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Neurocognitive morbidity has been reported in individuals with chronic hepatitis C virus (HCV) infection, but the magnitude of such dysfunction in the absence of disease-correlated factors known to affect the central nervous system (e.g., substance abuse, cirrhosis, depression, interferon treatment) and the impact of any such change on functioning is unclear. We investigated a cohort of individuals with HCV, all of whom were carefully screened to exclude relevant comorbidities, to elucidate virus-related changes in the brain using neuropsychological tests and magnetic resonance spectroscopy (MRS). A cohort of 37 patients with chronic HCV infection was culled from 300 consecutive patients presenting to a tertiary care liver clinic. A comparison group of healthy controls (n = 46) was also assessed. Of 10 neurocognitive measures evaluated, the HCV group showed marginally poorer learning efficiency compared with controls; only 13% of patients demonstrated a clinical level of impairment on this test (defined as 1.5 SD below the normative standard). Although patients reported greater levels of fatigue and symptoms of depression, these factors did not correlate with the degree of learning inefficiency. With respect to MRS, the HCV group demonstrated increased choline and reduced N-acetyl aspartate relative to controls in the central white matter. Indicators of liver disease severity did not correlate with either memory or MRS abnormalities. In conclusion, while our findings support an association between hepatitis C and indicators of central nervous system involvement in a cohort of patients carefully screened to eliminate other factors influencing neurocognitive integrity, the clinical significance of these effects is limited.
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PMID:Prevalence and significance of neurocognitive dysfunction in hepatitis C in the absence of correlated risk factors. 1579 53

Hepatitis C is an RNA virus responsible for chronic infection in at least 4 million Americans. Patients are often unaware that they have contracted the virus until the appearance of long-term consequences of the infection, primarily cirrhosis and hepatocellular carcinoma. Many patients with hepatitis C have comorbid psychiatric and/or substance abuse disorders. Treatments for hepatitis C infection are based on interferon-alfa therapy and have shown increasing effectiveness in recent years; however, interferon-alfa therapy also poses significant risks for physical and neuropsychiatric side effects. Since psychiatrists often serve as primary caregivers for patients who are at higher risk for hepatitis C infection, knowledge about the diagnosis, prognosis, and treatment of this disease is needed. In the first half of this article, the authors review the epidemiology, transmission, pathophysiology and disease course of hepatitis C, as well as the neuropsychiatric complications of hepatitis C infection. They also discuss the incidence of comorbid psychiatric disorders in patients with hepatitis C infection and consider the impact of the infection on patients' quality of life. The authors then provide an overview of the clinical management of HCV infection, including screening procedures, decision-making about treatment, available treatments (interferon-alfa, pegylated interferon-alpha, combination therapy with interferon and ribavirin) and their side effects and potential drug-drug interactions, and prediction of treatment response. The authors then discuss management of the neuropsychiatric complications of treatment with interferon-alpha and ribavirin, including depression, mania and psychosis, and cognitive and neurological complications. The final section of the article focuses on special issues related to the treatment of hepatitis C infection in patients with substance abuse or dependence and/or other comorbid psychiatric illness.
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PMID:Comprehensive review of hepatitis C for psychiatrists: risks, screening, diagnosis, treatment, and interferon-based therapy complications. 1598 20

Patients with chronic hepatitis C virus (HCV) infection frequently describe neuropsychological symptoms. Although hepatic encephalopathy is the best established neurological association of HCV infection, there is a growing body of literature on cerebral dysfunction, occurring at an early stage of chronic HCV infection, well before the development of cirrhosis. In this review we describe recent studies that have documented mild, but significant neurocognitive impairment in HCV infection. These deficits in patients with minimal or absent liver disease do not appear to be attributable to a history of substance abuse, coexistent depression or hepatic encephalopathy. Recent studies employing in-vivo magnetic resonance spectroscopy have suggested that a biological mechanism associated with the virus may be responsible. The hypothesis that HCV infection of the central nervous system may be related to the reported neuropsychological symptoms and cognitive impairment is supported by molecular virological studies of post-mortem brain tissue.
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PMID:Central nervous system changes in hepatitis C virus infection. 1653 3

