Treating Opioid Use Disorder and Related Infectious Diseases in the Criminal Justice System.

This article provides an overview of the diagnosis and management of opioid use disorder and its infectious complications among populations with criminal justice involvement. Opioid use disorder and chronic infections such as human immunodeficiency virus and hepatitis C virus are highly prevalent among incarcerated individuals and some of the unique features of correctional facilities present challenges for their appropriate medical management. We outline evidence-based strategies for integrated, patient-centered treatment during incarceration and the potentially hazardous transition back to the community upon release.

Opportunistic treatment of hepatitis C virus infection (OPPORTUNI-C): study protocol for a pragmatic stepped wedge cluster randomized trial of immediate versus outpatient treatment initiation among hospitalized people who inject drugs.

BACKGROUND: Scaled-up direct-acting antiviral (DAA) treatment of hepatitis C virus (HCV) infection among people who inject drugs (PWID) is crucial to reach the World Health Organization HCV elimination targets within 2030. One of the critical obstacles to HCV care in this population is the lack of treatment models within specialist healthcare adapted to marginalized individuals. METHODS: OPPORTUNI-C is a pragmatic stepped wedge cluster randomized trial comparing the efficacy of immediate initiation of HCV treatment with the current standard of care among PWID admitted for inpatient care. Screening for HCV RNA will be performed as soon as possible after admission. The intervention includes immediate non-invasive liver disease assessment, counseling, and initiation of pan-genotypic DAA treatment with individualized follow-up. Standard of care is a referral to outpatient care at discharge. To mimic usual clinical practice as closely as possible, we will use a pragmatic clinical trial approach utilizing clinical infrastructure, broad eligibility criteria, flexible intervention delivery, clinically relevant outcomes, and collection of data readily available from the electronic patient files. The stepped wedge design involves a sequential rollout of the intervention over 16 months, in which seven participating clusters will be randomized from standard of care to intervention in a stepwise manner. Randomization will be stratified according to cluster size to keep high prevalence clusters separated. The trial will include approximately 220 HCV RNA positive individuals recruited from departments of internal medicine, addiction medicine, and psychiatry at Akershus University Hospital, Oslo University Hospital, and Lovisenberg Diaconal Hospital, Oslo, Norway. Individuals not able or willing to give informed consent and those with ongoing HCV assessment or treatment will be excluded. The primary outcome is treatment completion, defined as dispensing of the final prescribed DAA package from the pharmacy within 6 months after inclusion. Secondary outcomes include treatment uptake, virologic response, reinfection incidence, and resistance-associated substitutions. DISCUSSION: Representing a novel model of care suited to reach and engage marginalized PWID in HCV care, this study will inform HCV elimination efforts locally and internationally. If the model proves efficacious and feasible, it should be considered for broader implementation, replacing the current standard of care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04220645. Registered on 7 January 2020.

Integrated treatment of hepatitis C virus infection among people who inject drugs: study protocol for a randomised controlled trial (INTRO-HCV).

BACKGROUND: A large proportion of people who inject drugs (PWID) living with hepatitis C virus (HCV) infection have not been treated. It is unknown whether inclusion of HCV diagnostics and treatment into integrated substance use disorder treatment and care clinics will improve uptake and outcome of HCV treatment in PWID. The aim is to assess the efficacy of integrating HCV treatment to PWID and this paper will present the protocol for an ongoing trial. METHODS: INTRO-HCV is a multicentre, randomised controlled clinical trial that will compare the efficacy of integrated treatment of HCV in PWID with the current standard treatment. Integrated treatment includes testing for HCV, assessing liver fibrosis with transient elastography, counselling, treatment delivery, follow-up and evaluation provided by integrated substance use disorder treatment and care clinics. Most of these clinics for PWID provide opioid agonist therapy while some clinics provide low-threshold care without opioid agonist therapy. Standard care involves referral to further diagnostics, treatment and treatment follow-up given in a hospital outpatient clinic with equivalent medications. The differences between the delivery platforms in the two trial arms involve use of a drop-in approach rather than specific appointment times, no need for additional travelling, less blood samples taken during treatment, and treatment given from already known clinicians. The trial will recruit approximately 200 HCV infected individuals in Bergen and Stavanger, Norway. The primary outcomes are time to treatment initiation and sustained virologic response, defined as undetectable HCV RNA 12 weeks after end of treatment. Secondary outcomes are cost-effectiveness, treatment adherence, changes in quality of life, fatigue and psychological well-being, changes in drug use, infection related risk behaviour, and risk of reinfection. The target group is PWID with HCV diagnosed receiving treatment and care within clinics for PWID. DISCUSSION: This study will inform on the effects of an integrated treatment program for HCV in clinics for PWID compared to standard care aiming to increase access to treatment and improving treatment adherence. If the integrated treatment model is found to be safe and efficacious, it can be considered for further scale-up. TRIAL REGISTRATION: ClinicalTrials.gov.no. NCT03155906.

