Treatment and monitoring of children with chronic hepatitis C in the Pre‐DAA era: A European survey of 38 paediatric specialists

The burden of paediatric Hepatitis C virus (HCV) infection across Europe is unknown, as are current policies regarding monitoring and treatment. This collaborative study aimed to collect aggregate data to characterise the population of ≤18‐year‐olds with HCV infection in specialist follow up in a 12‐month period (2016) across the PENTAHep European consortium, and investigate current policies around monitoring and treatment. A cross‐sectional, web‐based survey was distributed in April 2017 to 50 paediatricians in 19 European countries, covering patients' profile, and monitoring and treatment practices. Responses were received from 38/50 clinicians collectively caring for 663 children with chronic HCV infection of whom three‐quarters were aged ≥6 years and 90% vertically infected. HCV genotype 1 was the most common (n 380; 57.3%), followed by genotype 3, 4 and 2. Seventeen children (3%) with chronic HCV infection were diagnosed with cirrhosis, and six were reported to have received liver transplantation for HCV‐related liver disease. The majority (n 425; 64.1%) of the European children with HCV infection remained treatment‐naive in 2016. Age affected clinicians' attitudes towards treatment; 94% reported being willing to use direct‐acting antivirals, if available, in adolescents (aged ≥11 years), 78% in children aged 6‐10 and 42% in those 3‐5 years of age (Pearson correlation coefficient ?0.98; P 0.0001). This survey provides the largest characterisation of the population of children in clinical follow‐up for chronic HCV infection in Europe, alongside important contextual information on their management and treatment. Discussion is needed around strategies and criteria for use of direct‐acting antivirals in these children.     

Rare occurrence of occult hepatitis C virus in apparently uninfected injecting drug users: a two‐centre,masked, case–control study

Occult hepatitis C virus (HCV) is a phenomenon where serum HCV RNA is not detected by sensitive commercial assays, but viral RNA is detected by ultrasensitive techniques. Occult HCV infection has not previously been studied in highly exposed, but apparently uninfected (EU) individuals. Two studies examining occult infection in EU subjects were undertaken – an initial two‐centre, masked, case–control study based on cross‐sectional samples (n = 35 subjects) and a single‐centre confirmatory study based on longitudinal samples (n = 32 subjects). Plasma and peripheral blood mononuclear cells were tested for HCV RNA using an ultrasensitive nested polymerase chain reaction assays. Two EU subjects in the first study (10%) and one in the second study (3%) were found to have consistently detectable HCV RNA. Occult HCV infection occurs in high‐risk, apparently uninfected subjects.     

A meta‐analytic assessment of the risk of chronic kidney disease in patients with chronic hepatitis C virus infection

Epidemiological studies have reported conflicting results regarding hepatitis C virus (HCV) infection and the risk of chronic kidney disease (CKD). We systematically reviewed the literature to determine the risk of developing CKD in HCV‐infected individuals compared to uninfected individuals. MEDLINE and PUBMED were searched to identify observational studies that had reported an association between HCV and CKD or end‐stage renal disease (ESRD) through January 2015. Quantitative estimates [hazard ratio (HR) or odds ratio (OR)] and their 95% confidence intervals (CI) were extracted from each study. A random‐effects meta‐analysis was performed. Fourteen studies evaluating the risk of developing CKD/ESRD in HCV‐infected individuals (n = 336 227) compared to uninfected controls (n = 2 665 631) were identified‐ nine cohort studies and five cross‐sectional studies. The summary estimate indicated that individuals with HCV had a 23% greater risk of presenting with CKD compared to uninfected individuals (risk ratio = 1.23; 95% CI: 1.12–1.34). Results were similar by study type, for cohorts (HR = 1.26; 95% CI: 1.12–1.40) and cross‐sectional studies (OR = 1.21; 95% CI: 1.09–1.32). Country‐stratified analysis demonstrated a significantly increased risk between HCV and CKD in the Taiwanese subgroup (risk ratio = 1.28; 95% CI: 1.12–1.34) and the US subgroup (risk ratio = 1.17; 95% CI: 1.01–1.32). Egger regression revealed no evidence of publication bias. HCV infection is associated with a greater risk of developing and progression of CKD compared to uninfected controls.     

