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Kamar N, Abravanel F, Behrendt P, et al.

AbstractBackgroundRibavirin is currently recommended for treating chronic hepatitis E virus (HEV) infection. This retrospective European multicenter study aimed to assess the sustained virological response (SVR) in a large cohort of solid organ transplant (SOT) recipients with chronic HEV infection treated with ribavirin monotherapy (N = 255), to identify the predictive factors for SVR, and to evaluate the impact of HEV RNA mutations on virological response.MethodsData from 255 SOT recipients with chronic HEV infection from 30 European centers were analyzed. Ribavirin was given at the median dose of 600 (range, 29–1200) mg/day (mean, 8.6 ± 3.6 mg/kg/day) for a median duration of 3 (range, 0.25–18) months.ResultsAfter a first course of ribavirin, the SVR rate was 81.2%. It increased to 89.8% when some patients were offered a second course of ribavirin. An increased lymphocyte count at the initiation of therapy was a predictive factor for SVR, while poor hematological tolerance of ribavirin requiring its dose reduction (28%) and blood transfusion (15.7%) were associated with more relapse after ribavirin cessation. Pretreatment HEV polymerase mutations and de novo mutations under ribavirin did not have a negative impact on HEV clearance. Anemia was the main adverse event.ConclusionsThis large-scale retrospective study confirms that ribavirin is highly efficient for treating chronic HEV infection in SOT recipients and shows that the predominant HEV RNA polymerase mutations found in this study do not affect the rate of HEV clearance.This large-scale retrospective study that included 255 solid organ transplant recipients confirms that ribavirin is highly efficient for treating chronic hepatitis E virus (HEV) infection and shows that HEV RNA polymerase mutations do not play a role in HEV clearance.

Crum-Cianflone N.

hepatitis Etreatmentribavirinreview…

Abstract Background Viral hepatitis is a global public health problem affecting millions of people worldwide, causing thousands of deaths due to acute and persistent infection, cirrhosis, and liver cancer. Providing updated serologic data can improve both surveillance and disease control programs. This study is aimed to determine the seroprevalence of markers for viral hepatitis (A, B, C, D and E) and the epidemiology of such infections in the general population of southern Iran’s Hormozgan province. Methods Between 2016 and 2017, a total of 562 individuals with ages ranging from 1 to 86 years, who visited governmental public laboratories for routine check-ups, were tested for the presence of serological markers to hepatitis virus types A to E using enzyme-linked immunosorbent assays. Results The overall anti-hepatitis A virus (HAV) antibody seroprevalence was 93.2% (524/562). The prevalence of anti-hepatitis E virus (HEV) antibodies was 15.8% (89/562) among which 1.6% (9/562) of the seropositive individuals also had evidence of recent exposure to the virus (IgM positivity). Two and a half percent (14/562) were positive for hepatitis B surface (HBs) antigen, whereas 11.6% (65/562) tested positive for anti-hepatitis B core (HBc) antibodies. Among anti-HBc positive patients, 11% (7/65) had HBs Ag and 5% (3/65) were positive for anti-hepatitis D virus (HDV) antibodies. The prevalence of anti-hepatitis C virus (HCV) antibodies was 0.7% (4/562). The seroprevalence of anti-HAV, HEV IgG, anti-HBc antibodies, and HBs Ag increased with age. Conclusion The present study confirms a high seroprevalence of HAV infection among the examined population and reveals high levels of endemicity for HEV in the region. Planned vaccination policies against HAV should be considered in all parts of Iran. In addition, improvements on public sanitation and hygiene management of drinking water sources for the studied area are recommended.…

Abstract Background Few countries in sub-Saharan Africa know the magnitude of their HIV epidemic among people who inject drugs (PWID). This was the first study in Mozambique to measure prevalence of HIV, HBV, and HCV, and to assess demographic characteristics and risk behaviors in this key population. Methods We used respondent-driven sampling (RDS) to conduct a cross-sectional behavioral surveillance survey of PWID in two cities of Mozambique lasting six months. Participants were persons who had ever injected drugs without a prescription. Participants completed a behavioral questionnaire and provided blood specimens for HIV, hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (anti-HCV) testing. We performed RDS-adjusted analysis in R 3.2 using RDSAT 7.1 weights. Results We enrolled 353 PWID in Maputo and 139 in Nampula/Nacala; approximately 95% of participants were men. Disease prevalence in Maputo and Nampula/Nacala, respectively, was 50.1 and 19.9% for HIV, 32.1 and 36.4% for HBsAg positivity, and 44.6 and 7.0% for anti-HCV positivity. Additionally, 8% (Maputo) and 28.6% (Nampula/Nacala) of PWID reported having a genital sore or ulcer in the 12 months preceding the survey. Among PWID who injected drugs in the last month, 50.3% (Maputo) and 49.6% (Nampula/Nacala) shared a needle at least once that month. Condomless sex in the last 12 months was reported by 52.4% of PWID in Maputo and 29.1% in Nampula/Nacala. Among PWID, 31.6% (Maputo) and 41.0% (Nampula/Nacala) had never tested for HIV. In multivariable analysis, PWID who used heroin had 4.3 (Maputo; 95% confidence interval [CI]: 1.2, 18.2) and 2.3 (Nampula/Nacala; 95% CI: 1.2, 4.9) greater odds of having HIV. Conclusion Unsafe sexual behaviors and injection practices are frequent among PWID in Mozambique, and likely contribute to the disproportionate burden of disease we found. Intensified efforts in prevention, care, and treatment specific for PWID have the potential to limit disease transmission.…

