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Talha Burki

The prizes, given annually for achievements in medicine and public health, have gone this year to scientists working on hepatitis C virus and trachoma. Talha Burki reports.

de Lazzari, Elisa; Lonca, Montserrat; Rojas, Jhon; Gonzalez-Cordon, Ana; Blanch, Jordi; Inciarte, Alexy; Tricas, Amparo; Rodriguez, Ana; Martinez-Rebollar, Maria; Laguno, Montserrat; Mallolas, Josep; Sanchez-Palomino, Sonsoles; Plana, Montserrat; Blanco, Jose L.; Martinez, Esteban

Background: There is an increasing interest in two-drug regimens. We hypothesized that maintenance therapy with raltegravir plus lamivudine would keep HIV-1 suppressed and be well tolerated. Methods: Virally suppressed HIV-1-infected adults without previous viral failures or known resistance mutations to integrase inhibitors or 3TC/FTC or chronic hepatitis B were randomized 2:1 to switch to fixed-dose combination 150 mg lamivudine/300 mg raltegravir twice daily or to continue therapy. Primary outcome was the proportion of patients free of therapeutic failure (defined as viral failure, change in treatment for any reason, consent withdrawal, loss to follow-up or death) at week 24. Secondary outcomes were changes in laboratory, body composition, sleep quality, adherence, and adverse effects. Results: There were 75 patients included: men 78%; median age 50 years; median CD4 622/mm3. At week 24, 7 (9%) patients had therapeutic failure: raltegravir plus lamivudine 2 (4%) vs. control 5 (20%). The difference in proportions of therapeutic failures raltegravir plus lamivudine minus control was -0.159 (95% confidence interval: -0.353; -0.012). There was a trend to more weight gain with raltegravir plus lamivudine, but no significant changes in other secondary outcomes. Sixty four percent of patients in each arm had at least one adverse effect. Two (6%) patients in control arm and 4 (7%) patients in raltegravir plus lamivudine arm had severe adverse effects. Conclusion: This pilot study suggests that switching to raltegravir plus lamivudine in patients with viral suppression maintains efficacy and is well tolerated. A larger study of longer duration is required to confirm these findings. Correspondence to Esteban Martinez, PhD, Senior Consultant & Associate Professor of Medicine, Infectious Diseases Unit, Hospital Clínic & University of Barcelona, 08036 Barcelona, Spain. Tel: +34 93 227 55 74; fax: +34 93 451 44 38; e-mail: estebanm@clinic.cat Received 21 December, 2018 Revised 1 May, 2019 Accepted 26 May, 2019 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2019 Wolters Kluwer Health, Inc.

Norton B, Litwin A.

As the United States experiences an unprecedented opioid epidemic, the number of people who inject drugs (PWID) continues to rise, paralleled by increasing rates of hepatitis C virus (HCV) [1, 2]. Mortality from HCV has now surpassed the combined death rates from the 60 other reportable infectious diseases, including human immunodeficiency virus (HIV) [3, 4]. Direct acting antiviral medications (DAA) have changed the paradigm of HCV treatment, providing highly effective (over 95% cure rates), all oral medications with few side effects and short treatment durations [5]. Given this tremendous opportunity, the World Health Organization (WHO) issued its first global strategy on HCV, with the goal to reach HCV elimination by 2030 [6]. Due to the lack of engagement and treatment of HCV-infected PWID, the United States is not on track to meet these targets [7]. Due to clinician concerns about poor adherence and low cure rates, as well as a fragmented healthcare system, most PWID living in the US have yet to be offered life-saving HCV treatment [8–10].

Abstract Background Intestinal infectious diseases (IIDs) have caused numerous deaths worldwide, particularly among children. In China, eight IIDs are listed as notifiable infectious diseases, including cholera, poliomyelitis, dysentery, typhoid and paratyphoid (TAP), viral Hepatitis A, viral Hepatitis E, hand-foot-mouth disease (HFMD) and other infectious diarrhoeal diseases (OIDDs). The aim of the study is to analyse the spatio-temporal distribution of IIDs from 2006 to 2016. Methods Data on the incidence of IIDs from 2006 to 2016 were collected from the public health science data centre issued by the Chinese Center for Disease Control and Prevention. This study applied seasonal decomposition analysis, spatial autocorrelation analysis and space-time scan analysis. Plots and maps were constructed to visualize the spatio-temporal distribution of IIDs. Results Regarding temporal analysis, the incidence of HFMD and Hepatitis E showed a distinct increasing trend, while the incidence of TAP, dysentery, and Hepatitis A presented decreasing trends over the last decade. The incidence of OIID remained steady. Summer is the season with the greatest number of cases of different IIDs. Regarding the spatial distribution, approximately all p values for the global Moran’s I from 2006 to 2016 were less than 0.05, indicating that the incidences of the epidemics were unevenly distributed throughout the country. The high-risk areas for HFMD and OIDD were located in the Beijing-Tianjin-Tangshan (BTT) region and south China. The high-risk areas for TAP were located in some parts of southwest China. A higher incidence rates for dysentery and Hepatitis A were observed in the BTT region and some west provincial units. The high-risk areas for Hepatitis E were the BTT region and the Yangtze River Delta area. Conclusions Based on our temporal and spatial analysis of IIDs, we identified the high-risk periods and clusters of regions for the diseases. HFMD and OIDD exhibited high incidence rates, which reflected the negligence of Class C diseases by the government. At the same time, the incidence rate of Hepatitis E gradually surpassed Hepatitis A. The authorities should pay more attention to Class C diseases and Hepatitis E. Regardless of the various distribution patterns of IIDs, disease-specific, location-specific, and disease-combined interventions should be established.…

Abstract Background Hepatitis C virus (HCV) is a leading cause of chronic liver disease. As yet there is no approved vaccine protects against contracting hepatitis C. HCV seriously affects many people’s health in the world. Methods In this article, an epidemiological model is proposed and discussed to understand the transmission and prevalence of hepatitis C in mainland China. This research concentrates on hepatitis C data from Chinese Center for Disease Control and Prevention (China’s CDC). The optimal parameters of the model are obtained by calculating the minimum chi-square value. Sensitivity analyses of the basic reproduction number and the endemic equilibrium are conducted to evaluate the effectiveness of control measures. Results Vertical infection is not the most important factor that causes hepatitis C epidemic, but contact transmission is. The proportion of acute patients who are transformed into chronic patients is about 82.62%. The possibility of the hospitalized patients who are restored to health is about 76.24%. There are about 92.32% of acute infected are not treated. The reproduction number of hepatitis C in mainland China is estimated as approximately 1.6592. Conclusion We find that small changes of transmission infection rate of acutely infected population, transmission infection rate of exposed population, transition rate for the acutely infected, and rate of progression to acute stage from the exposed can achieve the purpose of controlling HCV through sensitivity analysis. Finally, based on the results of sensitivity analysis, we find out several preventions and control strategies to control the Hepatitis C.…

Zhao, N., Jia, B., Zhao, H., Xu, J., Sheng, X., Luo, L., Huang, Z., Wang, X., Ren, Q., Zhang, Y., Zhao, X., Cui, Y.

