Hepatitis C Viremia Patterns in Incident Hepatitis C Infection and One Year Later in 150 Prospectively Tested Persons Who Inject Drugs

Objectives

To assess HCV viremia levels just before, during and one year after anti-HCV seroconversion in people who inject drugs (PWID).

Methods

PWID enrolling into a needle exchange program in Malmö, Sweden, 1997–2005 constituted the source population. Sera were obtained at enrolment and at approximately 3–4 monthly intervals afterwards, and were initially tested for anti-HIV, HBsAg/anti-HBc and anti-HCV and thereafter for markers previously negative. Seroconversion to anti-HCV had occurred during the study period in 186 out of 332 seronegative subjects. In these anti-HCV seroconverters, quantitative HCV RNA PCR was retrospectively performed on frozen sera to determine viremia levels in the last anti-HCV negative, the first anti-HCV positive and in one year follow-up samples.

Results

Among 150 subjects seroconverting to anti-HCV with samples available from all three defined time-points, eight different patterns of viremia were observed. Spontaneous clearance at one year was noted in 48 cases (32%) and was associated with female gender (p = 0.03, CI 0.17–1.00). In 13 cases HCV-RNA was not detected in any study sample. Among 61 subjects with pre-seroconversion viremia, viral load was significantly higher in the pre-seroconversion samples compared to subsequent samples. For the whole group, viral load declined to undetectable levels at seroconversion in 28% of cases (but with recurrent viremia in 15%).

Conclusions

Different patterns of HCV RNA kinetics were observed among PWID with documented seroconversion to anti-HCV. The frequently observed absence of detectable HCV RNA in the first anti-HCV positive sample (irrespective of subsequent viremia) demonstrates the importance of repeated sampling and RNA testing for determination of the outcome of acute infection.     

Viral Hepatitis and Rapid Diagnostic Test Based Screening for HBsAg in HIV-infected Patients in Rural Tanzania

Background

Co-infection with hepatitis B virus (HBV) is highly prevalent in people living with HIV in Sub-Saharan Africa. Screening for HBV surface antigen (HBsAg) before initiation of combination antiretroviral therapy (cART) is recommended. However, it is not part of diagnostic routines in HIV programs in many resource-limited countries although patients could benefit from optimized antiretroviral therapy covering both infections. Screening could be facilitated by rapid diagnostic tests for HBsAg. Operating experience with these point of care devices in HIV-positive patients in Sub-Saharan Africa is largely lacking. We determined the prevalence of HBV and Hepatitis C virus (HCV) infection as well as the diagnostic accuracy of the rapid test device Determine HBsAg in an HIV cohort in rural Tanzania.

Methods

Prospectively collected blood samples from adult, HIV-1 positive and antiretroviral treatment-naïve patients in the Kilombero and Ulanga antiretroviral cohort (KIULARCO) in rural Tanzania were analyzed at the point of care with Determine HBsAg, a reference HBsAg EIA and an anti-HCV EIA.

Results

Samples of 272 patients were included. Median age was 38 years (interquartile range [IQR] 32–47), 169/272 (63%) subjects were females and median CD4+ count was 250 cells/µL (IQR 97–439). HBsAg was detected in 25/272 (9.2%, 95% confidence interval [CI] 6.2–13.0%) subjects. Of these, 7/25 (28%) were positive for HBeAg. Sensitivity of Determine HBsAg was rated at 96% (95% CI 82.8–99.6%) and specificity at 100% (95% CI, 98.9–100%). Antibodies to HCV (anti-HCV) were found in 10/272 (3.7%, 95% CI 2.0–6.4%) of patients.

Conclusion

This study reports a high prevalence of HBV in HIV-positive patients in a rural Tanzanian setting. The rapid diagnostic test Determine HBsAg is an accurate assay for screening for HBsAg in HIV-1 infected patients at the point of care and may further help to guide cART in Sub-Saharan Africa.     

