Hepatitis C Pretreatment Profile and Gender Differences: Cognition and Disease Severity Effects.

BACKGROUND: The hepatitis C virus (HCV) is known to infect the brain, however, the findings based on associated neuropsychiatric syndrome are controversial and the association itself remains unclear. Gender research in HCV infection is limited, failing to integrate the role of gender differences in neurocognitive syndrome. The aim of this study was to characterize psychological and neurocognitive profiles in HCV-infected patients before treatment and to explore gender differences in those profiles, as well as the impact of disease severity. METHODS: A total of 86 patients diagnosed with chronic hepatitis C were included. Depression and anxiety were assessed using Hamilton anxiety scale (HAM-A), Hamilton depression scale (HAM-D), Beck Depression Inventory (BDI). For cognition, a neuropsychological battery to measure attention, concentration and memory was used, and executive function components validated for the Portuguese population was also used before starting treatment. To identify the disease severity, platelet ratio index, and FibroScan® were used. RESULTS: A statistically significant gender effect was found on HAM-A (B = 0.64, CI: 0.17-1.11) and HAM-D (B = 0.62, CI: 0.14-1.09), with women scoring higher compared to men. Regarding neuropsychological scores, significant differences between gender were identified in executive functions measured by Trail Making Test (TMT B) (B = 0.48, CI: 0.02-0.97), TMT B-A (B = 0.26, CI: -39.2 to -3.7) and in digit span total (B = -0.52, CI: -1.0 to -0.04), with women performing worse than men. Controlling for years of substance dependence, TMT-B and TMT B-A showed significant gender differences. Regarding the presence or absence of substance dependence, only HAM-A and HAM-D remained significant. For categorical variables, Digit Span Total was also influenced by gender, with women being more likely to be impaired: odds ratio (OR) = 7.07, CI: 2.04-24.45), and a trend was observed for Digit Span Backward (OR = 3.57, CI: 1.31-9.75). No significant differences were found between disease severity and neurocognitive performance. CONCLUSION: Data suggest that gender has an influence on depression, anxiety and cognitive functions with women showing greater impairment compared with men. This effect seems to be influenced by substance dependence.

Factor analyses differentiate clinical phenotypes of idiopathic and interferon-alpha-induced depression.

The discovery that prolonged administration of interferon-alpha (a pro-inflammatory cytokine) readily precipitates depressive symptoms has played a key role in development of the inflammation theory of major depressive disorder (MDD). However, it remains unclear whether the clinical phenotype of patients with inflammation-associated depression significantly overlaps with, or can be distinguished from that of patients with 'idiopathic' depression. Here we explored the Hamilton depression scale factor structure of 172 patients undergoing interferon-alpha treatment for hepatitis-C at the point of transition to a depressive episode of DSM IV defined major depression severity. The resulting factor structure was first compared with a model derived from 6 previous studies of 'idiopathic' MDD (Cole et al., 2004). This confirmatory factor analysis revealed that the factor structure of HAMD scores in our interferon-alpha treated cohort did not plausibly fit that previously described for 'idiopathic' MDD. Instead, subsequent exploratory factor analysis revealed a distinct four factor model with a novel primary factor grouping cognitive symptoms of depression and anxiety (HAMD items 1, 2, 9, 10, 11, 15). The second sleep disorder factor (items 4, 5, 6) replicated previous findings in 'idiopathic' depression. A third and unique factor grouped somatic symptoms and function (items 7, 12, 13, 14 and item 1). The final factor (also common in idiopathic depression studies), grouped gastrointestinal symptoms and weight loss (items 12 and 16). Severe depression items (3, 8, and 17) were excluded from analysis due to very low variance. At transition, interferon-alpha induced major depressive episodes therefore appears to have more associated anxiety features that covary with depressed mood than classical or 'idiopathic' MDD and a low likelihood of severe features such as suicidal ideation. Identification of this clinical phenotype may help identify patients with an inflammatory depression etiology and support the development of more effective and personalized therapies.

A longitudinal study assessing depression in hepatitis C: Does gender play a role in the new-onset depression during interferon-alpha treatment?