GLS4 is a novel inhibitor of the hepatitis B virus (HBV) capsid assembly with inhibitory activities against nucleot(s)ide-resistant HBV strains. This study investigated the pharmacokinetics, safety, and tolerability of GLS4 and the effects of food and ritonavir in healthy adults. GLS4 was administered in a single-ascending-dose study over 1-240 mg and multiple-ascending-dose study that ranged from 30 mg once daily to 180 mg thrice daily. The drug interaction study included sequential-design (day 1 for 120 mg GLS4 alone, day 5 for 100 mg ritonavir alone followed by 9 days of both drugs) and a placebo-control (9 days of both 240 mg GLS4 and 100 mg ritonavir). The results showed that the steady-state trough concentration of multiple dosing of GLS4 alone was significantly lower than the 90% effective concentration (EC90) of 55.7 ng/ml, even with increasing dosing frequency and dosage. An initial dose of 100 mg ritonavir significantly boosted plasma concentration at 24 h of 120 mg GLS4 from 2.40 ng/ml to 49.8 ng/ml (geometric mean ratio of 20.7, 90% confidence interval 17.0-25.3), while a milder effect was observed on the area under the curve (AUC)0-24h with a 7.42-fold increase and on Cmax, with a 4.82-fold increase. The pharmacokinetics change in GLS4 persisted after 9 days of chronic dosing, with a trough concentration of 182 ng/ml. Both single and multiple doses of GLS4 up to 240 mg with or without ritonavir were well tolerated. These results support the investigation of a novel HBV treatment regimen containing GLS4 with 100 mg ritonavir added solely to enhance GLS4 concentrations in plasma.…

Ko, C., Bester, R., Zhou, X., Xu, Z., Blossey, C., Sacherl, J., Vondran, F. W. R., Gao, L., Protzer, U.

Hepatitis B virus (HBV) is a major human pathogen killing an estimated 887,000 humans per year. Therefore, potentially curative therapies are of high need. Following infection, HBV deposits a covalently closed circular (ccc) DNA in the nucleus of infected cells that serves as transcription template and is not affected by current therapies. HBV core protein allosteric modulators (CpAMs) prevent correct capsid assembly but may also affect early stages of HBV infection. In this study, we aimed to determine the antiviral efficacy of a novel, structurally distinct heteroaryldihydropyrimidine (HAP)-type CpAM, HAP_R01, and investigated whether and how HAP_R01 prevents the establishment of HBV infection. HAP_R01 shows a significant inhibition of cccDNA formation when applied during the first 48 h of HBV infection. Inhibiting cccDNA formation, however, requires >1 log10 higher concentrations than inhibition of the assembly of newly forming capsids (half-maximal effective concentration (EC50) 345-918 nM versus 26.8-43.5 nM, respectively). Biophysical studies using a new method to detect the incoming capsid in de novo infection revealed that HAP_R01 can physically change mature capsids of incoming virus particles and affect particle integrity. Treating purified HBV virions with HAP_R01 reduced their infectivity, highlighting the unique antiviral activity of CpAMs to target the capsid within mature HBV particles. Accordingly, HAP_R01 shows an additive antiviral effect in limiting de novo infection when combined with viral entry inhibitors. In summary, HAP_R01 perturbs capsid integrity of incoming virus particle, reduces their infectivity and thus inhibits cccDNA formation in addition to preventing HBV capsid assembly.…

Belaynew Wasie Taye

Abstract. Ethiopia’s hepatitis C virus (HCV) prevalence is predicted to rise by 2030. To halt this increasing trend, a suitable approach to the elimination of HCV is needed. This review explores the current status, challenges, and opportunities and outlines a strategy for the micro-elimination approach in Ethiopia. I searched PubMed and EMBASE using combined Medical Subject Heading databases for the literature on HCV micro-elimination. A phased public health approach to HCV micro-elimination, including preparation/capacity building (phase I), implementation (phase II), and rollout and scale-up (phase III), targeting people living with HIV, prisoners, chronic hepatitis and cancer patients, blood donors, and pregnant women is a pragmatic strategy to Ethiopia. This can be implemented at general and tertiary care referral hospitals with a future scale-up to district hospitals through task-shifting by training general practitioners, nurses, laboratory technologists, and pharmacists. Availability of the highly effective direct-acting antivirals (DAAs) can be ensured by expanding the existing program that provides highly subsidized DAAs through an agreement with Gilead Sciences, Inc. and eventually aiming at domestic generic manufacturing. The significant enablers to HCV micro-elimination in Ethiopia include the control of healthcare–associated HCV infection, blood safety, access to affordable testing and pan-genotypic DAAs, task-shifting, multisectoral partnership, and regulatory support. General population-based HCV screening and treatment are not cost-effective for Ethiopia because of high cost, program complexity, and disease epidemiology.…

Kempker, R. R., Alghamdi, W. A., Al-Shaer, M. H., Burch, G., Peloquin, C. A.

Tuberculosis (TB) and hepatitis C virus (HCV) infection are both major public health problems. Despite high rates of co-infection there is scarce literature addressing the convergence of the two diseases. One particularly unexplored area is the potential for simultaneous treatment of TB and HCV which would allow for leveraging an extensive global TB treatment infrastructure to help scale up HCV treatment. We review the drug metabolism of anti-TB and HCV drugs and the known and potential drug-drug interactions between recommended HCV regimens and individual anti-TB drugs. Rifampin is the only anti-TB drug to have been formally studied for potential drug interactions with anti-HCV direct-acting antivirals (DAAs) and existing data precludes these combinations. However, based on known pathways of drug metabolism and enzyme effects, the combination of HCV DAA regimens with all other anti-TB drugs may be feasible. Pharmacokinetic studies are needed next to help move co treatment regimens forward for clinical use among patients coinfected with TB and HCV.…

Abstract Background Hepatitis A, caused by the hepatitis A virus (HAV), is a vaccine preventable disease. In Low and Middle-Income Countries (LMICs), poor hygiene and sanitation conditions are the main risk factors contributing to HAV infection. There have been, however, notable improvements in hygiene and sanitation conditions in many LMICs. As a result, there are studies showing a possible transition of some LMICs from high to intermediate HAV endemicity. The World Health Organization (WHO) recommends that countries should routinely collect, analyse and review local factors (including disease burden) to guide the development of hepatitis A vaccination programs. Up-to-date information on hepatitis A burden is, therefore, critical in aiding the development of country-specific recommendations on hepatitis A vaccination. Methods We conducted a systematic review to present an up-to-date, comprehensive synthesis of hepatitis A epidemiological data in Africa. Results The main results of this review include: 1) the reported HAV seroprevalence data suggests that Africa, as a whole, should not be considered as a high HAV endemic region; 2) the IgM anti-HAV seroprevalence data showed similar risk of acute hepatitis A infection among all age-groups; 3) South Africa could be experiencing a possible transition from high to intermediate HAV endemicity. The results of this review should be interpreted with caution as the reported data represents research work with significant sociocultural, economic and environmental diversity from 13 out of 54 African countries. Conclusions Our findings show that priority should be given to collecting HAV seroprevalence data and re-assessing the current hepatitis A control strategies in Africa to prevent future disease outbreaks.…

