Improvements in brain and behavior following eradication of hepatitis C.

Despite recent advances in treatment, hepatitis C remains a significant public health problem. The hepatitis C virus (HCV) is known to infiltrate the brain, yet findings from studies on associated neurocognitive and neuropathological changes are mixed. Furthermore, it remains unclear if HCV eradication improves HCV-associated neurological compromise. This study examined the longitudinal relationship between neurocognitive and neurophysiologic markers among healthy HCV- controls and HCV+ adults following successful HCV eradication. We hypothesized that neurocognitive outcomes following treatment would be related to both improved cognition and white matter integrity. Participants included 57 HCV+ participants who successfully cleared the virus at the end of treatment (sustained virologic responders [SVRs]) and 22 HCV- controls. Participants underwent neuropsychological testing and, for a nested subset of participants, neuroimaging (diffusion tensor imaging) at baseline and 12 weeks following completion of HCV therapy. Contrary to expectation, group-level longitudinal analyses did not reveal significant improvement in neurocognitive performance in the SVRs compared to the control group. However, a subgroup of SVRs demonstrated a significant improvement in cognition relative to controls, which was related to improved white matter integrity. Indeed, neuroimaging data revealed beneficial effects associated with clearing the virus, particularly in the posterior corona radiata and the superior longitudinal fasciculus. Findings suggest that a subgroup of HCV+ patients experienced improvements in cognitive functioning following eradication of HCV, which appears related to positive changes in white matter integrity. Future research should examine whether any additional improvements in neurocognition and white matter integrity among SVRs occur with longer follow-up periods.

Predictors of continued HIV-risk behaviors among drug users in methadone maintenance therapy program in China--a prospective study.

BACKGROUND: To examine the predictors of continued drug- and sex-related HIV-risk behaviors among drug users in methadone maintenance therapy (MMT) programs in China. METHODS: We followed a sample of 5,035 drug users enrolled for the first time in MMT programs at baseline, 6 months, and 12 months utilizing a longitudinal prospective study design. Drug users' HIV-risk behaviors, MMT characteristics, and drug use, were assessed at all three waves using a structured interview and HIV/HCV status was assessed at baseline and 12-month follow-up using biological specimens. RESULTS: The point prevalence of HIV was 7.6% and 78.4% for HCV at baseline. Results of generalized linear mixed logistic regression models revealed that HIV-positive MMT clients were more likely to engage in drug injection (aOR = 1.70) and syringe sharing (aOR = 4.73). HCV-positive clients were more likely to inject drugs (aOR = 2.58), share syringes (aOR = 1.97), and have multiple sexual partners (aOR = 1.47). Adherence to MMT was the most significant predictor of reduced HIV-risk behaviors. CONCLUSIONS: Our data confirmed the positive effects of MMT on HIV prevention and underscored the urgency for programs to reduce HIV risk in HIV- and HCV-positive clients. There is a pressing need to strengthen existing counseling services for HIV-positive drug users to reduce their drug-related risk behaviors and to provide counseling for HCV-positive drug users. Further studies are needed to explore interventions to address high dropout rates and low adherence among MMT clients.

Management of the extrahepatic symptoms of chronic hepatitis C: feasibility of a randomized controlled trial of exercise.

OBJECTIVE: The aim of this study was to explore the feasibility and the efficacy of a physiotherapy-led exercise program in changing the health status of a sample of patients with chronic hepatitis C. DESIGN: A single-blind randomized controlled trial was conducted in a sample of patients with iatrogenically acquired hepatitis C in Ireland. Twenty-two participants were recruited and randomly assigned to exercise (n = 10) and control (n = 12) groups. Both groups received a generic exercise advice leaflet, and the exercise group attended 12 exercise sessions for 6 wks. A battery of physical performance measures and patient-reported outcome measures were assessed at baseline and 6 wks, with 1-yr follow-up of the self-reported measures. RESULTS: Significant group by time interactions during the 6-wk period were found for pain (F(1,20) = 5.15, P = 0.034), grip strength (F(1,20) = 5.94, P = 0.024), aerobic capacity (F(1,20) = 5.73, P = 0.024), and depression (F(1,20) = 6.16, P = 0.022), with the exercise group showing greater positive change. The exercise group also had superior gains in the 36-Item Short-Form Health Survey vitality and social function scores (P < 0.05). The short-term gains were not sustained at 1 yr. CONCLUSIONS: This pilot study shows the feasibility of exercise in hepatitis C management, improving physical fitness, psychologic function, and quality-of-life without worsening symptoms in the short term.