In this prospective study conducted from October 2013 to June 2015 in Brighton, England, we examined differences between men and women in new-onset major depressive disorder (MDD) during interferon-alpha-based (IFN-α) therapy for hepatitis C virus (HCV). We included 155 HCV-infected patients (47 women), eligible to receive HCV therapy, including direct-acting antivirals. The Semi-Structured Clinical Interview was used to assess MDD. Severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale. Patients were assessed at baseline, during treatment and 6 months after treatment completion. A significant increase in depressive symptoms was observed in the total sample from baseline to week 4, and a significant decrease was observed from end of treatment (week 24) to the sustained virological response (SVR) end point at 6 months posttreatment. Women were more likely to have a MDD at week 24. In both men and women, neurovegetative and mood-cognitive syndromes increased significantly at the early stage of treatment but remitted by the end of HCV therapy. Proportions with SVR were similar among females and males (91.5 percent vs. 87 percent). Under an inflammatory condition, boosted by interferon-based treatments, these results suggest that female gender is not associated with increased vulnerability for developing depression during IFN-α therapy.

Psychosocial and Neurocognitive Factors Associated With Hepatitis C - Implications for Future Health and Wellbeing.

Background: Hepatitis C virus (HCV) infection involves changes not only from the point of view of physical health, but also emotional, and social that have a significant impact on the quality of life of these patients. According to the literature review, it seems that there is an important association between psychosocial factors, in particular on a cognitive level and disease progression. The aim of this mini-review is to summarize recent literature looking at the associations between psychosocial and neurocognitive factors and HCV. Methods: PubMed/Medline was systematically searched for psychosocial and neurocognitive factors associated with hepatitis C, treatment adherence, and patient wellbeing. Results: Patients present with a range of extrahepatic symptoms including fatigue, anxiety, depression, and neurocognitive dysfunction. HCV's impact on quality of life and wellbeing has serious clinical and social implications. Conclusion: Hepatitis C and its management continue to have a profound impact on health and psychologic wellbeing. Considering the serious extrahepatic implications for individuals, it is imperative that healthcare professionals pay close attention to psychosocial and neurocognitive factors. The focus on combined clinical approaches could enhance understanding about the health and social impacts of hepatitis C along the life course.

Co-infection with HIV associated with reduced vulnerability to symptoms of depression during antiviral treatment for hepatitis C.

In this prospective study, we examined new-onset major depressive disorder (MDD) and the differential expression of depressive symptoms in a sample of 132 HCV mono-infected and 40 HIV/HCV co-infected patients initiating pegylated interferon-based treatment, including protease inhibitor therapy. The semi-structured clinical interview (SCID-I) was used to assess MDD. Severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale. Of the total sample, 60 patients (34.9%) developed SCID-I defined MDD during antiviral treatment. The proportion of HCV mono- and HIV/HCV patients developing MDD during treatment was not significantly different (37.9% vs. 25%; p=0.185). In both groups, there was a significant increase in HAMD total score from baseline to week 4, and a significant decrease between week 24 and 6 months post-treatment cessation. The greatest increase was observed in the symptoms of the neurovegetative syndrome. HCV mono-infected patients reported higher scores than co-infected patients, particularly impaired activity and somatic symptoms, but the differences were only significant at week 12. The finding that co-infected patients appear less vulnerable to the development of depressive symptoms during HCV treatment than HCV mono-infected patients warrants further exploration, including a thorough analysis of the biological and psychosocial factors associated with this emergence.

Depression in HIV and HCV co-infected patients: a systematic review and meta-analysis.

The aim of this study was to carry out a systematic review and meta-analysis of the differences in the prevalence of depression and presence of depressive symptoms between HIV/HCV co-infection, HIV mono-infection, and hepatitis C virus (HCV) mono-infection. A systematic electronic search of bibliographic databases was performed to locate articles published from the earliest available online until December 2014. Outcomes of depression were based on clinical interviews and validated self-reported measures of depression/depressive symptoms. Of the 188 records initially screened, 29 articles were included in the descriptive systematic review and six were included in the meta-analysis. The meta-analytic results indicated that, as measured by self-reported measures of depression, HIV/HCV co-infected patients were significantly more likely to report depressive symptoms than either HIV (SMD = .24, 95% CI: .03-.46, p = .02) or HCV mono-infected (SMD = .55, 95% CI: .17-.94, p = .005) patients. The variability of the results of the reviewed studies, largely dependent on the samples' characteristics and the methods of assessment of depression, suggests that a clear interpretation of how depression outcomes are affected by the presence of HIV/HCV co-infection is still needed. Failing to diagnose depression or to early screen depressive symptoms may have a significant impact on patients' overall functioning and compromise treatments' outcomes.

Assessment of factors associated with the quality of life of patients living with HIV/HCV co-infection.