Abstract Background Chronic hepatitis C is a major public health burden. With new interferon-free direct-acting agents (showing sustained viral response rates of more than 98%), elimination of HCV seems feasible for the first time. However, as HCV infection often remains undiagnosed, screening is crucial for improving health outcomes of HCV-patients. Our aim was to assess the long-term cost-effectiveness of a nationwide screening strategy in Germany. Methods We used a Markov cohort model to simulate disease progression and examine long-term population outcomes, HCV associated costs and cost-effectiveness of HCV screening. The model divides the total population into three subpopulations: general population (GEP), people who inject drugs (PWID) and HIV-infected men who have sex with men (MSM), with total infection numbers being highest in GEP, but new infections occurring only in PWIDs and MSM. The model compares four alternative screening strategies (no/basic/advanced/total screening) differing in participation and treatment rates. Results Total number of HCV-infected patients declined from 275,000 in 2015 to between 125,000 (no screening) and 14,000 (total screening) in 2040. Similarly, lost quality adjusted life years (QALYs) were 320,000 QALYs lower, while costs were 2.4 billion EUR higher in total screening compared to no screening. While incremental cost-effectiveness ratio (ICER) increased sharply in GEP and MSM with more comprehensive strategies (30,000 EUR per QALY for total vs. advanced screening), ICER decreased in PWIDs (30 EUR per QALY for total vs. advanced screening). Conclusions Screening is key to have an efficient decline of the HCV-infected population in Germany. Recommendation for an overall population screening is to screen the total PWID subpopulation, and to apply less comprehensive advanced screening for MSM and GEP.…

Yurdaydin C, Toy M.

Miao Z, Zhang S, Ou X, et al.

AbstractBackgroundHepatitis delta virus (HDV) co-infects with hepatitis B virus (HBV) causing the most severe form of viral hepatitis. However, its exact global disease burden remains largely obscure. We aim to establish the global epidemiology, infection mode-stratified disease progression and clinical outcome of HDV infection.MethodsWe conducted a meta-analysis with a random-effects model, and performed data synthesis.ResultsThe pooled prevalence of HDV is 0.80% (95% CI 0.63-1.00) among the general population and 13.02% (95% CI 11.96-14.11) among HBV carriers, corresponding to 48-60 million infections globally. Among HBV patients with fulminant hepatitis, cirrhosis or hepatocellular carcinoma, HDV prevalence is 26.75% (95% CI 19.84-34.29), 25.77% (95% CI 20.62-31.27), and 19.80% (95% CI 10.97-30.45), respectively. The odds ratio (OR) of HDV infection among HBV patients with chronic liver disease compared to asymptomatic controls is 4.55 (95% CI 3.65-5.67). HDV co-infected patients are more likely to develop cirrhosis than HBV mono-infected patients with OR of 3.84 (95% CI 1.79-8.24). Overall, HDV infection progresses to cirrhosis within 5 years, and to hepatocellular carcinoma within 10 years in average.ConclusionsFindings suggest that HDV poses a heavy global burden with rapid progression to severe liver diseases, urging effective strategies for screening, prevention and treatment.

Ogawa E, Toyoda H, Iio E, et al.

AbstractBackgroundThe cure rate of hepatitis C virus (HCV) treatment with direct-acting antivirals (DAAs) for patients with active and inactive hepatocellular carcinoma (HCC) may differ, but well-controlled studies are limited. We aimed to evaluate DAA outcomes in a large East Asian HCV/HCC population compared to HCV/non-HCC patients.MethodsUsing data from the REAL-C registry (Hong Kong, Japan, South Korea, and Taiwan), we used propensity score matching (PSM) to match HCC and non-HCC (1:1) groups for age, sex, cirrhosis, prior treatment, HCV genotype, treatment regimen, baseline platelet count, HCV RNA, total bilirubin, alanine aminotransferase, and albumin level to evaluate DAA treatment outcomes in a large population of HCV/HCC compared to HCV/non-HCC patients.ResultsWe included 6,081 patients (HCC, n=465; non-HCC, n=5,616) treated with interferon-free DAAs. PSM of the entire study population yielded 436 matched pairs with similar baseline characteristics. There was no statistically significant difference in the overall SVR rate of the HCC (92.7%) and non-HCC (95.0%) groups. Rates of treatment discontinuation, adverse effects, and death were also similar between the HCC and non-HCC groups. Among patients with HCC, those with active HCC had a lower SVR than inactive HCC cases (85.5% vs. 93.7%, P=0.03). On multivariable analysis, active HCC, but not inactive HCC, was significantly associated with lower SVR (OR 0.28, P=0.01) when compared to non-HCC.ConclusionsActive HCC but not inactive HCC was independently associated with lower SVR compared to non-HCC patients undergoing DAA therapy, though cure rate was still relatively high (85%) in active HCC patients.

Elliott, Tamara; Cooke, Graham S.; Garvey, Lucy

Purpose of review The WHO has set ambitious targets for hepatitis C virus (HCV) elimination by 2030. In this review, we explore the possibility of HCV micro-elimination in HIV-positive (+) MSM, discussing strategies for reducing acute HCV incidence and the likely interventions required to meet these targets. Recent findings With wider availability of directly acting antivirals (DAAs) in recent years, reductions in acute HCV incidence have been reported in some cohorts of HIV+ MSM. Recent evidence demonstrates that treatment in early infection is well tolerated, cost effective and may reduce the risk of onward transmission. Modelling studies suggest that to reduce incidence, a combination approach including behavioural interventions and access to early treatment, targeting both HIV+ and negative high-risk groups, will be required. HCV vaccine trials have not yet demonstrated efficacy in human studies, however phase one and two studies are ongoing. Summary Some progress towards the WHO HCV elimination targets has been reported. Achieving sustained HCV elimination is likely to require a combination approach including early access to DAAs in acute infection and reinfection, validated and reproducible behavioural interventions and an efficacious HCV vaccine. Correspondence to Lucy Garvey, Jefferiss Wing, St Mary's Hospital, Imperial College Healthcare NHS Trust, London W2 1NY, UK. E-mail: lucy.garvey@nhs.net Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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 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.…

Balagopal A, Hwang H, Grudda T, et al.

