare three different DAA treatment scenarios: 1) immediate treatment, 2) treatment delayed to chronic infection allowing spontaneous clearance to occur, 3) treatment delayed until F2 fibrosis stage. All scenarios are simulated from 2015 onwards. Total costs, quality adjusted life years (QALY), incremental cost-effectiveness ratios (ICERs), and epidemiological impact were calculated from a providers perspective over a lifetime horizon. We used a DAA price of €35,000 and 3% discounting rates for cost and QALYs. Results Immediate DAA treatment lowers the incidence from 1.2/100 person-years to 0.2/100 person-years (interquartile range 0.1–0.2) and the prevalence from 5.0/100 person-years to 0.5/100 person-years (0.4–0.6) after 20 years. Delayed treatment awaiting spontaneous clearance will result in a similar reduction. However, further delayed treatment to F2 will increases the incidence and prevalence. Earlier treatment will cost society €68.3 and €75.1 million over a lifetime for immediate and awaiting until the chronic stage, respectively. The cost will increase if treatment is further delayed until F2 to €98.4 million. Immediate treatment will prevent 7070 new infections and gains 3419 (3019–3854) QALYs compared to F2 treatment resulting in a cost saving ICER. Treatment in the chronic stage is however dominated. Conclusions Early DAA treatment for HIV-infected MSM is an excellent and sustainable tool to meet the WHO goal of eliminating HCV in 2030.…

Sayyad Khanizadeh, Banafsheh Hasanvand, Hadi Razavi Nikoo, Khatereh Anbari, Hemanta Adhikary, Somayeh Shirkhani, Hamed Esmaeili Lashgarian

Abstract Hepatitis B virus (HBV) infection is one of the clinical dilemmas in chronic liver diseases. MicroRNAs (miRNAs) are small non‐codding RNA molecules that play an important role in the pathogenesis of liver diseases and single nucleotide polymorphisms (SNPs) in miRNA genes affect the clinical course of HBV infection. Previous studies have shown that miRNA‐146a rs2910164 polymorphism can be associated with the pathogenesis of liver diseases such as hepatocellular carcinoma (HCC). The present study investigated the association between miRNA‐146a ‐2 rs2910164 polymorphism and susceptibility to HBV infection in an Iranian population. The study comprised 266 patients with chronic HBV infection, 172 patients with spontaneous viral clearance (SVC) after acute HBV infection, and 266 healthy control (HCL) adjusted for gender and age. The genotyping of the miRNA‐146a rs2910164 polymorphism was performed by PCR‐RFLP method. Our data revealed that GG genotype and G allele of miRNA‐146a rs2910164 SNP is dominated (P

Yi-Hao Yen, Kwong-Ming Kee, Chien-Hung Chen, Tsung-Hui Hu, Sheng-Nan Lu, Jing-Houng Wang, Chao-Hung Hung

by Yi-Hao Yen, Kwong-Ming Kee, Chien-Hung Chen, Tsung-Hui Hu, Sheng-Nan Lu, Jing-Houng Wang, Chao-Hung Hung Background and aim Previous studies have reported that sustained virological response (SVR) to interferon-based treatment reduces the risk of mortality in chronic hepatitis C (CHC) patients, mainly in cirrhotic patients. A population-based study reported that metabolic risk factors increase the risk of mortality in CHC patients. We aim to investigate the association between SVR, metabolic risk factors and mortality in CHC patients with and without advanced fibrosis. Methods We collected data from 1452 CHC patients who underwent interferon-based therapy. All patients underwent liver biopsy prior to therapy. Mild fibrosis was defined as a modified Knodell score of 0–2, while advanced fibrosis was defined as a score of 3–4. Results 1452 patients were followed up for a median (IQR) of 6.6 (4.2–9.4) years, 1124 patients (77.4%) achieved SVR, 619 patients (42.6%) were advanced fibrosis. 14 patients with mild fibrosis and 55 patients with advanced fibrosis died during follow-up period. According to multivariate Cox regression analyses, SVR reduced the risks of all-cause mortality (HR, 0.21; 95% CI, 0.12–0.37; P…

Philippe COLSON, Patrick BORENTAIN, René GEROLAMI

McAuley J, Close R.

Hepatitis CPregnancyDirect Acting Agents…

Breskin A, Westreich D, Hurt C, et al.

AbstractBackgroundThe cost of direct-acting antivirals (DAA) for hepatitis C virus (HCV) prompted many payers to restrict treatment to patients who met non-evidence-based criteria. These restrictions have implications for survival of people with HCV, especially for people with HIV/HCVco-infection who are at high risk for liver disease progression. The goal of this work was to estimate the effects of DAA access policies on 10-year all-cause mortality among people with HIV.MethodsThe study population included 3,056 adults with HIV in the Women’s Interagency HIV Study and Multicenter AIDS Cohort Study from October 1, 1994 through September 30, 2015. We used the parametric g-formula to estimate 10-year all-cause mortality under DAA access policies that included treating: 1) all people with HCV; 2) only people with suppressed HIV; 3) only people with severe fibrosis; and 4) only people with HIV suppression and severe fibrosis.ResultsThe 10-year risk difference (RD) of treating all co-infected persons with DAAs compared with no treatment was -3.7% (95% CI: -9.1%, 0.6%). Treating only those with suppressed HIV and severe fibrosis yielded a RD of -1.1% (95% CI: -2.8%, 0.6%), with 51% (95% CI: 38%, 59%) of co-infected persons receiving DAAs. Treating a random selection of 51% of co-infected persons at baseline decreased the risk by 1.9% (95% CI: -4.7%, 0.3%).ConclusionsRestrictive DAA access policies may decrease survival compared to treating similar proportions of people with HIV/HCV coinfection with DAAs at random. These findings suggest that lives could be saved by thoughtfully revising access policies.