El interferón en el tratamiento de la hepatitis C crónica. Inmunobiología básica e inmunopatología del hígado / Interferon treatment of chronic hepatitis C. Basic immunobiology and immunopathology of the liver

Este artículo revisa los principales aspectos de la hepatitis C crónica (epidemiológicos y genómicos, relacionados con un mejor conocimiento molecular del ciclo vital del virus de la hepatitis C, VHC) y de modo notable la terapia estándar con interferón apegilado y ribavirina. El énfasis se ha puesto especialmente en los aspectos biológicos de la respuesta inmunológica del hígado frente al VHC y en la valoración del grado de fibrosis hepática mediante la elastografía de transición(AU)

This article reviews the main aspects of chronic hepatitis C (epidemiological, genomic related to enhanced molecular understanding of the life cycle of the hepatitis C virus, HCV) especially standard therapy with pegilated interferon a and ribavirin. Emphasis is also placed on the immune response of the liver to HCV and the assessment of liver fibrosis via transient elastography(AU)

[Influence of immunotropic preparation cycloferon and phytopreparations of Cynara scolimus L. on blood cytokines profile of the patients with chronic viral hepatitis C in medical rehabilitation period].

The effect of the immunotropic drug cycloferon and herbal medicine resources on the basis of Cynara scolimus L. on the blood cytokine profile in the patients with chronic viral hepatitis C (CVHC) in medical rehabilitation (MR) period. Established that prior to MR period in the patients with CVHC was noted significantly increased levels of proinflammatory cytokines (CK) at the blood serum, and the level of antiinflammatory CK changed significantly. The use of cycloferon and herbal medicine resources on the basis of Cynara scolimus L. in the MR complex provided to normalize the studied CK concentration in the serum of the patients with CVHC.

Buprenorphine for human immunodeficiency virus/hepatitis C virus-coinfected patients: does it serve as a bridge to hepatitis C virus therapy?

OBJECTIVES: Buprenorphine is associated with enhanced human immunodeficiency virus (HIV) treatment outcomes including increased antiretroviral therapy initiation rates, adherence, and CD4 cell counts among HIV-infected opioid-dependent individuals. Buprenorphine facilitates hepatitis C virus (HCV) treatment in opioid-dependent patients with HCV monoinfection. Less is known about buprenorphine's role in HIV/HCV coinfection. METHODS: We conducted a retrospective chart review to evaluate HCV care for HIV-infected buprenorphine patients in the first 4 years of buprenorphine's integration into a Rhode Island HIV clinic. RESULTS: Sixty-one patients initiated buprenorphine. All had HCV antibody testing; 57 (93%) were antibody-positive. All antibody-positive patients underwent HCV RNA testing; 48 (84%) were RNA-positive. Of these, 15 (31%) were not referred to HCV care. Among chronically infected patients, 3 received HCV treatment after buprenorphine; all had cirrhosis and none achieved viral eradication. At buprenorphine induction, most patients had inadequately controlled HIV infection, with detectable HIV RNA (59%) or CD4 cell count less than or equal to 350/µL (38%). CONCLUSIONS: Buprenorphine has shown limited success to date as a bridge to HCV treatment within an HIV clinic. Buprenorphine's stabilization of opioid dependence and HIV disease may permit the use of HCV therapy over time.

Biographical data of patients in drug substitution programmes.

BACKGROUND: We investigated drug substitution patients' biographical data for counselling, to recognize social and other risk factors and additionally consumed drugs. METHODS: We decided on a retrospective, descriptive investigation in one practice. A preformed pattern of questions was applied to the charts of drug-substituted patients. RESULTS: We found data on 332 men and 114 women. Statistical connections were counted by SPSS 11.5 and Chi-square-tests. Two-thirds had completed compulsory school, one third had some kind of vocational training, and current occupation was frequently different to training. 72% of the patients claimed to have "a supportive family relationship with their families". 25% were in touch with their children. Drug abuse started early, below the age of 14 for nearly 25% of our group.179 patients had withdrawal treatment.138 patients (31%) confirmed hepatitis C infection, 23 out of 441 had tested HIV positive (5.2%). CONCLUSIONS: Inconstant relationships to family, education and profession combine to early drug use.

