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The original version of this article unfortunately contained a mistake. The name of the author Mara Caroprese was rendered wrongly. The correct name is shown above.
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.
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.
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.
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.
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.
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.
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.
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
CD40, encoded by TNFRSF5, participates in the survival of B cells, process of antigen presentation and generation of CD8+ T cell memory. It also has an important effect on HCV antiviral immune response. This study aims to investigate whether TNFRSF5 gene polymorphisms are associated with HCV infection outcomes among Chinese population.
Three single nucleotide polymorphism (SNPs) (rs1535045, rs1883832, rs4810485) on TNFRSF5 were genotyped by TaqMan assay among Chinese population, including 1513 uninfected subjects, 496 spontaneous viral clearance subjects and 768 persistent HCV-infected subjects. Logistic analysis was used to compare these SNPs among different groups in this cross-sectional study. Functional annotations of the identified SNPs were further evaluated by bioinformatics analysis.
After adjusted by age, gender and routes of infection, the results of logistic analysis indicated that individuals carrying rs1535045 T allele had a higher risk to infect HCV compared with C allele (in recessive model, adjusted OR = 1.368, 95%CI = 1.070-1.749, P = 0.012). Subjects carried rs1535045 TT genotype were more likely to infect HCV than wild CC genotype (adjusted OR = 1.397, 95%CI = 1.078-1.809, P = 0.011). For rs1883832, T allele was significantly associated with an increased risk of HCV infection (in recessive model, adjusted OR = 1.337, 95%CI = 1.069-1.673, P = 0.011). Subjects with TT genotype had more possibility to infect HCV (adjusted OR = 1.351, 95%CI = 1.060-1.702, P = 0.015). In the stratified analysis, rs1535045 and rs1883832 were remained in various subgroups and the heterogeneity test showed no pronounced heterogeneity in any pairwise comparison (all P > 0.05). In addition, the results of the cumulative effects showed a tendency of that the more risk alleles (rs1535045 T and rs1883832 T) subjects carried, the more possibility of HCV infection exhibited (P
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:
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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%).
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.
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 . 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 . Due to the lack of engagement and treatment of HCV-infected PWID, the United States is not on track to meet these targets . 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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
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.
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.
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.
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: email@example.com, 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: firstname.lastname@example.org
Received 20 February, 2019
Revised 20 June, 2019
Accepted 29 June, 2019
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Copyright © 2019 Wolters Kluwer Health, Inc.
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.
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.
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.
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.
Our results suggested that the TGF-ß1–509C/T polymorphism may effect an increased risk of chronic HCV infection, especially in Egyptian population.
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%).
Saeed S, Strumpf E, Moodie E, et al.
AbstractBackgroundHigh costs of direct acting antivirals (DAAs) led healthcare insurers to limit access worldwide. Using a natural experiment, we evaluated the impact of removing fibrosis stage restrictions on hepatitis C (HCV) treatment initiation rates among people living with HIV and then examined who was left to be treated.MethodsUsing data from the Canadian HIV-HCV Co-Infection Cohort, we applied a difference-in-differences approach. Changes in treatment initiation rates following the removal of fibrosis stage restrictions was assessed using a negative binomial regression with generalized estimating equations. The policy change was then specifically assessed among people who inject drugs (PWID). We then identified characteristics of participants who remained to be treated using a modified Poisson regression.ResultsBetween 2010-2018, there were a total of 585 HCV initiations among 1130 eligible participants. After removing fibrosis stage restrictions, DAA initiations increased by 1.8-fold (95% CI 1.3, 2.4) controlling for time-invariant differences and secular trends. Among PWID the impact appeared even stronger; adjusted incidence rate ratios (aIRR) (95% CI), 3.6 (1.8, 7.4). However, this increased treatment uptake was not sustained. One year following universal access, treatment rates declined, 0.8 (0.5, 1.1). Marginalized participants (PWID and Indigenous ethnicity) and those disengaged from care were more likely to remain HCV RNA positive.ConclusionAfter the removal of fibrosis restrictions HCV treatment initiations nearly doubled immediately but this treatment rate was not sustained. To meet the WHO elimination targets, minimization of structural barriers and adoption of tailored interventions are needed to engage and treat all vulnerable populations.
Kushner T, Chen Z, Tressler S, et al.
AbstractBackgroundThe current opioid injection drug use epidemic has been associated with an increase in hepatitis C (HCV) infections among women of childbearing age in the US, but changes in hepatitis B (HBV) infection have not been studied.MethodsA retrospective analysis of HBV status among women of childbearing age nationally and by state was conducted utilizing the Quest Diagnostics database. Rates of HBV in women born before and after implementation of universal HBV vaccination recommendations were determined.ResultsWe identified 8,871,965 women tested for HBV from 2011-2017. Nationally, the annual rate of acute HBV infections was stable, but increased in Kentucky, Alabama and Indiana (p
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