Abstract Background Up until now, there are limited studies available on the epidemiology of infectious diseases in Democratic People’s Republic of Korea (DPRK, North Korea). However, different types of infectious diseases have been found in North Korean travelers at Dandong port. Entry surveillance data of those North Korean travelers may provide some insight into the probable epidemiology of some infectious diseases in DPRK. Methods We actively analyzed the medical test result of North Korean travelers entering China through Dandong port. Detection of hepatitis B virus (HBV), tuberculosis (TB), syphilis and malaria was made by specific laboratory tests according to the national technical guidelines. Infectious diseases surveillance data for 2015–17 was analyzed and compared among subgroups. Results Between Jan 1, 2014, and Dec 31, 2016, 557 cases of infectious diseases were identified among 18,494 North Korean travelers, HBV active infection (466 cases), active TB infection (33 cases), current active syphilis infection (57) cases, Plasmodium falciparum (P.falciparum) malaria infection (1 case). The incidence of HBV, TB and syphilis in North Korean travelers was high. Incidence of TB increased from 11.7256 (1/10,000) in 2015 to 28.2738 (1/10,000) in 2017. HBV immunization rate in in North Korean travelers was relatively high in 0–10 age group. Conclusion This report is the first to characterize the profile of infectious diseases among arriving North Korean travelers in mainland China. Our findings suggest high incidence of HBV, TB and syphilis among North Korean travelers. The screening for TB in North Korean workers should be strengthened in order to prevent infections imported into China.…

Patel E, Thio C, Boon D, et al.

AbstractIn the U.S. household population aged 18 years (2011–2016), prevalence of hepatitis B surface antigen (HBsAg) was 0.36% overall, and was highest in non-Hispanic Asians (3.4%). Among adult HBsAg-carriers, 42% (95% confidence interval: 29%-56%) had antibodies to hepatitis D virus (anti-HDV). Routine anti-HDV testing should be performed for HBsAg-carriers.

Raghwani J, Wu C, Ho C, et al.

AbstractBackgroundDespite the recent breakthroughs in the treatment of HCV infection, we have a limited understanding of how virus diversity generated within individuals impacts the evolution and spread of HCV variants at the population scale. Addressing this gap is important for identifying the main sources of disease transmission and for evaluating the risk of drug-resistance mutations emerging and disseminating in a population.MethodWe have undertaken a high-resolution analysis of HCV within-host evolution from four individuals co-infected with HIV. We used long-read, deep-sequenced data of the full-length HCV envelope glycoprotein, longitudinally sampled from acute to chronic HCV infection to investigate the underlying viral population and evolutionary dynamics.ResultsWe found statistical support for population structure maintaining the within-host HCV genetic diversity in three out of four individuals. We also report the first population genetic estimate of the within-host recombination rate for HCV (0.28x10 -7 recombination/site/year), which is considerably lower than that estimated for HIV-1 and the overall nucleotide substitution rate estimated during HCV infection.ConclusionTogether, these observations indicate that population structure and strong genetic linkage shapes within-host HCV evolutionary dynamics. These results will guide the future investigation of potential HCV drug resistance adaptation during infection, and at the population scale.

Loomba R, Decaris M, Li K, et al.

AbstractIn a pilot study, heavy water labeling was used to determine HBsAg turnover rates in chronic hepatitis B (CHB) patients. The mean (SD) half-life of HBsAg in blood was 6.7 (5.5) days which therefore reflects recent production in liver and supports strategies aimed at reducing HBsAg production in CHB patients.

Kuehn B.

Large outbreaks of acute hepatitis A in California, Kentucky, Michigan, and Utah that predominantly affected individuals who were homeless or reported using drugs signal a shift in the epidemiology of US hepatitis A outbreaks, according to a CDC report.

Chen-Hua Liu, Chun-Jen Liu, Tung-Hung Su, Hung-Chih Yang, Chun-Ming Hong, Tai-Chung Tseng, Pei-Jer Chen, Ding-Shinn Chen, Jia-Horng Kao

by Chen-Hua Liu, Chun-Jen Liu, Tung-Hung Su, Hung-Chih Yang, Chun-Ming Hong, Tai-Chung Tseng, Pei-Jer Chen, Ding-Shinn Chen, Jia-Horng Kao Background The real-world data for the effectiveness and safety of sofosbuvir/ledipasvir (SOF/LDV) with or without ribavirin (RBV) in patients with hepatitis C virus genotype 1 (HCV-1) infection remain limited in Taiwan. Methods A total of 273 chronic HCV-1 patients receiving 8, 12, or 24 weeks of SOF/LDV with or without RBV were enrolled. The sustained virologic response rate at week 12 off-therapy (SVR12) by evaluable population (EP) and per-protocol population (PP) were assessed for effectiveness. The treatment discontinuation rate due to adverse events (AEs) and serious AE rate were assessed for safety. Baseline patient characteristics and on-treatment HCV viral kinetics associated with SVR12 were analyzed. Results The SVR12 rates by EP and PP analyses were 96.7% (95% confidence interval [CI]: 93.9%-98.3%) and 97.5% (95% CI: 94.8%-98.8%), respectively. The rates of treatment discontinuation due to AE and serious AE were 0.4% and 4.4%, respectively. Seven patients with true virologic failure were relapsers. In 2 patients who were lost-to follow-up, one expired at treatment week 3 due to pneumonia which was considered not related to treatment, and one declined follow-up at off-therapy week 4. The SVR12 rates were comparable in terms of baseline patient characteristics and viral decline at week 4 of treatment. Conclusions SOF/LDV with or without RBV for 8–24 weeks is well tolerated and achieves a high SVR12 rate in patients with HCV-1 infection in Taiwan.…

Kai Yang, Shihe Guan, Hao Zhang, Zhiwu Chen

Abstract Interleukin‐6 (IL‐6) is a pleiotropic cytokine with pivotal functions in the regulation of the biological responses of several target cells, including hepatocytes. Previous studies have shown that serum IL‐6 levels are increased in hepatitis B patients. However, the role of IL‐6 in modulating the anti‐HBV activity of interferon‐alpha (IFN‐α) remains unclear. In this study, we found that both HBV and viral proteins could induce the expression of IL‐6 in hepatocytes (LO2 and HepG2). Exogenous IL‐6 had no effect on HBV replication, whereas knockdown of IL‐6 expression by RNAi inhibited that. Interestingly, IFN‐α markedly induced IL‐6 expression in hepatocytes, especially in HBV replicating hepatocytes. In turn, IL‐6 impaired the anti‐HBV efficiency of IFN‐α by decreases the expression of IFN‐α downstream effectors by up‐regulation of SOCS3. Furthermore, we demonstrated that down‐regulation of SOCS3 improved IFN antiviral activity to some extent in HBV replicating hepatocytes. These data provided new insights for a better understanding of the mechanism of IFN‐α resistance and may represent a novel therapeutic strategy to efficiently target HBV infection. This article is protected by copyright. All rights reserved.