HIV and Hepatitis C Virus Testing Delays at Methadone Clinics in Guangdong Province,China

In China, injection drug use is a major transmission route for HIV and hepatitis C virus (HCV) infection. Timely HIV and HCV testing among drug users is vital to earlier diagnosis, linkage to care, and retention. This study aimed to examine HIV and hepatitis C virus (HCV) testing delays at methadone clinics in Guangdong Province, China, and identify individual-level and clinic-level factors associated with delayed testing. Data from 13,270 individuals at 45 methadone clinics in Guangdong were abstracted from a national web-based surveillance database. A two-level binomial logit model was used to examine the association between individual- and clinic-level factors and delayed HIV and HCV testing, defined as receiving a test seven or more days after initial entry into the methadone system. Among 10,046 patients tested for HIV, 1882 (18.7%) had delayed testing; among 10,404 patients tested for HCV, 1542 (14.8%) had delayed testing. Among delayed testers, the median time to HCV testing was significantly longer than the median time to HIV testing (73 vs. 54 days, p<0.05). In the multivariate analysis, the likelihood of delayed HIV testing was higher among individuals with high school or greater education (adjusted odds ratio [aOR] 1.32, 95% confidence interval [CI] 1.02–1.72) and individuals enrolled at clinics with more patients (aOR 1.41, 95% CI 1.05–1.91, for each increase in 100). The likelihood of delayed HCV testing was higher among women (aOR 1.51, 95% CI 1.11–2.06) and employed individuals (aOR 1.21, 95% CI 1.02–1.43). Delayed testing for HIV and HCV is common among patients at methadone clinics in Guangdong, with many patients experiencing delays of two or more months. Structural interventions are needed to expedite testing once individuals enter the methadone maintenance program.     

Influence of Hepatitis C Virus and IL28B Genotypes on Liver Stiffness

Objective

Liver fibrosis has been associated with hepatitis C virus (HCV) genotype and genetic variation near the interleukin 28B (IL28B) gene, but the relative contribution is unknown. We aimed to investigate the relation between HCV genotypes, IL28B and development of liver stiffness.

Patients and Methods

This cross-sectional study consists of 369 patients with chronic hepatitis C (CHC). Liver stiffness was evaluated using transient elastograhy (TE). Factors associated with development of liver fibrosis were identified by logistic regression analysis.

Results

We identified 369 patients with CHC. 235 were male, 297 Caucasians, and 223 had been exposed to HCV through intravenous drug use. The overall median TE value was 7.4 kPa (interquartile range (IQR) 5.7–12.1). HCV replication was enhanced in patients carrying the IL28B CC genotype compared to TT and TC (5.8 vs. 5.4 log₁₀ IU/mL, p = 0.03). Patients infected with HCV genotype 3 had significantly higher TE values (8.2 kPa; IQR, 5.9–14.5) compared to genotype 1 (6.9 kPa; IQR, 5.4–10.9) and 2 (6.7 kPa; IQR, 4.9–8.8) (p = 0.02). Within patients with genotype 3, IL28B CC genotype had the highest TE values (p = 0.04). However, in multivariate logistic regression, using various cut-off values for fibrosis and cirrhosis, only increasing age (odds ratio (OR) 1.09 (95% confidence interval (CI), 1.05–1.14 per year increment)), ALT (OR 1.01 (95% CI, 1.002–1.011), per unit increment) and HCV genotype 3 compared to genotype 1 (OR 2.40 (95% CI, 1.19–4.81), were consistently associated with cirrhosis (TE>17.1 kPa).

Conclusions

Age, ALT and infection with HCV genotype 3 were associated with cirrhosis assessed by TE. However, IL28B genotype was not an independent predictor of fibrosis in our study.     

Low Levels of Microbial Translocation Marker LBP Are Associated with Sustained Viral Response after Anti-HCV Treatment in HIV-1/HCV Co-Infected Patients

Background

Microbial translocation (MT) contributes to immune activation during HIV and HCV infections. We investigated the kinetics of MT markers during anti-HCV and anti-HIV treatments, and if baseline plasma levels of lipopolysaccharide (LPS), lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) could predict anti-HCV treatment outcome.

Methods

Plasma from 78 HIV-infected patients was evaluated for LPS, LBP and sCD14. The patients starting anti-HCV treatment (with ongoing antiretroviral (ART) treatment) were categorized into sustained viral responders (SVR; n = 21) or non-responders (NR; n = 15) based on treatment outcome. ART starting subjects—were categorized into chronically HCV-infected (CH; n = 24) and mono-infected (HIV; n = 18), based on the HCV infection status. Samples were collected before start (at baseline) of pegylated-interferon-alpha/ribavirin (peg-IFN/RBV) or antiretroviral-therapy and two years after treatment start (at follow up). χ²–test, non-parametric statistics and logistic regression were applied to determine the associations with treatment response and changes of the soluble markers.