Hepatitis C treatment eligibility and comorbid medical illness in methadone maintenance (MMT) and non-MMT patients: a case-control study.

Comorbid medical illness is common in patients with chronic hepatitis C (HCV) infection and in methadone treatment (MMT) patients, yet little is known about the impact of medical illness on HCV treatment eligibility. Medical illness and HCV treatment eligibility were compared in a case-control study of 80 MMT patients entering an HCV treatment trial and 80 matched non-MMT patients entering HCV treatment in a gastroenterology clinic. 91% of MMT and 85% of non-MMT patients had chronic medical conditions. Despite similar medical severity ratings, a significantly higher proportion (77%) of non-MMT patients were eligible for HCV treatment than were MMT patients (56%) (p<.01). Specific comorbid medical and psychiatric illness led to ineligibility in only 18% of MMT and 16% of non-MMT patients. However, failure to complete the medical evaluation process was significantly (p<.001) more likely to cause ineligibility among MMT patients (19%) than non-MMT patients (0%).

Psychiatric and substance use disorders comorbidities in veterans with hepatitis C virus and HIV coinfection.

PURPOSE OF REVIEW: A growing number of veterans in the Veterans Health Administration are coinfected with HIV and hepatitis C virus. This review covers timely research relative to comorbid conditions that are common in this population including psychiatric diagnoses, substance use disorders and neurocognitive problems. RECENT FINDINGS: Current literature on the psychiatric, substance use disorders and cognitive problems of the coinfected population show that not only are rates of morbidity higher in the coinfected population but that this affects antiviral treatments as well. There is new evidence that brain injuries and infiltration of the virus into the central nervous system may be responsible for cognitive dysfunction. Cotesting, particularly in hepatitis C infected individuals, is not done routinely despite shared risk factors. SUMMARY: With this understanding of the comorbidities of the coinfected population, integrated healthcare models involving mental health, internal medicine, substance abuse treatment and internal medicine are crucial to work with these medically and psychologically complex patients.

[Chronic fatigue. IV--Assessment of a 40-year-old patient]. / Chronische Müdigkeit. IV-Abklärung eines 40-jährigen Exploranden.

A forty year old patient was referred by the federal insurance for medical assessment. His presenting complaint was chronic fatigue. The patient had been an intravenous drug user for years and had been infected with hepatitis C. He was treated with interferon. The patient history showed that he also suffered from anaemia and depression. He participated in a methadone substitution program. Our diagnostic procedures showed that he also has Hashimoto's thyroiditis.

Hepatitis C treatment of opioid dependants receiving maintenance treatment: results of a Norwegian pilot study.

BACKGROUND: Many physicians are still skeptic to treat opioid dependants, with or without maintenance treatment, for hepatitis C (HCV) because of concerns about psychiatric comorbidity, stability and adherence. In Norway, there are about 3,500 patients participating in the restrictive medication-assisted rehabilitation (LAR) programs in which all patients are given methadone or buprenorphine maintenance therapy. This study was undertaken to determine whether HCV combination therapy with pegylated interferon alpha-2a plus ribavirin is feasible, efficient and safe in this patient group. METHOD: Seventeen patients with HCV genotype 3a were treated for 24 weeks. To optimize compliance, the treatment was given from a department of infectious diseases in cooperation with an LAR center. All injections were given in the LAR center and the patients were given psychosocial support. RESULTS: The compliance was 100%. All responded to the therapy and 16 (94%) were sustained responders. DISCUSSION/CONCLUSION: This study indicates that compliance and treatment outcome of opioid dependants on methadone or buprenorphine maintenance after 24 weeks of HCV treatment corresponds to that for non-dependants if extra support is given. The treatment should be undertaken in collaboration with specialists in addiction medicine, hepatology and infectious diseases.

Efficacy of amantadine on quality of life in patients with chronic hepatitis C treated with interferon-alpha and ribavirin: results from a randomized, placebo-controlled, double-blind trial.