Daily cannabis and reduced risk of steatosis in human immunodeficiency virus and hepatitis C virus‐co‐infected patients (ANRS CO13‐HEPAVIH)

Liver steatosis is common in human immunodeficiency virus (HIV)‐hepatitis C virus (HCV)‐co‐infected patients. Some recent studies have found that cannabis use is negatively associated with insulin resistance in the general population and in HIV‐HCV‐co‐infected patients. Given the causal link between insulin resistance and steatosis, we hypothesized that cannabis use has a positive impact on steatosis. Therefore, we aimed to study whether cannabis use in this population was associated with a reduced risk of steatosis, measured by ultrasound examination. ANRS CO13‐HEPAVIH is a French nationwide multicentre cohort of HIV‐HCV‐co‐infected patients. Medical and socio‐behavioural data from clinical follow‐up visits and annual self‐administered questionnaires were prospectively collected. A cross‐sectional analysis was conducted using data from the first visit where both ultrasound examination data for steatosis (positive or negative diagnosis) and data on cannabis use were available. A logistic regression model was used to evaluate the association between cannabis use and steatosis. Among study sample patients (n = 838), 40.1% had steatosis. Fourteen per cent reported daily cannabis use, 11.7% regular use and 74.7% no use or occasional use (“never or sometimes”). Daily cannabis use was independently associated with a reduced prevalence of steatosis (adjusted odds ratio [95% CI] = 0.64 [0.42;0.99]; P = .046), after adjusting for body mass index, hazardous alcohol consumption and current or lifetime use of lamivudine/zidovudine. Daily cannabis use may be a protective factor against steatosis in HIV‐HCV‐co‐infected patients. These findings confirm the need for a clinical evaluation of cannabis‐based pharmacotherapies in this population. Eudract.ema.europa.eu number, DGS050367.     

Performance of the Pooled Cohort atherosclerotic cardiovascular disease risk score in hepatitis C virus‐infected persons

Chronic hepatitis C virus (HCV) infection has been associated with an increased risk for cardiovascular disease (CVD). The recommended Pooled Cohort atherosclerotic cardiovascular disease (ASCVD) risk equation for estimation of 10‐year CVD risk has not been validated in HCV‐infected populations. We examined the performance of the ASCVD risk score in HCV‐infected persons, using the national Electronically Retrieved Cohort of HCV Infected Veterans to derive a cohort of HCV‐infected and uninfected subjects without baseline ASCVD, hepatitis B, or HIV infection, and with low‐density lipoprotein cholesterol level<190 mg/dL. Performance of the ASCVD risk equation was assessed by Cox proportional hazard regression, C‐statistics and Hosmer‐Lemeshow statistic. The cohort included 70 490 HCV‐infected and 97 766 HCV‐uninfected men with mean age of 55 years, 56% White and 29% Black. Incident CVD event rates were similar between the two groups (13.2 and 13.4 events/1000 person‐years), with a higher incidence of coronary heart disease events in the HCV‐uninfected group and of stroke events in the HCV‐infected group. Adjusting for ASCVD risk score, HCV infection was associated with higher risk for an ASCVD event in the subgroup with baseline ASCVD risk ≥7.5% (HR: 1.19, P<.0001). C‐statistics were poor in both the HCV‐infected and uninfected groups (0.60 and 0.61, respectively). By Hosmer‐Lemeshow test, the ASCVD risk equation overestimated risk amongst lower risk patients and underestimated risk amongst higher risk patients in both the HCV‐infected and uninfected groups. Further investigation is needed to determine whether a modified equation to accurately predict ASCVD risk in HCV‐infected persons is warranted.     