Results

Plasma levels of LPS and sCD14 were elevated in all subjects before antiviral-treatment but remained unchanged at follow-up. Elevated levels of LBP were present in patients with HIV and HIV/HCV co-infection and were reduced by ART. Additionally, higher levels of LBP were present at baseline in NR vs. SVR. Higher levels of LBP at baseline were associated with non-response to peg-IFN/RBV treatment in both bivariate (OR: 0.19 95% CI: 0.06–0.31, p = 0.004) and multivariate analysis (OR: 1.43, 95% CI: 1.1–1.86, p = 0.07).

Conclusion

In HIV/HCV co-infected patients high baseline LBP levels are associated with non-response to peg-IFN/RBV therapy. Plasma LBP (decreased by ART) may be a more relevant MT marker than LPS and sCD14.     

The Epidemiology of Hepatitis C Virus in the Fertile Crescent: Systematic Review and Meta-Analysis

Objective

To characterize hepatitis C virus (HCV) epidemiology in countries of the Fertile Crescent region of the Middle East and North Africa (MENA), namely Iraq, Jordan, Lebanon, Palestine, and Syria.

Methods

We systematically reviewed and synthesized available records of HCV incidence and prevalence following PRISMA guidelines. Meta-analyses were implemented using a DerSimonian-Laird random effects model with inverse weighting to estimate the country-specific HCV prevalence among the various at risk population groups.

Results

We identified eight HCV incidence and 240 HCV prevalence measures in the Fertile Crescent. HCV sero-conversion risk among hemodialysis patients was 9.2% in Jordan and 40.3% in Iraq, and ranged between 0% and 3.5% among other populations in Iraq over different follow-up times. Our meta-analyses estimated HCV prevalence among the general population at 0.2% in Iraq (range: 0–7.2%; 95% CI: 0.1–0.3%), 0.3% in Jordan (range: 0–2.0%; 95% CI: 0.1–0.5%), 0.2% in Lebanon (range: 0–3.4%; 95% CI: 0.1–0.3%), 0.2% in Palestine (range: 0–9.0%; 95% CI: 0.2–0.3%), and 0.4% in Syria (range: 0.3–0.9%; 95% CI: 0.4–0.5%). Among populations at high risk, HCV prevalence was estimated at 19.5% in Iraq (range: 0–67.3%; 95% CI: 14.9–24.5%), 37.0% in Jordan (range: 21–59.5%; 95% CI: 29.3–45.0%), 14.5% in Lebanon (range: 0–52.8%; 95% CI: 5.6–26.5%), and 47.4% in Syria (range: 21.0–75.0%; 95% CI: 32.5–62.5%). Genotypes 4 and 1 appear to be the dominant circulating strains.

Conclusions

HCV prevalence in the population at large appears to be below 1%, lower than that in other MENA sub-regions, and tending towards the lower end of the global range. However, there is evidence for ongoing HCV transmission within medical facilities and among people who inject drugs (PWID). Migration dynamics appear to have played a role in determining the circulating genotypes. HCV prevention efforts should be targeted, and focus on infection control in clinical settings and harm reduction among PWID.     

Genetic Variation in the Interleukin-28B Gene Is Associated with Spontaneous Clearance and Progression of Hepatitis C Virus in Moroccan Patients

Background

Genetic variation in the IL28B gene has been strongly associated with treatment outcomes, spontaneous clearance and progression of the hepatitis C virus infection (HCV). The aim of the present study was to investigate the role of polymorphisms at this locus with progression and outcome of HCV infection in a Moroccan population.

Methods

We analyzed a cohort of 438 individuals among them 232 patients with persistent HCV infection, of whom 115 patients had mild chronic hepatitis and 117 had advanced liver disease (cirrhosis and hepatocellular carcinoma), 68 individuals who had naturally cleared HCV and 138 healthy subjects. The IL28B SNPs rs12979860 and rs8099917 were genotyped using a TaqMan 5′ allelic discrimination assay.

Results

The protective rs12979860-C and rs8099917-T alleles were more common in subjects with spontaneous clearance (77.9% vs 55.2%; p = 0.00001 and 95.6% vs 83.2%; p = 0.0025, respectively). Individuals with clearance were 4.69 (95% CI, 1.99–11.07) times more likely to have the C/C genotype for rs12979860 polymorphism (p = 0.0017) and 3.55 (95% CI, 0.19–66.89) times more likely to have the T/T genotype at rs8099917. Patients with advanced liver disease carried the rs12979860-T/T genotype more frequently than patients with mild chronic hepatitis C (OR = 1.89; 95% CI, 0.99–3.61; p = 0.0532) and this risk was even more pronounced when we compared them with healthy controls (OR = 4.27; 95% CI, 2.08–8.76; p = 0.0005). The rs8099917-G allele was also associated with advanced liver disease (OR = 2.34; 95% CI, 1.40–3.93; p = 0.0100).

