HCV-infected Injection Drug Users Research Articles

Chronic Human Pegivirus 2 without Hepatitis C Virus Co-infection.

Most human pegivirus 2 (HPgV-2) infections are associated with past or current hepatitis C virus (HCV) infection. HPgV-2 is thought to be a bloodborne virus: higher prevalence of active infection has been found in populations with a history of parenteral exposure to viruses. We evaluated longitudinally collected blood samples obtained from injection drug users (IDUs) for active and resolved HPgV-2 infections using a combination of HPgV-2–specific molecular and serologic tests. We found evidence of HPgV-2 infection in 11.2% (22/197) of past or current HCV-infected IDUs, compared with 1.9% (4/205) of an HCV-negative IDU population. Testing of available longitudinal blood samples from HPgV-2–positive participants identified 5 with chronic infection (>6 months viremia in >3 timepoints); 2 were identified among the HCV-positive IDUs and 3 among the HCV-negative IDUs. Our findings indicate that HPgV-2 can establish chronic infection and replicate in the absence of HCV.

Diverse origins of hepatitis C virus in HIV co-infected men who have sex with men in Hong Kong.

BackgroundWorldwide, Hepatitis C (HCV) infection has been increasingly recognized in HIV-positive men who have sex with men (MSM). The objective of this study was to characterize the transmission dynamics of acute HCV infection in HIV-positive MSM in Hong Kong using a molecular approach.FindingsWe retrospectively examined 24 HIV-positive MSM with acute HCV infection diagnosed between 2009 and 2014 in Hong Kong. Detection and molecular characterization of HCV was successfully performed in 22 (91.7 %) patients. Genotype 3a was the most prevalent as identified in 14 (63.6 %) MSM, followed by 1a in 4 (18.2 %), 6a in 2 (9.1 %), and 1each (4.5 %) for 1b and 2a. The high prevalence of genotype 3a in MSM was in stark contrast to its rarity among HCV infected injection drug users (IDU) in Hong Kong. Phylogenetic analyses revealed a monophyletic HCV-3a cluster composing of MSM without injection history, and a homologous pair with HCV-6a genotype. There was otherwise no temporal or genetic clustering of the corresponding HIV sequences.ConclusionsThe origin of sexually acquired acute HCV infections in HIV-positive MSM was diverse and not directly linked with local IDU. The transmission dynamics of HIV and HCV infections in MSM in Hong Kong were evidently unrelated.

Absence of neurocognitive impairment in a large Chinese sample of HCV-infected injection drug users receiving methadone treatment

BackgroundPrior research has demonstrated neuropsychological (NP) impairment in persons with histories of injection drug use (IDU), hepatitis C virus (HCV) infection, and methadone maintenance treatment (MMT), individually, but little is known about the NP effects of these three risk factors in combination. This issue is particularly important in China, which is addressing its highly HCV-comorbid IDU epidemic with widespread government sponsored MMT, especially in light of recent evidence suggesting that methadone may be neuroprotective in some circumstances. MethodsWe administered a comprehensive NP test battery to 195 Chinese heroin IDU individuals taking MMT (IDU+ group), the majority of whom were also HCV+ (87%; n=169), and compared their NP performance to that of 198 demographically comparable, non-IDU Chinese controls (IDU− group). All participants in both groups tested negative for HIV infection, which is also a common comorbidity in the Chinese IDU population. ResultsThe IDU+ group did not have an increased rate of global NP impairment, or perform significantly worse on any individual NP test measure. Within the IDU+ group, liver disease characteristics and reported details of heroin use were not significantly associated with NP performance. ConclusionFailure to detect NP impairment in IDU+ subjects with or without HCV infection was surprising, particularly considering the previously demonstrated sensitivity of our NP battery to neurocognitive disorders associated with HIV infection in China. One possible explanation, which should be explored in future research, is the potential neuroprotective effect of methadone in the context of HCV infection and/or heroin withdrawal.

