Trends in hepatocellular carcinoma incidence and survival among people with hepatitis C: An international study.

This study evaluates trends in hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) incidence and survival in three settings, prior to introduction of direct-acting antiviral (DAA) therapies. HCV notifications from British Columbia (BC), Canada; New South Wales (NSW), Australia; and Scotland (1995-2011/2012/2013, respectively) were linked to HCC diagnosis data via hospital admissions (2001-2012/2013/2014, respectively) and mortality (1995-2013/2014/2015, respectively). Age-standardized HCC incidence rates were evaluated, associated factors were assessed using Cox regression, and median survival time after HCC diagnosis was calculated. Among 58 487, 84 529 and 31 924 people with HCV in BC, NSW and Scotland, 734 (1.3%), 1045 (1.2%) and 345 (1.1%) had an HCC diagnosis. Since mid-2000s, HCC diagnosis numbers increased in all jurisdictions. Age-standardized HCC incidence rates remained stable in BC and Scotland and increased in NSW. The strongest predictor of HCC diagnosis was older age [birth <1945, aHR in BC 5.74, 95% CI 4.84, 6.82; NSW 9.26, 95% CI 7.93, 10.82; Scotland 12.55, 95% CI 9.19, 17.15]. Median survival after HCC diagnosis remained stable in BC (0.8 years in 2001-2006 and 2007-2011) and NSW (0.9 years in 2001-2006 and 2007-2013) and improved in Scotland (0.7 years in 2001-2006 to 1.5 years in 2007-2014). Across the settings, HCC burden increased, individual-level risk of HCC remained stable or increased, and HCC survival remained extremely low. These findings highlight the minimal impact of HCC prevention and management strategies during the interferon-based HCV treatment era and form the basis for evaluating the impact of DAA therapy in the coming years.

Drug use and phylogenetic clustering of hepatitis C virus infection among people who use drugs in Vancouver, Canada: A latent class analysis approach.

This study estimated latent classes (ie, unobserved subgroups in a population) of people who use drugs in Vancouver, Canada, and examined how these classes relate to phylogenetic clustering of hepatitis C virus (HCV) infection. HCV antibody-positive people who use drugs from two cohorts in Vancouver, Canada (1996-2012), with a Core-E2 sequence were included. Time-stamped phylogenetic trees were inferred, and phylogenetic clustering was determined by time to most common recent ancestor. Latent classes were estimated, and the association with the phylogenetic clustering outcome was assessed using an inclusive classify/analyse approach. Among 699 HCV RNA-positive participants (26% female, 24% HIV+), recent drug use included injecting cocaine (80%), injecting heroin (70%), injecting cocaine/heroin (ie, speedball, 38%) and crack cocaine smoking (28%). Latent class analysis identified four distinct subgroups of drug use typologies: (i) cocaine injecting, (ii) opioid and cocaine injecting, (iii) crack cocaine smoking and (iv) heroin injecting and currently receiving opioid substitution therapy. After adjusting for age and HIV infection, compared to the group defined by heroin injecting and currently receiving opioid substitution therapy, the odds of phylogenetic cluster membership was greater in the cocaine injecting group (adjusted OR [aOR]: 3.06; 95% CI: 1.73, 5.42) and lower in the crack cocaine smoking group (aOR: 0.06; 95% CI: 0.01, 0.48). Combining latent class and phylogenetic clustering analyses provides novel insights into the complex dynamics of HCV transmission. Incorporating differing risk profiles associated with drug use may provide opportunities to further optimize and target HCV treatment and prevention strategies.

Role of primary T-cell immunodeficiency and hepatitis B coinfection on spontaneous clearance of hepatitis C: The BC Hepatitis Testers Cohort.