Conclusions

In the Moroccan population, polymorphisms near the IL28B gene play a role both in spontaneous clearance and progression of HCV infection.     

CCR5 Haplotypes Influence HCV Serostatus in Caucasian Intravenous Drug Users

Background

Up to 90% HIV-1 positive intravenous drug users (IDUs) are co-infected with HCV. Although best recognized for its function as a major co-receptor for cell entry of HIV, CC chemokine receptor 5 (CCR5) has also been implicated in the pathogenesis of HCV infection. Here, we investigated whether CCR5 haplotypes influence HIV-1 and HCV seropositivity among 373 Caucasian IDUs from Estonia.

Methods

Of these IDUs, 56% and 44% were HIV and HCV seropositive, respectively, and 47% were coinfected. 500 blood donors seronegative for HIV and HCV were also evaluated. CCR5 haplotypes (HHA to HHG*2) were derived after genotyping nine CCR2–CCR5 polymorphisms. The association between CCR5 haplotypes with HIV and/or HCV seropositivity was determined using logistic regression analysis. Co-variates included in the models were length of intravenous drug use, HBV serostatus and copy number of CCL3L1, the gene encoding the most potent HIV-suppressive chemokine and ligand for CCR5.

Results

Compared to IDUs seronegative for both HCV and HIV (HCV−/HIV-), IDUs who were HCV+/HIV- and HCV+/HIV+were 92% and 82%, respectively, less likely to possess the CCR5-HHG*1 haplotype, after controlling for co-variates (P_adjusted = 1.89×10⁻⁴ and 0.003, respectively). This association was mostly due to subjects bearing the CCR5 HHE and HHG*1 haplotype pairs. Approximately 25% and<10% of HCV−/HIV- IDUs and HCV−/HIV- blood donors, respectively, possessed the HHE/HHG*1 genotype.

Conclusions

Our findings suggest that HHG*1-bearing CCR5 genotypes influence HCV seropositivity in a group of Caucasian IDUs.     

Frequent Transient Hepatitis C viremia without Seroconversion among Healthcare Workers in Cairo,Egypt

Backgrounds

With 10% of the general population aged 15–59 years chronically infected with hepatitis C virus (HCV), Egypt is the country with the highest HCV prevalence worldwide. Healthcare workers (HCWs) are therefore at particularly high risk of HCV infection. Our aim was to study HCV infection risk after occupational blood exposure among HCWs in Cairo.

Methodology/Principal Findings

The study was conducted in 2008–2010 at Ain Shams University Hospital, Cairo. HCWs reporting an occupational blood exposure at screening, having neither anti-HCV antibodies (anti-HCV) nor HCV RNA, and exposed to a HCV RNA positive patient, were enrolled in a 6-month prospective cohort with follow-up visits at weeks 2, 4, 8, 12 and 24. During follow-up, anti-HCV, HCV RNA and ALT were tested. Among 597 HCWs who reported a blood exposure, anti-HCV prevalence at screening was 7.2%, not different from that of the general population of Cairo after age-standardization (11.6% and 10.4% respectively, p = 0.62). The proportion of HCV viremia among index patients was 37%. Of 73 HCWs exposed to HCV RNA from index patients, nine (12.3%; 95%CI, 5.8–22.1%) presented transient viremia, the majority of which occurred within the first two weeks after exposure. None of the workers presented seroconversion or elevation of ALT.

Conclusions/Significance

HCWs of a general University hospital in Cairo were exposed to a highly viremic patient population. They experienced frequent occupational blood exposures, particularly in early stages of training. These exposures resulted in transient viremic episodes without established infection. These findings call for further investigation of potential immune protection against HCV persistence in this high risk group.     

Hepatitis C Viremia Is Associated with Cytomegalovirus IgG Antibody Levels in HIV-Infected Women

Background

Individuals with HIV infection exhibit high cytomegalovirus (CMV) IgG levels, but there are few data regarding the association of hepatitis C virus (HCV) with the immune response against CMV.

