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

Abstract and Introduction

Abstract

Background and Aims: New therapies for HCV are rapidly emerging and providers are advising select patients to defer treatment and elect 'watchful waiting'. During the watchful waiting period, patients have been shown to have high rates of illness uncertainty and depression. We sought to answer the question of whether reassuring histological data (showing minimal fibrosis or no fibrosis progression over time) is associated with less illness uncertainty and depressive symptoms.

Methods: This was a single-centre outpatient prospective cohort study to determine whether stage of fibrosis, fibrosis progression and reasons for treatment deferral were related to illness uncertainty and depressive symptoms in patients following watchful waiting.

Results: Illness uncertainty was significantly related to depressive symptoms (r = 0.49, P < 0.01). More than half of the participants (54%) had moderate levels of uncertainty. About 40% of the participants were at risk for clinical depression (21.7% at mild to moderate risk and 18.5% at high risk). Treatment naïve subjects had lower mean scores on both the CES-D (depressive symptoms measure) and the MUIS-A (illness uncertainty measure) total score, MUIS-A Ambiguity subscale and MUIS-A Inconsistency subscale than subjects who failed treatment or were interferon intolerant or ineligible. Surprisingly, liver fibrosis stage and progression were not significantly associated with overall illness uncertainty or depressive symptoms.

Conclusion: Patients with chronic hepatitis C on watchful waiting are at high risk for significant illness uncertainty and depressive symptoms. Reassuring histological data does not seem to correlate with less uncertainty or depressive symptoms.

Introduction

Hepatitis C (HCV) is a worldwide public health problem, with an estimated 130–170 million people infected and approximately 4 million new infections each year.[1] Chronic hepatitis C (CHC) is the leading indication for liver transplantation and leads to more than 15 000 hepatitis C-related deaths annually in the United States.[2,3] While CHC can lead to significant morbidity and mortality, disease can progress slowly or not at all in some patients with mean time to cirrhosis of 30 years and nonprogression in almost one-third of patients.[4–10]

For slow or nonprogressors, a reasonable management strategy is watchful waiting (treatment is deferred with at least annual visits with a medical provider for monitoring). This management strategy is especially relevant as rapidly emerging new therapies, still in clinical trials and not yet commercially available, are promising high cure rates with better side-effect profiles.

While advising patients on management options, clinicians weigh the individual's chance of a sustained viral response, the stage and rate of progression of their disease, the risk of severe side effects and patient preference. Informed deferral of treatment requires a discussion with the patient of the risks and benefits of watchful waiting[11] Although CHC may progress slowly, patients are aware of potential complications. This can lead to illness uncertainty as they are unsure about what will happen to them over time with a disease that offers few cues to progression until symptoms appear.

Illness uncertainty is defined by Mishel as the inability to determine the meaning of illness-related events and occurs if the patient cannot structure a framework in which to place those events because of insufficient cues to assign value to the experience or predict the outcome.[12,13] Uncertainty exists in illness because of unpredictable and inconsistent symptom experience, the unknown future of living with debilitating effects of an illness and/or the continual questions about the possibility of disease recurrence or exacerbation.[12] The four domains of uncertainty described by Mishel Uncertainty in Illness Scale (MUIS-A) are Ambiguity, Complexity, Inconsistency and Unpredictability (see Table 1 ).[14]

In addition to illness uncertainty, depressive symptoms are also common (rates of 35–59%) in patients with untreated CHC, even in the absence of active medical or psychiatric comorbidities.[15,16] Illness uncertainty and time since diagnosis were found to be related to depressive symptoms in these patients.[17,18] In a study of 135 individuals with CHC, subjects who knew their diagnosis for more than 5 years had higher scores for anxiety and depressive symptoms than those recently diagnosed.[18]

Patients with CHC experience illness uncertainty and depressive symptoms, with time from diagnosis being a risk factor for depressive symptoms. The stage of fibrosis and progression of disease play a large part in the physician's management recommendation. However, there is no data on whether the histological data (stage of fibrosis and disease progression) affect illness uncertainty and depressive symptoms in patients with CHC on watchful waiting. We hypothesized that reassuring histological data (low stage of fibrosis and stable histology) would decrease illness uncertainty and depressive symptoms.

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