The Lancet

On Dec 11, US Food and Drug Administration Commissioner Scott Gottlieb announced a set of rules that would change the way insulin production is regulated in the USA, potentially leading to increased accessibility and lower prices for the drug. Those changes will not take effect until 2020. The soaring cost and limited supply of insulin (which has been available for nearly a century) is just one example of an ongoing crisis of global drug prices, from treatments for hepatitis C that cost US$100 000 for a single course to cancer drugs that cost $400 000 per year per patient.

Abstract Background Hepatitis E virus (HEV) is a leading cause of hepatitis worldwide. However, its infection biology and pathogenesis remain largely elusive. Furthermore, no proven medication is available for treating hepatitis E. Robust experimental models are urgently required to advance the research of HEV infection. Because of the lacking of a sophisticated small animal model, this study aimed to establish a mouse model of HEV infection. Methods We constructed a full-length swine HEV cDNA clone of genotype 4 (named as pGEM-HEV) by reverse genetics approach. And we inoculated with HEV RNA in BALB/c mice to establish small animal model for HEV infection and pathogenesis studies. Results The capped RNA transcripts of pGEM-HEV prepared in vitro were replication-competent in HepG2 cells. Importantly, BALB/c mice intravenously inoculated with RNA transcripts of pGEM-HEV developed an active infection as shown by shedding viruses in feces, detectable negative strand of HEV in the liver, spleen and kidney, and causing liver inflammation. Conclusion In this study, we successfully established of BALB/c mice-based small animal model for HEV provides an opportunity to further understand HEV pathogenesis and to develop effective antiviral medications.…

Abstract Background The number of cases of Lymphogranuloma venereum (LGV) is increasing in Europe. The described epidemic is mostly confined to HIV positive men who have sex with men (MSM). However, dissemination of LGV from HIV positive to HIV negative MSM could take place due to the implementation of pre-exposure prophylaxis (PrEP) and subsequent possible decrease in condom use. We describe here the LGV epidemiology in Belgium before the PrEP-era, starting from 2011 up to the end of the first half of 2017. Methods A descriptive analysis of the socio-demographic and clinical characteristics of all LGV cases was performed. Fisher’s exact test was used to compare symptomatic to asymptomatic patients. Logistic regression models were used to check for trends over time for: number of LGV cases, HIV status and symptoms. Results The number of LGV cases rose by a factor four, from 21 in 2011 to 88 in 2016, and regression models showed a positive trend estimate of 14% increase per half year (p 

María Celeste Torres, Elida Civetta, Claudia D’amico, Luciana Barbini

Abstract Aims to describe the molecular epidemiology and perform a genomic characterization of Hepatitis B virus (HBV) circulating in Mar del Plata and to identify the origin and diversification patterns of the most prevalent genotype. The S gene and the region encompassing the X gene, basal core promoter (BCP) and precore (preC) was analyzed in 56 samples. They were genotyped as: 80% F1b, 9% A2, 7% D3 and 2% D1. A recombinant F4/D2 genome was detected. The double substitution G1764A/A1762T at the BCP (reduced HBeAg expression) was found in 20% F1b, 2% A2, 2% D1 and 2% D3 samples. A unique D3 presented the G1896A substitution at the preC (HBeAg negative phenotype). A 13% of the samples showed mutations at the HBsAg "a" immunodeterminant (escape from neutralizing antibodies). Mutations at the polymerase (antiviral resistance) were found in 52% of the samples. Coalescent analysis of subgentype F1b, the most prevalent in the city, showed that viral diversification in Mar del Plata started by year 2000. Conclusion: F1b was the most prevalent genotype detected, being a characteristic of actual HBV infections in Mar del Plata. Local HBV exhibit clinically relevant mutations, but a minority of them was shown to be associated to potential vaccination escape or antiviral resistance. Nevertheless, further studies are needed to determine whether any of these mutants could pose a threat to prevention, diagnosis or treatment. This article is protected by copyright. All rights reserved.

Su W, Chen S, Yang C, et al.

AbstractBackgroundThe hepatitis B virus (HBV) status of pregnant women affects HBV vaccine failure in their offspring. This study is aimed to investigate the impact of the universal infant HBV vaccination program on the long-term hepatitis B surface antigen (HBsAg) rate in pregnant women.MethodsUsing the National Immunization Information System, we examined a 32-year period of cross-sectional data on a maternal HBsAg and hepatitis B e antigen (HBeAg) screening program launched in July 1984. An age-period-cohort model analysis of 940,180 pregnant women screened for July 1996–June 1997, and years 2001, 2006, 2011, and 2016 was applied.ResultsThe annual HBsAg and HBeAg seropositive rates decreased from 13.4% and 6.4%, respectively, for the period 1984–1985 to 5.9% and 1.0% in 2016 (p for both trends < 0.0001). Pregnant women with birth years after July 1986 (the HBV vaccination cohort) had the lowest relative risk (0.27, 95% CI 0.26–0.28) of HBsAg positivity compared with birth years before June 1984.ConclusionThe birth cohort effect in relation to the universal infant HBV immunization program has effectively reduced the HBV carrier rate in pregnant women and the burden of perinatal HBV infection on the next generation.

Nastasio S, Jonas M.