T-cell host immune response against hepatitis C virus (HCV) has been suggested to play an important role in determining HCV infection outcome. However, data from human studies are not available. This study examined the effect of primary T-cell deficiency along with other factors on the spontaneous clearance of HCV in a large population-based cohort in British Columbia, Canada. The BC Hepatitis Testers Cohort includes all individuals tested for HCV in BC in 1990-2013 linked with data on their medical visits, hospitalizations and prescription drugs. HCV-positive individuals with at least one valid HCV PCR test on/after HCV diagnosis (n=46 783) were included in this study. To examine factors associated with the spontaneous clearance of HCV, multivariable logistic regression was fitted on the full sample, and Cox proportional hazards model on the HCV seroconverters. Spontaneous clearance was observed in 25.1% (n=11 737) of those tested for HCV. After adjusting for potential confounders, the odds of spontaneous clearance of HCV was lower in people with primary T-cell immunodeficiency (adjusted odds ratio [aOR]: 0.55, 95% CI: 0.32-0.94), and higher in females (aOR: 1.61, 95% CI: 1.54-1.68) and in those coinfected with HBV (aOR: 2.31, 95% CI: 1.93-2.77). Similar results were observed in HCV seroconverters except HBV coinfection was not significant. In conclusion, primary T-cell immunodeficiency is associated with a lower spontaneous clearance of HCV while female sex and coinfection with HBV are associated with a higher spontaneous clearance.

Shift in disparities in hepatitis C treatment from interferon to DAA era: A population-based cohort study.

We evaluated the shift in the characteristics of people who received interferon-based hepatitis C virus (HCV) treatments and those who received recently introduced direct-acting antivirals (DAAs) in British Columbia (BC), Canada. The BC Hepatitis Testers Cohort includes 1.5 million individuals tested for HCV or HIV, or reported cases of hepatitis B and active tuberculosis in BC from 1990 to 2013 linked to medical visits, hospitalization, cancer, prescription drugs and mortality data. This analysis included all patients who filled at least one prescription for HCV treatment until 31 July 2015. HCV treatments were classified as older interferon-based treatments including pegylated interferon/ribavirin (PegIFN/RBV) with/without boceprevir or telaprevir, DAAs with RBV or PegIFN/RBV, and newer interferon-free DAAs. Of 11 886 people treated for HCV between 2000 and 2015, 1164 (9.8%) received interferon-free DAAs (ledipasvir/sofosbuvir: n=1075; 92.4%), while 452 (3.8%) received a combination of DAAs and RBV or PegIFN/RBV. Compared to those receiving interferon-based treatment, people with HIV co-infection (adjusted odds ratio [aOR]: 2.96, 95% CI: 2.31-3.81), cirrhosis (aOR: 1.77, 95% CI: 1.45-2.15), decompensated cirrhosis (aOR: 1.72, 95% CI: 1.31-2.28), diabetes (aOR: 1.30, 95% CI: 1.10-1.54), a history of injection drug use (aOR: 1.34, 95% CI: 1.09-1.65) and opioid substitution therapy (aOR: 1.30, 95% CI: 1.01-1.67) were more likely to receive interferon-free DAAs. Socio-economically marginalized individuals were significantly less likely (most deprived vs most privileged: aOR: 0.71, 95% CI: 0.58-0.87) to receive DAAs. In conclusion, there is a shift in prescription of new HCV treatments to previously excluded groups (eg HIV-co-infected), although gaps remain for the socio-economically marginalized populations.

Phylogenetic clustering of hepatitis C virus among people who inject drugs in Vancouver, Canada.

UNLABELLED: Little is known about factors associated with hepatitis C virus (HCV) transmission among people who inject drugs (PWID). Phylogenetic clustering and associated factors were evaluated among PWID in Vancouver, Canada. Data were derived from the Vancouver Injection Drug Users Study. Participants who were HCV antibody-positive at enrolment and those with HCV antibody seroconversion during follow-up (1996 to 2012) were tested for HCV RNA and sequenced (Core-E2 region). Phylogenetic trees were inferred using maximum likelihood analysis and clusters were identified using ClusterPicker (90% bootstrap threshold, 0.05 genetic distance threshold). Factors associated with clustering were assessed using logistic regression. Among 655 eligible participants, HCV genotype prevalence was: G1a: 48% (n=313), G1b: 6% (n=41), G2a: 3% (n=20), G2b: 7% (n=46), G3a: 33% (n=213), G4a: <1% (n=4), G6a: 1% (n=8), G6e: <1% (n=1), and unclassifiable: 1% (n=9). The mean age was 36 years, 162 (25%) were female, and 164 (25%) were HIV+. Among 501 participants with HCV G1a and G3a, 31% (n=156) were in a pair/cluster. Factors independently associated with phylogenetic clustering included: age <40 (versus age≥40, adjusted odds ratio [AOR]=1.64; 95% confidence interval [CI] 1.03, 2.63), human immunodeficiency virus (HIV) infection (AOR=1.82; 95% CI 1.18, 2.81), HCV seroconversion (AOR=3.05; 95% CI 1.40, 6.66), and recent syringe borrowing (AOR 1.59; 95% CI 1.07, 2.36). CONCLUSION: In this sample of PWID, one-third demonstrated phylogenetic clustering. Factors independently associated with phylogenetic clustering included younger age, recent HCV seroconversion, prevalent HIV infection, and recent syringe borrowing. Strategies to enhance the delivery of prevention and/or treatment strategies to those with HIV and recent HCV seroconversion should be explored, given an increased likelihood of HCV transmission in these subpopulations.