Risk factors for hepatitis C infection among adult patients in Kedah state, Malaysia: A case-control study.

Hepatitis C infection is a global public health problem. This study was designed to identify the risk factors associated with hepatitis C infection among adult patients in Kedah state, Malaysia. A matched, hospital-based, case-control study was conducted at a tertiary hospital. Cases were adult (aged ≥ 18 years) patients with positive serology test results for hepatitis C virus antibody and detectable hepatitis C virus RNA from January 2015 to December 2018, and controls were age-, sex- and ethnicity-matched patients who were not infected with hepatitis C virus. Self-administered questionnaires were used to collect data on demographic characteristics and previous exposure to selected risk factors among the study participants. Associations between hepatitis C and demographic and risk factors were assessed using univariable and multivariable logistic regression analyses. A total of 255 case-control patient pairs were enrolled. The multivariable analysis indicated that having a history of blood or blood product transfusion before 1992 (adjusted odds ratio [AOR] = 6.99, 95% confidence interval [CI]: 3.73-13.81), injection drug use (AOR = 6.60, 95% CI: 3.66-12.43), imprisonment (AOR = 4.58, 95% CI: 1.62-16.40), tattooing (AOR = 3.73, 95% CI: 1.37-12.00), having more than one sexual partner (AOR = 2.06, 95% CI: 1.16-3.69), piercing (AOR = 1.71, 95% CI: 1.04-2.80), and having only secondary education (AOR = 1.92, 95% CI: 1.06-3.57) were independently associated with hepatitis C. No associations were found between health care occupation, needle-prick injury, surgical procedures, haemodialysis, acupuncture, cupping, or contact sports and hepatitis C infection. These findings demonstrate that hepatitis C risk is multifactorial. Having a history of blood or blood product transfusion before 1992, injection drug use, imprisonment, tattooing, having more than one sexual partner, piercing, and having only secondary education were associated with increased odds of hepatitis C.

HIV, HCV, and Health-Related Harms Among Women Who Inject Drugs: Implications for Prevention and Treatment.

BACKGROUND: Although an estimated 3.5 million women inject drugs globally, women are outnumbered 4 to one by men who inject drugs and are often ignored or overlooked in the development and delivery of prevention and treatment services for this population. This study aimed to identify key comorbidities prevalent among women who inject drugs (WWID), consider factors that contribute to vulnerability of this population, and examine implications for prevention and treatment. METHODS: The literature was reviewed to examine the specific challenges and needs of WWID. We searched health-related bibliographic databases and grey literature to identify studies conducted among WWID and studies conducted among people who inject drugs (PWID), where results were disaggregated by gender and policies/guidelines/reports relevant to WWID. RESULTS: WWID face a range of unique, gender-specific, and often additional challenges and barriers. The lack of a targeted focus on WWID by prevention and treatment services and harm-reduction programs increases women's vulnerability to a range of health-related harms, including blood-borne viral and sexually transmitted infections, injection-related injuries, mental health issues, physical and sexual violence, poor sexual and reproductive health, issues in relation to childbearing and child care, and pervasive stigma and discrimination. CONCLUSIONS: There is a need to improve the collection and reporting of gender-disaggregated data on prevalence of key infections and prevention and treatment service access and program coverage. Women-focussed services and integrating gender equity and human rights into the harm-reduction programming will be a prerequisite if improvements in the health, safety, and well-being of this often invisible and highly vulnerable population are to be achieved.

Less-established risk factors are common in Asian Americans with hepatitis C virus: a case-controlled study.

BACKGROUND AND AIMS: The Centers for Disease Control and Prevention recommend screening for hepatitis C virus (HCV) in patients with injection drug use, blood transfusion before 1992, stigmata of liver disease, or born between 1945 and 1965. The purpose of this study was to examine risk factors for HCV acquisition in Asian Americans. METHODS: This was a case-controlled study, with 471 consecutive patients testing positive for anti-HCV between January 2001 and December 2008. Controls included 471 patients with negative HCV matched at a one-to-one ratio for sex, age (±5 years), and ethnicity. RESULTS: For Asian patients, the most common risk factors were blood transfusion and acupuncture or exposure to dirty needles (27 and 20 %, respectively). On multiple logistic regression, potential predictors for a positive anti-HCV test in Asians were acupuncture or exposure to dirty needles (OR = 12.9, P < 0.0001), body tattoo (OR = 12.0, P = 0.001), and history of blood transfusion (OR = 5.7, P < 0.0001). DISCUSSION: Acupuncture and exposure to dirty needles are independent risk factors of HCV infection. Asians coming from endemic areas should be screened for HCV even when commonly-known risk factors for Western patients are not present.