The aim of our study is to evaluate the temporal trend of deaths in a cohort of i.v. drug users (IVDU) followed in a city of Northen Italy (Bologna), and to assess its relationship with HIV infection and AIDS, and availability of potent anti-retroviral therapy. One thousand and 214 IVDUs (mainly heroin addicts), 916 males and 298 females, attending an out-patient service for treatment and prevention of substance abuse between 1977 and November 1996, were enrolled into our observational cohort, and their vital status was ascertained up to December 31, 2002. The large majority of enrolled subjects were born in the Bologna metropolitan area and surroundings; no extra-European immigrants were present. During the observation period, 271 IVDUs (22.3%) died, 211 males (23.0%), and 60 females (20.1%). No death was recorded before 1984. Main death causes result as follows: AIDS (52.8% of episodes), heroin overdose (22.1%), street accidents (7.4%), decompensated liver cirrhosis (6.3%), and suicide (2.9%). The highest absolute number of deaths was observed between years 1991 and 1996. Crude mortality rate caused by AIDS was 10.0 per 1000 for males and 13.2/1000 for females; the rate of death due to other causes proved 11.1/1000 among males and 5.2/1000 among females. In most recent years, a sharp decrease in the number of AIDS-related deaths, attributable to the increased use of potent antiretroviral regimens, was recorded among IVDUs, although overall mortality rate remained appreciable.
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PMID:Trend of mortality observed in a cohort of drug addicts of the metropolitan area of Bologna, North-Eastern Italy, during a 25-year-period. 1705 11

Studies suggest that cytokines have a role in the biology of depression. In this study, we evaluated depression and cytokine levels in patients with and without chronic hepatitis C (HCV) to better assess how chronic infection alters cytokines levels and may contribute to depressive symptomotology. Twenty-three adults with (n=16) and without (n=7) HCV were recruited through the Portland VA Medical Center. Research participants were excluded for current substance abuse, psychotic disorder, liver cirrhosis, or interferon (IFN) therapy. Participants completed the Beck Depression Inventory-II (BDI-II) and a blood draw to evaluate plasma cytokine levels [i.e., interleukin (IL)-1beta, IL-10 and tumor necrosis factor (TNF)-alpha]. t-Tests were performed to compare cytokine levels in patients with or without HCV. HCV patients showed higher TNF-alpha values compared to patients without HCV (group means=7.94 vs. 3.41pg/mL, respectively, p=0.047). There were no significant differences between the groups for the other cytokines assessed. In patients with HCV, TNF-alpha and IL-1beta levels (but not IL-10) were correlated with BDI-II scores [r=0.594, p=0.020 and r=0.489, p=0.055 (trend), respectively]. Taken together, these results show an association between severity of depressive symptoms and expression of pro-inflammatory cytokines in patients with HCV. Future studies should investigate how inflammatory mediators play a role in the expression of specific depressive symptoms in patients with chronic infection. Patients with HCV represent an interesting model to examine this relationship.
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PMID:Depressive symptoms in patients with chronic hepatitis C are correlated with elevated plasma levels of interleukin-1beta and tumor necrosis factor-alpha. 1806 7

Comorbidities may affect the decision to treat chronic hepatitis C virus (HCV) infection. We undertook this study to determine the prevalence of these conditions in the HCV-infected persons compared with HCV-uninfected controls. Demographic and comorbidity data were retrieved for HCV-infected and -uninfected subjects from the VA National Patient Care Database using ICD-9 codes. Logistic regression was used to determine the odds of comorbid conditions in the HCV-infected subjects. HCV-uninfected controls were identified matched on age, race/ethnicity and sex. We identified 126 926 HCV-infected subjects and 126 926 controls. The HCV-infected subjects had a higher prevalence of diabetes, anaemia, hypertension, chronic obstructive pulmonary disease (COPD)/asthma, cirrhosis, hepatitis B and cancer, but had a lower prevalence of coronary artery disease and stroke. The prevalence of all psychiatric comorbidities and substance abuse was higher in the HCV-infected subjects. In the HCV-infected persons, the odds of being diagnosed with congestive heart failure, diabetes, anaemia, hypertension, COPD/asthma, cirrhosis, hepatitis B and cancer were higher, but lower for coronary artery disease and stroke. After adjusting for alcohol and drug abuse and dependence, the odds of psychiatric illness were not higher in the HCV-infected persons. The prevalence and patterns of comorbidities in HCV-infected veterans are different from those in HCV-uninfected controls. The association between HCV and psychiatric diagnoses is at least partly attributable to alcohol and drug abuse and dependence. These factors should be taken into account when evaluating patients for treatment and designing new intervention strategies.
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PMID:Co-morbid medical and psychiatric illness and substance abuse in HCV-infected and uninfected veterans. 1807 Feb 93