Abstract Background Leishmaniasis is an emerging infectious disease. Due to human migration and tourism, visceral leishmaniasis may become more common in non-endemic areas. In the Mediterranean basin, visceral leishmaniasis typically occurs in rural regions. Case presentation We present an unusual urban case of acute liver failure due to visceral leishmaniasis, following a prolonged fever of unknown origin. After obtaining negative results from the bone marrow aspirate, we performed a liver biopsy that elucidated the diagnosis. The liver involvement in visceral leishmaniasis may appear as chronic granulomatous hepatitis. However diffuse hepatitis process, a necro-inflammatory pattern, without forming granulomas were observed in the liver biopsy specimens in this case. Intracytoplasmic Leishmania amastigotes were observed in the liver biopsy specimens and a polymerase chain reaction confirmed the diagnosis. Only five pathological confirmed cases of acute hepatitis due to visceral leishmaniasis have been described so far, just two in adults and both from Barcelona. A revision of the literature is performed. Conclusions Acute hepatitis is an uncommon debut of visceral leishmaniasis in immunocompetent patients. Furthermore there are only few cases in the literature that describe the histopathological changes that we found in this patient. In conclusion, in case of acute hepatitis leading to liver failure, leishmaniasis should be considered a differential diagnosis (even in non-endemic countries and without clear epidemiological exposure) and liver biopsy can elucidate the diagnosis.…

Cunningham E, Hajarizadeh B, Amin J, et al.

AbstractBackgroundThis study investigated treatment adherence and associated factors among people with recent injecting drug use or current opioid agonist therapy (OAT) and compared once-daily to twice-daily DAA therapy.MethodsSIMPLIFY and D3FEAT are international, multicentre studies which recruited participants with recent injecting drug use (previous six months; SIMPLIFY, D3FEAT) or current OAT (D3FEAT) between March 2016 and February 2017 in eight countries. Participants received sofosbuvir/velpatasvir (once-daily; SIMPLIFY) or paritaprevir/ritonavir/ombitasvir, dasabuvir (twice-daily) ±ribavirin (D3FEAT) for 12 weeks administered in electronic blister-packs. We evaluated overall adherence (proportion of prescribed doses taken) and non-adherence (

Underwood, Michelle L.; Nguyen, Thuan; Uebelhoer, Luke S.; Kunkel, Lynn E.; Korthuis, Philip T.; Lancioni, Christina L.

Background: Opioid-use disorders (OUD) and hepatitis C or B co-infection (HEP) are common among people living with HIV (PLHIV). The impact of OUD on innate and adaptive immunity among PLHIV with and without HEP is unknown. Objectives: To investigate the impact of OUD on monocyte and T-cell phenotypes, cytokine responses to lipopolysaccharide (LPS) and phytohemagglutinin (PHA), and plasma inflammatory markers, among PLHIV with and without HEP. Methods: Cross-sectional study enrolling PLHIV receiving ART, with and without OUD. Flow cytometry determined monocyte and T-cell phenotypes; LPS and PHA-induced cytokine production was assessed following LPS and PHA stimulation by multiplex cytokine array; plasma IL-6, soluble CD163, and soluble CD14+ were measured by ELISA. Results: Twenty-two PLHIV with OUD and 37 PLHIV without OUD were included. PLHIV with OUD exhibited higher frequencies of intermediate (CD14++CD16+) and nonclassical (CD14dimCD16+) monocytes when compared with PLHIV without OUD (P = 0.0025; P = 0.0001, respectively), regardless of HEP co-infection. Soluble CD163 and monocyte cell surface CD163 expression was increased among PLHIV with OUD and HEP, specifically. Regardless of HEP co-infection, PLHIV with OUD exhibited reduced production of IL-10, IL-8, IL-6, IL-1alpha, and TNF-alpha in response to LPS when compared with PLHIV without OUD; PHA-induced production of IL-10, IL-1alpha, IL-1beta, IL-6, and TNF-alpha were also reduced among individuals with OUD. Conclusion: OUD among PLHIV are associated with altered monocyte phenotypes and a dysregulated innate cytokine response. Defining underlying mechanisms of opioid-associated innate immune dysregulation among PLHIV should be prioritized to identify optimal OUD treatment strategies. Correspondence to Christina L. Lancioni, MD, Department of Pediatrics, Oregon Health & Science University, 707 SW Gaines Street, CDRC-P, Portland, OR 97239, USA. Tel: +1 503 418 1484; fax: +1 503 494 1542; e-mail: Lancioni@ohsu.edu Received 7 June, 2019 Revised 13 September, 2019 Accepted 3 October, 2019 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). 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. http://creativecommons.org/licenses/by-nc-nd/4.0 Copyright © 2019 Wolters Kluwer Health, Inc.

Paul Loubet, Odile Launay

Hepatitis B virus (HBV) infection is a major public health problem with an estimated 257 million people with chronic HBV infection and around 650 000 annual deaths due to long-term HBV-related liver disease (cirrhosis and hepatocellular carcinoma).1 Vaccination represents the cornerstone of public health measures to eradicate HBV. The implementation of effective infant vaccination programmes in many countries has resulted in a significant decrease in the prevalence of HBV infection and in the incidence of liver cancer in children and young adults.

Abstract Background Hepatitis B virus is one of the major public health concerns globally. It is highly infectious and can be transmitted from person to person through vertically or horizontally via contaminated body fluids. Despite the provision of an effective vaccine, it remains a major problem worldwide, particularly among the developing countries. Methods Online electronic databases including PubMed, Google Scholar, Science Direct, African Index Medicus, African Journals Online, and WHO Afro Library were searched and published articles from 2010 to June 8, 2019, were considered. Both authors independently screened articles and extracted the data. Funnel-Plots and Egger’s test statistics were used to determine the presence of small-study effects and publication bias. The pooled prevalence of HBV was analyzed using the random-effects model. The possible sources of heterogeneity was analyzed through subgroup analysis, sensitivity analysis, and meta-regression. Results The overall pooled prevalence of HBV was 6% and among subgroups, pregnant women, healthcare workers, and HIV positive patients accounted for 5% for each group. Relatively low prevalence (4%) was obtained among blood donors. The Egger’s test statistics (p = 0.747) indicated the absence of publication bias. In addition, from the sensitivity analysis, there was no influence on the overall effect estimate while removing a single study at a time. The level of heterogeneity was reduced among pregnant women, HIV positive and studies with unknown sampling techniques. After conducting meta-regression, province, study group, screening method, and quality of papers were identified as sources of heterogeneity. Conclusions The overall pooled prevalence of HBV in Ethiopia was high. Strengthening and scaling up of the scope of the existing vaccination program and implementing novel approaches including screen-and-treat could be implemented to reduce the burden of the disease. Generally, the study can provide current prevalence estimate of HBV that could vital for intervention to tackle the disease.…

Martinec, O., Huliciak, M., Staud, F., Cecka, F., Vokral, I., Cerveny, L.