AbstractHepatitis B virus (HBV) is a leading cause of liver failure and hepatocellular carcinoma worldwide. Approximately 10% of people with HIV also have HBV, and are at higher risk of liver disease progression than in HBV mono-infection. Antivirals, common to HIV and HBV, suppress HBV DNA levels but do not eradicate the virus because the transcriptional template, covalently closed circular DNA (cccDNA), is long-lived in every infected hepatocyte. Using single-cell laser capture microdissection, we isolated >1100 hepatocytes from five HIV/HBV co-infected persons with increasing exposure to HBV antivirals (HB1-5; no exposure to >7 years of exposure), quantifying cccDNA and pre-genomic RNA (pgRNA) in each cell using droplet-digital PCR. The proportion of infected hepatocytes decreased with antiviral exposure from 96.4% (HB1) to 29.8% (HB5). Both the upper cccDNA range and the median pgRNA decreased from HB1 to HB5 (p

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.

Dionne-Odom J, Westfall A, Dombrowski J, et al.

AbstractBackgroundRates of early syphilis in US women are steadily increasing but predictors of infection in this group are not clearly defined.MethodsThis retrospective analysis focused on women enrolled in the US CFAR Network of Integrated Clinical Systems cohort between January 2005 and December 2016 with syphilis testing performed. The primary outcome of incident syphilis infection was defined serologically as a newly positive test with positive confirmatory testing after a negative test or a 2-dilution increase in RPR titer. Infection rates were calculated for each woman-year in care with testing. Predictors of syphilis were sought among socio-demographics, clinical information, and self-reported behaviors. Multivariable logistic regression models were created and a subgroup analysis assessed predictors in women of reproductive age.ResultsThe annual rate of incident syphilis among 4416 women engaged in HIV care and tested during the 12-year study period was 760 per 100,000 person-years. Independent predictors of infection were injection drug use (IDU) as a risk factor for HIV acquisition (aOR 2.2, CI 1.3-3.9), hepatitis C infection (aOR 1.9, CI 1.1-3.4), black race (aOR 2.2, CI 1.3-3.7 compared to white race) and more recent entry to care (since 2005 compared to 1994-2004). Predictors were similar in women age 18-49.ConclusionsSyphilis infection is common among US women in HIV care. Syphilis screening and prevention efforts should focus on women reporting drug use and with hepatitis C co-infection. Future studies should identify specific behaviors that mediate syphilis acquisition risk in women who use drugs.

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 …

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.

Abstract Background Identification and knowledge of settings with high prevalence of hepatitis C virus (HCV) infection is important when aiming for elimination of HCV. The primary aim of this study was to estimate the prevalence of viremic HCV infection among Swedish prisoners. Secondary aims were to estimate the prevalence of hepatitis B surface antigen (HBsAg), human immunodeficiency virus (HIV), and the proportion who have received hepatitis B virus (HBV) vaccination. Methods A cross-sectional study of all incarcerated persons (n = 667) at all prisons (n = 9) in Stockholm County was conducted. All prisoners are routinely offered opt-in screening for HCV antibodies (anti-HCV), HCV RNA, HBsAg, anti-HBs, anti-HBc and HIV Ag/Ab at prison in Sweden. Data on the results of these tests and the number of received HBV vaccine doses were collected from the prison medical records. The parameters of HCV RNA, anti-HCV, and occurrence of testing for HCV were analysed in multiple logistic regression models in relation to age, sex and prison security class. Results The median age was 35 (IQR 26–44) years, and 93.4% were men. Seventy-one percent (n = 471) had been tested for anti-HCV, 70% (n = 465) for HBsAg and 71% (n = 471) for HIV. The prevalence of anti-HCV, HCV RNA, HBsAg and HIV Ag/Ab was 17.0, 11.5, 1.9, and 0.2%, respectively among tested persons. The proportion of prisoners who had received full HBV vaccination was 40.6% (n = 271) among all study subjects. Conclusions The prevalence of viremic HCV infection among Swedish prisoners in Stockholm County was 11.5%, which is high in comparison to the general population. Therefore, when aiming for the WHO goal of HCV elimination, prisons could suit as a platform for identification and treatment of HCV infection. There is a need to increase testing for blood-borne viruses and to improve vaccination coverage against HBV in Swedish prisons.…

Abstract Background A large proportion of people who inject drugs (PWID) living with hepatitis C virus (HCV) infection have not been treated. It is unknown whether inclusion of HCV diagnostics and treatment into integrated substance use disorder treatment and care clinics will improve uptake and outcome of HCV treatment in PWID. The aim is to assess the efficacy of integrating HCV treatment to PWID and this paper will present the protocol for an ongoing trial. Methods INTRO-HCV is a multicentre, randomised controlled clinical trial that will compare the efficacy of integrated treatment of HCV in PWID with the current standard treatment. Integrated treatment includes testing for HCV, assessing liver fibrosis with transient elastography, counselling, treatment delivery, follow-up and evaluation provided by integrated substance use disorder treatment and care clinics. Most of these clinics for PWID provide opioid agonist therapy while some clinics provide low-threshold care without opioid agonist therapy. Standard care involves referral to further diagnostics, treatment and treatment follow-up given in a hospital outpatient clinic with equivalent medications. The differences between the delivery platforms in the two trial arms involve use of a drop-in approach rather than specific appointment times, no need for additional travelling, less blood samples taken during treatment, and treatment given from already known clinicians. The trial will recruit approximately 200 HCV infected individuals in Bergen and Stavanger, Norway. The primary outcomes are time to treatment initiation and sustained virologic response, defined as undetectable HCV RNA 12 weeks after end of treatment. Secondary outcomes are cost-effectiveness, treatment adherence, changes in quality of life, fatigue and psychological well-being, changes in drug use, infection related risk behaviour, and risk of reinfection. The target group is PWID with HCV diagnosed receiving treatment and care within clinics for PWID. Discussion This study will inform on the effects of an integrated treatment program for HCV in clinics for PWID compared to standard care aiming to increase access to treatment and improving treatment adherence. If the integrated treatment model is found to be safe and efficacious, it can be considered for further scale-up. Trial registration ClinicalTrials.gov.no. NCT03155906.…

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.…

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.