Gosset, Andréa; Protopopescu, Camelia; Larmarange, Joseph; Orne-Gliemann, Joanna; Mcgrath, Nuala; Pillay, Deenan; Dabis, François; Iwuji, Collins; Boyer, Sylvie

Objective: To study retention in care (RIC) trajectories and associated factors in patients eligible for antiretroviral treatment (ART) in a universal test-and-treat setting (TasP trial, South Africa, 2012-2016). Design: A cluster-randomized trial whereby individuals identified HIV-positive after home-based testing were invited to initiate ART immediately (intervention) or following national guidelines (control). Methods: Exiting care was defined as ≥3 months late for a clinic appointment, transferring elsewhere, or death. Group-Based Trajectory Modelling was performed to estimate RIC trajectories over 18 months and associated factors in 777 ART-eligible patients. Results: Four RIC trajectory groups were identified: i) group 1 “remained” in care (reference, n=554, 71.3%), ii) group 2 exited care then “returned” after (median [interquartile range]) 4 [3-9] months (n=40, 5.2%), iii) group 3 “exited care rapidly” (after 4 [4-6] months, n=98, 12.6%), iv) group 4 “exited care later” (after 11 [9-13] months, n=85, 10.9%). Group 2 patients were less likely to have initiated ART within 1 month and more likely to be male, young (350 cells/mm3. Group 3 patients were more likely to be women without social support, newly diagnosed, young, and less likely to have initiated ART within 1 month. Group 4 patients were more likely to be newly diagnosed and aged ≤39 years. Conclusions: High CD4 counts at care initiation were not associated with a higher risk of exiting care. Prompt ART initiation and special support for young and newly diagnosed HIV-patients are needed to maximize RIC. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Corresponding Author: Andréa Gosset, INSERM UMR1252 – SESSTIM Méditerranée Infection – IHU, 19-21 Bd Jean Moulin, 13005 Marseille, Tel.: +33 4 13 73 22 94 ; email : andrea.gosset@inserm.fr The authors report no conflicts of interest related to this work. Preliminary results were presented as a poster at the 9th IAS conference on HIV science - Paris, France, 23-26 July 2017. Declaration of interests: CI has received honoraria for consulting services from Gilead Sciences. All other authors declare no competing interests. Funding: The French National Agency for AIDS and Viral Hepatitis Research (ANRS; grant number, 2011-375) sponsored and co-founded the trial. The Deutsche Gesellschaft fur Internationale Zusammenarbeit (GIZ; grant number, 81151938), and the Bill & Melinda Gates Foundation through the 3ie Initiative co-founded the trial. Merck and Gilead Sciences supported the trial by providing Atripla. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Lemoine, Maud; Assoumou, Lambert; De Wit, Stephane; Girard, Pierre-Marie; Valantin, Marc Antoine; Katlama, Christine; Necsoi, Coca; Campa, Pauline; Huefner, Anja D.; Schulze zur Wiesch, Julian; Rougier, Hayette; Bastard, Jean-Philippe; Stocker, Hartmut; Mauss, Stefan; Serfaty, Lawrence; Ratziu, Vlad; Menu, Yves; Schlue, Jerome; Behrens, Georg; Bedossa, Pierre; Capeau, Jacqueline; Ingiliz, Patrick; Costagliola, Dominique

Background: HIV-monoinfected individuals are at high risk of non-alcoholic fatty liver disease (NAFLD). Non-invasive tests of steatosis, nonalcoholic steatohepatitis (NASH) and fibrosis have been poorly assessed in this population. Using liver biopsy (LB) as a reference, we assessed the accuracy of noninvasive methods for their respective diagnosis: MRI proton-density-fat-fraction (MRI-PDFF), Fibroscan®/CAPTM and biochemical tests. Methods: We enrolled ART-controlled participants with persistently elevated transaminases and/or metabolic syndrome, and/or lipodystrophy. All had hepatic MRI-PDFF, Fibroscan®/CAP, FibrotestTM/NashtestTM/SteatotestTM, APRI, FIB-4 and NFS. A LB was indicated if suspected significant fibrosis (Fibroscan≥7.1 kPa and/or Fibrotest≥0.49). Performance was considered as good if area under a ROC curve (AUROC) was >0.80. Results: Among the 140 patients with suspected significant fibrosis out of the 402 eligible patients, 49 had had a LB: median age 54 years (53-65), BMI: 26 kg/m2 (24-30), steatosis in 37 (76%), NASH in 23 (47%) and fibrosis in 31 (63%) patients [F2:7(14%); F3:6(12%); F4:2(4%)]. Regarding steatosis, MRI-PDFF had excellent and CAP good performances with AUROC at 0.98 (95%CI:0.96-1.00) and 0.88 (0.76-0.99) respectively, whilst the AUROC of SteatotestTM was 0.68 (0.51-0.85). Regarding fibrosis (≥F2), APRI and FIB-4 had good performance with AUROC at 0.86 (0.74-0.98) and 0.81 (0.67-0.95). In contrast, Fibroscan® and Fibrotest® had poor AUROC (0.61 (0.43-0.79) and 0.61 (0.44-0.78), with very low specificity. Regarding NASH, ALT≥36IU/l had good performance with AUROC of 0.83 (0.71-0.94) while NASHtestTM had an AUROC of 0.60 (0.44-0.76). Conclusion: In HIV-monoinfected patients, MRI-PDFF and Fibroscan®/CAP are highly accurate for the diagnosis of steatosis. ALT level and APRI should be considered for the detection of NASH and fibrosis. Corresponding author: Maud Lemoine Imperial College London Department of surgery and liver cancer, liver unit St Mary’s hospital South Wharf Street London, UK Email: m.lemoine@imperial.ac.uk Tel: + 44 (0) 20 331 25 212 * equally contributed Funding: The study was funded by the HIV-ERANET European program (01KI1205A) and French Research Agency on HIV and viral hepatitis (ANRS) The authors report no conflicts of interest related to this work. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Abstract Background Hepatitis C virus (HCV) infection is a recognised cause of secondary immune thrombocytopenia (ITP). While its incidence has been largely described during chronic HCV infection, only one case of ITP secondary to acute HCV infection has been reported at this time. Case presentation We report herein the case of severe ITP secondary to an acute HCV genotype 1a reinfection in a human immunodeficiency virus (HIV)-negative man having sex with men who had been cured several years before of a previous acute genotype 4d HCV infection. After an unsuccessful standard therapy with two courses of intravenous immunoglobulin (at 1 g/kg daily for 2 days) associated with methylprednisolone 1 mg/kg daily, antiviral treatment with sofosbuvir-ledipasvir rapidly achieved virological response and normalised the platelet count. Conclusions As a direct effect of HCV on megakaryocytes could be the predominant cause of ITP during acute infection, early antiviral treatment may be beneficial in this case.…

Benmassaoud A, Nitulescu R, Pembroke T, et al.