AIM: The aim of this study was to investigate whether amantadine reduces deterioration of quality of life in patients with chronic hepatitis C during and after treatment with interferon-alpha (IFN-alpha) and ribavirin. PATIENTS AND METHODS: In this randomized, prospective, placebo-controlled, multicenter trial, previously untreated patients with chronic hepatitis C were treated with IFN-alpha plus ribavirin [17] and randomized for treatment with amantadine (200 mg/day, orally, n=136) or placebo (n=131). Quality of life was assessed with the 'Profile of Mood States' scale and the 'Everyday Life' questionnaire at baseline, treatment week (TW) 8, TW24, TW48, and at follow-up. RESULTS: Early during treatment at TW8, quality of life was not different between patients in the control and the amantadine group. At TW24, the control group but not the amantadine group, however, showed significant deterioration of the modalities depression, fatigue, and vigor compared with baseline. Especially, nonresponders in the amantadine group showed significantly lower deterioration of depression, anger, mind function, everyday life, and zest for life than those in the placebo group. After treatment, the beneficial effects of amantadine disappeared. CONCLUSION: The addition of amantadine to IFN-alpha plus ribavirin combination therapy may reduce deterioration of depression, fatigue, and vigor during treatment but does not affect quality of life after treatment.

Hazardous alcohol consumption and other barriers to antiviral treatment among hepatitis C positive people receiving opioid maintenance treatment.

Amongst people on opioid maintenance treatment (OMT), chronic hepatitis C (HCV) is common but infrequently treated. Numerous barriers, including misuse of alcohol may limit efforts at anti-viral treatment. The aim of this study was to define barriers, including alcohol misuse, to the effective treatment of HCV amongst OMT recipients. Ninety-four OMT patients completed the 3-item Alcohol Use Disorders Identification Test (AUDIT-C). A semi-structured interview was used in 53 subjects to assess alcohol use in detail, psychological health, discrimination and access to HCV treatment. Feasibility of brief intervention for alcohol misuse was assessed. Of the screening participants, 73% reported they were HCV positive. Of the detailed interview participants, 26% reported no drinking in the past month, but 53% scored 8 or more on AUDIT and 42% exceeded NHMRC drinking guidelines. Twenty subjects received brief intervention and among 17 re-interviewed at one month, alcohol consumption fell by 3.1 g/day (p = 0.003). Severe or extremely severe depression, stress and anxiety were found in 57%, 51% and 40% of interviewees respectively. Episodic heavy drinking, mental health problems, perceived discrimination, limited knowledge concerning HCV were all common and uptake of HCV treatment was poor. Brief intervention for alcohol use problems was acceptable to OMT patients, and warrants further study.

Hepatitis C management by addiction medicine physicians: results from a national survey.

Drug users are disproportionately affected by hepatitis C virus (HCV), yet they face barriers to health care that place them at risk for levels of HCV-related care that are lower than those of nondrug users. Substance abuse treatment physicians may treat more HCV-infected persons than other generalist physicians, yet little is known about how such physicians facilitate HCV-related care. We conducted a nationwide survey of American Society of Addiction Medicine physicians (n = 320) to determine substance abuse physicians' HCV-related management practices and to describe factors associated with these practices. We found that substance abuse treatment physicians promote several elements of HCV-related care, including screening for HCV antibodies, recommending vaccinations against hepatitis A and B, and referring patients to subspecialists for HCV treatment. Substance abuse physicians who also provide primary medical or HIV-related care were most likely to facilitate HCV-related care. A significant minority of physicians were either providing HCV antiviral treatment or willing to provide HCV antiviral treatment.

[Treatment of chronic hepatitis C within a heroine-assisted treatment program]. / Therapie der chronischen Hepatitis C im Rahmen einer heroingestützten Behandlung.