Effect of hepatitis B virus on steatosis in hepatitis C virus co‐infected subjects: A multi‐centre study and systematic review

It remains unclear whether hepatitis B virus (HBV) infection may modify the severity of viral steatosis in patients coinfected with chronic hepatitis C virus (HCV). We examined the influence of coinfection with HBV on prevalence of steatosis in chronic hepatitis C in a multi‐centre cohort of HBV‐HCV subjects, and by performing a systematic review and meta‐analysis of the literature. We centrally and blindly assessed steatosis prevalence and severity in a cohort of HBV‐HCV coinfected subjects compared to HCV and HBV monoinfected controls and we performed a systematic review of studies addressing the prevalence of steatosis in HBV‐HCV subjects compared to HCV controls. In the clinical cohort, we included 85 HBV‐HCV, 69 HBV and 112 HCV subjects from 16 international centres. There was no significant difference in steatosis prevalence between the HBV‐HCV and the HCV groups (33% vs 45%, P = .11). In subgroup analysis, lean HBV‐HCV subjects with detectable HBV DNA had less steatosis than lean HCV subjects matched for HCV viremia (15% vs 45%, P = .02). Our literature search identified 5 additional studies included in a systematic review. Overall, prevalence of steatosis > 5% was similar in HBV‐HCV infection compared to HCV (pooled odds ratio [OR] 0.91, 95% CI 0.53‐1.6) although there was significant heterogeneity (I² 69%, P = .007). In conclusion, although the prevalence of steatosis is similar in HBV‐HCV compared to HCV subjects, our analysis suggests that there may be an inhibitory effect of HCV‐induced steatogenesis by HBV in certain subgroups of patients.     

Longitudinal evolution of vertically HIV/HCV–co‐infected vs HCV–mono‐infected children

HIV co‐infection has been suggested to play a deleterious role on the pathogenesis of liver fibrosis among vertically HCV‐infected children. The aim of this study was to describe the longitudinal evolution of vertically acquired HIV/HCV co‐infection in youths, in comparison with HCV infection alone. This was a retrospective, multicentre study including vertically HIV/HCV–co‐infected patients and age‐ and sex‐matched vertically HCV–mono‐infected patients. Progression to advanced liver fibrosis, defined as F3 or more by elastography or METAVIR biopsy staging, and response to treatment were compared by means of univariate and multivariate regression analyses and Cox regression models. Sixty‐seven co‐infected patients were compared with 67 matched HCV–mono‐infected patients. No progression to advanced liver disease was observed during the first decade. At a median age of 20.0 [19.0, 22.0] years, 26.7% co‐infected vs 20% mono‐infected had progressed to advanced fibrosis (P = .617). Peg‐IFN/RBV for HCV treatment was given to 37.9% vs 86.6% (P‐value < .001). At treatment initiation, co‐infected patients were older (16.9 ± 4.1 vs 11.7 ± 4.5 years, P < .001), and 47.1% vs 7.1% showed advanced fibrosis (P < .003), with no differences in hard‐to‐treat genotype distribution. Sustained viral response was comparable between groups (43.5% vs 44.0%, P = .122). In vertically HIV/HCV–co‐infected patients, the progression to liver fibrosis was rare during childhood. At the end of adolescence, over 25% of patients displayed advanced liver disease. Response to Peg‐IFN/RBV was poor and comparable in both groups, supporting the need for fast access to early treatment with direct‐acting antivirals against HCV for vertically co‐infected patients.     

Risk of transmission associated with sharing drug injecting paraphernalia: analysis of recent hepatitis C virus (HCV) infection using cross‐sectional survey data

Sharing injecting paraphernalia (containers, filters and water) poses a risk of transmitting the hepatitis C virus (HCV). The prevalence of, and risk of HCV from, such behaviour has not been extensively reported in Europe. People who inject drugs (PWID) were recruited in cross‐sectional surveys from services providing sterile injecting equipment across Scotland between 2008 and 2010. Participants completed a questionnaire and provided a blood spot for anonymous testing. Logistic regression was used to examine the association between recent HCV infection (anti‐HCV negative and HCV‐RNA positive) and self‐reported measures of injecting equipment sharing in the 6 months preceding interview. Twelve per cent of the sample reported sharing needles/syringes, and 40% reported sharing paraphernalia in the previous 6 months. The adjusted odds ratios (AOR) for sharing needles/syringes (+/− paraphernalia), and sharing only paraphernalia in the last 6 months were 6.7 (95% CI 2.6–17.1) and 3.0 (95% CI 1.2–7.5), respectively. Among those who reported not sharing needles/syringes, sharing containers and filters were both significantly associated with recent HCV infection (AOR 3.1, 95% CI 1.3–7.8 and 3.1, 95% CI 1.3–7.5, respectively); sharing water was not. We present the first study to apply a cross‐sectional approach to the analysis of the association between sharing paraphernalia and incident HCV infection and demonstrate consistent results with previous longitudinal studies. The prevalence of paraphernalia sharing in our study population is high, representing significant potential for HCV transmission.     