This study compared the quality of life (QoL) of HIV-infected patients with and without hepatitis C and examined the sociodemographic, HIV-related and psychological symptoms associated with the QoL domains in patients with HIV/HCV co-infection. The sample consisted of 248 HIV/HCV co-infected patients (18-74 years, 81.5 % male) and 482 patients only with HIV (24-78 years, 62.7 % male). Participants completed the WHOQOL-HIV-Bref questionnaire and the Brief Symptom Inventory. The HIV/HCV co-infected patients reported significantly lower QoL in all domains, as well as significantly lower scores in 10 of the 17 specific facets. Overall, among the co-infected patients, male gender, employment, combination antiretroviral therapy use and fewer depressive and anxiety symptoms were significantly associated with higher QoL. Symptoms of psychological distress accounted for significant variability in the QoL scores of co-infected patients. These data reinforce the need for tailored interventions to improve the overall well-being of HIV/HCV co-infected patients.

Norepinephrine-enhancing antidepressant exposure associated with reduced antiviral effect of interferon alpha on hepatitis C.

RATIONALE: Major depressive disorder is a common consequence of exposure to the pro-inflammatory cytokine interferon alpha, which is treated effectively with antidepressant medication. Antidepressant mode of action may conflict with interferon alpha's mechanism in treating hepatitis C however. OBJECTIVES: The purpose of this study is to prospectively explore, in a large naturalistic cohort, whether antidepressant exposure influenced end of treatment response of hepatitis C to interferon alpha. METHODS: Two hundred thirty-nine patients infected with chronic hepatitis C and due to receive treatment were recruited. All participants initiated peg-interferon-2-alpha 180 µg weekly sub-cutaneously plus oral ribavirin 800-1200 mg daily. Participants were assessed for DSM-IV major depression at baseline and four weekly during treatment. RESULTS: 32.6 % of the cohort was exposed to an antidepressant (serotonin-reuptake inhibitor: other categorised antidepressants 49:29). At baseline, 3.8 % had major depression and 55.2 % developed major depression during interferon alpha treatment. Exposure to an antidepressant not classified as a serotonin-reuptake inhibitor, of which all were norepinephrine-enhancing (OR 0.15, 95 % CI 0.04-0.60) and having a past history of psychiatric disorder (OR 4.41, 95 % CI 1.39-13.96) independently reduced the likelihood of end of treatment response. Serotonin-reuptake inhibitor exposure did not influence end of treatment response (OR 1.21, 95 % CI 0.35-4.19), neither did major depression at baseline (OR 2.31, 95 % CI 0.55-9.60) or during treatment (OR 0.69, 95 % CI 0.36-1.33). CONCLUSIONS: Our findings support a lack of conflict of therapeutic mechanism of serotonin-reuptake inhibitor antidepressants with interferon alpha in treating hepatitis C, which may include inflammatory influence. This appears not to be true for norepinephrine-enhancing antidepressant types and warrants investigation using more direct methods.

Cognitive impairment in HIV and HCV co-infected patients: a systematic review and meta-analysis.

Cognitive impairment has been well documented in HIV and hepatitis C virus (HCV) mono-infections. However, in the context of HIV/HCV co-infection the research is more limited. The aim of this systematic review was to describe the characteristics of cognitive impairment in HIV/HCV co-infection and to examine the differences in cognitive performance between HIV/HCV and HIV and HCV mono-infected patients. Of the 437 records initially screened, 24 papers met the inclusion criteria and were included in the systematic review. Four studies were included in the meta-analysis. Most studies indicated that HIV/HCV co-infected patients had a higher level of cognitive impairment than HIV mono-infected patients. Meta-analysis indicated, however, that HIV mono-infected patients had a significantly higher global deficit score than co-infected patients. The results also indicated that co-infected patients were more likely to be impaired in information processing speed than HIV mono-infected patients. These findings can be challenged by biasing factors such as the small number of studies, heterogeneity of the samples, and a large diversity of methodological procedures. Future research with consistent and comprehensive neuropsychological batteries and covering a greater diversity of risk factors is needed, in order to clarify the effects of both viruses on cognitive function and the mechanisms that underlie these effects. Because cognitive impairments may pose significant challenges to medication adherence, quality of life and overall functioning, such knowledge may have important implications to the planning and implementation of effective interventions aimed at optimising the clinical management of these infections.

Effectiveness and Predictors of Continuation of Paliperidone Palmitate Long-Acting Injection Treatment: A 12-Month Naturalistic Cohort Study.

