Functional MRI and delay discounting in patients infected with hepatitis C.

Hepatitis C virus-infected (HCV+) adults evidence increased rates of psychiatric and cognitive difficulties. This is the first study to use functional magnetic resonance imaging (fMRI) to examine brain activation in untreated HCV+ adults. To determine whether, relative to non-infected controls (CTLs), HCV+ adults exhibit differences in brain activation during a delay discounting task (DDT), a measure of one's tendency to choose smaller immediate rewards over larger delayed rewards-one aspect of impulsivity. Twenty adults with HCV and 26 CTLs completed an fMRI protocol during the DDT. Mixed effects regression analyses of hard versus easy trials of the DDT showed that, compared with CTLs, the HCV+ group exhibited less activation in the left lateral occipital gyrus, precuneus, and superior frontal gyrus. There were also significant interactive effects for hard-easy contrasts in the bilateral medial frontal gyrus, left insula, left precuneus, left inferior parietal lobule, and right temporal occipital gyrus; the CTL group evidenced a positive relationship between impulsivity and activation, while the HCV+ group exhibited a negative relationship. Within the HCV+ group, those with high viral load chose immediate rewards more often than those with low viral load, regardless of choice difficulty; those with low viral load chose immediate rewards more often on hard choices relative to easy choices. Results show that HCV+ patients exhibit greater impulsive behavior when presented with difficult choices, and impulsivity is negatively related to activation in regions important for cognitive control. Thus, interventions that decrease impulsive choice may be warranted with some HCV+ patients.

Protective effects of higher cognitive reserve for neuropsychological and daily functioning among individuals infected with hepatitis C.

Higher levels of cognitive reserve (CR) can be protective against the neuropsychological manifestation of neural injury across a variety of clinical disorders. However, the role of CR in the expression of neurocognitive deficits among persons infected with the hepatitis C virus (HCV) is not well understood. Thirty-nine HCV-infected participants were classified as having either high (n = 19) or low (n = 20) CR based on educational attainment, oral word reading, and IQ scores. A sample of 40 demographically comparable healthy adults (HA) was also included. All participants completed the Neuropsychological Assessment Battery, Delis-Kaplan Executive Function System, and Behavioral Rating Inventory of Executive Function, Adult Version (BRIEF-A). Linear regression analyses, controlling for gender, depression, and lifetime substance use disorders, found significant effects of HCV/CR group on verbal fluency, executive functions, and daily functioning T scores, but not in learning or the BRIEF-A. Pairwise comparisons revealed that the HCV group with low CR performed significantly below the HCV high CR and HA cohorts, who did not differ from one another. Findings indicate that higher levels of CR may be a protective factor in the neurocognitive and real-world manifestation of neural injury commonly associated with HCV infection.

A longitudinal study evaluating the effects of interferon-alpha therapy on cognitive and psychiatric function in adults with chronic hepatitis C.

OBJECTIVE: To prospectively evaluate for changes in objective cognitive performance (attention, memory, and executive function) and psychiatric symptom severity (depression, anxiety, fatigue, and pain) in patients before, during and after interferon-alpha based therapy (IFN) for chronic hepatitis C virus infection (HCV). METHODS: 33 HCV+ adults were evaluated two months before IFN initiation (baseline), three months into IFN, and six months following IFN termination (IFN+ Group). 31 HCV+ adults who did not undergo IFN therapy were evaluated at baseline and six months later (IFN- Group). At each evaluation, participants completed the Neuropsychological Assessment Battery (NAB) Attention, Memory and Executive Functions Modules, the Beck Depression Inventory, Second Edition (BDI), Generalized Anxiety Disorder Inventory (GADI), Fatigue Severity Scale (FSS), and Brief Pain Inventory (BPI). RESULTS: Compared with the IFN- Group, the IFN+ Group experienced significantly (p<0.050) increased symptoms of depression, anxiety, fatigue and pain during IFN therapy relative to baseline. In the IFN+ Group, psychiatric symptoms generally returned to baseline levels following IFN termination. Sustained viral response was associated with significantly lower depression and fatigue. No significant changes in cognitive performance were observed. CONCLUSIONS: During IFN, patients with HCV evidence significantly increased psychiatric symptoms, including symptoms of depression, anxiety, fatigue and pain. These psychiatric symptoms are generally short-term and remit following IFN termination, with increased benefit if viral clearance is achieved. However, IFN is not associated with significant declines in objective cognitive performance during or following IFN.

