Evaluating the impact of methadone maintenance programmes on mortality due to overdose and aids in a cohort of heroin users in Spain

AIMS: To assess the relationship between methadone treatment (MT) and overdose and HIV/AIDS mortality among heroin users resident in Barcelona city. DESIGN: All patients who started treatment in any treatment centre between 1992 and 1997 were included in a cohort the first time they were admitted for heroin addiction treatment. Follow-up controls were carried out every 9 months, on average, until 31 December 1999. Variables, both constant and varying over time, were fitted into Cox regression models. FINDINGS: The study recruited 5049 patients, which provided 23,048.2 person-years. Fifty per cent were in MT during the study period; of the total cohort 1005 patients died: 38.4% due to AIDS, 34.7% to overdose and 27% to other causes. Overall mortality decreased from 5.9 deaths per 100 person-years in 1992 to 1.6 in 1999. Globally, life expectancy at birth was 39 years, 38 years lower than that of the general population. The main factor for overdose mortality was not being in MT at the time of death [relative ratio (RR) = 7.1]; other factors were being a current injector at baseline and being HIV positive. For AIDS mortality, the main factor was the calendar year (RR for 1996 versus 1999 = 4.6), the next major factor was more than 10 years of heroin consumption, followed by not being in MT, being unemployed, then having a prison record. CONCLUSIONS: The observed mortality decline could be linked to the effectiveness of low-threshold MT. The life expectancy of heroin users increased by 21 years during the study period.     

An increase in overdose mortality during the first 2 weeks after entering or re-entering methadone treatment in Amsterdam

Aims It has been suggested that starting and temporarily discontinuing methadone treatment is related to an increased risk in overdose mortality. This study describes the incidence of overdose mortality in relation to time after (re)entering or leaving treatment. Design A dynamic cohort of 5200 Amsterdam methadone clients was observed during treatment and (a maximum of 1 year) after treatment. Findings Between 1986 and 1998, 29 729 person‐years (py) and 68 overdose deaths were recorded, leading to an overdose mortality rate of 2.3/1000 py (2.2 during and 2.4 after treatment). A modest increase was observed during the first 2 weeks after (re)entering treatment; 6.0/1000 py (rate ratio: 2.9; 95% confidence interval 1.4; 5.8). Directly after leaving treatment no increase was observed. Conclusions Inhaling heroin, common among Amsterdam heroin users, is thought to account for low OD mortality rates both during and after treatment. Accumulation of methadone, inadequate assessment of tolerance of known clients re‐entering treatment and concurrent periods of stress or extreme heroin use when entering treatment are mentioned as possible explanations of the increased risk within the first 2 weeks. An Australian study reported a much higher increase. The modest increase in Amsterdam is explained by low background risk of overdose mortality, low starting dosage and the low threshold to treatment.     

Critical issues in the treatment of hepatitis C virus infection in methadone maintenance patients

AIMS: Hepatitis C virus (HCV) infection is a common chronic complication of injection drug use. Methadone maintenance programs contain large numbers of patients infected with HCV. This paper reviews HCV infection with emphasis on the medical care of HCV-infected, or HCV and human immunodeficiency virus co-infected, patients on methadone or buprenorphine maintenance. METHODS: Literature searches using PubMed, PsycINFO and SocINDEX were used to identify papers from 1990-present on antiviral therapy for HCV in methadone maintenance patients and on liver transplantation in methadone maintenance patients. RESULTS: Injection drug use is the most significant risk factor for HCV infection in most western countries. The prevalence of HCV antibody is high in injection drug users (53-96%) and in patients enrolled in methadone maintenance programs (67-96%). Studies of antiviral therapy for HCV in methadone maintenance patients show rates of sustained virological response (SVR), defined as negative HCV-RNA 24 weeks after the end of treatment, of 28-94%. In studies with contrast groups, no significant differences in SVR between methadone and contrast groups were found. Excellent completion rates of antiviral therapy (72-100%) were found in five of six studies. There are many barriers to methadone maintenance patients' receiving antiviral therapy, and research on overcoming barriers is discussed. Liver transplantation has been successful in methadone maintenance patients but has not been utilized widely. CONCLUSION: High quality medical care for all aspects of HCV infection can be provided to methadone maintenance patients. The literature supports the effectiveness of such services, but the reality is that most patients do not receive them.     