Stability of Liver Fibrosis among HCV-Infected Injection Drug Users

There are few published data characterizing patterns of liver stiffness measurements (LSMs) among HCV-infected persons and their potential impact on clinical decisions (for example, deferring treatment and hepatocellular carcinoma surveillance). A total of 591 HCV-infected injection drug users in a community-based cohort had four LSMs. We used semi-parametric latent class growth modelling to identify patterns, which then became a gold standard against which we characterized validity of information from the initial measurements. Median age was 49, 68% were male, 92% African-American and 33% HIV-coinfected. The median LSM at visit 1 was 6.7 kPa (IQR 5.3-8.8). Over a median 1.75 years, LSM measures were stable; median change between visits was 0 kPa (IQR -1.4-1.7). Only 3% had evidence of fibrosis progression. Other groups included stable patterns of no fibrosis (59%), moderate fibrosis (21%), severe fibrosis (7%) and cirrhosis (9%). Individuals with fibrosis progression were more likely to be HIV-infected than those with stable low fibrosis (P<0.001). The diagnostic accuracy of the first LSM for identification of need for cancer surveillance (cirrhosis ≥12.3 kPa) was high (positive predictive value =97%). Although no single low LSM had high negative predictive value for significant fibrosis (metavir <2), individuals with two or more low results rarely had progression. These data underscore the stability of liver fibrosis in a cohort of predominantly African-American HCV-infected persons over 1.75 years, support using LSMs to monitor untreated persons at risk for progression and assess need for hepatocellular carcinoma surveillance.

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

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.

Predictors and effects of alcohol use on liver function among young HCV-infected injection drug users in a behavioral intervention

Hepatitis C virus (HCV) screening can provide opportunities to reduce disease progression through counseling against alcohol use, but empirical data on this issue are sparse. We determined the efficacy of a behavioral intervention in reducing alcohol use among young, HCV-infected injection drug users (IDUs) (n=355) and assessed whether changes in liver enzymes were associated with changes in alcohol consumption. Both the intervention and attention-control groups were counseled to avoid alcohol use, but the intervention group received enhanced counseling. Logistic regression, ANOVA, and continuous time Markov models were used to identify factors associated with alcohol use, changes in mean ALT and AST levels, and change in alcohol use post-intervention. Six months post-intervention, alcohol abstinence increased 22.7% in both groups, with no difference by intervention arm. Transition from alcohol use to abstinence was associated with a decrease in liver enzymes, with a marginally greater decrease in the intervention group (p=0.05 for ALT; p=0.06 for AST). In multivariate Markov models, those who used marijuana transitioned from alcohol abstinence to consumption more rapidly than non-users (RR=3.11); those who were homeless transitioned more slowly to alcohol abstinence (RR=0.47); and those who had ever received a clinical diagnosis of liver disease transitioned more rapidly to abstinence (RR=1.88). Although, behavioral counseling to reduce alcohol consumption among HCV-infected IDUs had a modest effect, reductions in alcohol consumption were associated with marked improvements in liver function. Interventions to reduce alcohol use among HCV-infected IDUs may benefit from being integrated into clinical care and monitoring of HCV infection.

Treatment costs of hepatitis C infection among injection drug users in Canada, 2006–2026

Background Canadian injection drug users (IDUs) are at high risk of hepatitis C virus infection (HCV). However, little is known about the costs associated with their HCV-related medical treatment. We estimated the medical costs of treating HCV-infected IDUs from 2006 to 2026. Methods We employed a Markov model of entry through birth or immigration to exposure-related behaviours or experiences, HCV infection, progression to HCV sequelae and mortality for active and ex-IDUs in Canada. We estimated direct and indirect treatment costs using data from the Ontario Case Costing Initiative (OCCI). Result Approximately 137,000 IDUs will suffer from HCV-related disease each year until 2026. Applying the OCCI cost data to the prevalence of HCV-related disease from 2006 to 2026 yielded an estimated cost of $3.96 billion CND to treat HCV-infected IDUs. Conclusions Substantial costs are associated with the treatment of HCV-related disease among Canadian IDUs. Given the lack of effective HCV prevention strategies in Canada, we must develop targeted evidence-based responses to prevent HCV transmission and ensure appropriate allocation of medical resources to meet the present and future treatment needs of HCV-infected IDUs.

