Hepatitis: Grebely J

Matthews GV, Grebely J, Dore GJ. · No affiliation provided · J Hepatol. · Pubmed #18644647 No free full text.

This publication has no abstract.

Grebely J, deVlaming S, Duncan F, Viljoen M, Conway B. · Vancouver Coastal Health, Vancouver, British Columbia, Canada. · J Addict Dis. · Pubmed #18681189 No free full text.

Abstract: Injection drug use (IDU) accounts for 75% of incident cases of hepatitis C virus (HCV) infection in the developed world. Of those infected with HCV, up to 80% will go on to develop chronic disease. Intervention with effective treatment in eligible subjects will limit the impact of the long-term consequences of infection. The use of combination therapy with pegylated interferon and ribavirin may lead to a cure in up to 80% of treated individuals who carry genotype 2 or 3 isolates. Such individuals account for up to 45% of certain cohorts, such as in the inner city of Vancouver. Historically, many IDUs have not received treatment for HCV infection even if it were medically indicated. Recent data (including our own) suggest that, in the right context, response rates similar to those reported in clinical trials of HCV therapy can be achieved in IDUs, even with ongoing drug use. This is all the more important given that prior infection may protect against re-infection even in the presence of ongoing risk behaviors for HCV transmission. The keys to a successful program appear to be appropriate patient selection as well as the delivery of care within an appropriate setting, preferably with a multidisciplinary team in a way that addresses the issue of addiction and other conditions simultaneously. The development of such programs may be quite complex, but the ultimate benefit (for the treated population and for society as a whole) is certainly worth the effort.

Conway B, Grebely J, Tossonian H, Lefebvre D, de Vlaming S. · Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. · Clin Infect Dis. · Pubmed #16265619 No free full text.

Abstract: The treatment of injection drug users (IDUs) coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) presents multiple challenges, many of which could be addressed by the development of directly observed therapy programs. This is made all the more feasible by the validation of once-daily treatment regimens for HIV. We have demonstrated that virological suppression can be achieved and maintained in as many as 80% of active IDUs who have received highly active antiretroviral therapy for 48 months. This approach has now been validated in first- and second-line therapy, as well as for the treatment of bacterial infections in this population, achieving therapeutic results similar to those reported in the general population. The model is now being applied to the treatment of HCV infection, focusing on patients with infection due to HCV genotype 2 or 3, in whom the likelihood of response may exceed 80%. Our ultimate goal is to ensure that, even in treating IDUs in the inner city, no patient is left behind.

Grebely J, Raffa JD, Lai C, Krajden M, Kerr T, Fischer B, Tyndall MW. · National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, NSW, Australia. · J Viral Hepat. · Pubmed #19226330 No free full text.

Abstract: 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.

Grebely J, Genoway KA, Raffa JD, Dhadwal G, Rajan T, Showler G, Kalousek K, Duncan F, Tyndall MW, Fraser C, Conway B, Fischer B. · Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada. · Drug Alcohol Depend. · Pubmed #17997050 No free full text.

Abstract: BACKGROUND: Illicit drug users account for the majority of cases of HCV infection in the developed world, but few have received treatment. METHODS: We evaluated barriers to initiating HCV treatment -- including general treatment willingness -- and factors associated with these among HCV infected illicit drug users. Participants were recruited via convenience sampling from two community clinics in Canada. Individuals age >18 years with a history of illicit drug use completed interviewer-administered surveys. Those reporting positive HCV testing underwent additional questioning on willingness, uptake and barriers to treatment for HCV. RESULTS: Of 188 HCV positive illicit drug users, 16% (n=30) had received treatment for HCV. Factors associated with a decreased treatment uptake included current heroin use and HIV/HCV co-infection. Among those not having received therapy, 77% (117/153) indicated a willingness to receive HCV treatment. Factors associated with treatment willingness included not being infected with HIV, having not recently used drugs by injection and having reported physical health problems. Among those not having sought HCV treatment (n=107), the major reasons for not doing so were: lack of information about HCV or knowledge that treatment was available (23%), the absence of symptoms (20%) and the perceived side effects of treatment (14%). CONCLUSIONS: Among illicit drug users attending inner city clinics, we have observed a low uptake of HCV treatment, but a high willingness to receive therapy. An increased focus on improving education about the long-term consequences of HCV and the availability of effective treatment are important components for expanding HCV treatment among illicit drug users.