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 (

Zhang A, Shrum S, Williams S, et al.

AbstractBackgroundInjection drug use (IDU) is a known, but infrequent risk factor on candidemia, however, the opioid epidemic and increases in IDU may be changing the epidemiology of candidemia.MethodsActive population-based surveillance for candidemia was conducted in selected US counties. Cases of candidemia were categorized as IDU cases if IDU was indicated in the medical records in the 12 months prior to the date of initial culture.ResultsDuring 2017, 1191 candidemia cases were identified in patients over the age of 12 years (incidence: 6.9 per 100,000 population); 128 (10.7%) had IDU history and this proportion was especially high (34.6%) in patients with candidemia aged 19-44 years. Candidemia patients with IDU history were younger than those without (median age: 35 vs 63 years, p

Kandathil A, Balagopal A.

A revolution in biomedicine has yielded a glimpse of the nonhuman multitudes within us. As we pull back the covers, we are left with questions about which of our fellow travelers are commensals, and which are more sinister. The question is more pressing when we consider the safety of the blood supply. Because of their transmissibility, viruses that circulate in the bloodstream are particularly worrisome. Many viruses of medical consequence, hepatitis C virus (HCV), hepatitis B virus, and the human immunodeficiency virus (HIV) 1 (HIV-1), spread rapidly through the population, in part because they circulate in the blood supply. On that backdrop, we have long fretted about the implications of human hepegivirus-1 (HHpgV-1), a prevalent RNA virus that infects nearly 3% of Americans, with detectable viremia in 1–2% of US blood donors [1]. The meta-analysis by Fama et al [2] in this issue of Clinical Infectious Diseases brings us closer to understanding the pathogenic potential of HHpgV-1.

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.…

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

Abstract Background The advent of effective direct-acting antivirals (DAAs), has prompted an assessment of the French Hepatitis C virus (HCV) screening strategy, which historically targeted high-risk groups. One of the options put forward is the implementation of combined (i.e., simultaneous) HCV, Hepatitis B virus (HBV) and HIV screening for all adults at least once during their lifetime (“universal combined screening”). However, recent national survey-based data are lacking to guide decision-making regarding which new strategy to implement. Accordingly, we aimed to provide updated data for both chronic hepatitis C (CHC) and B (CHB) prevalence and for HCV and HBV screening history, using data from the BaroTest and 2016 Health Barometer (2016-HB) studies, respectively. Methods 2016-HB was a national cross-sectional phone based health survey conducted in 2016 among 20,032 randomly selected individuals from the general population in mainland France. BaroTest was a virological sub-study nested in 2016-HB. Data collected for BaroTest were based on home blood self-sampling on dried blood spots (DBS). Results From 6945 analyzed DBS, chronic hepatitis C (CHC) and B (CHB) prevalence was estimated at 0.30% (95% Confidence Interval (CI): 0.13-0.70) and 0.30% (95% CI: 0.13-0.70), respectively. The proportion of individuals aware of their status was estimated at 80.6% (95% CI: 44.2-95.6) for CHC and 17.5% (95% CI: 4.9-46.4) for CHB. Universal combined screening would involve testing between 32.6 and 85.3% of 15-75 year olds according to whether we consider only individuals not previously tested for any of the three viruses, or also those already tested for one or two of the viruses. Conclusions Our data are essential to guide decision-making regarding which new HCV screening recommendation to implement in France. They also highlight that efforts are still needed to achieve the WHO’s targets for eliminating these diseases. Home blood self-sampling may prove to be a useful tool for screening and epidemiological studies.…

Sebastiani, Giada; Saeed, Sahar; Lebouche, Bertrand; de Pokomandy, Alexandra; Szabo, Jason; Haraoui, Louis-Patrick; Routy, Jean-Pierre; Wong, Philip; Deschenes, Marc; Ghali, Peter; Klein, Marina; for the LIVEHIV Study Group

Objective: Human immunodeficiency virus (HIV)-infected patients are at increased risk of nonalcoholic steatohepatitis (NASH). Vitamin E is recommended for treatment of NASH in the general population. However, its safety and efficacy among HIV-infected patients remain unknown. Design: Single centre, phase IV, open-label, single arm clinical trial. Methods: HIV mono-infected patients without significant alcohol intake or viral hepatitis coinfection were included. The diagnosis of NASH was based on the co-existence of fatty liver, diagnosed by controlled attenuation parameter (CAP) ≥ 248 dB/m, and significant hepatocyte apoptosis, defined by the serum biomarker cytokeratin 18 (CK-18) >130.5 U/L. Participants were treated with 800 IU daily of oral vitamin E (alpha-tocopherol) for 24 weeks, and followed for an additional 24 weeks post-discontinuation. Generalized linear mixed effects models were used to evaluate changes in ALT, CAP and CK-18 at the completion of treatment and end of follow-up, controlling for pre-treatment trends. Results: A total of 27 patients were included. Four (15%) had a pretreatment liver biopsy, which confirmed the diagnosis of NASH in all cases. Compared to baseline, 24 weeks of vitamin E treatment improved ALT (−27 units/L; 95% confidence interval [CI] −37, -−17), CAP scores (−22 dB/m; 95% CI −42, −1) and CK-18 (−123 units/L; 95% CI −201, −46). Conversely, there was no change in BMI. No serious adverse event was reported and no patient was lost to follow-up. Conclusion: In this first clinical trial, we showed that vitamin E is an effective and well-tolerated treatment for NASH in HIV-infected patients. Correspondence to Dr Giada Sebastiani, MD, Chronic Viral Illness Service, Royal Victoria Hospital, MUHC, 1001 Boulevard Décarie, Montreal, QC H4A 3J1, Canada. E-mail: giada.sebastiani@mcgill.ca Received 9 August, 2019 Revised 12 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). Copyright © 2019 Wolters Kluwer Health, Inc.