Reinfection with hepatitis C virus following sustained virological response in injection drug users

Despite that 60-90% of injection drug users (IDUs) are infected with hepatitis C virus (HCV) infection, IDUs are often denied therapy based on concerns of reinfection following treatment. However, there are little data in this regard. We evaluated HCV re-infection following sustained virologic response (SVR) among HCV-infected IDUs having received HCV treatment in a multidisciplinary program. Following treatment, participants were encouraged to return at follow-up intervals of 1 year and illicit drug use histories were obtained. In those with SVR, HCV RNA testing by PCR was performed to determine if relapse or reinfection occurred. Among 58 receiving HCV treatment between January 2002 and December 2006, 60% (35 of 58) achieved an SVR. Patients were followed for a median of 2.0 years following SVR (range, 0.4-5.0 years), with ongoing illicit and injection drug use reported in 54% (19 of 35) and 46% (16 of 35). Of the 35 with SVR, 28 remained HCV RNA negative during follow-up (80%), with four lost to follow-up and one dying of hepatocellular carcinoma and two cases of reinfection were observed (2 of 35). The rates of reinfection were 3.2 per 100 p-y (95% CI:0.4, 11.5) overall and 5.3 per 100 p-y (95% CI:0.6, 19.0) among those reporting injecting following SVR (n = 16). One of two participants with HCV re-infection spontaneously cleared virus following reinfection. The rate of reinfection following treatment for HCV infection among current and former IDUs engaged in a multidisciplinary program is low.

Multiple routes of hepatitis C virus transmission among injection drug users in Hai Phong, Northern Vietnam

To identify hepatitis C virus (HCV) transmission routes among injection drug users in Northern Vietnam, plasma samples were collected from 486 drug users in Hai Phong. Plasma viral RNA was extracted from 323 (66.5%) samples that were positive for anti-HCV antibodies. Portions of the HCV 5'-untranslated (5'UTR)-Core and NS5B genes were amplified by reverse-transcriptase polymerase chain reaction, sequenced directly, and genotyped in 194 and 195 specimens, respectively. Both regions were genotyped in 137 specimens. In the 5'UTR-Core region, genotype 6a was predominant (32.5%), followed by genotype 1a (23.7%), genotype 1b (20.6%), and genotype 6e (14.4%). In the NS5B region, genotype 1a was predominant (42.6%), followed by genotype 1b (24.1%), genotype 6a (14.4%), genotype 3b (7.2%), and genotype 6e (5.1%). Of the 137 specimens with both regions genotyped, 23 (16.8%) showed discordant genotyping results between the two regions, suggesting possible recombination and/or dual infection. Phylogenetic analysis revealed close associations between Hai Phong strains and strains from Southern China: the Yunnan province for genotype 3b; the Guangxi province for genotype 6e; the USA for genotype 1a; and Southern Vietnam for genotypes 1a and 6e. The human immunodeficiency virus (HIV) infection rate among HCV-infected injection drug users was 52.6-55.4% and did not differ significantly by HCV genotype. Most drug users infected with HIV-1 [98.8% (171/173)] were co-infected with HCV. These results suggest multiple routes of HCV transmission among injection drug users in Northern Vietnam that may also be HIV transmission routes.

High rates of sustained virological response in hepatitis C virus-infected injection drug users receiving directly observed therapy with peginterferon alpha-2a (40KD) (PEGASYS) and once-daily ribavirin

This retrospective study evaluated the efficacy and tolerability of directly observed therapy with peginterferon alfa-2a and once-daily ribavirin (RBV) for chronic hepatitis C in 49 opioid-addicted injection drug users (IDUs) participating in a drug treatment program at a specialized outpatient center. Patients also received prophylactic citalopram to minimize the risk of interferon-induced depression. Patients had daily access to and support from specialist physicians, nurses and counseling services at the center, and a 24-hour helpline. Sustained virological response was achieved by 48 of 49 patients (98%) overall, including 20 of 21 (95%) hepatitis C virus (HCV) Genotype 1/4-infected patients and 28 of 28 (100%) Genotype 2/3-infected patients. Treatment was well tolerated, and no unexpected side effects of peginterferon treatment were seen. The safety profile of once-daily RBV was not different from twice-daily dosing. Decline in hemoglobin levels was similar to those reported in clinical trials including once-daily RBV and did not lead to dose reduction or treatment withdrawal. Our data demonstrate that HCV-infected IDUs on stable L-polamidone (methadone) or buprenorphine maintenance can be successfully and safely treated with peginterferon alfa-2a and RBV in an optimal substitution setting.

