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Watchful Waiting and Depressive Symptoms

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

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

We found a substantial rate of illness uncertainty (54%) and depressive symptoms (40%) in our cohort of patients with CHC on watchful waiting, consistent with the prior studies.[15,16] Surprisingly, the histological data did not correlate with overall illness uncertainty and depressive symptoms. The stage of fibrosis was significantly related to the Complexity subscale of illness uncertainty, but not to the overall illness uncertainty score or other illness uncertainty subscales. Clinicians often make recommendations for the patient to defer treatment and offer reassurances about their minimal and/or stable disease based on liver biopsy. However, reassuring histological data do not seem to lower the patients' feelings of illness uncertainty or depressive symptoms. Recognizing this paradox is important for clinicians and points to the need for additional research about how patients process relevant medical information.

We confirmed the previous finding of the association between overall illness uncertainty and depressive symptoms in patients with CHC following watchful waiting with a similar mean uncertainty score (86.5 vs 87.1).[17] Bailey et al.[17] found that patients with CHC following watchful waiting experience depressive symptoms associated with illness uncertainty. In his study on uncertainty, symptoms, and quality of life in patients with CHC, three constructs of illness uncertainty, Ambiguity, Inconsistency and Complexity, were significantly related to depressive symptoms. Unpredictability, another construct of illness uncertainty, was not significantly related to depressive symptoms.[17] In our study, we also found the Ambiguity and Inconsistency subscale scores to be positively significantly correlated with the CES-D scores, indicating a strong positive relationship between inconsistency and ambiguity in illness and depressive symptoms (See Table 3). The high rates of depressive symptoms and the correlation of the depressive symptoms to illness uncertainty point to the importance of illness uncertainty (especially the Ambiguity and Inconsistency components) as a possible target for intervention.

This correlational study was not designed to show clear cause and effect. While illness uncertainty is correlated with depressive symptoms, it is unclear whether illness uncertainty contributes directly to depressive symptoms or whether those who have depressive symptoms have higher levels of illness uncertainty because of their depressed disposition. It may be the case that those patients with depressive symptoms have higher levels of illness uncertainty and that the correlations are related to personality traits or neuropsychiatric attributes than knowledge of the disease or the extent of disease present. An intervention study to reduce illness uncertainty might help elucidate the causal relationship between illness uncertainty and depressive symptoms if the reduction of illness uncertainty resulted in decreased depressive symptoms. Measuring illness uncertainty before and after liver biopsy, and after treatment might also provide insight into the causal relationship of the two variables.

There is also data showing that patients with CHC experience cognitive impairment (in the areas of concentration, working memory, sustained attention and processing speed) and have cerebral metabolite abnormalities suggestive of frontal–subcortical dysfunction.[22–24] Patients with CHC were found to be impaired on more cognitive tasks than those who cleared hepatitis C, suggesting a direct viral effect. While these studies looked at cognitive function rather than depressive symptoms and illness uncertainty, they raise the questions of whether the depressive symptoms and illness uncertainty seen in patients with CHC might be from a direct viral effect and whether clearance of hepatitis C leads to decreased depressive symptoms and illness uncertainty because of its direct affect on the brain. Answering these questions would require brain imaging to be part of future studies.

Recent new information regarding medication advancements in hepatitis C treatment likely contributed to higher scores on the Inconsistency subscale of the MUIS-A for this population as new therapies were emerging at the time data were collected for this study. Advancement in treatment for HCV-infected patients probably raised concerns about the possible success or failure of viral eradication for this cohort, questions about the possibility of additional treatment advances, and concerns in general regarding the timing of treatment, the possibility of side effects of treatment and the duration of treatment. Some patients may have experienced more uncertainty, while others may have experienced less because hope for cure might have influenced uncertainty levels in both directions.

While the study was not powered to detect statistically significant differences in the scores between the different subgroups (reasons for deferral), the treatment naïve patients had lower mean scores on both the illness uncertainty and depressive symptoms scales. Additional studies with larger samples are required to explore the influence of the reasons for deferral on illness uncertainty and depressive symptoms.

There are no other studies available to provide insight into why the factors other than illness uncertainty might not have been significant in this population. More work is needed to determine the factors that cause and ameliorate patients' feelings of illness uncertainty and depressive symptoms while in watchful waiting. Qualitative studies designed to understand illness uncertainty in patients with hepatitis C on watchful waiting could provide insight into the illness experience of patients in this population. This insight can, in turn, help researchers design intervention studies using the Theory of Uncertainty in Illness, as has been carried out in populations who have other diseases.[25–29] We also hope to reassess illness uncertainty and depressive symptoms in this cohort of patients on follow-up after they have been treated to determine whether those who are cured have a decrease in their illness uncertainty and depressive symptoms.

With more efficacious and tolerable therapies on the horizon, many patients are advised to defer treatment. Given this population's high risk for illness uncertainty and depressive symptoms, part of the informed deferral process should be assessment for illness uncertainty and depressive symptoms.

In conclusion, we found that reassuring histological data were not correlated with less depressive symptoms and illness uncertainty in patients with CHC on watchful waiting. Clinicians who advise patients to defer treatment should be aware of the possibility of the symptoms and address them.

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