AbstractBackgroundHuman immunodeficiency virus (HIV)-infected patients are at increased risk of liver-related mortality. The effect of occult cirrhosis (OcC), defined as preclinical compensated cirrhosis without any clinical findings, on liver-related events is unknown.MethodsHIV-infected patients from two Canadian cohorts underwent transient elastography (TE) examination and were classified as: 1) OcC (TE ≥13 kPa with no sign of cirrhosis, including absence of thrombocytopenia and signs of advanced liver disease on ultrasound or gastroscopy); 2) overt cirrhosis (OvC) (TE ≥13 kPa with signs of cirrhosis); 3) non-cirrhotic patients (TE

Abstract Background Dengue has global importance as a dreaded arboviral infection. It has 4 serotypes of epidemiological imporatnce. The classification denotes two clinical spectrums- dengue fever (DF) and dengue haemorragic fever (DHF). Most cases are stereotype and amenable to fluid resuscitation. However, unusual manifestations cause fatalities and often overlooked. This study describes 10 such dengue cases to fill the knowledge gaps. Case presentation All 10 patients presented to the Teaching Hospital, Peradeniya, Sri Lanka during mid-year epidemic of dengue in 2016. The mean age is 27 years (range 12-51 years) comprising 6 females and 4 males. The group had 7 DHF, 3 DF and 2 primary dengue infections who predominantly had severe bleeding into gut. Other potentially life threatening problems were acute severe hepatitis, severe septic shock, myocarditis, erratic rapid plasma leak, intracranial bleeding, diarrhoea and decompenstaed dengue shock due to 3rd space fluid leak. Blood transfusions and other empirical therapeutic methods were used apart from meticulous fluid management to suit issues of each patient. Bedside ultrasound scanning helped early detection of critical phase. All recovered fully. Conclusions Dengue is an extremely challenging infection to treat in the globe today. Above unusual presentation and complications could be fatal, if not detected early where therapeutic window period is very short. Clinicians need awareness of these problems which are not uncommon, but underreported and often overlooked. The clinical management of each patient was described for the purpose sharing the experiences.…

Yong Liu, Guiyang Wang, Yuxin Chen, Rui Huang, Chen Tian, Yang Li, Xiang‐An Zhao, Chao Wu

Abstract During the natural history of chronic hepatitis B infection (CHB) the function of B cells is still obscure. Several limited studies have suggested that B cells are highly active in CHB patients. In present work, we reported that the 4‐1BB ligand (4‐1BBL) expression on B cells was significantly higher in CHB patients than that in healthy subjects, meanwhile the CHB patients had higher serological IgG levels. Further, after stimulated with sCD40L or HBcAg, B cells had higher levels of 4‐1BBL. After co‐cultured with 4‐1BBL+ B cells, the expressions of CD69 and 4‐1BB on CD4+ T cells were significantly higher than that co‐cultured with 4‐1BBL‐ B cells. Cytokines including IL‐2, IL‐4 and IL‐6 were significantly higher in the supernatant from 4‐1BBL+ B cells co‐culture group than those from co‐culture group of 4‐1BBL‐ B cells group, respectively; while IFN‐γ and TNF‐α in co‐cultured supernatant of 4‐1BBL+ B cells group were significantly lower. Consistently, the total IgG levels in culture supernatant were significantly higher in 4‐1BBL+ B cells group. Thus, hyperactive status of B cells in CHB patients could be partially derived from higher 4‐1BBL expression on B cells triggered by HBcAg. 4‐1BBL signaling pathway is involved in B cells activation, and further regulates B cell‐T cells interaction by modulating the cytokines secretion, which might be critical in B cells dysfunction during CHB infection. This article is protected by copyright. All rights reserved.

Ayman Yosry, Hadeel Gamal Eldeen, Eman Medhat, Mai Mehrez, Naglaa Zayed, Wafaa Elakel, Reham Abdelmoniem, Mona Kaddah, Ashraf Abdelaziz, Gamal Esmat, Magdy EL‐Serafy, Wahid Doss

Background and Aim Direct acting antiviral has offered treatment of hepatitis C virus (HCV) recurrence post liver transplantation (LT) with an all‐oral regimen for short duration, excellent safety profile, and high sustained virological response (SVR). The aim of this study was to evaluate the efficacy and safety of sofosbuvir (SOF)‐based regimens in the real world among a cohort of Egyptian patients with recurrent HCV post living donor LT (LDLT). Methods Patients with HCV‐G4 recurrence post‐LDLT were recruited from National Committee of Control of Viral Hepatitis, Egypt, from November 2014 to May 2017. They received different SOF‐based regimens according to the treatment protocols available during this period. Patients’ outcome and Adverse effects (AE) were evaluated. Results One hundred ninety patients (170 males, mean age 56.8 ± 7.9 years) were included. Calcineurin inhibitors were the main immunosuppression used (173 patients). Out of 190, 119 (62.6%) received SOF/ribavirin (RBV), 38 (20%) SOF/simeprevir (SMV), 22 (11.6%) SOF/daclatasvir (DSV)/ ± RBV, and 11 (5.8%) received SOF/LDV/ ± RBV. Overall SVR12 was 89.5%, 84.9% in SOF/RBV group, 94.7% in SOF/SMV, 100% in SOF/DCV, and 100% in SOF/LDV with no statistically significant difference ( P = 0.104). The AE reported were as follows: anemia (n = 65, 34.4%) mainly in SOF/RBV group, transient hyperbilirubinemia during SOF/SMV in 13 patients (34%), mild Acute cellular rejection in eight patients (4.2%), and hepatocellular carcinoma in two patients (1%) mainly driven by underlying liver condition. Two deaths were unlikely related to HCV therapy. Conclusion Different SOF‐based regimens were effective with high SVR12 rates in a difficult‐to‐treat population, recurrent HCV post LDLT.