Grebely J, Genoway K, Khara M, Duncan F, Viljoen M, Elliott D, Raffa JD, DeVlaming S, Conway B. · Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Canada. · Int J Drug Policy. · Pubmed #17854734 No free full text.

Abstract: Injection drug use accounts for the majority of incident and prevalent cases of hepatitis C virus (HCV) infection. However, very few injection drug users (IDUs) have received treatment for this condition given issues of medical or psychiatric co-morbidity, ongoing substance abuse and a widely held belief that such individuals will not be able to adhere to the requirements of therapy, including regular medical follow-up. With this in mind, we sought to evaluate HCV treatment uptake and outcomes among current and former IDUs attending a weekly peer support group and receiving directly observed HCV therapy. Utilizing the existing infrastructure for the management of addictive disease, we have developed a model of "one-stop shopping" whereby the treatment of addiction, HCV and other medical conditions are fully integrated, with the collaboration of nurses, counsellors, addiction specialists, infectious disease specialists, primary care physicians and researchers. Subjects interested in receiving treatment for HCV infection were referred to a weekly peer-support group and evaluated for treatment. Patients received therapy with pegylated interferon-alpha2a or -alpha2b, both in combination with ribavirin. All injections were directly observed. Overall, we observed a high uptake of HCV treatment among attendees, with 51 percent either receiving or about to receive therapy. To date, 18 patients have initiated treatment for HCV infection and 12 have completed therapy. Overall, 8/12 (67 percent) subjects achieved an end of treatment response (genotype 1, 67 percent; genotypes 2/3, 67 percent), despite ongoing drug use in 75 percent of patients during treatment. These data demonstrate that with the appropriate programs in place, a high uptake of HCV treatment can be achieved among IDUs referred to a peer-support group. Moreover, the treatment of HCV in current and former IDUs within a multidisciplinary DOT program can be successfully undertaken, resulting in ETRs similar to those reported in randomized controlled trials.

Grebely J, Raffa JD, Meagher C, Duncan F, Genoway KA, Khara M, McLean M, Mead A, Viljoen M, DeVlaming S, Fraser C, Conway B. · Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada. · J Gastroenterol Hepatol. · Pubmed #17645460 No free full text.

Abstract: BACKGROUND AND AIM: There are few studies investigating the treatment of hepatitis C virus (HCV) infection in current and former drug users. With this in mind, we sought to evaluate the antiviral efficacy of interferon alpha-2b (IFN alpha-2b) or pegylated-interferon alpha-2b (PEG-IFN alpha-2b) and ribavirin (RBV) in injection drug users (IDU) enrolled in a directly observed therapy (DOT) program, as measured by sustained virologic response (SVR). METHODS: Viremic HCV-infected IDU, with alanine aminotransferase (ALT) >1.5x upper limit of normal (ULN) were offered 24-48 week (based on HCV genotype) therapy with RBV (800-1200 mg/day, based on weight) along with IFN alpha-2b (3 million IU thrice weekly) replaced by PEG-IFN alpha-2b (1.5 ìg/kg once weekly) as it became available. All injections were directly observed. The primary endpoint was SVR. RESULTS: Overall, 40 patients (33 males) received IFN alpha-2b (12) or PEG-IFN alpha-2b (28), 55% with HCV genotypes 2 or 3. Only 14 discontinued therapy, 5 due to toxicity, 6 due to illicit drug use and 3 did not achieve an early virologic response. In an intent-to-treat analysis, the overall SVR was 55% (22/40), 64% (14/22) in subjects with genotypes 2/3. There was no significant difference in response rates among those with >6 (50%) or <or=6 months (64%) drug abstinence (P = 0.51) or among those with (53%) and without (57%) intercurrent drug use (P = 0.99); however, frequent users (n = 9) had a decreased SVR (22%) when compared with occasional users (n = 10, 80%, P = 0.12). CONCLUSION: Treatment of HCV in current and former IDU within a multidisciplinary DOT program can be successfully undertaken, resulting in SVR similar to those in randomized controlled trials.