Markers for hepatitis A, B and C in methadone maintained patients: an unexpectedly high co-infection with silent hepatitis B

AIMS: To determine the prevalence of hepatitis A, B and C viruses in patients attending a methadone maintenance clinic in New York City. DESIGN: Cross-sectional. SETTING: The Adult Services Clinic of Weill Cornell Medical College, an urban hospital-affiliated methadone program. PARTICIPANTS: Former heroin addicted adults (n = 103) on methadone maintenance therapy. MEASUREMENTS: Markers for hepatitis A virus [HAV immunoglobulin M (IgM) and imunoglobulin G (IgG)], hepatitis B [hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb)] and hepatitis C virus (HCVAb). Serum alanine aminotransferase (ALT) and quantitative HCV RNA were also obtained. Qualitative detection of HBV DNA and HCV genotype were obtained in a subset of subjects. FINDINGS: More than 40% of subjects had markers for all three viruses. HCVAb was the most prevalent (83.5%), followed by HBcAb (65.0%), HAV IgG (46.1%) and HBsAb (41.1%). Hepatitis C RNA was detected in 70.6% of HCVAb positive subjects. While no subject had HBsAg, HBV DNA was detected in 26.4% of subjects who underwent this measure; all (n = 20) had HBcAb as their only HBV marker. The presence of HBV DNA did not influence ALT. Subjects with HCV RNA had higher ALTs than those without HCV RNA. CONCLUSIONS: Most methadone-maintained subjects had at least one marker for viral hepatitis, with 41.8% having markers for HAV, HBV and HCV. A quarter of subjects had silent HBV infection, defined as the presence of HBV DNA in the absence of HBsAg. These subjects should be considered infectious and pose a public health risk.     

Risk factors for hepatitis C virus infection in male adults in Rawalpindi-Islamabad, Pakistan

OBJECTIVE: To identify risk factors associated with HCV infection in Islamabad-Rawalpindi. METHODS: Fifty-seven cases and 180 controls were enrolled from various departments of the nine major hospitals of the Rawalpindi-Islamabad during July-September 1998. Cases were enzyme-linked immunosorbent assay (ELISA) positive for antibodies to HCV (anti-HCV), aged 20-70 years, and residents of Islamabad or Rawalpindi division. Controls were anti-HCV ELISA negatives of the same age range and from the same area. A structured questionnaire was used to collect data on demographic variables and potential risk factors, which was analysed by logistic regression to calculate crude and adjusted odds ratios (OR) and corresponding 95% confidence intervals (CI) for risk factors. RESULTS: The final multivariate logistic regression model revealed that after adjusting for age, cases were more likely to have received therapeutic injections in the past 10 years (1-10 vs. 0 therapeutic injections; adjusted OR=2.8, 95% CI: 1.1-7.1; > 10 vs. 0 therapeutic injections; adjusted OR=3.1, 95% CI: 1.2-7.9) and were significantly more likely to have daily face (adjusted OR=5.1, 95% CI: 1.5-17.0) and armpit shaves (adjusted OR=2.9, 95% CI: 1.3-6.5) by a barber. CONCLUSION: HCV control and prevention programs in this region should include safe injection practices and educate men about the risk of HCV infection from contaminated instruments used by barbers.     