Strategies to manage hepatitis C virus (HCV) disease burden.

The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.

Interim estimates of 2013/14 vaccine effectiveness against influenza A(H1N1)pdm09 from Canada s sentinel surveillance network, January 2014.

The 2013/14 influenza season to date in Canada has been characterised by predominant (90%) A(H1N1)pdm09 activity. Vaccine effectiveness (VE) was assessed in January 2014 by Canada's sentinel surveillance network using a test-negative case-control design. Interim adjusted-VE against medically-attended laboratory-confirmed influenza A(H1N1)pdm09 infection was 74% (95% CI: 58-83). Relative to vaccine, A(H1N1)pdm09 viruses were antigenically similar and genetically well conserved, with most showing just three mutations across the 50 amino acids comprising antigenic sites of the haemagglutinin protein.

Case of vaccine-associated measles five weeks post-immunisation, British Columbia, Canada, October 2013.

We describe a case of vaccine-associated measles in a two-year-old patient from British Columbia, Canada, in October 2013, who received her first dose of measles-containing vaccine 37 days prior to onset of prodromal symptoms. Identification of this delayed vaccine-associated case occurred in the context of an outbreak investigation of a measles cluster.

Interim estimates of influenza vaccine effectiveness in 2012/13 from Canada's sentinel surveillance network, January 2013.

The 2012/13 influenza season in Canada has been characterised to date by early and moderately severe activity, dominated (90%) by the A(H3N2) subtype. Vaccine effectiveness (VE) was assessed in January 2013 by Canada's sentinel surveillance network using a test-negative case-control design. Interim adjusted-VE against medically attended laboratory-confirmed influenza A(H3N2) infection was 45% (95% CI: 13-66). Influenza A(H3N2) viruses in Canada are similar to the vaccine, based on haemagglutination inhibition; however, antigenic site mutations are described in the haemagglutinin gene.

Primary cervical cancer screening with HPV testing compared with liquid-based cytology: results of round 1 of a randomised controlled trial -- the HPV FOCAL Study.

BACKGROUND: Round 1 data of human papillomavirus (HPV) FOCAL, a three-arm, randomised trial, which aims to establish the efficacy of HPV DNA testing as a primary screen for cervical cancer, are presented. METHODS: The three arms are: Control arm - liquid based cytology with atypical squamous cells of unknown significance (ASC-US) triage with hrHPV testing; Intervention Arm - hrHPV at entry with liquid-based cytology (LBC) triage of hrHPV positives, with exit screen at 4 years; Safety check arm - hrHPV at entry with LBC triage of hrHPV positives with exit screen at 2 years. RESULTS: A total of 6154 women were randomised to the control arm and 12 494 to the HPV arms (intervention and safety check). In the HPV arm, the baseline cervical intraepithelial neoplasia (CIN)2+ and CIN3+ rate was 9.2/1000 (95%CI; 7.4, 10.9) and 4.8/1000 (95%CI; 3.6, 6.1), which increased to 16.1/1000 (95%CI 13.2, 18.9) for CIN2+ and to 8.0/1000 (95%CI; 5.9, 10.0) for CIN3+ after subsequent screening of HPV-DNA-positive/cytology-negative women. Detection rate in the control arm remained unchanged after subsequent screening of ASC-US-positive/hrHPV DNA-negative women at 11.0/1000 for CIN2+ and 5.0/1000 for CIN3+. CONCLUSION: After subsequent screening of women who were either hrHPV positive/cytology negative or ASC-US positive/HPV negative, women randomised to the HPV arms had increased CIN2+ detection compared with women randomised to the cytology arm.