P-glycoprotein (ABCB1), an ATP-binding-cassette efflux transporter, limits intestinal absorption of its substrates and is a common site of drug-drug interactions (DDIs). ABCB1 has been suggested to interact with many antivirals used to treat human immunodeficiency virus (HIV) and/or chronic hepatitis C virus (HCV) infections. Using bi-directional transport experiments in Caco-2 cells and a recently established ex vivo model of accumulation in precision cut intestinal slices (PCIS) prepared from rat ileum or human jejunum, we evaluated the potential of anti-HIV and anti-HCV antivirals to inhibit intestinal ABCB1. Lopinavir, ritonavir, saquinavir, atazanavir, maraviroc, ledipasvir, and daclatasvir inhibited the efflux of a model ABCB1 substrate, rhodamine123 (RHD123), in Caco-2 cells and rat-derived PCIS. Lopinavir, ritonavir, saquinavir, and atazanavir also significantly inhibited RHD123 efflux in human-derived PCIS, while possible inter-individual variability was observed in the inhibition of intestinal ABCB1 by maraviroc, ledipasvir, and daclatasvir. Abacavir, zidovudine, tenofovir disoproxil fumarate, etravirine, and rilpivirine did not inhibit intestinal ABCB1. In conclusion, using recently established ex vivo methods for measuring drug accumulation in rat- and human-derived PCIS, we have demonstrated that some antivirals have a high potential for DDIs on intestinal ABCB1. Our data help clarify the molecular mechanisms responsible for reported increases in the bioavailability of ABCB1 substrates including antivirals and drugs prescribed to treat co-morbidity. These results could help guide the selection of combination pharmacotherapies and/or suitable dosing schemes for patients infected with HIV and/or HCV.…

Yao Lei, Junjun Shao, Furong Zhao, Yangfan Li, Chenglin Lei, Feifei Ma, Huiyun Chang, Yongguang Zhang

Journal of Medical Virology, Volume 0, Issue ja, -Not available-.

Nduaguba, Sabina O.; Barner, Jamie C.; Ford, Kentya H.; Lawson, Kenneth A.; Barnes, James N.; Wilson, James P.

Objectives: Multiple care quality indicators for HIV infection exist but few studies examine their impact on health outcomes. This study assessed, which HIV quality indicators were associated with healthcare resource utilization and costs. Design: Retrospective analysis of Texas Medicaid claims data (01 January 2012 to 31 September 2016). Methods: Included patients had at least two HIV-related medical claims during the identification period (01 July 2012 to 31 August 2014) (index = date of first HIV claim), were 18–62 years at index, and were continuously enrolled in the 6-month pre-index and 1-year post-index periods. Dependent variables included emergency department (ED) visits, inpatient hospitalizations, prescription count, and all-cause healthcare costs. Independent variables included CD4+ cell count monitoring, syphilis, chlamydia, gonorrhea, hepatitis B, hepatitis C, and tuberculosis screenings, influenza and pneumococcal vaccinations, retention in care, and HAART initiation. Covariates included age, chronic hepatitis C virus infection, AIDS diagnosis, sex, and baseline healthcare cost. The study objective was addressed using generalized linear modeling. Results: CD4+ cell count monitoring and HAART initiation were significantly associated with reduced emergency department visits (P …

Jang J, Yoo S, Nam H, et al.

AbstractPurposeThe effect of prophylactic antiviral therapy (AVT) on survival of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains unknown. This study aimed to determine whether prophylactic AVT could improve long-term survival in patients undergoing transarterial therapy (TAC).Experimental designBetween 2002 and 2016, 2,890 newly diagnosed HBV-related HCC patients treated with TAC were screened to analyze two groups based on prophylactic use of antivirals. Treatment effects were analyzed using propensity score (PS) matching (1:1) separately for the entire cohort and each subgroup. The primary endpoint was overall survival.ResultsA total of 1,547 patients met the inclusion criteria and 1,084 were PS-matched for the two groups. Median follow-up duration was 16.55 months. In the entire unmatched cohort, patients receiving prophylactic AVT survived significantly longer than those not. Among AVT-untreated patients, baseline high-viremia and HBV reactivation during treatment were significantly associated with shorter survival. Regarding types of antivirals, survival was significantly longer for patients receiving high-potency antivirals than those receiving low-potency antivirals. Survival differed with antiviral response. In the PS-matched cohort, the prophylactic AVT group survived significantly longer than the non-prophylactic group, irrespective of viral status or tumor stage. Prophylactic AVT remained an independent factor for survival. The association of prophylactic AVT with decreased risk of mortality persisted in patient subgroups after adjusting for baseline risk factors. Sensitivity analyses also confirmed estimated treatment effects.ConclusionsProphylactic AVT is associated with significantly improved long-term survival among patients undergoing TAC. High-potency antivirals are indicated for this approach.

Abstract Background Although several researches have reported the connection between the transforming growth factor-beta 1 (TGF-β1) gene polymorphisms and chronic hepatitis C virus (HCV) infection, the conclusions of these studies were not always consistent. Here, this paper proposed a meta-analysis to evaluate whether the TGF-ß1 gene polymorphisms, −509C/T (rs1800469), codon 10 T/C (rs1982073) and codon 25G/C (rs1800471), were associated with chronic HCV infection. Methods The summary odds ratios (ORs) of chronic HCV infected patients and controls with all SNPs were obtained by adaptive fixed or random effect model. A series of statistical tools were employed to guarantee the accuracy of related pooling ORs, including the Hardy-Weinberg equilibrium (HWE) test, sensitivity analysis and publication bias test. Results This paper analyzed 18 case-control studies in 17 articles which totally contains 2718 chronic HCV infection cases corresponding to 1964 controls. The results of the meta-analysis indicated that the −509C/T polymorphism effected an increased risk of chronic HCV infection in all gene models. More specifically by ethnicity stratification, the Egyptians shared the similar association with the above overall study. Moreover, the meta-fusion of healthy control studies showed that − 509 T allele carriers (TT + TA) had nearly 2.00 and 3.36 fold higher risk of chronic HCV infection in the total and Egyptian populations, respectively (OR = 2.004, 95% CI = 1.138–3.528, P = 0.016; OR = 3.363, 95% CI = 1.477–7.655, P = 0.004, respectively). However, our meta-analysis did not find any significant association between the codon 10 T/C or codon 25G/C polymorphisms and chronic HCV infection. Conclusions Our results suggested that the TGF-ß1–509C/T polymorphism may effect an increased risk of chronic HCV infection, especially in Egyptian population.…

Baisong Zheng, Jun Zhang, Tianhang Zheng, Hong Wang, Zhaolong Li, Chen Huan, Shanshan Ning, Yingchao Wang, Wenyan Zhang

Journal of Medical Virology, EarlyView.

Sun L, Fan J, Gao H, et al.

Anuisa Ranjan, Kate Shannon, Jill Chettiar, Melissa Braschel, Lianping Ti, Shira Goldenberg

McMahon B, Townshend-Bulson L, Homan C, et al.

AbstractMost persons with chronic HCV infection in the United States are undiagnosed or linked to care. We describe a program for the management of Alaska Native patients with HCV infection utilizing a computerized registry and statewide liver clinics resulting in higher linkage to care (86%) compared to national estimates (~25%).

Eda Rogers, Michelle Todd, F. William Pierson, Scott P. Kenney, C. Lynn Heffron, Danielle M. Yugo, Shannon R. Matzinger, Elena Mircoff, Irene Ngo, Charles Kirby, Michaela Jones, Paul Siegel, Peter Jobst, Karen Hall, Robert J. Etches, Xiang‐Jin Meng, Tanya LeRoith

Journal of Medical Virology, Volume 0, Issue ja, -Not available-.