Correlation between hepatitis C virus prevalence and hepatocellular carcinoma mortality in Europe

In Europe, as worldwide, hepatocellular carcinoma (HCC) death rates are highly variable. Recent studies have reported that hepatitis C virus (HCV) infection may be responsible for the increased mortality from HCC in the UK and in France. We investigate here the potential relationship between HCC mortality and HCV prevalence in Europe. Population and mortality data of HCC were obtained for 22 European countries from the World Health Organization (WHO) databank. Age-standardized death rates were computed. The HCV prevalence among blood donors and the WHO estimate of HCV prevalence were used as two indicators of prevalence in the general population, when data were available. Spearman rank analysis was conducted between HCC mortality and HCV prevalence. For men, age-standardized death rates per 100 000 varied from 0.61 (Greece) to 12.19 (Hungary). HCC mortality among men was positively correlated with HCV prevalence among blood donors and with the WHO estimate: rank correlation coefficients were, respectively, 0.76 ( P = 0.02) and 0.72 ( P = 0.03). This study showed that the reported differences of HCC mortality in Europe correlate with HCV prevalence.     

Molecular epidemiologic analysis of hepatitis C virus infection in injecting drug users with acute hepatitis C in Japan

BACKGROUND AND AIM: The aim of this study was to examine whether particular hepatitis C virus (HCV) subtypes are spreading among injecting drug users (IDUs) in Yamaguchi prefecture, on the south-western tip of the island of Honshu in Japan, as found in European countries. METHODS: We prospectively enrolled acute hepatitis C patients from January 2001 to March 2003. E2 gene sequences of HCV isolates from IDUs with acute hepatitis C were phylogenetically compared to those from 30 chronic hepatitis C patients with the same HCV subtypes who had or did not have a history of intravenous drug use. RESULTS: Nine of 11 patients (82%) with acute hepatitis C were IDUs. The HCV subtypes were 2a in four and 2b in five, which contrasted with the high prevalence of subtype 1b in patients with chronic liver diseases in Japan. IDUs with acute hepatitis C (22.0 +/- 2.4 years old) were significantly younger than those with chronic hepatitis C (49.5 +/- 9.5 years old) for subtype 2a (P = 0.0005), but not for subtype 2b (25.6 +/- 5.4 vs 28.1 +/- 2.4 years old). Some HCV isolates of subtype 2b from IDUs with acute hepatitis C were phylogenetically related to those from IDUs with chronic hepatitis C. By contrast, there was no phylogenetic segregation of HCV in IDUs with subtype 2a. HCV isolates from non-IDUs were genetically divergent from each other and those from IDUs, irrespective of the HCV subtype. CONCLUSION: Hepatitis C virus of the non-1b subtype, particularly subtype 2b, seemed to be transmitted between IDUs very recently in Yamaguchi prefecture, Japan.     

Mortality among a cohort of drug users after their release from prison: an evaluation of the effectiveness of a harm reduction program in Taiwan

Aims To determine the effect of methadone maintenance therapy (MMT) on mortality among injection drug users. Design A cohort of prisoners with a history of injecting opiates who were followed after their release from prison in July 2007. Mortality between July 2007 and December 2008 was determined by linking the National Death Registry with the Methadone Maintenance Treatment (MMT) database. Setting Taiwan. Participants A total of 4357 amnestied prisoners with a history of opiate injection. Measurements The total mortality rates (MR) among the cohort were calculated based on their person‐time contribution to methadone attendance and re‐incarceration during follow‐up. We used survival methods with MMT and re‐incarceration as time‐varying covariates adjusted for length of follow‐up in the community. Results A total of 142 deaths occurred: 13 in the 1st week after release [MR = 13.7/100 person‐years (pyrs)], which was greater than that in the next 4 weeks [MR = 3.2/100 pyrs, relative rate (RR) = 4.3, P < 0.001]. Overall, 1982 (46%) subjects enrolled in MMT; however, 1282 of them discontinued MMT after enrolling. Findings The mortality among those who continued in MMT attendance was lower (MR = 0.24/100 pyrs) than those who never enrolled in MMT (MR = 2.6/100 pyrs) or those who enrolled but dropped out of MMT (MR = 7.0/100 pyrs) after adjusting for age, gender and human immunodeficiency virus status at amnesty (RR = 0.07). Conclusions In ex‐prisoners in Taiwan with a history of opiate injecting, enrollment and continued participation in methadone maintenance treatment is associated with substantially lower mortality.     