Antipsychotic long-acting injectable (LAI) medication has an important place as a treatment option in schizophrenia with evolving evidence to support clinical benefit over oral medication. Paliperidone palmitate is recently licensed as an LAI. We studied a naturalistic cohort of all identifiable patients who initiated paliperidone LAI in a specific United Kingdom region (Sussex) from first availability up to January 2013 (n = 179). Favorably, 60% of the cohort continued paliperidone LAI beyond 12 months from initiation. Schizophrenia diagnosis was significantly associated with 12-month continuation on univariate analysis (65% continuation rate at 12 months in this diagnostic subgroup). No baseline variables were identified as independently associated with 12-month continuation. However, fewer inpatient days after initiation (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.003-1.011; P = 0.002), dose adjustment up or down (OR, 3.46; 95% CI, 1.26-9.51; P = 0.016), and a higher maintenance dose (OR, 8.31; 95% CI, 1.84-37.51; P = 0.006) during treatment course were all independently associated with continuation on multivariate analysis. Our findings support the importance of a collaborative approach with the LAI recipient in treatment decision making to enhance treatment effectiveness.

Psychomotor retardation and vulnerability to interferon alpha induced major depressive disorder: Prospective study of a chronic hepatitis C cohort.

BACKGROUND: Major depressive disorder (MDD) is a common consequence of interferon alpha (IFNα) treatment and important supporting evidence of a role of inflammation in the aetiology of depression. OBJECTIVE: This study aimed to expand the knowledge of baseline clinical vulnerability characteristics to IFNα induced MDD, particularly exploring sub-threshold depressive symptoms. METHODS: A prospective cohort of chronic HCV patients undergoing treatment with pegylated-IFNα and ribavirin was studied. MDD was assessed using the Structured Clinical Interview for DSM-IV (SCID-I). Depressive symptoms and severity were assessed at baseline and monthly with the Hamilton Depression Rating Scale (HAMD). Subjects with MDD or taking antidepressant treatment at baseline were excluded. RESULTS: 278 patients were assessed for this cohort with a final study sample of 190. 94.2% had contracted HCV through intravenous drug use. During six months IFNα treatment, 53.2% of patients transitioned to DSM-IV threshold MDD. In the multivariate logistic analysis, independent factors significantly associated with development of MDD were younger age (OR 0.96, 95% CI 0.93-1.00, p=0.028), past history of MDD (OR 3.82, 95% CI 1.63-8.92, p=0.002), baseline HAMD items psychomotor retardation (OR 15.21, 95% CI 1.33-173.41, p=0.032) and somatic symptoms (general) (OR 2.96, 95% CI 1.44-6.08, p=0.003), and HCV genotype 2 (OR 2.27, 95% CI 1.07-4.78, p=0.032). CONCLUSIONS: During IFNα treatment, the rate of transition to MDD was high in this cohort. Psychomotor retardation and somatic symptoms may represent a greater inflamed state pre-treatment. This iatrogenic model of MDD may offer important insights into wider depression aetiology.

HCV triple therapy in co-infection HIV/HCV is not associated with a different risk of developing major depressive disorder.

INTRODUCTION: Hepatitis C (HCV) treatment options have changed with the development of direct activity antivirals (DAAs) and the availability of triple therapies have improved HCV cure rates. A common neuropsychiatric side effect of pegylated-interferon and ribavirin treatment is major depressive disorder (MDD), however little is known about such adverse events with protease inhibitor-based triple therapy. The aim of this study was to assess the rate of MDD in co-infected HIV HCV patients undergoing different HCV treatments. METHODS: All participants were co-infected HIV HCV attending the Royal Sussex County Hospital Brighton hepatology outpatient clinic between 2010 and 2014. Participants were assessed for DSM-IV MDD and depression severity (using the Hamilton depression scale (HAMD)) at baseline and monthly after treatment initiation. HIV and HCV stages, genotype, reinfection and standard demographic variables were recorded. Influence of HCV stage (acute vs. chronic) and type of treatment (classic vs triple), emergence of MDD and clearance outcomes were analyzed using repeated measures and logistic regression models. RESULTS: Fifty participants with a mean age of 42.65 years (SD=10.32) were included; most were male (98%). The majority had contracted HCV genotype 1 (64%) or 4 (26%). The HCV stage and treatment groups were matched for age and depression at baseline. No significant differences were found on virological outcomes considering HCV stage and treatment. From baseline to SVR, there was a significant increase in HAMD scores, F(4,36)=10.09, p<.001; this was not significantly influenced by HCV stage, F(4,35)=0.54, p=.708 or HCV treatment group, F(4,35)=0.60, p=.664. Those with chronic HCV were more likely to transition to MDD than acute infection (OR 7.77, 95% CI 2.04-29.54, p=.003). No differences were found for depression emergence by HCV treatment group (OR 0.83, 95% CI 0.22-3.13, p=.787). CONCLUSIONS: HCV triple therapy was not associated with a different risk of emergence of MDD versus classic treatment. MDD should be assessed before therapy initiation and monitored throughout treatment for any HCV treatment regime. Future research could usefully clarify mechanisms of MDD emergence and risk factors for this.