Zinc and liver disease.

Zinc is an essential trace element required for normal cell growth, development, and differentiation. It is involved in DNA synthesis, RNA transcription, and cell division and activation. It is a critical component in many zinc protein/enzymes, including critical zinc transcription factors. Zinc deficiency/altered metabolism is observed in many types of liver disease, including alcoholic liver disease (ALD) and viral liver disease. Some of the mechanisms for zinc deficiency/altered metabolism include decreased dietary intake, increased urinary excretion, activation of certain zinc transporters, and induction of hepatic metallothionein. Zinc deficiency may manifest itself in many ways in liver disease, including skin lesions, poor wound healing/liver regeneration, altered mental status, or altered immune function. Zinc supplementation has been documented to block/attenuate experimental ALD through multiple processes, including stabilization of gut-barrier function, decreasing endotoxemia, decreasing proinflammatory cytokine production, decreasing oxidative stress, and attenuating apoptotic hepatocyte death. Clinical trials in human liver disease are limited in size and quality, but it is clear that zinc supplementation reverses clinical signs of zinc deficiency in patients with liver disease. Some studies suggest improvement in liver function in both ALD and hepatitis C following zinc supplementation, and 1 study suggested improved fibrosis markers in hepatitis C patients. The dose of zinc used for treatment of liver disease is usually 50 mg of elemental zinc taken with a meal to decrease the potential side effect of nausea.

Harm reduction, hepatitis C and opioid pharmacotherapy: an opportunity for integrated hepatitis C virus-specific harm reduction.

While harm reduction advocates, policy makers and practitioners have a right to be proud of the impact of interventions such as needle and syringe programmes on HIV risk, we can be less sanguine about the ongoing high levels of HCV transmission among injecting drug users (IDUs) and the expanding burden of hepatitis C virus (HCV)-related liver disease. In this Harm Reduction Digest Drs Byrne and Hallinan from the Redfern Clinic and Dr Dore from the National Centre in HIV Epidemiology and Clinical Research offer a model of integrated HCV prevention and treatment services within the setting of opioid pharmacotherapy. In their experience, this common-sense approach provides an opportunity to reduce the burden of HCV and improve overall patient management. They believe that the key elements of a HCV-specific harm reduction model include: regular HCV testing; clinical assessment and determination of need for HCV treatment referral; use of broader HCV treatment inclusion criteria; and flexibility in opioid pharmacotherapy dosing. In an environment when our macro harm reduction interventions seem to have, at best, modest impact on HCV transmission, good clinical practice may be our most effective strategy against the HCV epidemic. This paper provides some practical suggestions as to how this can be done.

Integrating services for injection drug users infected with hepatitis C virus with methadone maintenance treatment: challenges and opportunities.

Despite the high prevalence of hepatitis C virus (HCV) infection among drug users enrolled in methadone maintenance treatment programs, few drug users are being treated with combination therapy. The most significant barrier to treatment is lack of access to comprehensive HCV-related care. We describe a pilot program to integrate care for HCV infection with substance abuse treatment in a setting of maintenance treatment with methadone. This on-site, multidisciplinary model of care includes comprehensive screening and treatment for HCV infection, assessment of eligibility, counseling with regard to substance abuse, psychiatric services, HCV support groups, directly observed therapy, and enhanced linkages to a tertiary care system for diagnostic procedures. Our approach has led to high levels of adherence, with liver biopsy and substantial rates of initiation of antiviral therapy. Two cases illustrate the successful application of this model to patients with HCV infection complicated by active substance abuse and psychiatric comorbidity.

Hepatitis C virus NS5A-regulated gene expression and signaling revealed via microarray and comparative promoter analyses.