Abstract Background Hepatitis B (HBV) and Human Immunodeficiency Virus (HIV) share common risk factors for exposure. Co-infected patients have an increased liver-related mortality risk and may have accelerated HIV progression. The epidemiology and demographic characteristics of HIV-HBV co-infection in Canada remain poorly defined. We compared the demographic and clinical characteristics and factors associated with advanced hepatic fibrosis between HIV and HIV-HBV co-infected patients. Methods A retrospective cohort analysis was conducted using data from the Canadian Observational Cohort (CANOC) Collaboration, including eight sites from British Columbia, Quebec, and Ontario. Eligible participants were HIV-infected patients who initiated combination ARV between January 1, 2000 and December 14, 2014. Demographic and clinical characteristics were compared between HIV-HBV co-infected and HIV-infected groups using chi-square or Fisher exact tests for categorical variables, and Wilcoxon’s Rank Sum test for continuous variables. Liver fibrosis was estimated by the AST to Platelet Ratio Index (APRI). Results HBV status and APRI values were available for 2419 cohort participants. 199 (8%) were HBV co-infected. Compared to HIV-infected participants, HIV-HBV co-infected participants were more likely to use injection drugs (28% vs. 21%, p = 0.03) and be HCV-positive (31%, vs. 23%, p = 0.02). HIV-HBV co-infected participants had lower baseline CD4 T cell counts (188 cells/mm3, IQR: 120–360) compared to 235 cells/mm3 in HIV-infected participants (IQR: 85–294) (p = 0.0002) and higher baseline median APRI scores (0.50 vs. 0.37, p 

Abstract Background With one in every 20 Pakistanis already infected, Pakistan has the second largest number of hepatitis C virus (HCV) infections globally. The aim of this study was to present a quantitative and analytical characterization of the HCV epidemic in Pakistan. Methods A standardized database of HCV antibody incidence and prevalence and HCV genotypes in all subpopulations was systematically assembled. Random-effects meta-analyses and random-effects meta-regressions were performed. Shannon Diversity Index was calculated to determine genotype diversity. Results The database included two incidence, 309 prevalence, and 48 genotype measures. Pooled mean HCV prevalence ranged between 7.0% (95% confidence interval (CI): 5.8–8.3%) in Sindh and 0.9% (95% CI: 0.1–2.4%) in Federally Administered Tribal Areas (F.A.T.A). Estimated number of chronically-infected persons ranged between 4.2 million in Punjab and 0.03 million in F.A.T.A. HCV prevalence was stable over time [adjusted odds ratio (AOR) of 1.0 (95% CI: 1.0–1.0)]. Population classification was the strongest predictor of HCV prevalence, explaining 51.8% of prevalence variation. Relative to the general population, HCV prevalence was higher in people who inject drugs [AOR of 23.8 (95% CI: 13.0–43.6)], populations with liver-related conditions [AOR of 22.3 (95% CI: 15.7–31.6)], and high-risk clinical populations [AOR of 7.8 (95% CI: 4.8–12.7)]. Low genotype diversity was observed (Shannon diversity index of 0.67 out of 1.95; 34.5%). There were only minor differences in genotype diversity by province, with genotype 3 being most common in all provinces. Conclusion Pakistan’s HCV epidemic shows homogeneity across the provinces, and over time. HCV prevalence is strikingly persistent at high level, with no evidence for a decline over the last three decades. Scale up of HCV treatment and prevention is urgently needed.…

Abstract Background Hepatitis E virus (HEV) infection is now recognized as a major cause of acute hepatitis worldwide. HEV specific antibodies develop shortly after infection and are thought to confer protection. Case presentation We report an immunocompromised patient who developed chronic HEV infection despite the presence of high level antibodies. HEV infection was detected using RT-PCR upon diagnostic evaluation due to increased liver enzymes. Upon retrospective analysis of stored serum samples we found that the patient was HEV RNA positive since 7 months. Chronic HEV infection was successfully treated with ribavirin. Conclusions In conclusion, the patient suffered from a chronic course of HEV infection, which was successfully treated with ribavirin. Our case underlines the importance of RT-PCR for HEV diagnostics in immunosuppressed patients and supports the notion that HEV antibodies do not confer universal protection. Counseling patients at risk for chronic HEV infection seems advisable. The role of the humoral and T-cell mediated immune response in cases of HEV reinfection deserves further study.…

Qing‐qin Hao, Qing‐hui Wang, Wei Xia, Hui‐zhong Qian

Journal of Medical Virology, EarlyView.

Hongxia Cui, Yizi Jin, Fang Chen, Hengli Ni, Caihong Hu, Yudong Xu, He Xuan, Duanmin Hu, Wei Deng, Yongsheng Zhang, Yao Liu

Journal of Medical Virology, Volume 0, Issue ja, -Not available-.

Le Berre, Anne-Pascale; Fama, Rosemary; Sassoon, Stephanie A.; Zahr, Natalie M.; Pfefferbaum, Adolf; Sullivan, Edith V.

Objectives: The comorbidity of Human Immunodeficiency Virus (HIV) infection and alcoholism (ALC) is prevalent. Wernicke's encephalopathy (WE), a neurological disorder resulting from thiamine depletion, has been generally associated with alcoholism but has also been reported in HIV infection. This study examined whether subclinical WE signs could contribute to the heterogeneity of cognitive and motor deficits observed in individuals with both disease conditions (HIV+ALC). Design: 61 HIV+ALC individuals and 59 controls were assessed on attention and working memory, production, immediate and delayed episodic memory, visuospatial abilities, and upper limb motor function. Methods: Using Caine criteria (dietary deficiency, oculomotor abnormality, cerebellar dysfunction, and altered mental state), HIV+ALC individuals were classified by subclinical WE risk factors. Results: Signs of subclinical WE were present in 20% of the HIV+ALC participants. For attention/working memory, delayed memory, and upper limb motor function, HIV+ALC Caine 2+ (i.e., meeting two or three criteria) demonstrated the most severe deficits, scoring lower than HIV+ALC Caine 1 (i.e., meeting one criterion), HIV+ALC Caine 0 (i.e., meeting no criteria), and controls. Conclusions: The high prevalence of subclinical signs of WE and relevance to performance indicate that this condition should be considered in assessment of HIV-infected individuals, especially when alcoholism comorbidity is known or suspected. Above and beyond clinical factors such as depression, alcoholism and HIV disease-related variables, AIDS, hepatitis C and drug history known to mediate neuropsychological performance, subclinical WE signs could partly explain the heterogeneity in patterns and severity of cognitive and motor impairments in HIV-infected individuals with alcoholism comorbidity. Correspondence to Anne-Pascale Le Berre, PhD, Stanford University School of Medicine, Department of Psychiatry and Behavioral Sciences, 401 Quarry Road, Stanford, CA 94305-5723, USA. Tel: +650 859 2155; e-mail: aleberre@stanford.edu Received 18 July, 2019 Revised 22 October, 2019 Accepted 23 October, 2019 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2019 Wolters Kluwer Health, Inc.