HCV RNA decline in chronic HCV genotype 2 and 3 during standard of care treatment according to IL28B polymorphism

The IL28 gene is highly associated with sustained viral response (SVR) in patients infected with genotype 1 after standard of care (SOC) treatment with peg‐IFN and ribavirin. It is also associated with a steeper first phase HCV RNA decline during treatment. In genotype 2 and 3 infections, these correlations are less obvious. We studied the IL28B association to rapid viral response (RVR), SVR, first and second phase HCV RNA decline during treatment in 100 HCV mono‐infected and 13 HCV/HIV co‐infected patients. We found a significantly higher mean baseline HCV RNA level in IL28B SNP CC than non‐CC mono‐infected patients, 6.99 vs 6.30 log₁₀ IU/mL (P = 0.02), and a significantly larger median 1st phase decline in patients with CC than non‐CC genotype, 2.03 vs 1.37 log₁₀ IU/mL, respectively. The overall SVR rate in HCV mono‐infected patients was 87% vs 77% in HCV/HIV co‐infected patients, with no correlation to IL28B SNP. In mono‐infected patients with RVR, the SVR rate was high and independent of IL28B genotype. In mono‐infected patients who failed to achieve RVR who had IL28B CC and non‐CC genotype, 64% and 67% achieved SVR, respectively. In genotype 2 and 3 infected patients, the 1st phase HCV RNA decline was steeper in patients with IL28B CC vs non‐CC genotype during SOC treatment. This did not translate into a higher frequency of RVR or SVR. Hence, the clinical relevance of pretreatment analysis of IL28B polymorphisms in genotype 2 and 3 infected patients can be questioned in patients with expected high SVR rate.     

Uptake of hepatitis C treatment among people who inject drugs attending Needle and Syringe Programs in Australia, 1999–2011

The majority of new and existing cases of hepatitis C virus (HCV) infection occur among people who inject drugs (PWID). Despite safe and efficacious HCV antiviral therapy, uptake remains low in this population. This study examined trends in HCV treatment uptake among a large national sample of PWID attending Australian Needle and Syringe Programs between 1999 and 2011. Annual cross‐sectional sero‐surveys conducted among PWID since 1995 involve completion of a self‐administered questionnaire and provision of a dried blood spot for HCV antibody testing. Multivariate logistic regression identified variables independently associated with HCV treatment uptake among 9478 participants with both self‐reported and serologically confirmed prior HCV infection. Between 1999 and 2011, the proportion currently receiving treatment increased from 1.1% to 2.1% (P < 0.001), while the proportion having ever received treatment increased from 3.4% to 8.6% (P < 0.001). Men were significantly more likely than women to have undertaken HCV treatment (P = 0.002). Among men, independent predictors of HCV treatment uptake were homosexual identity and older age; among women, independent predictors included homosexual identity and an incarceration history. Despite increases in HCV treatment among Australian PWID between 1999 and 2011, uptake remains low. Strategies are required to increase the proportion of PWID assessed and treated for HCV infection to address the increasing burden of disease. Specific approaches that target women may also be warranted. Continued surveillance of HCV treatment uptake among PWID will be important to monitor the roll‐out of simple, safe and more effective HCV treatments expected to be available in the future.     

Hepatitis C virus coinfection and the risk of cardiovascular disease among HIV‐infected patients

Background

Among HIV‐infected patients, hepatitis C virus (HCV) coinfection is associated with lower cholesterol levels, but it remains unclear how it affects cardiovascular outcomes.