Most individuals exposed to hepatitis C virus (HCV) become chronically infected and are predisposed to liver disease. The mechanisms underlying viral persistence and disease progression are unknown. A role for the HCV NS5A protein in viral replication and interferon resistance has been demonstrated. To identify mechanisms affected by NS5A, we analyzed the gene expression of Huh7 cells expressing NS5A and control cells using oligonucleotide microarrays. A set of 103 genes (43 up-regulated, 60 down-regulated) whose expression was modified by at least twofold was selected. These included genes involved in cell adhesion and motility, calcium homeostasis, lipid transport and metabolism, and genes regulating immune responses. The finding of modulated expression of genes related to the TGF-beta superfamily and liver fibrosis was observed. Interestingly, both the tumor necrosis factor and lymphotoxin beta receptors were down-regulated by NS5A. Similar data were obtained following expression of four NS5A mutants obtained from patients who were not responsive or were sensitive to interferon therapy. Through computational analysis, we determined that 39 of the 43 genes up-regulated by NS5A contained one or more nuclear factor kappaB (NF-kappaB) binding sites within their promoter region. Using the Gibbs sampling method, we also detected enrichment of NF-kappaB consensus binding sites in the upstream regions of the 43 coexpressed genes. Activation of NF-kappaB by NS5A was subsequently demonstrated in luciferase reporter assays. Adenovirus-mediated expression of IkappaBalpha reverted NS5A mediated up-regulation of gene expression. In conclusion, this study suggests a role of NS5A and NF-kappaB in HCV pathogenesis and related liver disease. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).

Hepatitis B and C virus prevalence in a rural area of South Korea: the role of acupuncture.

A cross-sectional study evaluated the prevalence of and the risk factors for hepatitis C and B viruses among 700 adults above the age of 40 years in a rural area of South Korea. Seropositivity for hepatitis C virus antibody (11.0%, 95% confidence interval: 8.7-13.6) was higher than that for hepatitis B surface antigen (4.4%, 95% confidence interval: 3.0-6.2). Anti-hepatitis C virus seropositivity was associated with a history of repeated acupuncture (odds ratio=2.1, 95% confidence interval: 1.1-4.0), and blood transfusion (odds ratio=5.5, 95% confidence interval: 1.6-19.3) before 1992 when hepatitis C virus screening in blood donors became mandatory. Hepatitis C virus 2a was the most prevalent genotype, followed by 1b. Hepatitis C virus risk attributable to acupuncture was 38% (9% for men and 55% for women). Safer acupuncture practice has become a priority for hepatitis C virus prevention in South Korea.

A nationwide survey of hepatitis C services provided by drug treatment programs.

Drug treatment programs are a site of opportunity for the delivery of primary and secondary hepatitis C (HCV) prevention services to drug users, a population at great risk for contracting and transmitting the virus. Using data collected from a random nationwide sample (N = 439) of drug treatment programs in the United States, this study examines the extent to which various types of HCV services are provided to their patients. Findings indicate that the majority of drug treatment programs educate at least some of their patients about HCV, and provide some type of support for patients who are infected with the virus. Only 29 of the programs in the sample test all of their patients for HCV, however, and 99 programs test none of them. For the most part, residential treatment programs offer more HCV related services than outpatient drug-free programs.

Evolucion de la gravedad de la adiccion a los dos años de tratamiento en pacientes heroinomanos / Evolution of the severity of addiction after two years of treatment in heroin addicts

Objetivos: Analizar la evolución de la gravedad de la dependencia, a los dos años, de una muestra de pacientes heroinómanos y averiguar el efecto que sobre dicha evolución tiene el hecho de mantenerse, o no, en contacto con el centro de tratamiento.Pacientes y metodo: Durante septiembre 1998 - diciembre 1999 se ha procedido a la evaluación de una muestra compuesta por 100 pacientes heroinómanos que previamente (dos años antes) habían demandado tratamiento en la Unidad de Tratamiento de Toxicomanías de Mieres (Asturias). Evaluación: Protocolo "ad hoc", versión europea del Addiction Severity Index (EuropASI).Resultados y conclusiones: En el momento de inclusión en el estudio, 31 pacientes fueron asignados a un programa de mantenimiento con metadona (PMM) y los 69 restantes, a tratamiento con naltrexona o a un programa libre de drogas (PLD). A los dos años, se localizaron 75 pacientes (3 fallecidos), por lo que se realizó el seguimiento a 72. En el momento basal, la gravedad de la adicción era bastante similar en los pacientes asignados a ambos tipos de programas (diferencias en el área médica, con mayor gravedad en los pacientes en PMM; p= .017). A los dos años se constata que el hecho de haber recibido tratamiento y, sobre todo, el mantener contacto terapéutico con el centro disminuye la gravedad en la adicción en prácticamente todas las áreas a excepción de aquellas cuya evolución depende en menor medida del tratamiento específico de la dependencia: área médica y legal. (AU)

Correlates of benzodiazepine abuse in methadone maintenance treatment. A 1 year prospective study in an Israeli clinic.