Antonio Sampedro, Isabel Casanovas, Julian Ceballos, Javier Rodriguez‐Granger, Fernando Cobo, Jose Maria Navarro

Journal of Medical Virology, EarlyView.

Abstract Background The technique most frequently used to genotype HCV is quantitative RT-PCR. This technique is unable to provide an accurate genotype/subtype for many samples; we decided to develop an in-house method with the goal of accurately identifying the genotype of all samples. As a Belgium National Centre of reference for hepatitis, we developed in-house sequencing not only for 5’UTR and core regions starting from VERSANT LiPA amplicons but also for NS5B regions. The sequencing of VERSANT LiPA amplicons might be useful for many laboratories worldwide using the VERSANT LiPA assay to overcome undetermined results. Methods 100 samples from Hepatitis C virus infected patients analysed by the VERSANT HCV Genotype 2.0 LiPA Assay covering frequent HCV types and subtypes were included in this study. NS5B, 5’UTR and Core home-made sequencing were then performed on these samples. The sequences obtained were compared with the HCV genomic BLAST bank. Results All the samples were characterised by the VERSANT LiPA assay (8 G1a, 17 G1b, 6 G2, 11 G3, 13 G4, and 10 G6). It was not possible to discriminate between G6 and G1 by the VERSANT LiPA assay for 8 samples and 27 had an undetermined genotype. Forty-one samples were sequenced for the three regions: NS5B, 5’UTR and Core. Twenty-three samples were sequenced for two regions: 5′ UTR and Core and 36 samples were sequenced only for NS5B. Of the 100 samples included, 64 samples were analysed for 5’UTR and Core sequencing and 79 samples were analysed for NS5B sequencing. The global agreement between VERSANT LiPA assay and sequencing was greater than 95%. Conclusions In this study, we describe a new, original method to confirm HCV genotypes of samples not discriminated by a commercial assay, using amplicons already obtained by the screening method, here the VERSANT LiPA assay. This method thus saves one step if a confirmation assay is needed and might be of usefulness for many laboratories worldwide performing VERSANT LiPA assay in particular.…

Yamaguchi, Julie; McArthur, Carole; Vallari, Ana; Sthreshley, Larry; Cloherty, Gavin A.; Berg, Michael G.; Rodgers, Mary A.

Background: The full spectrum of HIV-1 diversity can be found in central Africa, including two divergent HIV-1 strains collected in 1983 and 1990 in Democratic Republic of Congo (DRC) that were preliminarily classified as group M subtype L. However, a third epidemiologically distinct subtype L genome must be identified to designate L as a true subtype. Methods: Specimen CG-0018a-01 was collected in 2001 in DRC as part of an HIV prevention of mother to child transmission (PMTCT) study. Prior sub-genomic HIV-1 sequences from this specimen branched closely with proposed subtype L references. Metagenomic (mNGS) and HIV-specific target enriched (HIV-xGen) libraries were combined for next generation sequencing (NGS) to extend genome coverage. mNGS reads were analyzed for the presence of other co-infections with the SURPI bioinformatics pipeline. Results: A complete HIV-1 genome was generated with an average coverage depth of 47,783x. After bioinformatic analysis also identified Hepatitis B virus (HBV) reads, a complete HBV genotype A genome was assembled with an average coverage depth of 73,830x. The CG-0018a-01 HIV-1 genome branched basal to the two previous putative subtype L strains with strong bootstrap support of 100. With no evidence of recombination present, the strain was classified as subtype L. Conclusions: The CG-0018a-01 HIV-1 genome establishes subtype L and confirms ongoing transmission in DRC as recently as 2001. Since CG-0018a-01 is more closely related to an ancestral strain than to isolates from 1983 or 1990, additional strains are likely circulating in DRC and possibly elsewhere. Corresponding author: Mary A Rodgers, 100 Abbott Park Rd, Abbott Park, IL 60064 Phone: 224-668-8936 Fax: 224-668-3271 e-mail: mary.rodgers@abbott.com Conflicts of Interest and Sources of Funding: JY, AV, GAC, MGB, and MAR are employees and shareholders of Abbott Laboratories. The study was funded by Abbott Laboratories. 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. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Cedarbaum, Emily; Ma, Yifei; Scherzer, Rebecca; Price, Jennifer C.; Adimora, Adaora A.; Bamman, Marcas; Cohen, Mardge; Fischl, Margaret A.; Matsushita, Kunihiro; Ofotokun, Igho; Plankey, Michael; Seaberg, Eric C.; Yin, Michael T.; Grunfeld, Carl; Vartanian, Shant; Sharma, Anjali; Tien, Phyllis C.

Objectives: Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) have been associated with cardiovascular disease (CVD), but it is unclear whether HIV and HCV are also associated with peripheral artery disease (PAD). We examined the association of HIV, HCV, and traditional CVD risk factors with PAD in the Women's Interagency HIV Study (WIHS), a multicenter U.S. cohort. Methods: In this cross-sectional study, ankle-brachial index (ABI) was estimated using Doppler ultrasound and manual sphygmomanometer in 1,899 participants aged >40 years with HIV/HCV coinfection, HCV or HIV monoinfection, or neither infection. Multivariable logistic regression was used to estimate the odds of PAD (ABI≤0.9) after controlling for demographic, behavioral, and CVD risk factors. Results: Over two-thirds were African-American, median age was 50 years, and PAD prevalence was 7.7% with little difference by infection status. After multivariable adjustment, neither HIV nor HCV infection was associated with greater odds of PAD. Factors associated with PAD included older age [adjusted(a) OR:2.15 for age>61-70 vs 40-50 years;95%CI:1.13,4.11)], Black race (aOR:2.24;95%CI:1.12,4.47), smoking (aOR:1.25 per 10-pack-year increment;95%CI:1.07,1.45), and higher systolic blood pressure (aOR:1.14 per 10mmHg;95%CI:1.02,1.29). Conclusions: The high PAD prevalence in this nationally representative cohort of women with or at risk for HIV is on par with general population studies in individuals a decade older than our study's median age. HIV and HCV infection are not associated with greater PAD risk relative to uninfected women with similar risk factors. Modifiable traditional CVD risk factors may be important early intervention targets in women with and at risk for HIV. Correspondence to Phyllis C. Tien, University of California, San Francisco, VAMC, Infectious Disease Section, 111W, 4150 Clement Street, San Francisco, CA 94121. Tel: +415 221 4810; ext 22577; fax: +415 379 5523; (e-mail: Phyllis.tien@ucsf.edu), Emily R. Cedarbaum, MD, MPH, University of California, San Francisco, 505 Parnassus Ave, San Francisco, CA 94143, Tel: +360 480 9600; fax: +415 379 5523; (e-mail: emily.cedarbaum@ucsf.edu). Received 27 February, 2019 Revised 28 May, 2019 Accepted 16 June, 2019 Copyright © 2019 Wolters Kluwer Health, Inc.

Following publication of the original article1, the authors noted the following:…

Stevens E, Nucifora K, Hagan H, et al.