Reply:

We would like to thank the authors of the three submitted letters for their comments regarding the updated guidelines on the management and treatment of infection with hepatitis C virus (HCV), and we are happy to respond to the issues they raise. Concerning the letter from Dr. Puoti and colleagues about what constitutes a normal alanine aminotransferase (ALT) level, we agree that the definition we used of two normal values on two to three occasions separated by at least 1 month over a 6-month period is somewhat arbitrary. We agree also that that their proposal of more frequent ALT measurements over an 18-month period more accurately defines persistent ALT normality. However, we do not believe that the widely accepted definition we use negates the concept of the presence of generally normal ALT values and its significance. Indeed, among studies in which this definition is used and liver biopsies are performed, advanced liver disease is reportedly found in only 5%-15% of subjects.1-3 Moreover, we do advocate continued monitoring of persons with normal ALT values so that, if the values should become abnormal, further evaluation would be warranted. Regarding the issue of treatment of persons with normal ALT values, we indicate that “the treatment regimen for HCV-infected persons with normal aminotransferase levels should be the same as that used for persons with elevated serum aminotransferase levels.” We agree and so state that for patients with genotype 1 HCV infection and “normal” ALT levels, a liver biopsy is appropriate in order to detect the minority with advanced chronic liver disease who would then merit treatment. We indicate also in these guidelines that, because of the high response rate to treatment of those with genotype 2 infection, therapy can be offered them without the need for a liver biopsy, regardless of the ALT status. The letter from Swan and Curry identifies a regrettable error in the area devoted to treatment of HCV-infected injection drug users who continue to use illicit drugs. We indicate in Recommendation 59 of that section that treatment can be considered even if such persons continue to use illicit drugs, contingent upon certain requirements.4 However, we neglected to change a holdover from the previous iteration of these guidelines which states, in Table 11, that treatment can be offered current users of illicit drugs and alcohol, but that, “Candidates should be abstinent for a minimum period of 6 months.” This sentence should be struck and will so appear in the online version of these guidelines. Finally, we note that Drs. Dalgard and Mangia disagree with our recommendation that all patients with genotype 2 or 3 HCV infection should be treated for 24 weeks, suggesting that, even though there is a higher relapse rate with a 12-week to 14-week treatment course, this could be compensated for by careful patient selection, and that furthermore, this would result in improved cost-effectiveness of the treatment. They point to two of their own publications to support these views,5, 6 one of which had not yet been published when the literature search of these guidelines was completed.6 While acknowledging the additional relevant data of these publications, we believe that our recommendation for treatment for 24 weeks remains appropriate for most patients with genotype 2 or 3 HCV infection. In making our recommendation, we placed greater emphasis on treatment efficacy as determined in a large international, multicenter trial7 than on data from smaller trials or on considerations of cost.5, 6 We agree that some patients with HCV genotype 2 and 3 may prefer to receive the 12-week to 14-week treatment regimen or there may be specific instances in which 12-14 weeks of treatment might be justifiable. For example, treatment might be appropriately abbreviated in a nonobese person who achieved a rapid virologic response and has significant adverse events. Such decisions should be made on a case-by-case basis after careful consultation with the patient. Thus, until more data demonstrate at least equivalency in sustained virologic response rates between those treated for 12-14 weeks compared to those treated for 24 weeks, we will continue to recommend the 24-week course. Leonard B. Seeff M.D.*, Marc G. Ghany M.D. , Doris B. Strader M.D. , David L. Thomas M.D.§, * Liver Disease Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD, Liver Disease Branch, NIDDK, NIH, Bethesda, MD, Fletcher Allen Health Care, University of Vermont College of Medicine, Burlington, VT, § The Johns Hopkins University School of Medicine, Baltimore, MD.

