Pegylated interferon pharmacokinetics and self-reported depressive symptoms during antiviral treatment for chronic hepatitis C.

BACKGROUND: Pegylated interferon-2a (PegIFN-2a)+ribavirin treatment for chronic hepatitis C is often associated with depressive symptoms. Previous studies have failed to explore whether PegIFN-2a pharmacokinetic variability plays an etiologic role in PegIFN-2a-induced mood disorders. The objective of this investigation was to evaluate the association between trough PegIFN-2a concentration at treatment week 4 ("PegIFN-2a Cmin4") and an increase in depressive symptoms. METHODS: Using data from Virahep-C, the association between PegIFN-2a Cmin4 and the following depression outcomes were evaluated using the Center for Epidemiological Studies-Depression scale (CES-D): (1) change in CES-D score from baseline to week 12; (2) greatest difference in CES-D score between baseline and weeks 4, 12, or 24; and (3) occurrence of severe depressive symptoms (CES-D greater than 23) at weeks 4, 12, or 24. One post-hoc analysis examined whether PegIFN-2a exposure during the first week of treatment was associated with change in CES-D score from baseline to week 4. RESULTS: No significant associations between PegIFN-2a Cmin4 and the depression outcomes were observed (p>0.05). Exploratory analyses suggest a possible relationship between PegIFN-2a exposure during the first week of therapy and CES-D score change from baseline to week 4 (p=0.03). CONCLUSIONS: PegIFN-2a concentration levels from baseline to week 4 do not predict the onset and severity of depressive symptoms during 24 weeks of antiviral therapy; however PegIFN-2a levels during the first week of treatment may predict depressive symptoms in the first 4 weeks, earlier than anticipated and warrants further exploration.

Adherence to PEG/ribavirin treatment for chronic hepatitis C: prevalence, patterns, and predictors of missed doses and nonpersistence.

Adherence to treatment for hepatitis C virus (HCV) maximizes treatment efficacy. Missed doses and failing to persist on treatment are two patient-level processes that are rarely defined or analysed separately from other factors affecting treatment adherence. We evaluated the prevalence and patterns of missed doses and nonpersistence, and identified patient characteristics associated with these outcomes. Missed doses of ribavirin (RBV) and peginterferon (PEG), measured prospectively in Virahep-C using electronic monitoring technology, were analysed using generalized estimating equations. Cox proportional hazards models analysed time to nonpersistence from baseline to week 24 (N = 401) and from week 24 to 48 in Responders (N = 242). Average proportion of PEG- and RBV-missed doses increased over time from 5% to 15% and 7% to 27%, respectively. Patients who were younger, African-American, unemployed, or unmarried were at greater risk of missing PEG from week 0 to 24; higher baseline depression predicted missing PEG from weeks 24 to 48. Patients who were younger or African-American were more likely to miss daily RBV from weeks 0 to 24; and those without private insurance or employment were more likely to miss RBV from weeks 24 to 48. Fifty-two patients failed to persist on treatment for patient-driven deviations. Predictors of nonpersistence from weeks 0 to 24 included younger age, lower education, public or no insurance, or worse baseline headaches. In conclusion, electronic monitoring and the prospective Virahep-C design afforded a unique opportunity to evaluate missing doses and nonpersistence separately, and identify patients at risk of nonadherence. These processes will be important to investigate as the dosing schedules of antiviral regimens become increasingly complex.

Reliability and validity of a self-efficacy instrument for hepatitis C antiviral treatment regimens.

Self-efficacy or confidence in one's ability to successfully engage in goal-directed behaviour has been shown to influence medication adherence across many chronic illnesses. In the present study, we investigated the psychometric properties of a self-efficacy instrument used during treatment for chronic hepatitis C viral infection (HCV). Baseline (n = 394) and treatment week 24 (n = 254) data from the prospective, longitudinal Viral Resistance to Antiviral Therapy of Chronic Hepatitis C study were examined. Baseline participants were randomly split into two equal-sized subsamples (S(1) and S(2) ). Initial exploratory and confirmatory factor analyses (EFA/CFA) were performed on S(1), while S(2) was used to validate the factor structure of the S(1) results using CFA. An additional CFA was performed on the treatment week 24 participants. Convergent and discriminant validity were assessed by comparing the revised instrument with other psychosocial measures: depression, social support, quality of life and medication-taking behaviour. Our findings supported a reduced 17-item global measure of HCV treatment self-efficacy (HCV-TSE) with four underlying factors: patient communication self-efficacy, general physical coping self-efficacy, general psychological coping self-efficacy and adherence self-efficacy. The global score (0.92-0.94) and four factors (0.85-0.96) demonstrated good internal consistency. Correlations of convergent and discriminant validity yielded low to moderate associations with other measures of psychosocial functioning. The revised HCV-TSE instrument provides a reliable and valid global estimate of confidence in one's ability to engage in and adhere to HCV antiviral treatment. The four-factor structure suggests different types of efficacy beliefs may function during HCV treatment and should be explored further in relation to clinical outcomes.