Abstract Background Multidrug-resistant tuberculosis (MDR-TB) requires lengthy use of second-line drugs, burdened by many side effects. Hepatitis C virus (HCV) chronic infection increases risk of drug-induced liver injury (DILI) in these patients. Data on MDR-TB patients with concurrent HCV chronic infection treated at the same time with second-line antitubercular drugs and new direct-acting antivirals (DAAs) are lacking. We evaluate if treating at the same time HCV infection and pulmonary MDR-TB is feasible and effective. Cases presentation In this study, we described two cases of patients with pulmonary MDR-TB and concurrent HCV chronic infection cured with DAAs at a Tertiary Infectious Diseases Hospital in Italy. During antitubercular treatment, both patients experienced a DILI before treating HCV infection. After DAAs liver enzymes normalized and HCV RNA was undetectable. Then antitubercular regimen was started according to the institutional protocol, drawn up following WHO MDR-TB guidelines. It was completed without further liver side effects and patients were declared cured from both HCV infection and MDR-TB. Conclusions We suggest to consider treatment of chronic hepatitis C with DAAs as a useful intervention for reintroduction of second-line antitubercular agents in those patients who developed DILI, reducing the risk of treatment interruption when re-exposed to these drugs.…

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.…

Abstract Background Hepatitis C virus (HCV) infection is a major cause of chronic liver disease globally. Direct acting antivirals (DAAs) have proven effective in curing HCV. However, the current standard of care (SOC) in Botswana remains PEGylated interferon-α (IFN-α) with ribavirin. Several mutations have been reported to confer resistance to interferon-based treatments. Therefore, there is a need to determine HCV genotypes in Botswana, as these data will guide new treatment guidelines and understanding of HCV epidemiology in Botswana. Methods This was a retrospective cross-sectional pilot study utilizing plasma obtained from 55 participants from Princess Marina Hospital in Gaborone, Botswana. The partial core region of HCV was amplified, and genotypes were determined using phylogenetic analysis. Results Four genotype 5a and two genotype 4v sequences were identified. Two significant mutations – K10Q and R70Q – were observed in genotype 5a sequences and have been associated with increased risk of hepatocellular carcinoma (HCC), while R70Q confers resistance to interferon-based treatments. Conclusion Genotypes 5a and 4v are circulating in Botswana. The presence of mutations in genotype 5 suggests that some patients may not respond to IFN-based regimens. The information obtained in this study, in addition to the World health organization (WHO) recommendations, can be utilized by policy makers to implement DAAs as the new SOC for HCV treatment in Botswana.…

Abstract Background The purpose of this study was to prospectively investigate the value of real-time ultrasound elastography (RTE) for the diagnosis of liver fibrosis (LF) in patients with chronic hepatitis B (CHB), to correlate the elastography findings with the histologic stage of LF and to compare RTE findings with those from noninvasive tests of LF calculated using laboratory blood parameters. Methods Liver biopsies, laboratory blood testing, and RTE were performed in 91 patients with CHB. The LF index (LFI) was calculated using a multiple linear regression equation involving 11 parameters, which represented the degree of LF. The higher the LFI is, the greater the degree of LF. Results The mean aspartate aminotransferase-to-platelet ratio index (APRI) and the mean fibrosis index based on four factors (FIB-4) were significantly different for the 5 stages of LF, respectively. The APRI (r = 0.43, P = 0.006), FIB-4 (r = 0.51, P = 0.012) and LFI (r = 0.562, P = 0.004) were correlated with the stages of LF. For discriminating stage F0 from F1, only the LFI had significant power (P = 0.026) for predicting stage F1. For discriminating stage F4 from F3, only the LFI had statistically significant power (P = 0.024) in predicting stage F4. The areas under the receiver operating characteristic curves (AUCs) of the LFI for diagnosing significant, advanced LF and liver cirrhosis were significantly higher than those of the APRI and FIB-4, and the LFI had better sensitivity and specificity. Conclusions The LFI calculated by RTE is reliable for the assessment of LF in patients with CHB and has better discrimination power than the APRI and FIB-4.…

Schulte B, Schmidt C, Strada L, et al.

AbstractBackgroundHepatitis C virus (HCV) infection is highly prevalent among people who inject drugs (PWID). Accurate data on HCV prevalence and incidence rates among patients receiving opioid substitution treatment (OST) are needed to estimate the current and future burden of HCV infections in this high-risk population.MethodsBaseline data from routine care were collected between October 2014 and June 2016 from randomly selected OST facilities in Germany. The primary outcome measure was the HCV status (antibody and RNA prevalence). Patients who were HCV antibody–negative at baseline were followed up after 12 months to calculate the HCV incidence rate.ResultsSixty-three facilities from 14 German Federal States provided clinical data for a total of 2466 OST patients. HCV antibody and HCV RNA prevalence were 58.8% (95% confidence interval [CI], 56.8%–60.8%) and 27.3% (95% CI, 25.5%–29.2%), respectively. At baseline, a total of 528 patients (21.4%) had previously undergone antiviral treatment. Moreover, lower HCV RNA prevalence was associated with female gender, employment, younger age, and shorter duration of OST and opioid dependence. The HCV incidence rate was 2.5 cases per 100 person-years.ConclusionsThe low HCV RNA prevalence and HCV incidence rates confirm that OST in Germany is an effective setting both for treating chronic HCV infections and for preventing new infections among PWID. Scaling up the provision of OST, HCV testing, and HCV treatment among OST patients are important public health strategies for reducing HCV infections in this high-risk population.This nationwide prospective cohort study supports the protective effects of opioid substitution treatment by confirming a low hepatitis C virus (HCV) RNA prevalence rate (27.3%) and low HCV incidence rate (2.5 cases per 100 person-years) among 2467 opioid-substituted patients in Germany.

Naidoo K, Hassan-Moosa R, Mlotshwa P, et al.