Limited Uptake of Hepatitis C Treatment Among Injection Drug Users

We characterized hepatitis C virus (HCV) treatment knowledge, experience and barriers in a cohort of community-based injection drug users (IDUs) in Baltimore, MD. In 2005, a questionnaire on HCV treatment knowledge, experience and barriers was administered to HCV-infected IDUs. Self-reported treatment was confirmed from medical records. Of 597 participants, 71% were male, 95% African-American, 31% HIV co-infected and 94% were infected with HCV genotype 1; 70% were aware that treatment was available, but only 22% understood that HCV could be cured. Of 418 who had heard of treatment, 86 (21%) reported an evaluation by a provider that included a discussion of treatment of whom 30 refused treatment, 20 deferred and 36 reported initiating treatment (6% overall). The most common reasons for refusal were related to treatment-related perceptions and a low perceived need of treatment. Compared to those who had discussed treatment with their provider, those who had not were more likely to be injecting drugs, less likely to have health insurance, and less knowledgeable about treatment. Low HCV treatment effectiveness was observed in this IDU population. Comprehensive integrated care strategies that incorporate education, case-management and peer support are needed to improve care and treatment of HCV-infected IDUs.

Self-Reported Hepatitis C Virus Antibody Status and Risk Behavior in Young Injectors

This study was conducted to assess the accuracy of self-reported hepatitis C virus (HCV) antibody (anti-HCV) serostatus in injection drug users (IDUs), and examine whether self-reported anti-HCV serostatus was associated with recent injection risk behavior. In five U.S. cities (Baltimore, Chicago, Los Angeles, New York, and Seattle), 3,004 IDUs from 15 to 30 years old were recruited for a baseline interview to determine eligibility for a randomized controlled trial of a behavioral intervention. HIV and HCV antibody testing were performed, and subject data (e.g., demographics, drug and sexual risk behavior, and history of HIV and HCV testing) were collected via audio computer-administered self-interview. Risk behavior during the previous three months was compared to self-reported anti-HCV serostatus. Anti-HCV prevalence in this sample of young IDUs was 34.1%. Seventy-two percent of anti-HCV-positive and 46% of anti-HCV-negative IDUs in this sample were not aware of their HCV serostatus. Drug treatment or needle exchange use was associated with increased awareness of HCV serostatus. Anti-HCV-negative IDUs who knew their serostatus were less likely than those unaware of their status to inject with a syringe used by another IDU or to share cottons to filter drug solutions. Knowledge of one's positive anti-HCV status was not associated with safer injection practices. Few anti-HCV-positive IDUs in this study were aware of their serostatus. Expanded availability of HCV screening with high quality counseling is clearly needed for this population to promote the health of chronically HCV-infected IDUs and to decrease risk among injectors susceptible to acquiring or transmitting HCV.

Factors associated with interest in initiating treatment for hepatitis C Virus (HCV) infection among young HCV-infected injection drug users.

We sought to identify factors associated with interest in receiving therapy for hepatitis C virus (HCV) infection among HCV-infected injection drug users (IDUs) in 3 United States cities. IDUs aged 18-35 years who were HCV-infected and seronegative for human immunodeficiency virus underwent surveys on behaviors, experience, and interest in treatment for HCV infection and readiness to quit drug use. Among treatment-naive IDUs (n=216), 81.5% were interested in treatment for HCV infection, but only 27.3% had seen a health-care provider since receiving a diagnosis of HCV infection. Interest in treatment for HCV infection was greater among IDUs with a high perceived threat of progressive liver disease, those with a usual source of care, those without evidence of alcohol dependence, and those with higher readiness scores for quitting drug use. Interest in treatment for HCV infection was 7-fold higher among IDUs who were told by their health-care provider that they were at risk for cirrhosis or liver cancer. Improving provider-patient communication and integrating treatments for substance abuse and HCV may increase the proportion of IDUs who initiate treatment for HCV infection.