Psychometric properties of the PROMIS short form measures in a U.S. cohort of 961 patients with chronic hepatitis C prescribed direct acting antiviral therapy.

BACKGROUND: To better understand symptoms experienced by patients infected with chronic hepatitis C virus (HCV), valid and reliable patient-reported outcome (PRO) measures are needed. AIM: To assess the reliability and validity of 10 patient-reported outcomes measurement information system (PROMIS) measures and the Headache Impact Test-6 (HIT-6) in a large national sample of patients with HCV. METHODS: Pre-treatment data from 961 patients with HCV starting direct acting antiviral therapy at 11 U.S. liver centers were analyzed. Internal reliability was evaluated using Cronbach's alpha coefficient; frequency distributions were examined for floor and ceiling effects; structural validity was investigated via item-response-theory models; convergent validity was evaluated using correlations with theoretically-similar items from the HCV-PRO and memorial symptom assessment scale (MSAS); and known-groups validity was investigated by observing PRO differences by liver disease status and number of comorbidities. RESULTS: The HIT-6 and the majority of the PROMIS measures yielded excellent reliability (alphas ≥ 0.87). Ceiling effects were infrequent ( < 4%), while 30%-59% of patients reported no symptoms (floor effects). The data supported structural validity of the HIT-6 and most PROMIS measures. The PROMIS measures showed moderate to strong correlations with theoretically-similar items from the HCV-PRO and MSAS (0.39-0.77). Trends were observed between worse PRO scores and advanced cirrhosis and greater number of comorbidities, lending support for known-groups validity. CONCLUSIONS: The psychometric properties of the HIT-6 and PROMIS measures performed satisfactorily in this large cohort of patients with HCV starting direct acting antiviral therapy. Opportunities exist for further refinement of these PROs. Evaluation of performance over time and in under-represented subgroups is needed.

Barriers to accessing care in patients with chronic hepatitis C: the impact of depression.

BACKGROUND: Patients with hepatitis C viral (HCV) may perceive barriers to accessing speciality care for HCV, and these barriers may be related to depressive symptoms. AIM: To evaluate the relationship between barriers to care, demographics, and depressive symptoms. METHODS: A cross-sectional analysis of 126 patients referred for HCV at two speciality HCV clinics. Barriers to care, depressive symptoms and sociodemographics were measured using standardized instruments. A retrospective chart review was conducted to collect clinical outcome data. RESULTS: Depressive symptoms were reported in 26%. Common barriers included lack of personal financial resources; lack of HCV knowledge in the community; lack of professionals competent in HCV care; stigmatization of HCV; and long distances to clinics offering care. After we controlled for sociodemographics, depression accounted for an additional 7-18% of variability in all barriers (all p values <0.01). Lower depression, marital and employment status were associated with subsequent receipt of HCV treatment in 38% (45/120) of patients; perceived barriers were not. CONCLUSIONS: Depression is independently associated with perceived barriers to care. Higher depressive scores, but not perceived barriers, were associated with nontreatment. Healthcare providers who diagnose HCV need to be cognizant of numerous perceived barriers to accessing HCV care, and the impact that depression may have on these perceptions and receipt of treatment.

Psychiatric symptoms during interferon treatment for hepatitis C: experiences from a tertiary care hepatology centre.

BACKGROUND: Most research on the psychiatric symptoms of peginterferon/ribavirin for the treatment of hepatitis C comes from VA centres and clinical trials with rigid entry criteria that often excluded patients with markers of mental health and substance use disturbance (MH/SUD). The findings from these lines of research may not be generalizable to patients treated under standard of care in a tertiary care setting. AIM: To investigate the incidence and outcomes of psychiatric symptoms in patients treated under standard of care protocol, not enrolled in clinical trials. METHODS: This is a retrospective analysis of 215 patients who underwent therapy from 2002 to 2006 at a university-based tertiary care centre. Survival curves explored the relationship between history of MH/SUD and the development of psychiatric symptoms on treatment. RESULTS: The cumulative history of MH/SUD was 67%. Of these, 39% had taken psychotropic medications previously, and 80% continued on them during therapy. On therapy, 46% developed depressive symptoms, 19% and 46% endorsed anxiety and irritability respectively. Cumulatively, 64% of patients indicated mood disturbance on therapy. Most symptoms developed between weeks 2 and 18, and rarely after week 20. Of those who developed mood symptoms, 66% required an intervention. Treatment discontinuation was infrequent. CONCLUSIONS: This large observational study provides important insights into the incidence and course of psychiatric symptoms in an unselected sample of patients treated in a tertiary care setting. Patients had higher rates of MH/SUD comorbidity, psychotropic medication use and exhibit higher rates of mood disturbance on therapy compared with previous reports, although a majority completed the prescribed treatment regimen.