Watchful Waiting: Role of Disease Progression on Uncertainty and Depressive Symptoms in Patients With Chronic Hepatitis C

J. P. Colagreco; D. E. Bailey; J. J. Fitzpatrick; C. M. Musil; N. H. Afdhal; M. Lai

Disclosures

J Viral Hepat. 2014;21(10):727-733. 

In This Article

Subjects

We enrolled adult subjects (age ≥18 years) with CHC (positive quantitative HCV RNA at any time after having a positive serum HCV antibody if treatment naïve or at least 6 months after having been treated with an interferon-based regimen) following watchful waiting. We defined watchful waiting as not receiving antiviral treatment for CHC at the time of enrolment in the study with at least annual follow-up by a medical provider and a history of treatment deferral of at least 6 months. Other inclusion criteria were a minimum of two liver biopsies at two different time points and the ability to read and write English. Patients were excluded if they had significant psychiatric histories or had received treatment with antiviral drugs within 6 months of study enrolment. Those co-infected with HIV, Hepatitis B, or any significant active medical co-morbidity were also excluded because active comorbidities might influence illness uncertainty and depressive symptoms.

Power Justification

A power analysis was performed to determine the sample size for this study. For a power of 0.8 and alpha of 0.05, a sample size of 84 was needed to conduct correlational analysis for a medium effect size using data from an early study.[17] This study was not designed to examine the difference in the CES-D and MUIS-A scores between the different subgroups (treatment naïve, treatment failures, interferon intolerant/ineligible); rather, it was designed to get estimates of depressive symptoms and illness uncertainty for this population.

Measures

At the single study visit, subjects completed two validated, standardized self-report questionnaires, the modified Mishel Uncertainty in Illness Scale (MUIS-A) and the Center for Epidemiological Studies Depression Scale (CES-D). The MUIS-A is a 33-item instrument that measures uncertainty in illness.[14] It has been used to evaluate illness uncertainty in a variety of disease states including hepatitis C and has good reliability.[14,17] It includes the four subscales measuring Ambiguity, Complexity, Inconsistency and Unpredictability with the total score ranging from 32 to 160. The ranges for the subscales are as follows: Ambiguity (13–65); Complexity (7–35); Inconsistency (7–35); Unpredictability (5–25). Higher scores on the MUIS-A indicate higher levels of uncertainty. A form modified by Bailey[17] for patients with CHC on watchful waiting was used.

The modified MUIS-A has reported internal consistency reliability of .90 for the total (subscale reliabilities were not reported), and in this sample, the Cronbach's alpha for the total MUIS-A was .84; reliabilities for subscales were as follows: ambiguity (Cronbach's alpha = 0.92), complexity (Cronbach's alpha = 0.74), inconsistency (Cronbach's alpha = 0.84) and unpredictability (Cronbach's alpha = 0.63). The CES-D is a 20-item instrument designed to measure current level of depressive symptomology.[19] Scores range from 0 to 60, with scores 16 to 23 indicating mild to moderate risk for clinical depression and scores greater than 23 indicating high risk.[19,20] The CES-D has reported internal consistency reliability of 0.88–0.92 for the total scale (Radloff, 1977), and in this sample, it was 0.80.

Additional Data

We collected additional data using a patient questionnaire and chart review form and these included age, gender, race, ethnicity, educational level, time from the diagnosis of HCV, stage of fibrosis, fibrosis progression, reason for watchful waiting, risk factors for CHC infection, concurrent antidepressant use and concurrently under the care of a therapist for depression. Liver fibrosis was staged using the Metavir system.[21] Fibrosis progression was defined as an increase in fibrosis stage between the two most recent liver biopsies and collected as a dichotomous variable. Reason for watchful waiting was obtained by chart review and subject report and categorized into treatment failure, treatment naïve and interferon intolerant or ineligible. The treatment failure group included nonresponders, partial responders and relapsers. Interferon intolerant or ineligible subjects had treatment stopped due to intolerable side effects of interferon or had a contraindication to interferon therapy. Ninety-five per cent of the subjects enrolled were being treated by a single hepatologist.

Statistical Analysis

The statistical software IBM/SPSS 19 Base was used to calculate descriptive statistics and correlations (IBM, Chicago, IL, USA). Pearson correlation coefficient (r) was calculated between MUIS-A (including subscales) and CES-D scores. Point bi-serial correlations were calculated between MUIS-A scores, CES-D scores and fibrosis progression when progression was a dichotomous variable. Spearman's correlations were calculated for progression when the degree of progression from one stage of fibrosis to another was rank ordered from −2 to 3. Regression by two stages would be categorized as −2, by 1 stage would be −1. No change in the stage of fibrosis would be categorized as 0. Progression by 1 stage would be categorized as 1, by 2 stages as 2, by 3 stages as 3. Spearman's correlations were calculated between MUIS-A scores, CES-D scores and stage of fibrosis because stage of fibrosis was ordinal. If data were non-normal, and an assumption of the statistic was normality, data were transformed using the Johnson family of transformation.

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