Ishida, Yuki; Hayashida, Tsunefusa; Sugiyama, Masaya; Tsuchiya, Kiyoto; Kikuchi, Yoshimi; Mizokami, Masashi; Oka, Shinichi; Gatanaga, Hiroyuki

Background. Acute hepatitis C virus (HCV) infection is increasing among HIV-1-infected individuals in Tokyo. Appropriate clinical management is needed. Setting. To delineate the epidemiological status of HCV transmission, we analyzed stocked plasma samples of HCV/HIV-1-coinfected patients seen at the largest referral center for HIV care in Tokyo. Methods. HCV full-genome sequences were amplified and determined using next-generation sequencing. HCV genotyping and phylogenetic and phylodynamic analyses of thus obtained sequences were performed and combined with the analysis of HIV-1 reverse transcripatese (RT) sequences. Results. HCV phylogenetic analysis identified three dense clusters containing cases of men who have sex with men (MSM) and injection drug users (IDU). Most of the confirmed acute infection cases were included within these clusters, indicating that the clustered viruses are currently being actively transmitted among HIV-1-infected MSM and IDU. Phylodynamic analysis indicated population expansion of one of these clusters from 2006 to 2008, during which the largest number of HIV-1-infected MSM were diagnosed in Tokyo. HIV-1 RT sequences of HCV-coinfected patients included in the same clusters did not converge together and did not form clusters, but rather diverged in the area of subtype B in the phylogenetic tree, indicating that they acquired HCV infection from individuals different from those they had acquired HIV-1 infection. It is considered that these MSM changed their sexual partners and that IDU changed their drug use groups. Conclusions. The results warrant careful monitoring of high-risk groups including MSM and IDU and early introduction of HCV treatment in order to prevent HCV epidemic. Corresponding author: Hiroyuki GATANAGA, M.D. AIDS Clinical Center, National Center for Global Health and Medicine 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan Tel: +81-3-3202-7181, Fax: +81-3-5273-6483, E-mail: higatana@acc.ncgm.go.jp Conflicts of Interests: All authors: No reported conflicts of interest. Funding: This work was supported by a Grant for National Center for Global Health and Medicine (28-1102) and a grant-in-aid for AIDS research from the Japan Agency for Medical Research and Development. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Abstract Background In Southeast Asia, though fishermen are known to be a key population at high risk of HIV, little is known about their co-infection rates with Hepatitis C virus (HCV), or how illness and risk behaviors vary by occupation or type of fishermen. In Myanmar, this lack of knowledge is particularly acute, despite the fact that much of the country’s border is coastline. Methods We conducted a retrospective analysis to assess clinical, demographic, and risk characteristics of HIV-infected, ≥15-year-old males under HIV care from 2004 to 2014. Subgroups of fishermen were categorized according to the location of fishing activities, boat ownership, and length of time at sea. Generalized linear models assessed odds of high risk behaviors, including MSM (men who have sex with men), transactional sex, injection drug use (IDU), and HCV co-infection among international, local subsistence, and national migrant fishermen. Results Of 2798 adult males who enrolled in HIV care between 2004 and 2014, 41.9% (n = 1172) were fishermen. Among these, migrants had the highest odds of engaging in risk behaviors such as sex work (Myanmar national migrants: OR 3.26 95% CI: 2.20 to 4.83), and injecting drugs (international migrants: OR 2.93, 95% CI: 1.22 to 3.87) when compared to the general male HIV clinic population. 15.9% of all fishermen reported past or current IDU (23.0% of international migrants). 22.8% of all fishermen were also co-infected with HCV, and though predictably injectors had the highest odds (OR 20.1, 95% CI: 13.7 to 29.5), even after controlling for other risk factors, fishermen retained higher odds (OR 2.37 95% CI: 1.70 to 3.32). Conclusions HIV positive fishermen in Myanmar had higher odds of HCV co-infection. They also disproportionally injected drugs and engaged in transactional sex more than other patients. This is especially pronounced among international migrant fishermen. HIV-infected fishermen should be counseled on high risk activities, screened for HCV, and targeted by harm reduction programs.…

Agostino Colli, Alessandra Berzuini, Daniele Prati

A 19-year-old man presented to our emergency department with abdominal pain and jaundice. He had emigrated from Senegal during infancy. He was found to be a carrier of hepatitis B virus, with a hepatitis B surface antigen serum DNA concentration persistently below 2000 IU/mL. He was negative for hepatitis B e antigen and positive for anti-hepatitis B e antibodies.

Abstract Background Liver transplant recipients are at high risk of developing invasive aspergillosis and in particular by Aspergillus fumigatus which is the most commonly encountered species in this population. Other non-fumigatus Aspergillus species with reduced susceptibility to antifungal drugs can also be involved. Accurate identification associated to antifungal susceptibility testing is essential for therapy adjustment. We report a case of invasive pulmonary aspergillosis due to Aspergillus pseudodeflectus in a liver transplant recipient. To our knowledge, this is the first reported case of invasive aspergillosis due to this species with a reduced susceptibility to azoles. Case presentation A 64 year-old woman with drug-induced fulminant hepatitis underwent liver transplantation. Prophylactic treatment with caspofungin was introduced due to aspergillosis risk factors consisting in hemodialysis and fulminant hepatitis. Six weeks after transplantation, CT scan showed a right pulmonary opacity associated with an increase of galactomannan (index 5.4). Culture of BAL grew with several colonies of Aspergillus sp. The diagnosis of invasive aspergillosis was probable according to the EORTC criteria. The antifungal susceptibility tests (Etest®) revealed low MICs to echinocandins and amphotericin B) but high MICs to azoles. After these results, voriconazole was switched to liposomal amphotericin B. The patient died one month after diagnosis from a refractory septic shock with multiple organ failure. A molecular identification of isolate, based on partial β-tubulin and calmodulin genes, was performed and identified A. pseudodeflectus. Conclusions Our case raises the question of pathogenicity of this species, which belongs to Aspergillus section Usti and is genetically and morphologically very close to Aspergillus calidoustus that was previously reported in human transplant recipients.…