Methods

We performed logistic regression to evaluate acute myocardial infarction (AMI) and cerebrovascular disease (CVD) events by HCV status among HIV‐infected US veterans in the highly active antiretroviral therapy (HAART) era (1996–2004). We then performed survival analyses to evaluate incident AMI and CVD, exploring antiretroviral therapy (ART) as a time‐dependent variable.

Results

A total of 19 424 HIV‐infected patients [31.6% of whom were HCV‐coinfected (HIV/HCV)] contributed 76 376 patient‐years of follow‐up. HCV coinfection was associated with lower rates of hypercholesterolaemia (18.0% in HIV/HCV vs. 30.7% in HIV‐only patients; P<0.001), but higher rates of hypertension (43.8%vs. 35.6%; P<0.0001), type 2 diabetes mellitus (16.2%vs. 11.1%; P<0.0001) and smoking (36.7%vs. 24.7%; P=0.009). Rates of AMI and CVD were significantly higher among HIV/HCV than HIV‐only patients: 4.19 vs. 3.36 events/1000 patient‐years, respectively (P<0.001), for AMI; and 12.47 vs. 11.12 events/1000 patient‐years, respectively (P<0.001), for CVD. When analyses were controlled for diabetes mellitus, hypertension, age and duration of ART, hazard ratios (HRs) among those with HIV/HCV (vs. HIV only) were 1.25 [95% confidence interval (CI) 0.98–1.61; P=0.072] for AMI and 1.20 (CI 1.04–1.38; P=0.013) for CVD. Hypertension (HR 2.05; P<0.001), greater age (HR 1.79; P<0.001) and longer duration (cumulative years) of antiretroviral use (HR 1.12; P=0.0411) were also associated with increased risk of AMI in the adjusted model.

Conclusions

In the HAART era, HCV coinfection was associated with a significantly increased risk of CVD and a trend towards an increased risk of AMI among HIV‐infected patients.     

Depression is not associated with peripheral insulin resistance in patients with chronic hepatitis C infection

Depression is common in individuals infected with hepatitis C virus (HCV), and both depression and HCV infection are independently associated with insulin resistance (IR). To evaluate the relationship between depression and IR, among other factors, in an HCV‐infected cohort. In this cross‐sectional analysis, seventy‐four non‐type 2 diabetic, noncirrhotic, HCV‐infected patients underwent comprehensive clinical, histologic and metabolic evaluation. IR was assessed directly with an insulin suppression test by measuring steady‐state plasma glucose (SSPG) levels during continuous infusions of octreotide, glucose and insulin. Logistic regression modelling was used to evaluate predictors associated with depression. Thirty‐nine (53%) patients were depressed, and 21 (54%) depressed patients were on at least one antidepressant. A higher estimated proportion of depressed patients were Caucasian (51% vs 20%, P = 0.005), unemployed (69% vs 49%, P = 0.07), heavier smokers (18 pack‐years vs 13 pack‐years, P = 0.07), on substance abuse therapy (16% vs 3%, P = 0.06) and had lower HDL levels (1.2 mmol/L vs 1.4 mmol/L, P = 0.01). The mean SSPG levels in depressed and nondepressed patients were 7.3 and 8.3 mmol/L (P = 0.45), respectively. In multipredictor adjusted analysis, only Caucasian race (OR 4.19, 95% CI 1.42–12.35, P = 0.009) and lower HDL (OR 0.95, 95% CI 0.89–0.99, P = 0.046) were associated with depression. In conclusion, although prevalent, depression was not associated with peripheral IR in this HCV‐infected cohort. Attention to other modifiable factors associated with depression in the HCV‐infected population is warranted.     