HISTORY AND FINDINGS: A 37-year-old man with a 19-years history of injection drug use (IDU) who had acquired a chronic hepatitis C virus (HCV-) infection 9 years ago, entered the German clinical study on heroine assisted treatment ("Modellprojekt zur heroingestützten Behandlung Opiatabhängiger"). Before study onset he received buprenorphine maintainance treatment, while at the same time engaging in illicit IDU (heroine, cocaine). He lived in a caravan and was on social welfare. INVESTIGATIONS: PCR revealed a genotype 2 and an HCV-viral load of 310,000 IU/ml. Liver biopsy showed a moderate chronic active hepatitis and a mild portal fibrosis without signs of liver cirrhosis. DIAGNOSIS, TREATMENT AND COURSE: Within the heroine-assisted treatment program the patient injected heroine under medical supervision several times a day and attended the standardized psychosocial program that comprised an intensive education on HCV-infection. Within a period of ten months of physical and social stabilization he managed to stop illicit drug use, found stable housing and started to work. We then initiated treatment of HCV-infection. Subcutaneous pegylated interferon alpha-2a, peroral ribavirin and intravenous heroine were administered as directly observed therapy. Based on the close mashed care of the heroine assisted treatment setting, side effects were well controllable and reversible after the end of antiviral therapy. A sustained response was obtained. CONCLUSION: After careful indication, heroine-assisted treatment with particularly intensive medical and psychological care can offer appropriate conditions for a save and successful treatment of hepatitis C as well as for a sustained result.

Substance abuse treatment and receipt of liver specialty care among persons coinfected with HIV/HCV who have alcohol problems.

We examined the association of substance abuse treatment with access to liver specialty care among 231 persons coinfected with HIV and hepatitis C virus (HCV) with a history of alcohol problems who were recruited and followed up in the HIV-Longitudinal Interrelationships of Viruses and Ethanol cohort study from 2001 to 2004. Variables regarding demographics, substance use, health service use, clinical variables, and substance abuse treatment were from a standardized research questionnaire administered biannually. We defined substance abuse treatment services as any of the following in the previous 6 months: 12 weeks in a halfway house or residential facility, 12 visits to a substance abuse counselor or mental health professional, day treatment for at least 30 days, or any participation in a methadone maintenance program. Liver specialty care was defined as a visit to a liver doctor, a hepatologist, or a specialist in treating hepatitis C in the past 6 months. At study entry, most of the 231 subjects (89%, n = 205) had seen a primary care physician, 50% had been exposed to substance abuse treatment, and 50 subjects (22%) had received liver specialty care. An additional 33 subjects (14%) reported receiving liver specialty care during the follow-up period. In the multivariable model, we observed a clinically important although not statistically significant association between having been in substance abuse treatment and receiving liver specialty care (adjusted odds ratio = 1.38; 95% confidence interval = 0.9-2.11). Substance abuse treatment systems should give attention to the need of patients to receive care for prevalent treatable diseases such as HIV/HCV coinfection and facilitate its medical care to improve the quality of care for individuals with substance use disorders. The data illustrate the need for clinical care models that give explicit attention to the coordination of primary health care with addiction and hepatitis C specialty care while providing ongoing support to engage and retain these patients with complex health needs.

Relative impact of fatigue and subclinical cognitive brain dysfunction on health-related quality of life in chronic hepatitis C infection.

OBJECTIVES: To assess the relative impact of fatigue and subclinical cognitive brain dysfunction on the impairment of health-related quality of life (HRQL) in hepatitis C virus (HCV) infection. DESIGN AND METHODS: We performed a cross-sectional study in 120 patients with untreated chronic HCV infection to test the hypothesis that the severity of fatigue had an independent effect on HCV-associated impairment of HRQL. Patients were investigated using the short-form-36 questionnaire, the fatigue impact scale, the brief fatigue inventory, and P300 event-related potentials, as an objective correlate of neurocognitive function. Patients with decompensated cirrhosis or clinical depression were excluded. RESULTS: Relative to healthy controls, HCV-infected patients showed significant levels of fatigue (Fatigue Impact Scale, 49 versus 26 points, brief fatigue inventory, 3.0 versus 1.6 points, P < 0.001). Fatigue impact scale and brief fatigue inventory scores were highly correlated (r = 0.77, P < 0.001), demonstrating concurrent validity. Severity of fatigue and age were the only factors independently associated with the impairment of HRQL (P < 0.001). Fatigue was not related to the severity of hepatitis or the degree of subclinical brain dysfunction. CONCLUSION: In untreated patients with chronic HCV infection, fatigue severity and age but not neurocognitive dysfunction or hepatic function are independently associated with impaired HRQL. Both the fatigue impact scale and the brief fatigue inventory are suitable tools to assess the subjective burden of fatigue. Our findings stress the need for effective therapeutic interventions to reduce the burden of fatigue in patients with HCV infection.