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

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.

Toll-like receptors 2 and 4 and the cryopyrin inflammasome in normal pregnancy and pre-eclampsia.

OBJECTIVE: Pre-eclampsia involves a maternal inflammatory response that differs from both normal pregnancy and normotensive intrauterine growth restriction (IUGR). Our objective was to examine neutrophil Toll-like receptor (TLR), cryopyrin, nuclear factor-kappaB (NF-kappaB) subunit and interleukin-1beta (IL-1beta), and inflammatory cytokine profiles in women with pre-eclampsia or normotensive IUGR, as well as in normal pregnancy and non-pregnancy controls. DESIGN AND METHOD: A case-control study was performed. We examined the messenger RNA (mRNA) and protein expressions of TLR4 and TLR2, mRNA levels of cryopyrin, IL-1beta, NF-kappaB subunits p50 and p65, as well as maternal serum inflammatory cytokine profiles (IL-2, IL-6, tumour necrosis factor-alpha [TNF-alpha], interferon-gamma [IFN-gamma] and IL-10) in women with and without pre-eclampsia using real-time reverse transcription polymerase chain reactions, flow cytometry and multiplex immunoassays. SETTING: A single tertiary maternity hospital in Vancouver, Canada. POPULATION: Women with early-onset pre-eclampsia (<34 weeks of gestation, n = 25), women with late-onset pre-eclampsia (>or=34(+0) weeks of gestation, n = 25), women with normotensive IUGR (n = 25), women with normal pregnancy (n = 75) and non-pregnancy (n = 25) controls. RESULTS: Women with pre-eclampsia (as a single combined group of early- and late-onset, and particularly in women with early-onset pre-eclampsia) had increased TLR2 and TLR4 mRNA and protein expressions elevated cryopyrin, NF-kappaB subunit, and IL-1beta mRNA expression, and TNF-alpha:IL-10 and IL-6:IL-10 ratios compared with other groups. CONCLUSIONS: These data suggest that TLRs and cryopyrin may modulate the innate immune response of the maternal syndrome of pre-eclampsia, and might also trigger the differential inflammatory response existing between early onset pre-eclampsia and normotensive IUGR.

Genotype D amongst injection drug users with acute hepatitis B virus infection in British Columbia.

The eight genotypes of hepatitis B virus (HBV) exhibit distinct geographical distributions. This study identified HBV genotypes and transmission modes associated with acute infection in British Columbia (BC), Canada, from 2001 to 2005. Seventy cases of acute HBV in BC were identified from laboratory reports using a standardized case definition. Interviews for risk factors and hepatitis history were conducted for each case. HBV genotypes were determined by BLAST comparison analysis of the surface (S) or preS gene sequence. To illustrate the distribution of genotypes identified amongst acute cases in BC, an annotated map was produced showing the global occurrence of HBV genotypes. The majority of acute HBV cases occurred in Caucasian, Canadian-born males, with 30% of cases reporting injection drug use (IDU) and 21% reporting incarceration. The most common genotype observed was genotype D (62.9%), followed by genotypes A (18.6%), C (11.4%), B (4.3%), and E (1.4%). A significant association was observed between Genotype D and IDU (P = 0.0025) and previous incarceration (P = 0.0067). Phylogenetic analysis of the S gene sequence demonstrated identical or high genetic relatedness amongst genotype D viral strains (86% sub-genotype D3), thus verifying transmission clustering amongst BC injection drug users. The association between acute HBV genotype and reported transmission modes has not been previously described in North America. Tracking of genotypes can help identify disease transmission patterns and target at-risk populations for preventive immunization.

Low uptake of treatment for hepatitis C virus infection in a large community-based study of inner city residents.