Association between chronic hepatitis C virus infection and low muscle mass in US adults

Given that low muscle mass can lead to worse health outcomes in patients with chronic infections, we assessed whether chronic hepatitis C virus (HCV) infection was associated with low muscle mass among US adults. We performed a cross‐sectional study of the National Health Examination and Nutrition Study (1999–2010). Chronic HCV‐infected patients had detectable HCV RNA. Low muscle mass was defined as <10th percentile for mid‐upper arm circumference (MUAC). Multivariable logistic regression was used to determine adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of low muscle mass associated with chronic HCV. Among 18 513 adults, chronic HCV‐infected patients (n = 303) had a higher prevalence of low muscle mass than uninfected persons (13.8% vs 6.7%; aOR, 2.22; 95% CI, 1.39–3.56), and this association remained when analyses were repeated among persons without significant liver fibrosis (aOR, 2.12; 95% CI, 1.30–3.47). This study demonstrates that chronic HCV infection is associated with low muscle mass, as assessed by MUAC measurements, even in the absence of advanced liver disease.     

HIV and HCV health beliefs in an inner-city community

Summary. Chronic infection with the hepatitis C virus (HCV) is more prevalent than human immunodeficiency virus (HIV) infection, but more public health resources are allocated to HIV than to HCV. Given shared risk factors and epidemiology, we compared accuracy of health beliefs about HIV and HCV in an at‐risk community. Between 2002 and 2003, we surveyed a random patient sample at a primary care clinic in New York. The survey was organized as domains of Common Sense Model of Self‐Regulation: causes (‘sharing needles’), timeline/consequences (‘remains in body for life’, ‘causes cancer’) and controllability (‘I can avoid this illness’, ‘medications may cure this illness’). We compared differences in accuracy of beliefs about HIV and HCV and used multivariable linear regression to identify factors associated with relative accuracy of beliefs. One hundred and twenty‐two subjects completed the survey (response rate 42%). Mean overall health belief accuracy was 12/15 questions (80%) for HIV vs 9/15 (60%) for HCV (P < 0.001). Belief accuracy was significantly different across all domains. Within the causes domain, 60% accurately believed sharing needles a risk factor for HCV compared to 92% for HIV (P < 0.001). Within the timeline/consequences domain, 42% accurately believed HCV results in lifelong infection compared to 89% for HIV (P < 0.001). Within the controllability domain, 25% accurately believed that there is a potential cure for HCV. Multivariable linear regression revealed female gender as significantly associated with greater health belief accuracy for HIV. Thus, study participants had significantly less accurate health beliefs about HCV than about HIV. Targeting inaccuracies might improve public health interventions to foster healthier behaviours and better hepatitis C outcomes.     

Outcome of cutaneous psoriasis in hepatitis C virus‐infected patients treated with Direct‐Acting Antiviral therapy

Apart from chronic liver disease, hepatitis C virus (HCV) may be responsible for several extra‐hepatic manifestations. Its involvement in psoriasis development is still controversial. The aim of this study was to evaluate the possible effect of anti‐HCV direct‐acting antiviral (DAA) treatment on cutaneous psoriasis. Thirty‐seven consecutive HCV patients with cutaneous psoriasis underwent efficacious DAA treatment, and all of them were efficiently cured as shown by HCV RNA negativity 24 weeks after stopping therapy (PT24W). An expert dermatologist evaluated the skin lesions at baseline, end of treatment (EOT) and PT24W using the psoriasis area severity index (PASI) scoring system. The impact on quality of life was measured with the Dermatologic Quality of Life Index (DLQI). Six patients had a stable disease throughout the study period, whereas 31/37 patients (83.8%) showed a significant improvement of the skin lesions at EOT (P < .0001). However, 24 of these 31 patients (77.4%) had a dramatic worsening of the psoriatic lesions at PT24W compared with EOT (P < .001), with lesion severity comparable to baseline. The outcome of psoriasis during and after treatment was independent of baseline PASI score, age, sex, HCV genotype, liver disease stage and of the presence of arterial hypertension, diabetes and autoimmune diseases. In conclusion, DAA‐based HCV cure has only a transient effect on skin lesions of patients with concomitant cutaneous psoriasis.     