Risk factors for liver-related and non-liver-related mortality following a sustained virological response after direct-acting antiviral treatment for hepatitis C virus infection in a real-world cohort

A direct-acting antiviral (DAA)-induced sustained virological response (SVR) reduces the risk of mortality. However, the risk factors associated with liver-related and non-liver-related mortality following a SVR after DAA treatment are unclear. We assessed the incidence and risk factors of liver-related and non-liver-related mortality in 1180 patients who achieved a SVR after DAA treatment. During the follow-up period after DAA treatment (median duration, 1099 [range: 84–2345] days), 53 (4.5%) patients died: 15 due to liver-related mortality, 25 due to non-liver-related mortality and 13 due to unknown causes. The all-cause, liver-related and non-liver-related mortality rates were 14.9, 4.2 and 7.0/1000 person-years, respectively. In a multivariate analysis, the development of hepatocellular carcinoma (HCC) after DAA treatment (p = .009; hazard ratio [HR], 31.484), an estimated glomerular filtration rate (eGFR) at baseline ≤61.68 ml/min/1.73 m² (p = .015; HR, 6.607), and an α-fetoprotein level post-treatment ≥7.6 ng/ml (p = .041; HR, 18.490) were significantly associated with liver-related mortality. Furthermore, eGFR ≤67.94 ml/min/1.73 m² at baseline (p = .012; HR, 3.407) and albumin–bilirubin (ALBI) grade ≥ 2 at SVR (p = .024; HR, 3.449) were significantly associated with non-liver-related mortality. Early diagnosis and therapeutic interventions for HCC development after DAA treatment are important to reduce liver-related mortality. The ALBI grade, which reflects the hepatic functional reserve, is a useful predictor of non-liver-related mortality after a SVR induced by DAA treatment. Furthermore, the renal dysfunction caused by metabolic syndrome may affect prognosis even after eliminating hepatitis C virus.     

Comparing retention in treatment and mortality in people after initial entry to methadone and buprenorphine treatment

Aim   To compare retention in treatment and mortality among people entering methadone and buprenorphine treatment for opioid dependence.
Data sources   The Pharmaceutical Drugs of Abuse System (PHDAS) database records start- and end-dates of all episodes of methadone and buprenorphine treatment in New South Wales, and the National Death Index (NDI) records all reported deaths.
Methods   Data linkage study. First entrants to treatment between June 2002 and June 2006 were identified from the PHDAS database. Retention in treatment was compared between methadone and buprenorphine. Names were linked to the NDI database, and 'good matches' were identified. Deaths were classified as occurring during induction, maintenance and either post-methadone or post-buprenorphine, depending on the latest episode of treatment prior to death. The numbers of inductions into treatment, of total person-years spent in each treatment, and person-years post-methadone or buprenorphine, were calculated. Risk of death in different periods, and different treatments, was analysed using Poisson regression.
Results   A total of 5992 people entered their first episode of treatment—3349 (56%) on buprenorphine, 2643 on methadone. Median retention was significantly longer in methadone (271 days) than buprenorphine (40 days). During induction, the risk of death was lower for buprenorphine (relative risk = 0.114, 95% confidence interval = 0.002–0.938, P  = 0.02, Fisher's exact test). Risk of death was lowest during treatment, significantly higher in the first 12 months after leaving both methadone and buprenorphine. Beyond 12 months after leaving treatment, risk of death was non-significantly higher than during treatment.
Conclusions   Buprenorphine was safer during induction. Despite shorter retention in treatment, buprenorphine maintenance was not associated with higher risk of death.     