Despite the availability of effective therapy for hepatitis C virus (HCV) infection, there are little data on the uptake of treatment. We evaluated factors associated with HCV infection and the uptake of HCV treatment in a large community-based inner city cohort in Vancouver, Canada. The Community Health and Safety Evaluation is a cohort study of inner city residents recruited from January 2003 to June 2004. HIV and HCV status and information on prescriptions for HCV treatment were determined through linkage with provincial databases. HCV prevalence was calculated and factors associated with HCV infection were identified. HCV treatment uptake and incidence of HCV infection from January 2000 to December 2004 were expressed in terms of person-years of observation. Among 2913 individuals, HCV antibody testing was performed in 2118 and the HCV seroprevalence was 64.2% (1360 of 2118). In total, 1.1% of HCV antibody-positive individuals (15 of 1360) initiated treatment for HCV infection from January 2000 to December 2004 [0.28 cases per 100 person-years (95% CI, 0.15-0.46)]. Three of 15 (20.0%) treated individuals achieved a sustained virological response. During the same period, the incidence of HCV infection was 7.26 cases (95% CI, 5.72-8.80) per 100 person-years. Overall, the rate of new HCV seroconversions in this cohort in the study period was about 25 times the rate of HCV treatment uptake. There are extremely low rates of HCV treatment initiation and very limited effectiveness, despite a high prevalence of HCV infection in this large community-based cohort of inner city residents with access to universal healthcare.

Self-collection of genital human papillomavirus specimens in heterosexual men.

BACKGROUND: We assessed the accuracy of self-collected human papillomavirus (HPV) specimens in men compared with clinician-collected specimens from men in British Columbia and determined the prevalence of HPV subtypes at different male genital sites. METHODS: Heterosexual men were recruited at the Provincial Sexually Transmitted Infection (STI) Clinic in Vancouver, Canada. Participants were randomly assigned to conduct self-collection or clinician-collected specimens first. Clinicians obtained specimens using emery paper followed by saline-moistened Dacron swab from three genitourinary sites: glans penis/foreskin, penile shaft (ventral and dorsal surfaces) and scrotum. Participants received written instructions and took specimens from one of the three sites using the same technique as clinicians. HPV testing was performed with the Roche Amplicor HPV test and samples found to be reactive were tested with the Roche Linear Array HPV typing assay to establish the HPV genotype(s) in the sample. RESULTS: Overall prevalence of any HPV genotype from any site was 69.8% in clinician-collected specimens and 55.3% in self-collected specimens. Order of collection (clinician vs self-collected) did not impact on the prevalence of HPV in the specimens. The kappa scores for agreement between clinician-collected and self-collected specimens ranged from fair to excellent. Overall, there was better agreement between self-collected and clinician-collected specimens for HPV-18 (range: kappa = 0.88 to 0.92) than for HPV-16 (range: kappa = 036 to 0.62). CONCLUSION: HPV is a prevalent genital tract infection in men. Site-specific agreement for specific HPV genotypes between clinician-collected and self-collected specimens varied broadly and neither clinicians nor patients routinely obtained samples with consistently higher or lower prevalence at specific genital sites, indicating there are continued opportunities to improve techniques for clinician-collected and self-collected male specimens for HPV.

Re-treatment with peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have relapsed or not responded to a first course of pegylated interferon-based therapy.