Methods

Associations of HCV with CMV seropositivity and CMV IgG levels were studied in 635 HIV-infected women, 187 of whom were HCV-seropositive, with adjustment in multivariable models for age, race/ethnicity, and HIV disease characteristics. Eighty one percent of the women reported receipt of highly active antiretroviral therapy (HAART) prior to or at CMV testing.

Results

In adjusted models women with chronic HCV had higher CMV IgG levels than those without HCV RNA (β = 2.86, 95% CI:0.89 – 4.83; P = 0.004). The association of HCV RNA with CMV IgG differed by age (P _interaction = 0.0007), with a strong association observed among women in the low and middle age tertiles (≤45.3 years of age; β = 6.21, 95% CI:3.30 – 9.11, P<0.0001) but not among women in the high age tertile. CMV IgG levels were not associated with non-invasive measures of liver disease, APRI and FIB-4, or with HCV RNA level and adjustment for Epstein-Barr virus (EBV) IgG levels did not affect the association between HCV and CMV.

Conclusions

CMV IgG levels are higher in HCV/HIV co-infected women than in HIV mono-infected women. Further research on the association of HCV with CMV IgG is indicated because prior studies have found CMV IgG to be associated with morbidity and mortality in the general population and subclinical carotid artery disease in HIV-infected patients.     

Prevalence of bloodborne infective agents among people admitted to a Canadian hospital.

OBJECTIVE: To determine the prevalence rates of hepatitis B surface antigen (HBsAg) and antibodies to the human immunodeficiency virus (anti-HIV) and the hepatitis C virus (anti-HCV) among people admitted to an urban Canadian hospital. DESIGN: Anonymous unlinked serosurvey. SETTING: A 420-bed teaching hospital in Toronto. PARTICIPANTS: All 3000 patients admitted to the hospital on weekdays from January to June 1990. An attempt was made to exclude those who were readmitted during the study period. INTERVENTIONS: Serum samples from all the patients were tested for HBsAg and anti-HIV, and 1306 samples were also tested for anti-HCV by means of enzyme immunosorbent assays; reactions were confirmed by means of specific antibody neutralization or immunoblot assay. MAIN RESULTS: The prevalence rates of HBsAg, anti-HIV and anti-HCV were 2.1% (95% confidence interval [CI] 1.6% to 2.6%), 0.6% (95% CI 0.3% to 0.9%) and 0.5% (95% CI 0.1% to 0.9%) respectively. CONCLUSIONS: This is the first report defining rates of infection with these bloodborne agents among patients admitted to a Canadian hospital. The observed rates likely reflect the patient population served by our hospital and do not necessarily apply to other Canadian centres. The results support the use of universal precautions in health care settings.     

HIV,HBV and HCV Coinfection Prevalence in Iran - A Systematic Review and Meta-Analysis

Background

worldwide, hepatitis C and B virus infections (HCV and HCV), are the two most common coinfections with human immunodeficiency virus (HIV) and has become a major threat to the survival of HIV-infected persons. The review aimed to estimate the prevalence of HIV, HBV, HCV, HIV/HCV and HIV/HBV and triple coinfections in different subpopulations in Iran.

Method

Following PRISMA guidelines, we conducted a systematic review and meta-analysis of reports on prevalence of HIV, HBV, HCV and HIV coinfections in different subpopulations in Iran. We systematically reviewed the literature to identify eligible studies from January 1996 to March 2012 in English or Persian/Farsi databases. We extracted the prevalence of HIV antibodies (diagnosed by Elisa confirmed with Western Blot test), HCV antibodies and HBsAg (with confirmatory laboratory test) as the main primary outcome. We reported the prevalence of the three infections and coinfections as point and 95% confidence intervals.

Findings

HIV prevalence varied from %0.00 (95% CI: 0.00–0.003) in the general population to %17.25 (95% CI: 2.94–31.57) in people who inject drugs (PWID). HBV prevalence ranged from % 0.00 (95% CI: 0.00–7.87) in health care workers to % 30.9 (95% CI: 27.88–33.92) in PWID. HCV prevalence ranged from %0.19 (95% CI: 0.00–0.66) in health care workers to %51.46 (95% CI: 34.30–68.62) in PWID. The coinfection of HIV/HBV and also HIV/HCV in the general population and in health care workers was zero, while the most common coinfections were HIV/HCV (10.95%), HIV/HBV (1.88%) and triple infections (1.25%) in PWID.