Prevalence of hepatitis C infection among intravenous drug users in Shanghai

AIM:To characterize the prevalence of hepatitis C virus(HCV)infection among Chinese intravenous drug users(IDUs).METHODS:A total of 432 adult IDUs(95 women and337 men)in Shanghai were included in the study.The third-generation Elecsys Anti-HCV assay(Roche Diagnostics GmbH,Sandhofer Strasse 116,D-68305,Mannheim,Germany)was used to screen for antibodies against HCV.The RIBA strip,a supplemental antiHCV test with high specificity,was performed on all of the samples that tested positive during the initial screening.All of the anti-HCV positive samples were analyzed with a Cobas TaqMan 48 Analyzer(Roche Diagnostics)for direct detection of HCV RNA.All of the HCV RNA-positive samples were sequenced for genotype determination.RESULTS:The preliminary screening identified 262(60.6%)subjects who were seropositive for HCV.Of the 62 females and 200 males seropositive subjects,16(16.7%)and 65(19.3%),respectively,were confirmed by RIBA,yielding an overall HCV seropositive rate of18.8%.Four female(6.5%)and 14 male(7.0%)subjects tested positive for HCV RNA,indicating an active infection rate of 4.2%for the entire study population.The 18 HCV RNA-positive serum samples were genotyped.Seven individuals were genotype 1b,and four were genotype 1a.One individual each was infected with genotypes 2a,2b and 3a.Four subjects were coinfected with multiple strains:two with genotypes 1a and 2a,and two with genotypes 1b and 2a.The active infection rate among HCV-seropositive individuals was22.2%,which was significantly lower than most estimates.CONCLUSION:The prevalence of HCV is relatively low among IDUs in Shanghai,with a spontaneous recovery rate much higher than previous estimates.     

The cost-effectiveness of screening and treatment for hepatitis C in prisons in England and Wales: a cost-utility analysis

Prisoners have a high prevalence of hepatitis C virus (HCV) infection compared with the general population in England and Wales and in many locations throughout the world. This is because of large numbers of injecting drug users that engage in behaviours likely to transmit HCV being present within prison populations. It is, therefore, suggested that prison may be an appropriate location for HCV screening and treatment to be administered. Using cost-utility analysis, this study considers the costs and benefits of administering a single round of screening on reception into prison to all individuals followed by possible later screening in the community and comparing this to individuals who may only be tested and treated in the community at a later date. The cost/QALY of one round of prison testing and treatment was found to be 54,852 pounds sterling, although probabilistic sensitivity analysis showed extensive uncertainty about this estimate. One-way sensitivity analysis revealed the importance of the parameters describing the progression of chronic HCV and the discount rates. While the results presented here at baseline would suggest that screening and treatment for HCV in prisons is not cost-effective, these results are subject to much uncertainty. The importance of the rates describing the progression of chronic HCV on the cost-effectiveness of this intervention has been demonstrated and this suggests that future work should be undertaken to gain further insight into the rates that individuals progress to the later stages of chronic HCV infection.     

Social capital strategies to enhance hepatitis C treatment awareness and uptake among men in prison

Prisoner populations are characterized by high rates of hepatitis C (HCV), up to thirty times that of the general population in Australia. Within Australian prisons, less than 1% of eligible inmates access treatment. Public health strategies informed by social capital could be important in addressing this inequality in access to HCV treatment. Twenty‐eight male inmates participated in qualitative interviews across three correctional centres in New South Wales, Australia. All participants had recently tested as HCV RNA positive or were receiving HCV treatment. Analysis was conducted with participants including men with experiences of HCV treatment (n=10) (including those currently accessing treatment and those with a history of treatment) and those who were treatment naïve (n=18). Social capital was a resourceful commodity for inmates considering and undergoing treatment while in custody. Inmates were a valuable resource for information regarding HCV treatment, including personal accounts and reassurance (bonding social capital), while nurses a resource for the provision of information and care (linking social capital). Although linking social capital between inmates and nurses appeared influential in HCV treatment access, there remained opportunities for increasing linking social capital within the prison setting (such as nurse‐led engagement within the prisons). Bonding and linking social capital can be valuable resources in promoting HCV treatment awareness, uptake and adherence. Peer‐based programmes are likely to be influential in promoting HCV outcomes in the prison setting. Engagement in prisons, outside of the clinics, would enhance opportunities for linking social capital to influence HCV treatment outcomes.     