AbstractBackgroundThere are too many plausible permutations and scale-up scenarios of combination hepatitis C (HCV) interventions for exhaustive testing in experimental trials. Therefore, we used computer simulation to project the health and economic impact of alternative combination intervention scenarios for people who inject drugs (PWID), focusing on direct anti-viral agents (DAA) and medication-assisted treatment combined with syringe access programs (MAT+).MethodsWe performed an allocative efficiency study using a mathematical model simulating the progression of HCV in PWID and its related consequences. Two previously validated simulations were combined to estimate the cost-effectiveness of intervention strategies that included a range of coverage levels. Analyses were performed from a health sector and societal perspective with a 15-year time horizon and a discount rate of 3%.ResultsFrom a health-sector perspective (excluding criminal justice system-related costs), four potential strategies fell on the cost-efficiency frontier. DAA at 20% coverage had an ICER of $27,251/QALY. Combinations of DAA 20% with MAT+ at 20%, 40%, and 80% coverage had ICERs of $165,985/QALY, $325,860/QALY, and $399,189/QALY, respectively. When analyzed from a societal perspective (including criminal justice system-related costs), DAA 20% with MAT+ 80% was most effective and was cost saving. While DAA 20% with MAT+ 80% was more expensive (e.g., less cost-saving) than MAT+ 80% alone without DAA, it offered favorable value compared to MAT+ 80% alone ($23,932/QALY).ConclusionWhen considering health sector costs alone, DAA alone was the most cost-effective intervention. However, with criminal justice system-related costs, DAA and MAT+ implemented together become the most cost-effective interventions.

Ly K, Miniño A, Liu S, et al.

AbstractBackgroundHepatitis C virus (HCV)-associated mortality is well-documented nationally, but examination across regions and jurisdictions may inform healthcare planning.MethodsTo document HCV-associated deaths sub-nationally, we calculated age-adjusted HCV-associated death rates, compared death rate ratios (DRR) for ten US regions, 50 states, and District of Columbia (DC) with the national rate and described rate changes between 2016 and 2017 to determine variability. We examined mean age at HCV-associated death and rates and proportions by sex, race/ethnicity, and birth year.ResultsIn 2017, there were 17,253 HCV-associated deaths, representing 4.13 (95% CI, 4.07-4.20) deaths/100,000 standard population, a significant 6.56% rate decline from 4.42 in 2016. Age-adjusted death rates significantly surpassed the US rate for the following jurisdictions: Oklahoma, DC, Oregon, New Mexico, Louisiana, Texas, Colorado, California, Kentucky, Tennessee, Arizona, and Washington (DRR, 2.87, 2.77, 2.24, 1.62, 1.57, 1.46, 1.36, 1.35, 1.35, 1.35, 1.32, 1.32, respectively) (P

Kuan‐Chieh Lee, Chih‐Lang Lin, Chao‐Wei Hsu, Ming‐Ling Chang, Yi‐Cheng Chen, Wey‐Ran Lin, Ming‐Wei Lai, Kwang‐Huei Lin, Mei Chao, Rong‐Nan Chien Chau‐Ting Yeh

Journal of Medical Virology, Volume 0, Issue ja, -Not available-.

Kuan‐Chieh Lee, Chih‐Lang Lin, Chao‐Wei Hsu, Ming‐Ling Chang, Yi‐Cheng Chen, Wey‐Ran Lin, Ming‐Wei Lai, Kwang‐Huei Lin, Mei Chao, Rong‐Nan Chien, Chau‐Ting Yeh

Journal of Medical Virology, Volume 92, Issue 1, Page 124-127, January 2020.

Abstract Background Vaccine escape mutants (VEMs) are one of the causes of breakthrough infections in the mother-to-child transmission of hepatitis B virus (HBV). We hypothesized that VEMs existing as minor populations in the maternal blood are associated with breakthrough infections in children. We sought to determine whether VEMs exist as minor populations in the preserved umbilical cords of children with breakthrough infections. Case presentation Two families (Family 1: three children, Family 2: two children) were enrolled. Despite immunoprophylaxis, a breakthrough infection occurred in two Family 1 children and two Family 2 children. Preserved umbilical cords, serum, and nails were used for the HBV DNA analysis. To detect VEMs, we performed direct and deep sequencing of hepatitis B surface antigen gene. The direct sequencing showed that there were no VEMs in the serum of the children or mother of Family 1 and family 2, but it identified a G145A mutant in the nails of the mother of Family 2. In Family 1, deep sequencing detected a T143S mutant as a minor population (1.7–2.0%) in the umbilical cords and serum of all three children and in the serum of the mother. A T126A mutant was also detected in the umbilical cord (9.2%) and serum (7.0%) of the first-born child of Family 1. In Family 2, the deep sequencing showed no VEMs in the umbilical cords, but it detected D144A (2.5%) and G145A (11.2%) mutants in the serum of the 2nd-born child. Conclusions VEMs were present as minor populations in the preserved umbilical cords of children with breakthrough infections. The VEMs did not become major populations after the breakthrough infections. The evolution of VEMs from a minor form to a major form might not be a prerequisite for breakthrough infections in mother-to-child transmission.…

Giscard Wilfried Koyaweda, Eunice Machuka, Rosaline Macharia, Juliette Rose Ongus, Narcisse Patrice Komas, Roger Pelle

Sheng Shen, Grace Lai‐Hung Wong, Zhe Kuang, Margo J.H. Campenhout, Rong Fan, Vincent Wai‐Sun Wong, Terry Cheuk‐Fung Yip, Heng Chi, Xieer Liang, Xiaoyun Hu, Weiyin Lin, Yaobo Wu, Xiaoju Liu, André Boonstra, Jinlin Hou, Jian Sun, Henry Lik‐Yuen Chan

Journal of Medical Virology, Volume 0, Issue ja, -Not available-.

Sheng Shen, Grace L.‐H. Wong, Zhe Kuang, Margo J. H. Campenhout, Rong Fan, Vincent W.‐S. Wong, Terry C.‐F. Yip, Heng Chi, Xieer Liang, Xiaoyun Hu, Weiyin Lin, Yaobo Wu, Xiaoju Liu, André Boonstra, Jinlin Hou, Jian Sun, Henry L.‐Y. Chan

Journal of Medical Virology, EarlyView.

Abstract Background HCV (Hepatitis C virus) is a prevalent chronic disease with potentially deadly consequences, especially for drug users. However, there are no special HCV or HIV (human immunodeficiency virus)-related intervention programs that are tailored for drug users in China; to fill this gap, the purpose of this study was to explore HCV and HIV-related knowledge among drug users in MMT (methadone maintenance treatment) sites of China and to investigate the effectiveness of HCV and HIV-related education for improving the knowledge of IDUs (injection drug users) and their awareness of infection. Methods The study was a randomized cluster controlled trial that compared a usual care group to a usual care plus HCV/HIV-REP (HCV/HIV-Reduction Education Program) group with a 24-week follow-up. The self-designed questionnaires, the HCV- and HIV-related knowledge questionnaire and the HIV/HCV infection awareness questionnaire, were used to collect the data. Four MMT clinics were selected for this project; two MMT clinics were randomly assigned to the research group, with subjects receiving their usual care plus HCV/HIV-REP, and the remaining two MMT clinics were the control group, with subjects receiving their usual care over 12 weeks. Sixty patients were recruited from each MMT clinic. A total of 240 patients were recruited. Follow-up studies were conducted at the end of the 12th week and the 24th week after the intervention. Results At baseline, the mean score (out of 20 possible correct answers) for HCV knowledge among the patients in the group receiving the intervention was 6.51 (SD = 3.5), and it was 20.57 (SD = 6.54) for HIV knowledge (out of 45 correct answers) and 8.35 (SD = 2.8) for HIV/HCV infection awareness (out of 20 correct answers). At the 12-week and 24-week follow-up assessments, the research group showed a greater increase in HCV−/HIV-related knowledge (group × time effect, F = 37.444/11.281, P  0.05). Conclusion An MMT-based HCV/HIV intervention program could be used to improve patient knowledge of HCV and HIV prevention, but more effort should be devoted to HIV/HCV infection awareness. Trial registration Protocols for this study were approved by institution review board (IRB) of Shanghai Mental Health Center (IRB:2009036), and registered in U.S national institutes of health (http://www.clinicaltrials.gov, NCT01647191). Registered 23 July 2012.…