Grebely J, Raffa JD, Lai C, Krajden M, Conway B, Tyndall MW. · Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada. · Can J Gastroenterol. · Pubmed #17637948 links to  free full text

Abstract: BACKGROUND: Spontaneous clearance of hepatitis C virus (HCV) occurs in approximately 25% of individuals. METHODS: To better understand the characteristics associated with clearance, the present study evaluated HCV clearance in a community-based cohort study. The Community Health and Safety Evaluation project recruited 3553 individuals via community organizations and door-to-door canvassing of a random sample of single occupancy hotels in the community to monitor uptake of health services and to estimate the incidence of communicable infections. Cohort data were linked with longitudinal laboratory databases, including HCV antibody and polymerase chain reaction assay results. RESULTS: Overall, 762 individuals had HCV antibody and RNA testing performed between 1999 and 2005. Spontaneous HCV clearance was observed in 179 individuals (23.5%), while HCV persistence was observed in 583 individuals (76.5%). The ability to develop protective immunity against HCV, as demonstrated by viral clearance, occurred more often in individuals of Aboriginal ethnicity (adjusted OR [AOR] 2.9, 95% CI 2.0 to 4.3; P<0.001) and female individuals (AOR 1.6, 95% CI 1.1 to 2.4; P=0.01). The rate of spontaneous HCV clearance was reduced in individuals using any type of illicit drugs (AOR 0.54, 95% CI 0.29 to 1.00; P=0.05) and those with HIV coinfection (AOR 0.58, 95% CI 0.38 to 0.88; P=0.01). Of 218 HIV-infected subjects, 48 of 51 (94%) in whom the order of HCV and HIV infection was established were infected with HCV a median of 2.4 years (range 0.2 to 10 years) before becoming infected with HIV. CONCLUSIONS: Aboriginal ethnicity and female sex were associated with increased rates of HCV clearance, while HIV coinfection and illicit drug use were associated with increased HCV persistence.

Grebely J, Conway B, Raffa JD, Lai C, Krajden M, Tyndall MW. · Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC, Canada. · Hepatology. · Pubmed #17058216 No free full text.

Abstract: Spontaneous clearance of hepatitis C (HCV) may provide protection against reinfection. In a large community-based cohort study of 3,553 inner-city residents (mainly injection drug users), we identified HCV-infected individuals in whom virological clearance had occurred and compared the rate of reinfection in this group with that observed in previously uninfected members of the same cohort. We identified 926 HCV-uninfected and 658 HCV-infected viremic subjects at baseline, with 152 of 658 (23.1%) spontaneously clearing viremia over a median follow-up of 5.2 years (IQR, 2.8-7.4). At baseline, individuals with HCV clearance were more likely to be HIV coinfected (P < .001) and to be engaged in frequent illicit drug use (P = .004) and injection drug use (P < .001). The occurrence of HCV infection was lower in individuals with previous infection (14/152, 9.2%) compared with that in those without previous infection (172/926, 18.6%), with incidence rates of 1.8 (95% CI, 0.9-3.0 cases/100 person-years) and 8.1 (95% CI, 6.9-9.4 cases/100 person-years) cases/100 person-years, respectively, after accounting for follow-up. In a logistic regression analysis, with previous HCV infection assessed as a covariate with other potential confounding variables (age, sex, ethnicity, HIV infection, housing status, and illicit and injection drug use), individuals with previous HCV infection and viral clearance were 4 times less likely to develop infection than those infected for the first time (adjusted odds ratio, 0.23; 95% CI, 0.10-0.51, P < .001). In conclusion, individuals with clearance of HCV infection may have a lower risk of acquiring HCV than individuals who have never been infected, despite ongoing exposure to HCV.