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Depressive Symptoms and Physical/Mental Functioning With Interferon/Ribavirin Treatment of Posttransplant Recurrent Hepatitis C

Received May 20, 2004; revised March 2, 2005; accepted June 10, 2005. From the Dept. of Psychiatry and Behavioral Sciences, Univ. of California Davis Medical Center; Div. of Gastroenterology and Hepatology, Dept. of Internal Medicine, UC Davis Medical Center; and the HIV Treatment Services, CA Medical Facility, CA Department of Corrections. Address correspondence and reprint requests to Dr. Bourgeois, Alan Stoudemire Professor of Psychosomatic Medicine, Dept. of Psychiatry and Behavioral Sciences, UC Davis Medical Center, 2230 Stockton Blvd., Sacramento, CA 95817. e-mail: james.bourgeois{at}ucdmc.ucdavis.edu

Key Words: hepatitis C • interferon • ribavirin • mood disorders • antidepressants • hepatic transplantation

INTRODUCTION

TOP INTRODUCTION METHOD RESULTS DISCUSSION REFERENCES

 
Psychiatric comorbidity is a common problem in both hepatitis C and its treatment with interferon/ribavirin.^1–4 We completed a study of depressive symptoms and physical/mental functioning in 10 liver-transplant patients with recurrent hepatitis C.

METHOD

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We recruited 10 liver-transplant recipients with biopsy-proven recurrent hepatitis C. One stopped treatment at Week 16 for decompensated liver disease. Nine completed at least 24 weeks of treatment; two discontinued before 48 weeks: one at Week 32 (worsening depression) and one at Week 38 (decompensated liver disease).

We derived DSM–IV diagnoses by use of the Structured Clinical Interview for DSM–IV: Clinician Version (SCID–CV).⁵ At 12-week intervals, patients reported on depressive symptoms and physical/mental functioning. Laboratory values for disease status (fibrosis and inflammation) and viral load (100K IU) were also monitored. We recorded psychotropic medication use at baseline and throughout treatment.

Physical/mental functioning was measured with the SF–36, a widely used instrument that measures functional status.⁶ It is a 36-item scale measuring social, physical, and mental functioning. We report scores on SF–36 Physical and Mental Component Scales, which capture patients’ perceptions on these two domains of functioning.⁷ We compared our patients’ scores with the Physical component scale and Mental component scale scores of participants with chronic medical conditions in the Medical Outcomes Study (from Appendix D [p 208] of the SF–36 study⁷).

Depressive symptoms were reported via the Center for Epidemiologic Studies Depression Scale (CES–D), a 20-item self-report scale of depressive symptoms.⁸ Items are scored 0–3, and the total score (0–60) is reported. We adopted a cutoff score of 16 to discriminate between patients with significant depressive symptoms and those without.⁹ Disease activity was denoted by viral load and serum levels of alanine aminotransferase (ALT). We report median scores at all time-points.

RESULTS

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Patients were all male, and had a mean age of 48.9 years. About half our sample had hepatitis C, genotype 1a. The median time since transplant was 47 months. Hepatitis C viral load at baseline was 1.8 MIU; median stage of fibrosis was 2 (Ishak method); median grade of inflammation was 5 (Ishak method). Five met criteria for at least one DSM–IV diagnosis. Two met criteria for opioid dependence; one was receiving methadone maintenance. Other diagnoses were adjustment, depressive, and anxiety disorders. At pretreatment, four were receiving antidepressants. During treatment, we started two on antidepressants.

At baseline, two were above our cutoff for moderate-to-severe depressive symptoms. The median baseline CES–D score was 9.5, in the average range for community samples. Over the next 12 weeks, the patients reported an increase in depressive symptoms that, as a group, almost reached the cutoff of 16. The levels of depressive symptoms dropped back to normal levels and then began to climb, reaching a median of 14.5.