Multi-analyte profile analysis of plasma immune proteins: altered expression of peripheral immune factors is associated with neuropsychiatric symptom severity in adults with and without chronic hepatitis C virus infection.

BackgroundThe purpose of this study was to characterize hepatitis C virus (HCV)-associated differences in the expression of 47 inflammatory factors and to evaluate the potential role of peripheral immune activation in HCV-associated neuropsychiatric symptoms-depression, anxiety, fatigue, and pain. An additional objective was to evaluate the role of immune factor dysregulation in the expression of specific neuropsychiatric symptoms to identify biomarkers that may be relevant to the treatment of these neuropsychiatric symptoms in adults with or without HCV. MethodsBlood samples and neuropsychiatric symptom severity scales were collected from HCV-infected adults (HCV+, n = 39) and demographically similar noninfected controls (HCV-, n = 40). Multi-analyte profile analysis was used to evaluate plasma biomarkers. ResultsCompared with HCV- controls, HCV+ adults reported significantly (P < 0.050) greater depression, anxiety, fatigue, and pain, and they were more likely to present with an increased inflammatory profile as indicated by significantly higher plasma levels of 40% (19/47) of the factors assessed (21%, after correcting for multiple comparisons). Within the HCV+ group, but not within the HCV- group, an increased inflammatory profile (indicated by the number of immune factors > the LDC) significantly correlated with depression, anxiety, and pain. Within the total sample, neuropsychiatric symptom severity was significantly predicted by protein signatures consisting of 4-10 plasma immune factors; protein signatures significantly accounted for 19-40% of the variance in depression, anxiety, fatigue, and pain. ConclusionsOverall, the results demonstrate that altered expression of a network of plasma immune factors contributes to neuropsychiatric symptom severity. These findings offer new biomarkers to potentially facilitate pharmacotherapeutic development and to increase our understanding of the molecular pathways associated with neuropsychiatric symptoms in adults with or without HCV.

Changing compliance to the American College of Gastroenterology guidelines for the management of variceal hemorrhage: a regional survey.

OBJECTIVES: In mid-1997 the American College of Gastroenterology (ACG) published guidelines for the management of varices. The aim of this study is to assess the change in regional practice patterns between early 1997 (preguidelines) and 2000 (postguidelines). METHODS: Gastroenterologists in Oregon and Southwestern Washington state were sent a self-reporting questionnaire regarding the management of varices in March 1997 (prior to the publication of the guidelines) and again in August 2000. RESULTS: Fifty-seven of 75 (76%) and 68 of 92 (74%) of the surveys were completed in 1997 and 2000, respectively. Fifty to 60% of the respondents saw between three and five cirrhotic patients per month. Significantly, more respondents followed the guidelines to screen and treat large varices to prevent initial variceal hemorrhage in 2000 than in 1997, 54% versus 18% (p < 0.005). Of the respondents who performed screening of EGDs, the majority treated large varices with beta-blocker therapy (93% in 1997 and 97% in 2000). All respondents used early endoscopy to treat variceal bleeding. Significantly, most of the respondents began pharmacologic therapy prior to endoscopy if active variceal hemorrhage was suspected (with most choosing octreotide) in 2000 than in 1997, 83% versus 56% (p < 0.005). The majority of the respondents pursued repeat endoscopic therapy after cessation of the initial variceal bleeding episode (96% in 1997 and 95% in 2000), and most performed surveillance EGD once the varices had been eradicated (72% in 1997 and 79% in 2000). CONCLUSIONS: After the publication of the ACG guidelines, significantly more gastroenterologists screened for varices to prevent initial variceal hemorrhage and significantly more used pharmacologic therapy prior to endoscopic treatment for variceal hemorrhage.