Prevalence and correlates of emotional distress in HIV/HCV coinfection.

The mental health needs of patients who are coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are increasingly addressed in medical settings. This study aimed at examining the prevalence and severity of emotional distress in a sample of HIV/HCV coinfected and HIV mono-infected patients and to examine their sociodemographic, clinical, and psychosocial correlates. The Brief Symptom Inventory and the quality of life instrument WHOQOL-HIV-Bref were administered to a sample of 248 HIV/HCV coinfected patients and 482 HIV mono-infected patients. Thirty-nine (15.9%) HIV/HCV coinfected patients and 55 (11.6%) HIV mono-infected patients reported a T-score ≥ 63 for global severity index (GSI), indicative of a need for further psychological evaluation. Coinfected patients reported significantly higher scores on eight of nine dimensions of psychopathology. The larger differences were found on somatization, hostility, paranoid ideation, anxiety, and the GSI. Among HIV/HCV patients, non-highly active antiretroviral therapy (ß = -0.19, p < 0.01) and lower scores for independence (ß = -0.24, p < 0.01) and spiritual (ß = -0.31, p < 0.001) dimensions were significantly associated with higher emotional distress and accounted for 47.2% of the total variance. Among HIV mono-infected patients, being diagnosed for a longer time (ß = 0.12, p < 0.05) and having lower scores on physical (ß = -0.23, p < 0.001), social relationships (ß = -0.11, p < 0.05), environmental (ß = -0.17, p < 0.01), and spiritual (ß = -0.21, p < 0.001) dimensions explained 39.4% of the variance of emotional distress. The findings suggest that coinfection with HCV may have an adverse effect on mental health and underscore the interplay of sociodemographic, clinical, and psychosocial variables on emotional distress. Additionally, these data reinforce the need for tailored interventions to improve the overall well-being of both HIV and HIV/HCV patients.

Depressive symptoms and neurocognitive performance among HIV-infected women.

The aims of this article were to explore the relationship between depressive symptoms and neuropsychological performance in a sample of HIV-infected women, and to examine the contribution of demographic, HIV-related variables, and depressive symptoms to neurocognitive performance. In this cross-sectional study, a sample of 103 HIV-infected women, recruited from February to December 2010, were assessed for depressive symptoms (with the Beck Depression Inventory) and neurocognitive performance (with the HIV Dementia Scale). Severe depressive symptoms were reported by 31.1% of the women. Findings indicated that severe levels of depressive symptoms were significantly associated with reduced cognitive functioning in HIV-infected women, particularly in domains of attention, psychomotor speed, and construction. Older age and low education level were significantly associated with neurocognitive impairment in univariate analyses. In the multivariate model, only depressive symptoms were significantly related to neurocognitive impairment. Compared to participants with none/minimal depressive symptoms, those with moderate and severe depressive symptoms had odds ratios for neurocognitive impairment of 5.03 (95% CI, 1.33-18.99) and 3.22 (95% CI, 1.15-9.06), respectively. These findings support continued investigation of the presence of neurocognitive impairment, particularly among women, and may help mental health providers with early detection, planning, and implementation of more effective interventions. The current study was supported by Abbott Laboratories, Portugal.

Advance directives: Portuguese palliative care professionals' views.

Advance directives are a controversial subject in Portugal at present, particularly among health professionals. Although some health professionals consider them to be important tools that are helpful in making proper decisions and promoting patient autonomy, others think that they may interfere with the human and relational dimension of care. It is therefore timely to investigate health professionals' views of advance directives in more detail. This study aimed to identify and reflect on Portuguese palliative care professionals' perspectives of advanced directives and their relevance to end-of-life decision making. A qualitative exploratory methodology was adopted in which interviews were conducted with two physicians, six nurses, two psychologists, and one social worker from four palliative care teams based across Portugal. The findings emphasize the relevance of advance directives to ethical decision-making processes in palliative care. However, debates are needed regarding whether advance directives should be legally binding.