Yuan Liao, Jiao Gong, Wenying Zhou, Huimin Dong, Jiayin Liang, Minqi Luo, Bo Hu

Chronic liver inflammation caused by chronic hepatitis B virus (CHB) infection leads to liver cirrhosis and hepatocellular carcinoma. Recently, the role of alanine aminotransferase (ALT) as a predictor of liver inflammation has been questioned. The aim of this study was to investigate the utility of noninvasive fibrosis markers including hyaluronic acid (HA), collagen type IV (CIV), N‐terminal propeptide of type III procollagen (PIIINP), and laminin (LN) in identifying significant liver inflammation in patients with CHB, especially in patients with normal or near‐normal ALT. A total of 242 CHB patients who underwent liver biopsy were enrolled. The serum levels of ALT, aspartate aminotransferase, HA, CIV, PIIINP, and LN were quantified and the relationship between histological staging and serum markers was systematically analyzed. Serum CIV, PIIINP, HA, and LN levels increased significantly along with the increasing severity of liver inflammation. Multivariate analysis showed that CIV and LN were independently associated with significant inflammation. CIV, PIIINP, HA, and LN levels were found to have high diagnostic values for predicting significant inflammation in patients with CHB (area under the curve, AUC = 0.807, 0.795, 0.767, and 0.703, respectively). The combined index for the identification of significant inflammation, including CIV, PIIINP, HA, and LN levels, significantly improved diagnostic performance (AUC = 0.851). Moreover, the combined index also achieved excellent diagnostic accuracy (AUC = 0.861) in patients with CHB with normal or near‐normal ALT. In conclusion, the combined index may be a strong indicator for discriminating significant liver inflammation, especially in patients with CHB with normal or near‐normal ALT.

Chloé Dimeglio, Frédéric Beau, Julien Broult, Patrice Gouy, Jacques Izopet, Stéphane Lastère, Florence Abravanel

by Chloé Dimeglio, Frédéric Beau, Julien Broult, Patrice Gouy, Jacques Izopet, Stéphane Lastère, Florence Abravanel The HEV seroprevalence in mainland France is elevated (22.4%). In contrast, anti-HEV seroprevalence appears to be lower in Oceania. However, none is available for French Polynesia. We assessed the anti-HEV IgG and IgM prevalence on samples from 300 consecutive blood donors living on Tahiti and Moorea islands. Epidemiological information was collected using a specific questionnaire. Overall IgM seroprevalence was 0.6% and overall IgG seroprevalence was 7.7%. The presence of anti-HEV IgG was associated with increasing age (p = 0.01), eating chicken offal (p = 0.01) and cooked rabbit (p = 0.02). Conversely, eating fafaru—traditional Polynesian condiment—was associated with a lower rate of anti-HEV IgG (p

Abstract Background The frequency of mild forms of hepatitis A, especially in children, could lead to underreporting. The objective of the study was to investigate the sensitivity of two surveillance systems, mandatory Statutory Disease Reports and the Microbiological Reporting System of Catalonia, using capture-recapture techniques. Methods The study was conducted in Catalonia between 2011 and 2015. Hepatitis A cases reported to two independent surveillance systems were included: Statutory Disease Reports (SDR) and Microbiological Reporting System of Catalonia (MRS). The variables collected were: age, sex, year of declaration, size of municipality (

El-Sadr, Wafaa M.; Beauchamp, Geetha; Hall, H. Irene; Torian, Lucia V.; Zingman, Barry S.; Lum, Garret; Elion, Richard A; Buchacz, Kate; Burns, David; Zerbe, Allison; Gamble, Theresa; Donnell, Deborah J.; for the HPTN 065 Study

Background: Results from the HPTN 065 study showed that financial incentives (FI) were associated with significantly higher viral load suppression and higher levels of engagement in care among patients at HIV care sites randomized to FI versus sites randomized to standard of care (SOC). We assessed HIV viral suppression and continuity in care after intervention withdrawal to determine the durability of FI on these outcomes. Setting: A total of 37 HIV test and 39 HIV care sites in the Bronx, New York and Washington, DC participated in the study. Methods: Laboratory data reported to the US National HIV Surveillance System were used to determine site-level viral suppression and continuity in care outcomes. Post-intervention effects were assessed for the three quarters after discontinuation of FI. Generalized estimation equations (GEE) were used to compare FI and SOC site-level outcomes after intervention withdrawal. Results: After FI withdrawal, a trend remained for an increase in viral suppression by 2.7% (-0.3%, 5.6%, p=0.076) at FI versus SOC sites, decreasing from the 3.8% increase noted during implementation of the intervention. The significant increase in continuity in care during the FI intervention was sustained post-intervention with 7.5% (p=0.007) higher continuity in care at FI versus SOC sites. Conclusion: Following the withdrawal of FI, findings at 9 months post-intervention withdrawal from this large study showed evidence of durable effects of FI on continuity in care, with encouraging trends for continued higher viral suppression. These findings are promising for adoption of such interventions to enhance key HIV-related care outcomes. 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. Corresponding Author: Wafaa El-Sadr, MD, MPH, ICAP, Mailman School of Public Health, Columbia University, 722 W 168th St, PO Box 18, 13th Flr, New York, NY 10032, email: wme1@cumc.columbia.edu; phone: (212) 342-0505; fax: (212) 342-1824 Meeting Presentation: Data included in this article were presented as a poster presentation at the Conference on Retroviruses and Opportunistic Infections (CROI); March 4-7 2018; Boston, Massachusetts. Sources of Support: The HIV Prevention Trials Network (HPTN) 065 study is sponsored by the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, and the National Institute on Drug Abuse, of the US National Institutes of Health, under Cooperative Agreements #UM1 AI 068619 and UM1 AI 068617, as well as the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention. Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, or the Centers for Disease Control and Prevention. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