GB virus C infection among young,HIV‐negative injection drug users with and without hepatitis C virus infection

Summary. Our study examined the association between GB virus C (GBV‐C) and (i) hepatitis C virus (HCV) infection status, (ii) biomedical indicators of liver disease (alanine and aspartate aminotransferases) and (iii) HCV RNA level among young injection drug users (IDUs) recruited using street outreach and respondent‐driven methods. Cross‐sectional and longitudinal analyses were completed. GBV‐C (active or resolved) infection was significantly (P < 0.05) more prevalent among HCV antibody‐positive (anti‐HCV+) (65.1%) than antibody‐negative (anti‐HCV?) (32.3%) (OR = 3.9, 95% CI: 2.3–6.9) IDUs. The prevalence of resolved GBV‐C infection was highest among those with chronic HCV infection (41.9%), followed by those with resolved HCV infection (34.4%) and significantly lower (P < 0.05) among anti‐HCV participants (16.9%). Although not statistically significant (P = 0.13), a similar pattern was observed for active GBV‐C infection. No association between GBV‐C infection status and biomedical indicators of liver disease or HCV RNA level over time was observed. In conclusion, GBV‐C infection prevalence was higher among anti‐HCV+ compared to anti‐HCV? young IDUs, similar to prior studies among older populations. In particular, chronically HCV‐infected young IDUs had an increased rate of GBV‐C clearance.     

Histological progression during short-term follow-up of patients with chronic hepatitis C virus infection

Assessment of prognosis from hepatitis requires liver histology. When the fibrosis stage is known, and if the fibrosis progression rate can be established, time to development of cirrhosis can be calculated. The fibrosis progression rate can be calculated from a single biopsy when duration of infection prior to biopsy is known. Sequential biopsies can also be examined. In this work, we studied histological activity and fibrosis stage in liver biopsies of 157 hepatitis C virus (HCV)-infected patients, including 92 for whom the approximate duration of infection was known. The mean fibrosis progression rate was 0.09 units per year, and was not influenced by mode of infection or viral genotype. Forty-six patients who had very mild histological changes in the initial biopsy underwent repeat biopsy 2 years later (with no intervening anti-viral treatment). Comparison of paired biopsies confirmed a tendency to histological progression and increasing hepatic fibrosis (mean, 0.15 fibrosis units per year). A normal baseline alanine aminotransferase (ALT) value was associated with slow fibrosis progression before baseline biopsy and between biopsies. These data do not differ from published cross-sectional and longitudinal studies, and suggest that histological progression will be observed during follow-up of most patients, including those with mild histological changes at time of initial assessment.     

Presence of hepatitis C virus in syringes confiscated in prisons in Australia

Background and Aims:  Needlestick injuries are an occupational hazard for prison officers. This study aimed to assess the presence of hepatitis C virus (HCV) in syringes found in prisons.
Methods:  Sixty-nine syringes found in prisons were tested for HCV RNA using previously published methods.
Results:  Three syringes tested positive for HCV RNA.
Conclusion:  Compared to the prevalence of HCV among injecting drug users in prisons, few syringes were found to contain HCV RNA. It is likely that conditions under which syringes are kept in prisons are not favorable for survival of detectable HCV RNA. Further work is needed to establish the risk of HCV transmission posed by needlestick injuries in prison settings.