Screening for depressive symptoms among HCV-infected injection drug users: examination of the utility of the CES-D and the Beck Depression Inventory.

The prevalence of depression is high among injection drug users (IDUs) and among those infected with the hepatitis C virus (HCV). Moreover, one of the drugs used in the standard treatment for HCV infection (interferon) has been known to exacerbate underlying psychiatric disorders such as depression and has been associated with the development of major depressive disorder among HCV-infected patients. For these reasons, the most recent National Institutes of Health consensus statement on the management of HCV infection recommends the identification and treatment of depression prior to the start of HCV treatment. This study aimed to examine the extent of current moderate/severe depressive symptoms in a cohort of HCV-infected IDUs as measured by two screening tools, the Center for Epidemiologic Studies Depression Scale (CES-D) and the Beck Depression Inventory (BDI). Subjects were participants in a multisite behavioral intervention trial among HCV-seropositive, human immunodeficiency virus-negative IDUs aged 18-35 years; the trial was designed to prevent secondary transmission of HCV and to enhance uptake of HCV treatment. Baseline data on demographics, risk behaviors, depression, alcohol use, and health care utilization were measured via audio computer-assisted self-interview. A factor analysis was conducted on each scale to examine the clustering of items used in each to measure depressive symptoms. Baseline depressive symptoms, as measured via the CES-D and the BDI, were also compared using Pearson's correlation coefficient. Of 193 HCV-infected individuals enrolled to date, 75.6% were male, and 65.3% were white. Median age was 25.8 years. Factor analyses revealed that these scales measured depression differently; a distinct somatic component was present in the BDI, but not the CES-D. Using cutoff scores of 23 for the CES-D and 19 for the BDI, 44.0% and 41.5% of the participants were identified as having moderate/severe depressive symptoms, respectively. Over half (56.0%) were identified as having depressive symptoms by either scale. However, there was only moderate agreement between the two scales (kappa=0.46). Depressive symptoms were highly prevalent in this cohort of HCV-infected IDUs. Results indicated that both scales should be used in tandem to have the most sensitive detection of depressive symptoms, thereby maximizing the potential for HCV treatment success.

High prevalence of occult hepatitis B in Baltimore injection drug users

Occult hepatitis B is defined by the presence of hepatitis B virus (HBV) DNA in a serum or liver in the absence of hepatitis B surface antigen (HBsAg). The prevalence and clinical correlates of occult hepatitis B remain incompletely defined. A cross-sectional study was performed to determine the prevalence of occult hepatitis B in a high-risk cohort composed of 188 injection drug users in Baltimore, Maryland. All individuals had chronic hepatitis C viral infections confirmed by RNA detection and liver biopsy. Serologic assays for HBsAg and core antibody (HBcAb) were performed. Serum HBV DNA was detected using the COBAS HBV AMPLICOR monitor assay (lower limit of detection, 200 HBV copies per milliliter) and a semi-nested polymerase chain reaction (PCR) assay (lower limit of detection, 15 HBV copies per milliliter). Although almost all individuals (96%) were anti-HBC positive, only 8 of 188 (4%) were HBsAg positive. Occult hepatitis B was not identified using the COBAS assay, but was found in 81 of 180 (45%) of individuals using semi-nested PCR. Of the 8 HBsAg positive individuals, HBV DNA was found in 1/8 using the COBAS assay and 6/8 using the nested PCR assay. Overall, liver disease was mild, with a median serum alanine aminotransferase (ALT) of 38 IU/L, median activity grade of 3/18, and median fibrosis stage of 1/6. No association was found between the serum AST (aspartate aminotransferase), activity grade, or stage of liver disease and the presence of occult hepatitis B. Serum ALT levels were slightly higher in patients without occult hepatitis B (46 vs. 35 IU/L), and the median years since first injection drug use was somewhat longer in those without occult hepatitis B (24 vs. 20 years). In conclusion, although further research is needed to assess its clinical significance, there is a high prevalence of occult HBV infection in this cohort of HCV-infected injection drug users.