Gerhardt, F., Maier, M., Liebert, U. G., Platzbecker, U., Wang, S.-Y., Papp, C. P., Bock, C. T., Berg, T., van Bömmel, F.

Treating chronic hepatitis E virus (HEV) infections with ribavirin (RBV) is a recommended option (1)....…

Gras, Julien; Mahjoub, Nadia; Charreau, Isabelle; Cotte, Laurent; Tremblay, Cécile; Chas, Julie; Raffi, François; Cua, Eric; Guillon, Brigitte; Guigue, Nicolas; Chaix, Marie Laure; Meyer, Laurence; Molina, Jean Michel; Delaugerre, Constance; and the Ipergay study group

Background: A high incidence of acute HCV (AHCV) infection has been reported among at-risk HIV-negative Men who have Sex with Men (MSM). The optimal strategy for early diagnosis of AHCV in this population is not clearly defined. Methods: In the ANRS IPERGAY PrEP trial among high risk HIV-negative MSM, HCV serology and serum ALT were used for screening at enrollment and during follow-up. Behavioral risk factors were compared at baseline between participants who were diagnosed with AHCV during the study compared to those who did not. In subjects with a positive HCV serology, we used stored sera to perform the following tests at diagnosis and on previous visits: HCV-antibodies rapid tests, plasma HCV viral load and HCV antigen immunoassay. We evaluated the sensitivity of each test for AHCV diagnosis. Results: Among 429 enrolled participants, 14 were diagnosed with AHCV infection, with a median follow-up of 2.1 (IQR: 1.5–2.8) years. AHCV incidence was 1.40 per 100 person-years (95%CI, 0.74–2.39). Patients with AHCV reported a significantly higher number of sexual acts and/or partners, and more frequent recreational drug use at baseline. At the prior visit before AHCV diagnosis (median of 2 months earlier), sensitivities of HCV RNA and HCV antigen tests were respectively 100% and 89%, whereas none of the patients had a positive serology, and only 25% had elevated ALT. Conclusion: HCV antigen and RNA tests were positive within a median of 2 months before the detection of antibodies and ALT elevation. These tests could be considered for HCV screening in high-risk MSM. Correspondence to Julien Gras, Infectious Diseases Department, APHP-Saint Louis Hospital, 1 avenue Claude Vellefaux, Paris, France. Tel: +33 1 42 49 49 91; fax: +33 1 42 49 90 67; e-mail: julien.gras@aphp.fr, Constance Delaugerre, Virology Department, APHP-Saint Louis Hospital, 1 avenue Claude Vellefaux, Paris, France. Tel: +33 1 42 49 94 93; fax: +33 1 42 49 92 00; e-mail: constance.delaugerre@aphp.fr Received 20 February, 2019 Revised 20 June, 2019 Accepted 29 June, 2019 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2019 Wolters Kluwer Health, Inc.

Jing Xu, Lin lin Tao, Li xian Ma

Journal of Medical Virology, Volume 0, Issue ja, -Not available-.

Graf C, Mücke M, Dultz G, et al.

AbstractBackgroundTreatment uptake for hepatitis C virus (HCV) infection in people who inject drugs (PWID) and patients on opioid substitution therapy (OST) is still low despite treatment guidelines that advocate the use of direct-acting antivirals (DAAs) in all patients. Our aim in this review was to investigate treatment outcomes among PWID and patients on OST in comparison to control cohorts.MethodsA search of Embase, Medline, PubMed, and Web of Science (from October 2010 to March 2018) was conducted to assess sustained virologic response (SVR), discontinuation rates, adherence, and HCV reinfection in PWID and patients on OST.ResultsWe identified 11 primary articles and 12 conference abstracts comprising 1702 patients on OST, 538 PWID, and 19 723 patients who served as controls. Among patients on OST, the pooled SVR was 90% (95% confidence interval [CI], 87% to 93%) and pooled treatment discontinuation rate was 7% (95% CI, 4% to 11%). Similarly, the pooled SVR was 88% (95% CI, 80% to 93%) in PWID and the pooled treatment discontinuation rate was 9% (95% CI, 5% to 15%). There was no significant difference regarding pooled rates of SVR, adherence, and discontinuation between patients on OST and controls as well as between PWID and controls. HCV reinfection rates among patients on OST ranged from 0.0 to 12.5 per 100 person-years.ConclusionsHCV treatment outcomes in PWID and patients on OST are similar to those in patients without a history of injecting drugs, supporting current guideline recommendations to treat HCV in these patient populations.

Abstract Background The virological or clinical relapse is common in chronic hepatitis B (CHB) patients after stopping long-term nucleos(t)ide analogue (NA) therapy. Soluble growth stimulation expressed gene 2 (sST2), one of the Toll-like/interleukin-1 receptor members, is involved in a variety of inflammatory processes and immune responses. However, the expression and function of serum sST2 in CHB patients after stopping NA treatment remains unknown. Methods A total of 91 non-cirrhotic Asian patients with CHB who discontinued NA therapy according to international guidelines were prospectively followed up to 240 weeks. All patients were divided into clinical relapse group and non-clinical relapse (including sustained virological response and only virological relapse) group according HBV DNA and ALT levels. The serum levels of sST2 of all participants were determined by ELISA and compared between each two groups. Results Clinical relapse occurred in 26 patients and virological relapse occurred in 57 patients. We found that there was a positive correlation between sST2 expression and HBsAg, ALT, HBV DNA, and anti-HBc levels in CHB patients after discontinuation of NA treatment. Levels of serum sST2 in clinical relapse patients showed a rising trend and most patients showed peak sST2 levels at the point of clinical relapse. Moreover, the sST2 levels of clinical relapse group at week 12, week 24 and week 48 were relatively higher than non-clinical relapse group. However, the level of sST2 at the end of treatment was not an effective biological marker for the early prediction of clinical relapse after discontinuation of long-term NA therapy. Conclusions In conclusion, we found that an increase in sST2 in clinical relapse patients might be associated with an inflammation-related immune response after discontinuation of NA treatment. Trial registration The trial was retrospectively registered at Chinese Clinical Trial Registry: ChiCTR-OOC-17013970. Registration date: December 15, 2017.…