IL28B genetic variation and hepatitis C virus–specific CD4+ T‐cell responses in anti‐HCV‐positive blood donors

Summary. Epidemiological, viral and host factors are associated with the outcome of hepatitis C virus (HCV) infection, and strong host immune responses against HCV favour viral clearance. Recently, genome‐wide association studies have shown a strong correlation between single‐nucleotide polymorphisms (SNPs) near the interleukin‐28B (IL28B) gene and spontaneous or treatment‐induced HCV clearance. We have investigated whether protective IL28B genetic variants are associated with HCV‐specific T‐cell responses among Spanish blood donors. The rs12979860 IL28B haplotype was determined in 69 anti‐HCV‐positive blood donors (21 HCV RNA negative and 48 HCV RNA positive) and 30 seronegative donors. In all cases, HCV‐specific CD4⁺ T‐cell responses to HCV recombinant proteins (core, NS3 and NS3 helicase) were assessed by ex vivo interferon‐γ ELISpot assay. The rs12979860‐CC genotype was highly overrepresented in donors with spontaneous HCV clearance when compared to those with chronic infection (76.2%vs 29.2%, P < 0.001; odds ratio, 7.77; 95% confidence interval, 2.4–25.3, P < 0.001). HCV‐specific CD4⁺ T‐cell responses were detected in 16 (76.2%) spontaneous resolvers especially towards nonstructural proteins, but with no correlation with IL28B genotype. Chronic individuals had a significantly lower overall T‐cell response again irrespective of IL28B genotype. When spontaneous resolvers and chronic individuals were stratified according to their IL28B genotype, significantly stronger T‐cell responses were only observed among those with non‐CC haplotypes. Although the protective rs12979860 IL28B CC genotype is associated with spontaneous HCV clearance, stronger CD4⁺ T‐cell responses towards NS3 were only evident among those with non‐CC haplotypes.     

Apolipoprotein E‐ε4 deficiency and cognitive function in hepatitis C virus‐infected patients

Hepatitis C virus (HCV) causes not only liver damage in certain patients but can also lead to neuropsychiatric symptoms. Previous studies have shown that the type 4 allele of the gene for apolipoprotein E (APOE) is strongly protective against HCV‐induced damage in liver. In this study, we have investigated the possibility that APOE genotype is involved in the action of HCV in brain. One hundred HCV‐infected patients with mild liver disease underwent a neurological examination and a comprehensive psychometric testing of attention and memory function. In addition, patients completed questionnaires for the assessment of fatigue, health‐related quality of life and mood disturbances. Apolipoprotein E gene genotyping was carried out on saliva using buccal swabs. The APOE‐ε4 allele frequency was significantly lower in patients with an impairment of working memory, compared to those with a normal working memory test result (P = 0.003). A lower APOE‐ε4 allele frequency was also observed in patients with definitely altered attention ability (P = 0.008), but here, the P‐value missed the level of significance after application of the Bonferroni correction. Our data suggest that the APOE‐ε4 allele is protective against attention deficit and especially against poor working memory in HCV‐infected subjects with mild liver disease. Considering the role of apolipoprotein E in the life cycle of the virus, the findings shed interesting new light upon possible pathomechanisms behind the development of neuropsychiatric symptoms in hepatitis C infection.     

Impact of hepatitis C virus infection on all‐cause and liver‐related mortality in a large community‐based cohort of inner city residents

Summary. The aim of this study was to measure the impact of hepatitis C virus (HCV) infection on mortality in a cohort of inner city residents. The Community Health and Safety Evaluation is a community‐based study of inner city residents followed retrospectively and prospectively through linkages with provincial virology and mortality databases. We identified participants having received HCV antibody testing, evaluated cause‐specific mortality rates and factors associated with all‐cause and liver‐related mortality using Cox Proportional Hazards models. Overall, 2332 participants received HCV antibody testing (recent non‐injection drug use – 81%). The prevalence of HCV and HIV was 64% (1495 of 2332) and 21% (485 of 2332), respectively. Between January 2003 and December 2007, there were 180 deaths (192 per 10 000 person‐years; 95% CI: 165, 222), with 21% HIV‐related, 20% drug‐related and 7% liver‐related. Mortality was associated with age >50 [adjusted hazard ratio (AHR) 2.80 vs <40 years (referent group); 95% CI 1.93, 4.07, P < 0.001] and HIV infection (AHR 3.81; 95% CI 2.72, 5.34, P < 0.001), but not positive HCV antibody status (AHR 1.19; 95% CI 0.83, 1.72, P = 0.35). Liver‐related mortality was associated with age >50 [AHR 18.49 vs <40 years (referent group); 95% CI 2.27, 150.41, P < 0.001] and positive HCV antibody status (AHR 7.69; 95% CI 0.99, 59.98, P = 0.052). This study demonstrates a high rate of mortality in this population, particularly those with HIV. HCV‐infected inner city residents >50 years of age were at significant risk of liver‐related mortality. Continued surveillance of this population infected with HCV in the 1970s and 1980s is important.     