Encouraging results have been demonstrated in large clinical trials in HIV-infected patients taking pegylated interferon and ribavirin for the treatment of hepatitis C virus (HCV) infection. However, only a minority of patients are being treated in the community. Medical providers cite chaotic lifestyles, unstable living situations, and ongoing substance abuse as barriers to these complicated therapies. The stable environment of the correctional system affords a path for intensive education, screening, and treatment of these hard-to-reach patients. Since HIV/HCV coinfected patients are at risk for cirrhosis, end-stage live disease, and hepatocellular carcinoma, incarceration should be viewed as a golden opportunity for important medical interventions.
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PMID:A golden opportunity: the treatment of hepatitis C in HIV-infected inmates. 1868 Nov 93

Language barrier, race, immigration status, mental health illness, substance abuse and socioeconomic status are often not considered when evaluating hepatitis C virus (HCV) sustained virological response (SVR) in human immunodeficiency virus (HIV) infection. The influence of these factors on HCV work-up, treatment initiation and SVR were assessed in an HIV-HCV coinfected population and compared to patients with HCV mono-infection. The setting was a publicly funded, urban-based, multidisciplinary viral hepatitis clinic. A clinical database was utilized to identify HIV and HCV consults between June 2000 and June 2007. Measures of access to HCV care (ie, liver biopsy and HCV antiviral initiation) and SVR as a function of the above variables were evaluated and compared between patients with HIV-HCV and HCV. HIV-HCV co-infected (n = 106) and HCV mono-infected (n = 802) patients were evaluated. HIV-HCV patients were more often white (94% versus 84%) and male (87% versus 69%). Bridging fibrosis or cirrhosis on biopsy was more frequent in HIV-HCV (37% versus 22%; P = 0.03). HIV infection itself did not influence access to biopsy (50% versus 52%) or treatment initiation (39% versus 38%). Race, language barrier, immigration status, injection drug history and socioeconomic status did not influence access to biopsy or treatment. SVR was 54% in HCV and 30% in HIV-HCV (P = 0.003). Genotype and HIV were the only evaluated variables to predict SVR. Within the context of a socialized, multidisciplinary clinic, HIV-HCV co-infected patients received similar access to HCV work-up and care as HCV mono-infected patients. SVR is diminished in HIV-HCV co-infection independent of language barrier, race, immigration status, or socioeconomic status.
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PMID:Equitable access to HCV care in HIV-HCV co-infection can be achieved despite barriers to health care provision. 2046 82

Approximately 3.2 million persons are chronically infected with the hepatitis C virus (HCV) in the U.S.; most are not aware of their infection. Our objectives were to examine HCV testing practices to determine which patient characteristics are associated with HCV testing and positivity, and to estimate the prevalence of HCV infection in a high-risk urban population. The study subjects were all patients included in the baseline phase of the Hepatitis C Assessment and Testing Project (HepCAT), a serial cross-sectional study of HCV screening strategies. We examined all patients with a clinic visit to Montefiore Medical Center from 1/1/08 to 2/29/08. Demographic information, laboratory data and ICD-9 diagnostic codes from 3/1/97-2/29/08 were extracted from the electronic medical record. Risk factors for HCV were defined based on birth date, ICD-9 codes and laboratory data. The prevalence of HCV infection was estimated assuming that untested subjects would test positive at the same rate as tested subjects, based on risk-factors. Of 9579 subjects examined, 3803 (39.7%) had been tested for HCV and 438 (11.5%) were positive. The overall prevalence of HCV infection was estimated to be 7.7%. Risk factors associated with being tested and anti-HCV positivity included: born in the high-prevalence birth-cohort (1945-64), substance abuse, HIV infection, alcohol abuse, diagnosis of cirrhosis, end-stage renal disease, and alanine transaminase elevation. In a high-risk urban population, a significant proportion of patients were tested for HCV and the prevalence of HCV infection was high. Physicians appear to use a risk-based screening strategy to identify HCV infection.
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PMID:Hepatitis C testing practices and prevalence in a high-risk urban ambulatory care setting. 2049 11

The success of liver transplantation for the treatment of patients with end-stage liver disease has resulted in a widening gap between the number of potential recipients and the numbers of grafts available. Allocation of these scarce resources to people who have developed liver failure as a consequence of their own and often illegal behaviour has attracted much controversy. For patients with alcoholic liver disease, there is relatively little evidence that many patients return to a damaging pattern of alcohol consumption and, at least in the short term, the outcome is no different compared with patients grafted for other causes of cirrhosis. There are well-validated markers which predict abstinence. For abusers of other substances, there is relatively little experience. Of concern is the variation between the priority-setting by the medical profession and the general public. The latter, who, in the UK, can be considered as providers of the donated organs and pay for the costs of the procedure, tend to rate patients with alcoholic liver disease and who have drug or substance abuse at a lower priority than those who develop liver failure from other causes. These differences need further debate and resolution.
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PMID:Allocating livers to substance and alcohol misusers. 2057 6


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