AbstractBackgroundNew onset or worsening drug-induced liver injury challenges coinfected patients on antiretroviral therapy (ART) initiation during antituberculosis (TB) treatment.MethodsPost hoc analysis within a randomized trial, the Starting Antiretroviral Therapy at Three Points in Tuberculosis trial, was conducted. Patients were randomized to initiate ART either early or late during TB treatment or after TB treatment completion. Liver enzymes were measured at baseline, 6-month intervals, and when clinically indicated.ResultsAmong 642 patients enrolled, the median age was 34 years (standard deviation, 28–40), and 17.6% had baseline CD4+ cell counts

Lin K, Lee Y, Huang S, et al.

Merat S, .

An error appeared in the “corrected proof” publication of this article [Merat S and the SD1000 Research Team. SD1000: High Sustained Viral Response Rate in 1361 Patients With Hepatitis C Genotypes 1, 2, 3, and 4 Using a Low-cost, Fixed-dose Combination Tablet of Generic Sofosbuvir and Daclatasvir: A Multicenter, Phase III Clinical Trial. Clin Infect Dis https://doi.org/10.1093/cid/ciz628]. This article was published with the following error:…

Abstract Background Tenofovir alafenamide (TAF)-containing combinations were introduced in Switzerland after October 2016 and are recommended over tenofovir disoproxil fumarate (TDF) in patients with osteoporosis or impaired renal function. Methods We included all participants of the Swiss HIV Cohort Study on TDF-containing antiretroviral therapy with follow-up visits after January 2016. We determined the proportion of switches from TDF to TAF overall, and among patients with risk factors for TDF toxicity, including osteoporosis, impaired renal function or marked proteinuria. We used multivariable logistic regression to explore predictors of switching from TDF to TAF. Results We included 5′012 patients, of whom 652 (13.0%) had risk factors for TDF toxicity. A switch from TDF to TAF was undertaken in 2′796 (55.8%) individuals overall, and in 465 (71.3%) with risk factors. Predictors of switching to TAF were male sex (adjusted odds ratio 1.27, 95% confidence interval 1.07–1.50), age > 50 years (1.43, 1.23–1.66) and the presence of risk factors for TDF toxicity (2.21, 1.77–2.75). In contrast, patients with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based single-pill regimen (0.11, 0.09–0.13), those treated in non-tertiary care centers (0.56, 0.46–0.70), as well as those with CD4 cell counts below 500/μL (0.77, 0.66–0.90) and with chronic hepatitis C infection (0.66, 0.54–0.80) were most likely to stay on TDF. Conclusions Over 50% of patients on TDF-containing therapy, including the majority of patients at risk for TDF toxicity, were switched to TAF within two years of its introduction in Switzerland. Individuals on NNRTI-based single-pill regimens were most likely to remain on TDF.…

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

Martinello M, Yee J, Bartlett S, et al.

AbstractBackgroundMicro-elimination of HCV among people living with HIV may be feasible in Australia, given unrestricted access to direct-acting antiviral (DAA) therapy from 2016. Our aim was to evaluate progress towards elimination goals within HIV/HCV co-infected adults in Australia following universal DAA access.MethodsThe CEASE prospective cohort study enrolled HIV/HCV positive adults, irrespective of viremic status, from 14 primary and tertiary clinics in Australia. Annual and cumulative HCV treatment uptake, outcome, and HCV RNA prevalence were evaluated, with follow-up through May 2018 (median follow-up: 2.63 years). Factors associated with DAA uptake were analysed.ResultsBetween July 2014 and March 2017, 402 HIV/HCV antibody-positive participants were enrolled (95% male [80% gay and bisexual men,], 13% cirrhosis, 80% history of injecting drug use [39% current injecting]). Following universal DAA access, annual HCV treatment uptake in those eligible increased from 7% and 11% per year in 2014 and 2015, respectively, to 80% in 2016. By 2018, cumulative HCV treatment uptake in those ever eligible for treatment was 91% (336/371). HCV viremic prevalence declined from 82% (95%CI 78%, 86%) in 2014 to 8% (95%CI 6%, 12%) in 2018. Reinfection was reported in only five participants for a reinfection incidence of 0.81 per 100-person years (95% CI 0.34, 1.94).ConclusionsHigh uptake and effectiveness of unrestricted DAA therapy in Australia has permitted rapid treatment scale-up, with a dramatic reduction in HCV infection burden and low reinfection rate among people living with HIV, suggesting that micro-elimination is feasible.

Tsertsvadze T, Gamkrelidze A, Chkhartishvili N, et al.

AbstractBackgroundIn April 2015, in collaboration with U.S. CDC and Gilead Sciences, Georgia embarked on the world’s first hepatitis C elimination program. We aimed to assess progress towards elimination targets after three years since the beginning of the elimination program.MethodsWe constructed an HCV care cascade for adults in Georgia, based on the estimated 150,000 persons age ≥ 18 years with active HCV infection. All patients who were screened or entered the treatment program during April 2015 - March 2018 were included in the analysis. Data on the number of persons screened for HCV was extracted from the national HCV screening database. For treatment component we utilized data from the Georgia National HCV treatment program database. Available treatment options included sofosbuvir (SOF) and ledipasvir/sofosbuvir (LDV/SOF) based regimens.ResultsSince April 2015, a cumulative 974,817 adults were screened for HCV antibodies, 86,624 persons tested positive, of which 61,925 underwent HCV confirmatory testing. Among estimated 150,000 adults living with chronic hepatitis C in Georgia, 52,856 (35.1%) were diagnosed, 45,334 (30.2%) initiated treatment with DAA, and 29,090 (19.4%) achieved sustained virologic response (SVR). Overall 37,256 persons were eligible for SVR assessment, of these only 29,620 (79.5%) returned for evaluation. In the per-protocol analysis, SVR rate achieved was 98.2% (29,090/29,620), and 78.1% (29,090/37,256) in the intent-to-treat analysis.ConclusionsGeorgia has made substantial progress in the path towards eliminating hepatitis C. Scaling-up testing and diagnosis, along with effective linkage to treatment services are needed to achieve the goal of elimination.