Conclusions

We found that PWID are severely and disproportionately affected by HIV and the other two infections, HCV and HBV. Screenings of such coinfections need to be reinforced to prevent new infections and also reduce further transmission in their community and to others.     

The Spectrum of Cancers in West Africa: Associations with Human Immunodeficiency Virus

Background

Cancer is a growing co-morbidity among HIV-infected patients worldwide. With the scale-up of antiretroviral therapy (ART) in developing countries, cancer will contribute more and more to the HIV/AIDS disease burden. Our objective was to estimate the association between HIV infection and selected types of cancers among patients hospitalized for diagnosis or treatment of cancer in West Africa.

Methods

A case-referent study was conducted in referral hospitals in Côte d’Ivoire and Benin. Each participating clinical ward enrolled all adult patients seeking care for a confirmed diagnosis of cancer and clinicians systematically proposed an HIV test. HIV prevalence was compared between AIDS-defining cancers and a subset of selected non-AIDS defining cancers to a referent group of non-AIDS defining cancers not reported in the literature to be positively or inversely associated with HIV. An unconditional logistic model was used to estimate odds ratios (OR) and their 95% confidence intervals (CI) of the risk of being HIV-infected for selected cancers sites compared to a referent group of other cancers.

Results

The HIV overall prevalence was 12.3% (CI 10.3–14.4) among the 1,017 cancer cases included. A total of 442 patients constituted the referent group with an HIV prevalence of 4.7% (CI 2.8–6.7). In multivariate analysis, Kaposi sarcoma (OR 62.2 [CI 22.1–175.5]), non-Hodgkin lymphoma (4.0 [CI 2.0–8.0]), cervical cancer (OR 7.9 [CI 3.8–16.7]), anogenital cancer (OR 11.6 [CI 2.9–46.3]) and liver cancer (OR 2.7 [CI 1.1–7.7]) were all associated with HIV infection.

Conclusions

In a time of expanding access to ART, AIDS-defining cancers remain highly associated with HIV infection. This is to our knowledge, the first study reporting a significant association between HIV infection and liver cancer in sub-Saharan Africa.     

Chronic Hepatitis C Virus Infection Is Associated with the Development of Rheumatoid Arthritis: A Nationwide Population-Based Study in Taiwan

ObjectiveThe association between chronic hepatitis virus infection and rheumatoid arthritis (RA) remains debatable. This nationwide population-based cohort study assessed the risk of RA among patients with a chronic infection of hepatitis B and/or C virus.ResultsAfter adjusting for covariates, chronic HCV infection alone was significantly associated with an increased risk for RA (hazard ratio (HR)  = 2.03, 95% confidence interval (CI)  = 1.27–3.22). The increased risk for RA among participants with chronic HCV infection remained significant after restricting the analysis to those who were prescribed disease-modifying anti-rheumatic drugs. The corresponding HR for the overall sample was 1.89 (95% CI  = 1.15–3.11). However, HBV carriers did not appear to be at a significantly higher risk for RA.ConclusionOur data imply that chronic HCV infection is associated with RA development.     

Predictors of Frequent Emergency Room Visits among a Homeless Population

Background

Homelessness, HIV, and substance use are interwoven problems. Furthermore, homeless individuals are frequent users of emergency services. The main purpose of this study was to identify risk factors for frequent emergency room (ER) visits and to examine the effects of housing status and HIV serostatus on ER utilization. The second purpose was to identify risk factors for frequent ER visits in patients with a history of illicit drug use.

Methods

A retrospective analysis was performed on 412 patients enrolled in a Boston-based health care for the homeless program (HCH). This study population was selected as a 2:1 HIV seronegative versus HIV seropositive match based on age, sex, and housing status. A subgroup analysis was performed on 287 patients with history of illicit drug use. Chart data were analyzed to compare demographics, health characteristics, and health service utilization. Results were stratified by housing status. Logistic models using generalized estimating equations were used to predict frequent ER visits.

Results

In homeless patients, hepatitis C was the only predictor of frequent ER visits (OR 4.49, p<0.01). HIV seropositivity was not predictive of frequent ER visits. In patients with history of illicit drug use, mental health (OR 2.53, 95% CI 1.07–5.95) and hepatitis C (OR 2.85, 95% CI 1.37–5.93) were predictors of frequent ER use. HIV seropositivity did not predict ER use (OR 0.45, 95% CI 0.21 – 0.97).