Risk behaviours of homeless people who inject drugs during an outbreak of hepatitis C,Northern Ireland, 2016‐2017

From July to August 2016, 4 homeless people who injected drugs (PWID) with acute or recent hepatitis C virus (HCV) infection were reported in Belfast. A multidisciplinary team including public health, homeless and addiction services undertook an investigation to identify risk behaviours and interrupt transmission chains. Recent HCV cases were defined as negative test within the previous year, or reported injecting for less than 1 year; acute cases had tested negative within the previous 6 months. Contacts in the injecting networks of cases were identified for testing. We undertook a cross‐sectional survey using structured questionnaires to elicit risk behaviours for PWID and compare behaviours between self‐reported hepatitis C positive and negative subjects. During the outbreak investigation until December 2017, 156 PWID were tested and 45 (29%) cases identified, including 7 (16%) recent and 13 (29%) acute infections. 68 PWID, including 12 cases, were interviewed. All respondents reported using heroin, with 76% injecting once or more daily. Sharing was reported for spoons (58%) and filters (53%), but also needles (27%) and syringes (29%). Hepatitis C positive individuals had higher odds to be injecting in public toilets (AOR 17, 95% CI 0.71‐400, P < .05) when compared with hepatitis C negative individuals. Hepatitis C positive individuals were more likely to inject in public spaces, but all respondents indicated concerning risk behaviours. We recommend active surveillance with ongoing testing, expanding existing harm reduction programmes and access to bespoke services.     

Hepatitis C virus treatment and survival in patients with hepatitis C and human immunodeficiency virus co‐infection and baseline anaemia

The impact of pretreatment anaemia on survival in individuals with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co‐infection is not known. Moreover, HCV treatment is offered less frequently to individuals with anaemia, due to haematological side effects of the treatment regimen. This study aimed to determine the effect of HCV treatment on survival among HCV/HIV co‐infected individuals with pretreatment anaemia using the Electronically Retrieved Cohort of HCV‐Infected Veterans (ERCHIVES). Individuals with HCV/HIV co‐infection were included in current analyses. Participants were considered treated if they were prescribed ≥4 weeks of HCV treatment. All‐cause mortality data were obtained using record linkage. Survival analyses were performed using Cox proportional hazard models. Among 5000 HCV/HIV co‐infected individuals, 1671 (33.4%) had pretreatment anaemia. In a follow‐up period of up to 7 years (19 500 person‐years), individuals with anaemia had significantly higher mortality rate compared with those without anaemia [144.2 (95% CI: 134.5–154.7) vs 47.5 (44.0–51.2) per 1000 person‐years, respectively]. Among individuals with anaemia, HCV treatment was associated with significantly lower mortality rate [66.6 (44.3–100.2) vs 149.6 (139.2–160.5) per 1000 person‐years, for treated vs untreated, respectively]. Treatment remained associated with substantial survival benefit after taking into account the effect of multiple comorbidities (hazards ratio: 0.34, 95% CI: 0.21–0.62). These data suggest that HCV/HIV co‐infected individuals with pretreatment anaemia have significantly higher mortality compared with those without anaemia. HCV treatment is associated with substantial survival benefit in this group. Additional studies are needed to determine strategies to improve HCV treatment rates among this group.