Chromy D, Schmidt R, Mandorfer M, et al.

AbstractBackgroundIncreasing numbers of hepatitis C virus (HCV) infections among men who have sex with men (MSM) are being observed in the Western world. The actual routes of HCV transmission during high-risk sex-practices and associated drug use remain poorly understood.Methods47 HCV patients were prospectively enrolled. Rectal and nasal swabs were collected to quantify HCV-RNA levels within rectal and nasal fluids. Contamination by occult rectal bleeding was ruled out by guaiac paper test. Risk-behaviour was assessed by standardized questionnaires.ResultsMedian age was 41.9 years, 89% were HIV+ (42/47) and of 85% (40/47) male, 58% (23/40) were MSM. Acute HCV infection was diagnosed in 32% (15/47) with all patients being HIV+MSM and 93% (14/15) having a documented history of sexually transmitted disease. Thirty-three (70%) patients had at least one HCV-positive swab sample (HCV+SS; 48%, 22/46 rectal; 62%, 29/47 nasal) and contamination with blood was ruled out in all patients. Individuals with HCV+SS had significantly higher serum HCV-RNA levels than patients with HCV-negative SS (6.28 IQR 0.85 logU/mL vs. 4.08 IQR 2.45 logU/mL; p

Ingiliz P, Wehmeyer M, Boesecke C, et al.

AbstractBackgroundMicro-elimination of the hepatitis C virus (HCV) includes treatment in populations at risk of ongoing HCV transmission such as men who have sex with men (MSM) or people who inject drugs (PWID). We analyzed the HCV reinfection incidence rates of in the German hepatitis C cohort (GECCO) and compared our data to previous findings from the interferon era.MethodsPatients with HCV reinfection in the multi-centric GECCO cohort were compared to patients in whom no reinfection occurred. The HCV reinfection incidence rate in MSM was also compared to the incidence rate in the interferon era (European AIDS Treatment Network, NEAT).ResultsSince 2014, 48 HCV reinfections occurred in 2298 individuals (2%) with 2346 cured HCV episodes. The median time to reinfection was 500 days (range 16 to 1160) and the overall HCV reinfection incidence rate was 1.89 per 100 person-years (95%-confidence interval (CI) 1.41 to 2.48). In multivariate analysis, the transmission risk MSM was the only independent risk factor of HCV reinfection (odds ratio 39.3, 95%-CI 4.57 to 334.40, p=0.001). The incidence rate in MSM was 9.02 (CI 6.48 to 12.26) per 100py compared to 1.14 per 100py in PWID (CI 0.56 to 2.09). The incidence rate for a first HCV reinfection in MSM was similar in the DAA era compared to the interferon era with a hazard ratio of 1.05 (CI 0.64-1.74, p=0.831).ConclusionsHCV reinfection remains a frequent finding among MSM in Germany. In addition to behavioral interventions, early HCV treatment and retreatment should be implemented for this subgroup to prevent HCV transmission.

Abstract Background Hepatitis B virus (HBV) infection is a major public health problem in China. Over a decade has passed since the last National Hepatitis Seroepidemiological Survey was conducted in 2006. The lack of updated data on hepatitis B in China makes assessing the current prevalence and burden of the disease inadequate. In response to the above situation, a systematic review and meta-analysis was conducted to provide a better understanding of hepatitis B epidemiology in the general population of China. Methods A systematic search was conducted in international databases (Medline through PubMed, EMBASE, Cochrane, Web of Science) and national databases (CBM, CNKI, WanFang Data) to retrieve primary studies published between January 1, 2013 and December 31, 2017. The pooled prevalence of HBV infection and 95% confidence intervals were calculated. Quality assessment, heterogeneity testing and publication bias assessment were also performed. Results Of the 27 studies included in the meta-analysis, the pooled estimated prevalence of HBV infection in the general population of China from 2013 to 2017 was 6.89% (95% CI:5.84–7.95%), which could be extrapolated to an estimated population of 84 million living with HBsAg in 2018. The prevalence of HBV infection in males was higher than that in females (5.88% vs 5.05%), and rural areas had a higher prevalence than urban areas (5.86% vs 3.29%). The highest prevalence of HBV infection was reported in Western provinces (8.92, 95% CI: 7.19–10.64%). In adults older than 20 years, the prevalence of HBV infection was approximately 7%, which was higher than that in children. Conclusion The prevalence of HBV infection in the general population of China was classified as higher intermediate prevalence (5–7.99%), of which more than 90% of the HBV infection population included adults older than 20 years. The blocking of mother-to-infant hepatitis B transmission and plans involving timely birth dose of hepatitis B vaccine within 24 h should be implemented. Additionally, improving the quality of life and survival rate of the infected population through antiviral therapy and high-risk adult vaccination will be the priority of our future work. Moreover, various control measures should be implemented in different provinces across China.…