Yogambigai Rajamoorthy, Alias Radam, Niazlin Mohd Taib, Khalid Ab Rahim, Abram Luther Wagner, Mudatsir Mudatsir, Subramaniam Munusamy, Harapan Harapan

by Yogambigai Rajamoorthy, Alias Radam, Niazlin Mohd Taib, Khalid Ab Rahim, Abram Luther Wagner, Mudatsir Mudatsir, Subramaniam Munusamy, Harapan Harapan Background Malaysia has a comprehensive, publicly-funded immunization program for hepatitis B (HepB) among infants, but adults must pay for the vaccine. The number of HepB carriers among adults is expected to increase in the future; therefore, we examined the impact of five constructs (cues to action, perceived barriers, perceived benefit, perceived severity, and perceived susceptibility) on adults’ willingness to pay (WTP) for HepB vaccine; secondarily, we examined the association between perceived barriers and perceived benefits. Methods Adults were selected through a stratified, two-stage cluster community sample in Selangor, Malaysia. The reliability, convergent validity, and discriminant validity of the measurement model were assessed before implementing a partial least squares structural equation model (PLS-SEM) to evaluate the significance of the structural paths. Results A total of 728 participants were enrolled. The five constructs all showed adequate internal reliability, convergent validity, and discriminant validity. There was a significant, positive relationship to WTP from constructs (perceived barriers [Path coefficient (β) = 0.082, P = 0.036], perceived susceptibility [β = 0.214, P…

Timothee Bonifay, Christelle Prince, Clarisse Neyra, Magalie Demar, Dominique Rousset, Hatem Kallel, Mathieu Nacher, Félix Djossou, Loïc Epelboin, and the Char Chik Working group

by Timothee Bonifay, Christelle Prince, Clarisse Neyra, Magalie Demar, Dominique Rousset, Hatem Kallel, Mathieu Nacher, Félix Djossou, Loïc Epelboin, and the Char Chik Working group Background French Guiana (FG) was the first country in South America to declare chikungunya virus infection (CHIKV). The outbreak affected about 16,000 persons between February 2014 and October 2015, with several atypical cases, but only two fatal cases. We aimed to describe the clinical presentation of patients hospitalized for CHIKV infection, to estimate and identify risk factors of unusual and severe forms in adult patients. Materials and methods A monocentric retrospective study was conducted in Cayenne hospital, the main city and the main hospital in FG, from March 1st 2014 to August 31st 2015. All patients admitted for at least one night with a biological diagnosis of CHIKV infection during the 2014/2015 outbreak were included, except pregnant women and children under 15 years. Results During the study period, 285 patients with a diagnosis of CHIKV infection were hospitalized in Cayenne hospital, among whom 96 nonpregnant adults were studied. Five were classified as severe forms (5.2%) and 23 as unusual forms (23.9%). The most frequent atypical and/or severe form was neurological (n = 20), followed by cardio-respiratory failure (acute respiratory failure n = 4, acute heart failure n = 2), digestive and hepatic disorders (acute hepatitis n = 3, acute pancreatitis n = 2), renal disorders (acute renal failure n = 5) and muscular impairment (rhabdomyolysis n = 3). Conclusion During the outbreak, hospitalizations were frequent, particularly for common forms, driven by algic clinical presentations and concerns due to the novelty of this infection. Despite atypical neurological and liver forms of CHIKV infection, case-fatality was low in French Guiana. No specific risk factor of atypical and/or severe forms was found in our study.…

Arnaud Tarantola and Cyrille Goarant

Abstract. Early names for leptospirosis often indicate occupational or environmental exposure. Leptospirosis is hard to identify in the tropical setting because of co-circulating diseases. This is not the case in the temperate setting, such as Europe, where the few historical differential diagnoses were malaria, typhoid, and viral hepatitis. Leptospirosis presumably caused community epidemics in Europe before 1900 and military epidemiologists carefully documented outbreaks in “constrained settings.” Achille Kelsch (1841–1911) synthesized available military data and epidemiological perspectives to define “epidemic jaundice” as a nosological continuum, caused by an infectious agent found in muds and water. He viewed Weil’s disease as being only one form of that now well-identified disease continuum. The causative pathogen and epidemiological determinants were identified years later. The role of soils and muds as intermediate reservoirs, as suggested by Kelsch, deserves further investigation.…

Charles Ampong Adjei, Fidelis Atibila, Felix Apiribu, Frederick Ahordzor, Priscilla Adumoah Attafuah, Michael Ansah-Nyarko, Richard Asamoah and William Menkah

Abstract. Global evidence suggests that hepatitis B viral (HBV) infection is endemic in Africa and perinatal transmission remains one of the most important modes of HBV transmission in this area. This cross-sectional survey examined the seroprevalence and knowledge of hepatitis B among pregnant women attending antenatal clinic (ANC) in a mission hospital in Ghana. Systematic sampling technique was used to recruit 196 pregnant women. The level of statistical significance was set at 0.05 alpha level. The hepatitis B prevalence estimate (hepatitis B surface antigen) was 10.2% (N = 20) and all of the participants were aware of HBV infection. Majority cited media (radio) as their main source of information. Approximately 86% of the participants (N = 168) associated HBV infection with a curse and 88.8% (N = 174) indicated witches and wizards as possible causes of the infection. Those with higher level of school education had high hepatitis B knowledge score (P < 0.01). Implementation of a health education program on the route of hepatitis B transmission is required in the study setting. Also, inclusion of hepatitis B education as part of ANC activities will enable HBV-positive pregnant women to appreciate the need for hepatitis B vaccination of their newborns at birth.…