AIMS: This study addressed the following questions for patients after 1 year of methadone maintenance treatment (MMT); (1) What are the demographic features and past history of drug use of benzodiazepine (BZD) abusers? (2) Do BZD abusers abuse more heroin, cocaine and/or cannabis and do they receive a higher methadone dosage level? (3) Do BZD abusers suffer more from hepatitis C (HCV) and do they have more HIV/HCV risk-taking behaviors than non-abusers? (4) Do BZD abusers have more psychopathology and more emotional distress than non-abusers? DESIGN: All 148 patients who completed 1 year of MMT underwent random and twice-weekly observed urine analysis for various drugs of abuse, responded to self-report questionnaires (SCL-90-R; POMS; HIV/HCV risk-taking behaviors), interviews (ASI) and underwent testing for hepatitis C. Abuse in this study is defined as any use during the 12th month of treatment. FINDINGS: After 1 year of MMT, more BZD abusers (n = 63) were single, had spent time in prison, were unemployed and had at least one parent with an addiction problem or mental illness in comparison to non-abusers (n = 85). They had started using heroin and cocaine earlier and currently abused more cocaine, heroin and cannabis. They had significantly more psychopathology and negative mood. They had significantly more HCV and reported more HIV/HCV risk-taking behavior. IMPLICATIONS: We suggest that this group of patients is in need of more intensive pharmacological and psychological treatment.

Prevalence of hepatitis C viral antibody in transfused and nontransfused Egyptian children.

Hepatitis C (HCV) virus is recognized as the major cause of what was previously referred to as parenterally acquired (blood-mediated) non-A, non-B hepatitis. A study involving 252 transfused and nontransfused Egyptian children was conducted from November 1990 through February 1991 to determine the prevalence of HCV and the role of blood and blood and blood product transfusions in the spread of the virus. Serum specimens were assayed by a second generation enzyme immunoassay and were considered reactive only after supplemental testing using the second generation recombinant immunoblot assay. Prevalence among 84 young study subjects with hematologic disorders was 55% (46 of 84), while no HCV antibodies were detected among the two nonhematologic pediatric populations studied: 84 hospital admissions and 84 acutely ill but otherwise healthy outpatients (seeking treatment for symptoms associated with a new condition less than three weeks old in the absence of any chronic health problem). Ninety-two percent (77 of 84) of the hematology-related cases had medical histories of multiple transfusions. Positive antibody responses (46) were significantly associated with increased duration of illness (P < 0.001) and the volume and number of transfusions (P < 0.01) when compared with negative ones (38). However, prior hospitalization and/or surgery were not related to HCV antibody status. The high prevalence of HCV antibody among multiply transfused infants and children suggests that blood and blood product supplies should be regularly screened for HCV antibody.

The regional blood center medical director's role in transfusion safety.

One of the medical director's primary roles in safety of transfusion practice involves promoting the appropriate use of blood and blood components. The medical director also has a direct role in establishing donor screening and blood testing procedures aimed at decreasing the risk of transfusion-transmitted diseases. The ultimate goal of providing the safest possible blood transfusion requires interaction among the blood center medical director, hospital transfusion service directors, and clinicians. The role of the regional blood center medical director must be viewed in this context.

Possible infectious causes in 651 patients with acute viral hepatitis during a 10-year period (1976-1985).

Six hundred and fifty-one patients with acute viral hepatitis were identified serologically between January 1976 and December 1985. Of these, 109 (17%) had hepatitis A, 135 (21%) had hepatitis B, and 407 (62%) had hepatitis non-A, non-B. The possible infectious causes for acquisition of viral hepatitis occurring within 6 months before the onset of hepatitis were analysed. Approximately 80% of cases of hepatitis A and 70% of hepatitis B had no known risk factor, while in 67% of cases of hepatitis non-A, non-B possible risk factors for infection were documented. Infectious causes for hepatitis A were ingestion of raw shellfish (11%) and previous familial contact with patients with hepatitis A (10%). For hepatitis B, risk factors included medicare (24%), such as transfusion, surgical operation, accidental needle stick and acupuncture, and sexual contact (6%). For hepatitis non-A, non-B, the most important infectious cause was medical procedures (65%). The numbers of hospital employees were 2 (2%) with hepatitis A, 15 (11%) with hepatitis B and 14 (3%) with hepatitis non-A, non-B. These data suggest that hepatitis non-A, non-B can be a kind of nosocomial disease.