Abstract Background Hepatitis C virus (HCV) is common in men who have sex with men (MSM) with HIV. The Swiss HCVree Trial targeted a micro-elimination by using a treat and counsel strategy. Self-reported condomless anal intercourse with non-steady partners was used as the selection criterion for participation in a counselling intervention designed to prevent HCV re-infection. The purpose of this study was to assess the ability of this criterion to identify men who engaged in other sexual risk behaviours associated with HCV re-infection. Methods Men who disclosed their sexual and drug- use behaviours during the prior 6 months, at study baseline, were included in the current study. Using a descriptive comparative study design, we explored self-reported sexual and drug-use risk behaviours, compared the odds of reporting each behaviour in men who reported and denied condomless anal intercourse with non-steady partners during the prior year and calculated the sensitivity/specificity (95% CI) of the screening question in relation to the other at-risk behaviours. Results Seventy-two (61%) of the 118 men meeting eligibity criteria reported condomless anal intercourse with non-steady partners during the prior year. Many also engaged in other potential HCV transmission risk behaviours, e.g., 52 (44%) had used drugs. In participants disclosing drug use, 44 (37%) reported sexualised drug use and 17 (14%) injected drugs. Unadjusted odds ratios (95% CI) for two well-known risk behaviours were 2.02 (0.80, 5.62) for fisting and 5.66 (1.49, 37.12) for injecting drug use. The odds ratio for sexualised drug use - a potential mediator for increased sexual risk taking - was 5.90 (2.44, 16.05). Condomless anal intercourse with non-steady partners showed varying sensitivity in relation to the other risk behaviours examined (66.7–88.2%). Conclusions Although condomless anal intercourse with non-steady partners was fairly sensitive in detecting other HCV relevant risk behaviours, using it as the only screening criterion could lead to missing a proportion of HIV-positive men at risk for HCV re-infection due to other behaviours. This work also points to the importance of providing access to behavioral interventions addressing other sexual and drug use practices as part of HCV treatment. Trial registration Clinical Trial Number: NCT02785666, 30.05.2016.…

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].

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 2016 ‘Start Free, Stay Free, AIDS Free’ global agenda, builds on the 2011-2015 ‘Global Plan’. It prioritises 22 countries where 90% of the world’s HIV-positive pregnant women live and aims to eliminate vertical  transmission of HIV (EMTCT) and to keep mothers alive. By 2019, no Global Plan priority country had achieved EMTCT; however, 11 non-priority countries had. This paper synthesises the characteristics of the first four countries validated for EMTCT, and of the 21 Global Plan priority countries located in Sub-Saharan Africa (SSA). We consider what drives vertical transmission of HIV (MTCT) in the 21 SSA Global Plan priority countries. Methods A literature review, using PubMed, Science direct and the google search engine was conducted to obtain global and national-level information on current HIV-related context and health system characteristics of the first four EMTCT-validated countries and the 21 SSA Global Plan priority countries. Data representing only one clinic, hospital or region were excluded. Additionally, key global experts working on EMTCT were contacted to obtain clarification on published data. We applied three theories (the World Health Organisation’s building blocks to strengthen health systems, van Olmen’s Health System Dynamics framework and Baral’s socio-ecological model for HIV risk) to understand and explain the differences between EMTCT-validated and non-validated countries. Additionally, structural equation modelling (SEM) and linear regression were used to explain associations between infant HIV exposure, access to antiretroviral therapy and two outcomes: (i) percent MTCT and (iii) number of new paediatric HIV infections per 100 000 live births (paediatric HIV case rate). Results EMTCT-validated countries have lower HIV prevalence, less breastfeeding, fewer challenges around leadership, governance within the health sector or country, infrastructure and service delivery compared with Global Plan priority countries. Although by 2016 EMTCT-validated countries and Global Plan priority countries had adopted a public health approach to HIV prevention, recommending lifelong antiretroviral therapy (ART) for all HIV-positive pregnant and lactating women, EMCT-validated countries had also included contact tracing such as assisted partner notification, and had integrated maternal and child health (MCH) and sexual and reproductive health (SRH) services, with services for HIV infection, sexually transmitted infections, and viral hepatitis. Additionally, Global Plan priority countries have limited data on key SRH indicators such as unmet need for family planning, with variable coverage of antenatal care, HIV testing and triple antiretroviral therapy (ART) and very limited contact tracing. Structural equation modelling (SEM) and linear regression analysis demonstrated that ART access protects against percent MTCT (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 Chronic infection with hepatitis B virus (HBV) is a serious global health problem. Persistence of the virus occurs as a result of stability of the replication intermediate comprising covalently closed circular DNA (cccDNA). Development of drugs that are capable of disabling this cccDNA is vital. Methods To investigate an epigenetic approach to inactivating viral DNA, we engineered transcriptional repressors that comprise an HBV DNA-binding domain of transcription activator like effectors (TALEs) and a fused Krüppel Associated Box (KRAB). These repressor TALEs (rTALEs) targeted the viral surface open reading frame and were placed under transcription control of constitutively active or liver-specific promoters. Results Evaluation in cultured cells and following hydrodynamic injection of mice revealed that the rTALEs significantly inhibited production of markers of HBV replication without evidence of hepatotoxicity. Increased methylation of HBV DNA at CpG island II showed that the rTALEs caused intended epigenetic modification. Conclusions Epigenetic modification of HBV DNA is a new and effective means of inactivating the virus in vivo. The approach has therapeutic potential and avoids potentially problematic unintended mutagenesis of gene editing.…

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.…

Tressler S, Kushner T, Bhandari R.

AbstractBackgroundWith the nation’s focus on the opioid crisis, methamphetamine has made a comeback, potentially increasing risk for hepatitis B. We examined factors associated with hepatitis B virus (HBV) exposure among people who reported ever using methamphetamine in a nationally representative survey.MethodsWe utilized the National Health and Nutrition Examination Survey to examine factors associated with HBV exposure among participants who reported ever using methamphetamine using bivariate and multivariable logistic regression.ResultsOverall, 847 participants met the study inclusion criteria. In multivariable logistic regression, female sex (aOR 3.83, 95% CI 1.65 – 8.90), living below the poverty threshold (aOR 3.17, 95% CI 1.39 – 7.21), injection drug use (IDU) (aOR 4.89, 95% CI 1.95 – 12.26), active hepatitis C (HCV) infection (aOR 3.39, 95% CI 1.10 – 12.26), and identifying as men who have sex with men (aOR 28.21, 95% CI 5.19 – 153.38) were significantly associated with HBV exposure.ConclusionsThe odds of HBV exposure for females who reported using methamphetamine was four times higher than males. Poverty, IDU, and HCV infection were also associated. As methamphetamine use increases, it is critical to identify those at risk of acquiring HBV infections in order to target testing and vaccination.