The SF–36 Physical and Mental component scores are detailed in Figure 1. The mean scores on the Physical Component Scale and Mental Component Scale of 3,445 participants in the Medical Outcomes Study (MOS) are represented by dashed lines.¹⁰ Our patients reported normative levels of mental functioning (55.9) at baseline but dropped to 38.9 at 12 weeks—a drop of 2 standard deviations (SD). After rebounding to average levels, the group showed a decline to lower-than-average functioning (Mental Component Scale: 40) at Week 48. These scores parallel the scores on the CES–D, which showed a similar profile. The groups’ physical functioning, as measured by the Physical Component Scale, was below average throughout treatment. Median scores on the Physical Component Scale ranged from a high of 40.7, at baseline, to a low of 30.3 at the final measurement. Our patients reported mental functioning within 1 SD of the Medical Outcomes Study mean of 48.4. Our sample’s reports of physical functioning were generally lower than the Medical Outcomes Study participants with chronic conditions by about to 1 SD.

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FIGURE 1.  Course of Mental and Physical Functioning (SF–36), Viral Load, and ALT Over 48 Weeks of Interferon/Ribavirin Treatment for Recurrent Hepatitis C The mean scores on the Physical component scale and Mental component scale of 3,445 participants in the Medical Outcomes Study (MOS) are represented by dashed lines. HCV: hepatitis C virus; ALT: alanine aminotransferase.

DISCUSSION

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Post-liver-transplant patients in interferon/ribavirin treatment for recurrent hepatitis C showed low levels of depressive symptoms during treatment and follow-up. Despite this, most reported poor physical functioning and slightly higher mental functioning. These patients maintained their mental functioning during treatment. Their level of physical functioning showed a slight decline. Our results suggest that, with careful dosing, adjunctive treatments, and psychiatric and medical monitoring, hepatitis C patients who suffer mental and physical impairment can tolerate and complete rigorous interferon/ribavirin treatment protocols. These patients were able to maintain their mental functioning over the longer term of interferon/ribavirin treatment, although several had significant depressive symptoms despite first-line antidepressant treatment. However, their level of physical functioning, which did not start out at levels typical of healthy individuals, showed a slight decline. As in other studies of chronically ill patients, reports of mental and physical functioning are not well correlated.

ACKNOWLEDGMENTS

 
This work was delivered in part as an oral presentation at the American Transplant Congress Meeting, June 2003, in Washington, DC; and as a poster at the Digestive Disease Meeting (DDW), in Orlando, FL, in May 2003. This study was supported in part by Integrated Therapeutics Group, Inc.

REFERENCES

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1. Dieperink E, Willenbring M, Ho SB: Neuropsychiatric symptoms associated with hepatitis C and interferon alpha: a review. Am J Psychiatry 2000; 157:867–876[Abstract/Free Full Text]
2. Yovtcheva AP, Rifai MA, Moles JK, et al: Psychiatric comorbidity among hepatitis C-positive patients. Psychosomatics 2001; 42:411–415[Abstract/Free Full Text]
3. Diepernink E, Ho SB, Thuras P, et al: A prospective study of neuropsychiatric symptoms associated with interferon-alpha-2b and ribavirin therapy for patients with chronic hepatitis C. Psychosomatics 2003; 44:104–112[Abstract/Free Full Text]
4. Crone C, Gabriel GM: Comprehensive review of hepatitis C for psychiatrists: risks, screening, diagnosis, treatment, and interferon-based therapy implications. Journal of Psychiatric Practice 2003; 9:93–110[CrossRef][Medline]
5. First MB, Spitzer RL, Gibbon M, et al: Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV). Washington, DC, American Psychiatric Press, Inc., 1996
6. Ware JE, Snow KK, Kosinski M, et al: SF-36 Health Survey: Manual and Interpretation Guide. Boston, MA, The Health Institute, New England Medical Center, 1993
7. Ware JE, Kosinski M: SF-36 Physical and Mental Health Summary Scales: A Manual for Users of Version 1, 2nd Edition. Lincoln, RI, QualityMetric, Inc., 2001
8. Radloff LS: The CES-D Scale: a self-report depression scale for research in the general population. Applied Psychological Measurement 1977; 1:385–401[Abstract]
9. Fechner-Bates S, Coyne JC, Schwenk TL: The relationship of self-reported distress to depressive disorders and other psychopathology. J Consult Clin Psychol 1994; 62:550–559[CrossRef][Medline]
10. Tarlov AR, Ware JE Jr, Greenfield S, et al: The Medical Outcomes Study: an application of methods for monitoring the results of medical care. JAMA 1989; 262:925–930[Abstract/Free Full Text]

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