BACKGROUND: Pegylated interferon (pegIFN) and ribavirin combination therapy remains the first-line treatment for chronic hepatitis C virus (HCV) infection. In contrast to the wealth of studies in treatment-naive patients, the effectiveness of retreatment in patients who have previously failed pegIFN-based therapy is largely unreported. AIM: To assess the effectiveness of the retreatment of patients who have previously failed an initial course of pegIFN-based therapy with pegIFNalpha-2a and ribavirin. METHODS: A post-hoc analysis of a multicentre open-label study was performed. Patients received pegIFNalpha-2a and ribavirin at a dose of 800 mg/day and later 1000 mg/day to 1200 mg/day for 24 to 48 weeks at the discretion of the investigator. Outcomes at week 12 (early virological response [EVR]) and week 24 (sustained virological response [SVR]) were analyzed. RESULTS: Eighty-seven patients who had relapsed after previous pegIFN-based therapy (n=28; 78% genotype 1) or were nonresponders (n=59; 71% genotype 1) were analyzed. Of the relapsers, 86% achieved an EVR and 68% achieved an SVR. In relapsers to pegIFN monotherapy (n=15) or pegIFN plus ribavirin (n=13), 60% and 77% achieved an SVR, respectively. Fibrosis and genotype did not affect the likelihood of SVR in relapsers although this may be the result of the relatively small number of patients. In previous nonresponders, an EVR was achieved in 53% but an SVR occurred in only 17%. In nonresponders to pegIFN monotherapy (n=9) and pegIFN plus ribavirin (n=50), 33% and 14% achieved an SVR, respectively. Genotype did not affect SVR in nonresponders. Only 10% with a METAVIR score of F3 or F4 on liver biopsy achieved an SVR. CONCLUSIONS: Relapse after previous pegIFN-based therapy is associated with a strong probability of treatment success whereas retreatment of those with previous nonresponse does not.

Hepatitis C and HIV prevalence using oral mucosal transudate, and reported drug use and sexual behaviours of youth in custody in British Columbia.

BACKGROUND: Youth in custody have high-risk drug use and sexual behaviours. HIV prevalence in this population was assessed in British Columbia (BC) in 1994 but hepatitis C virus (HCV) prevalence has never been measured. We sought to determine: 1) the performance of the OraSure, a non-invasive device for oral mucosal transudate (OMT) specimen collection, to detect HCV and HIV antibodies; 2) the prevalence of HCV and HIV among youth in custody; and 3) the factors associated with intravenous drug use and sex for trade. METHODS: OraSure was validated in 110 adults with known HIV and HCV sero-status. Nurses administered an anonymous survey and collected OMT samples from youth aged 14-19 years in BC youth custody centres. RESULTS: Antibody detection in OMT had 96.4% sensitivity for HIV and 94.6% for HCV. 417 youth were enrolled; 22% were female; 48% reported Aboriginal ethnicity. Although 98.3% reported ever using drugs, <8% reported injection drug use (IDU). IDU was independently associated with age of first sexual intercourse (inverse association) and sex for trade (sex in exchange for money, drugs, food or shelter) (OR 4.28; 95% CI: 1.56-11.75). Females were >9 times more likely to report sex for trade. Five Aboriginal youth were identified with HCV; prevalence estimate 1.2% (95% CI: 0.53-2.77%); 3 reported injecting drugs, the other 2 reported using cocaine/crack and sharing non-injection drug paraphernalia. Two youth were identified with HIV, prevalence estimate 0.48% (95% CI: 0.14%-1.72%). CONCLUSION: IDU, HCV and HIV prevalence remain low. Interventions are needed to prevent transition to IDU and further opportunities for prevention and harm reduction should be explored while the youth are in custody.

Treating chronic hepatitis C with pegylated interferon alfa-2a (40 KD) and ribavirin in clinical practice.

BACKGROUND: Pegylated interferon alfa-2a (40 KD) plus ribavirin therapy induces sustained virological response rates up to 63% in randomized-controlled trials. AIM: To conduct a prospective open-label programme to examine the efficacy and safety of this therapy in routine clinical practice. METHODS: Treatment-naive patients with chronic hepatitis C received, at the discretion of the investigator, pegylated interferon alfa-2a 180 microg/week + ribavirin 800 mg/day for 24 or 48 weeks. In total, 508 patients were enrolled [334 non-cirrhotic; 174 cirrhotic (defined as stage F3 and F4)]. RESULTS: In genotype 1 patients treated for 48 weeks, sustained virological response rates were 41% in non-cirrhotics and 34% in cirrhotics. Sustained virological response rates in genotype 2 or 3 non-cirrhotics were 79% (24 weeks) and 72% (48 weeks). Corresponding values for cirrhotic genotype 2/3 were 66% and 44%. The negative predictive value of an early virological response at week 12 was 94%. Predictive factors for sustained virological response on multivariate analysis were genotype (2/3 vs. 1), low viral load and degree of fibrosis. Rates of serious adverse events (