Conclusions

In a HCH population, hepatitis C predicted frequent ER visits in homeless patients. HIV seropositivity did not predict frequent ER visits, likely because HIV seropositive HCH patients are engaged in care. In patients with history of illicit drug use, hepatitis C and mental health disorders predicted frequent ER visits. Supportive housing for patients with mental health disorders and hepatitis C may help prevent unnecessary ER visits in this population.     

Host Genetic Factors Affecting Spontaneous HBsAg Seroclearance in Chronic Hepatitis B Patients

Spontaneous clearance of hepatitis B surface antigen (HBsAg) in chronic hepatitis B (CHB) patients usually indicates a remission of hepatitis activity and a favorable outcome. Two single nucleotide polymorphisms (SNP), rs3077 near HLA-DPA1 region and rs9277535 near HLA-DPB1 region, have been shown to be associated with HBV persistence after acute HBV infection. However, little is known about the impact of these 2 SNPs on spontaneous HBsAg clearance in CHB patients. In this case-control study, a total of 100 male HBeAg-negative chronic HBV carriers who cleared HBsAg spontaneously (case group) and 100 age-matched HBeAg-negative male patients with persistent HBsAg positivity (control group) were enrolled. We investigated the relationship between these 2 SNPs and HBsAg clearance. There was a higher frequency of rs9277535 non-GG genotype in the case group (57% vs. 42%). Patients with rs9277535 non-GG genotype had a higher chance to clear HBsAg [Odds ratio (OR): 1.83, 95% confidence interval (CI): 1.04∼3.21, P = 0.034]. Compared to GG haplotype of rs3077 and rs9277535, GA haplotype had a higher chance of achieving spontaneous HBsAg loss (OR: 2.17, 95% CI: 1.14∼4.16, P = 0.030). In conclusion, rs9277535 non-GG genotype is associated with a higher likelihood of spontaneous HBsAg seroclearance in CHB patients.     

Prevalence of hepatitis C Virus infection among hemophiliacs in Central Brazil

In order to investigate the hepatitis C virus (HCV) infection prevalence and risk factors in hemophiliacs in Central Brazil, 90 patients were interviewed and serum samples tested for HCV RNA and anti-HCV antibodies. An overall prevalence of 63.3% (CI 95%: 53.0-72.7) was found. Multivariate analysis of risk factors showed that number of blood transfusions was significantly associated with this infection. Most hemophiliacs received locally produced cryoprecipitate. All infected patients were transfused before the screening of blood units for anti-HCV. However, hemophiliacs who received exclusively screened cryoprecipitate were HCV negative. It confirms the expected decline in transfusion-acquired hepatitis C.     

Usefulness of a Fourth Generation ELISA Assay for the Reliable Identification of HCV Infection in HIV-Positive Adults from Gabon (Central Africa)

Background/Objectives

Guidelines for optimized HCV screening are urgently required in Africa, especially for patients infected with HIV, who sometimes show false positive or false negative reactivity in anti-HCV antibody assays. Here, we assessed the usefulness of a fourth-generation HCV Ag-Ab ELISA for the identification of active HCV infection in HIV-positive patients.

Methods

This cross-sectional study was conducted between 03/2010 and 01/2013 and included 762 Gabonese HIV-positive adult patients. The results of ELISA (Monolisa HCV Ag-Ab ULTRA, Bio-Rad) were compared with those obtained by RT-PCR (gold standard). The optimal ELISA signal-to-cutoff (S/CO) ratio to identify patients with active hepatitis C (positive HCV RNA) was determined. Specimens were further tested by the INNO-LIA HCV Score assay (Innogenetics) and the Architect HCV Ag kit (Abbott) to define the best diagnostic strategy.

Results

Sixty-seven patients tested positive for HCV (S/CO ratio ≥ 1) by ELISA. Of these, 47 (70.1%) tested positive for HCV RNA. The optimal S/CO associated with active HCV infection was 1.7. At this threshold, the sensitivity of ELISA was 97.9% (95% confidence interval (CI) 90.0–99.9%), its specificity was 91.3% (95% CI 85.0–95.5%), and HCV seroprevalence rate was 7.3% (56/762) (95% CI 5.6–9.4%). Among 57 HCV-seropositive patients with available INNO-LIA results, false reactivity was identified in 14 (24.6%), resolved HCV infection in two (3.5%), possible acute HCV infections in nine (15.8%) and likely chronic HCV infections in 32 (56.1%) patients. HCV core Ag was undetectable in 14/15 (93.3%) specimens that tested negative for HCV RNA whereas it was quantified in 34 (out of 39, 87.2%) samples that tested positive for HCV RNA.

Conclusions

Our study provides comprehensive guidance for HCV testing in Gabon, and will help greatly clinicians to improve case definitions for both the notification and surveillance of HCV in patients co-infected with HIV.     

Prognostic Value of the Fibrosis-4 Index in Human Immunodeficiency Virus Type-1 Infected Patients Initiating Antiretroviral Therapy with or without Hepatitis C Virus

Objective

To evaluate the Fibrosis (FIB)-4 index as a predictor of major liver-related events (LRE) and liver-related death (LRD) in human immunodeficiency virus (HIV) type-1 patients initiating combination antiretroviral therapy (cART).

Design

Retrospective analysis of a prospective cohort study.

Setting

Italian HIV care centers participating to the ICONA Foundation cohort.

Participants

Treatment-naive patients enrolled in ICONA were selected who: initiated cART, had hepatitis C virus (HCV) serology results, were HBsAg negative, had an available FIB-4 index at cART start and during follow up.

Methods

Cox regression models were used to determine the association of FIB4 with the risk of major LRE (gastrointestinal bleeding, ascites, hepatic encephalopathy, hepato-renal syndrome or hepatocellular carcinoma) or LRD.

Results

Three-thousand four-hundred seventy-five patients were enrolled: 73.3% were males, 27.2% HCV seropositive. At baseline (time of cART initiation) their median age was 39 years, had a median CD4+ T cell count of 260 cells/uL, and median HIV RNA 4.9 log copies/mL, 65.9% had a FIB-4 <1.45, 26.4% 1.45–3.25 and 7.7% >3.25. Over a follow up of 18,662 person-years, 41 events were observed: 25 major LRE and 16 LRD (incidence rate, IR, 2.2 per 1,000 PYFU [95% confidence interval, CI 1.6–3.0]). IR was higher in HCV seropositives as compared to negatives (5.9 vs 0.5 per 1,000 PYFU). Higher baseline FIB-4 category as compared to <1.45 (FIB-4 1.45–3.25: HR 3.55, 95% CI 1.09–11.58; FIB-4>3.25: HR 4.25, 1.21–14.92) and time-updated FIB-4 (FIB-4 1.45–3.25: HR 3.40, 1.02–11.40; FIB-4>3.25: HR 21.24, 6.75–66.84) were independently predictive of major LRE/LRD, after adjusting for HIV- and HCV-related variables, alcohol consumption and type of cART.

Conclusions

The FIB-4 index at cART initiation, and its modification over time are risk factors for major LRE or LRD, independently of infection with HCV and could be used to monitor patients on cART.     

Gaining greater insight into HCV emergence in HIV-infected men who have sex with men: the HEPAIG Study

Objectives

The HEPAIG study was conducted to better understand Hepatitis C virus (HCV) transmission among human immuno-deficiency (HIV)-infected men who have sex with men (MSM) and assess incidence of HCV infection among this population in France.

Methods and Results

Acute HCV infection defined by anti-HCV or HCV ribonucleic acid (RNA) positivity within one year of documented anti-HCV negativity was notified among HIV-infected MSM followed up in HIV/AIDS clinics from a nationwide sampling frame. HIV and HCV infection characteristics, HCV potential exposures and sexual behaviour were collected by the physicians and via self-administered questionnaires. Phylogenetic analysis of the HCV-NS5B region was conducted.HCV incidence was 48/10 000 [95% Confidence Interval (CI):43–54] and 36/10 000 [95% CI: 30–42] in 2006 and 2007, respectively. Among the 80 men enrolled (median age: 40 years), 55% were HIV-diagnosed before 2000, 56% had at least one sexually transmitted infection in the year before HCV diagnosis; 55% were HCV-infected with genotype 4 (15 men in one 4d-cluster), 32.5% with genotype 1 (three 1a-clusters); five men were HCV re-infected; in the six-month preceding HCV diagnosis, 92% reported having casual sexual partners sought online (75.5%) and at sex venues (79%), unprotected anal sex (90%) and fisting (65%); using recreational drugs (62%) and bleeding during sex (55%).

Conclusions

This study emphasizes the role of multiple unprotected sexual practices and recreational drugs use during sex in the HCV emergence in HIV-infected MSM. It becomes essential to adapt prevention strategies and inform HIV-infected MSM with recent acute HCV infection on risk of re-infection and on risk-reduction strategies.