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Interferon for Hepatitis C Patients With Psychiatric Disorders

To the Editor: We read with great interest the recent clinical case conference by Chiadi U. Onyike, M.D., M.H.S., et al. (1). Practicing psychiatrists are increasingly asked to assist gastroenterologists in making risk-benefit assessments regarding interferon alpha (IFN-) treatment of patients with chronic hepatitis C virus infection. Reluctance to treat patients with hepatitis C virus and psychiatric illnesses with IFN- is certainly understandable because of concerns of precipitating or worsening psychiatric comorbidity. However, the exclusion of patients with comorbid hepatitis C virus infection and psychiatric illnesses is not justifiable without a comprehensive risk-benefit analysis.

Although Mr. C came to the psychiatry service after the decision to treat him with a second course of IFN- had been made, Dr. Onyike et al. appropriately raised the question of whether he should be offered yet another trial of IFN- in the future despite neuropsychiatric toxicity associated with his first two courses of IFN-. The authors suggested that the answer was yes. We contend that critical information regarding this determination is missing from the case discussion. Specifically, Mr. C’s hepatitis C virus genotype and viral load bore directly on this risk-benefit analysis.

It is estimated that 70% of the U.S. population with hepatitis C virus is infected with genotype 1, and the remaining 20%–30% are infected with genotypes 2 or 3 (2). Pegylated IFN- with ribavirin achieves sustained virological response (i.e., complete eradication of hepatitis C virus; absent hepatitis C virus viral load 6 months after IFN- treatment is completed) in 50%–59% of the patients with genotype 1 and 80%–90% of the patients with genotypes 2 and 3 (2, 3). These sustained response rates, however, were derived from large clinical trials (3–5) and may not be applicable to the hepatitis C virus-infected population with psychiatric illness because these trials excluded all patients with a history of psychiatric illness and substance abuse. The following factors have all been associated with reduced sustained virological response rates: male gender, African American race, high body mass index, advanced age (>40 years), high hepatitis C viral load, and hepatitis C virus genotype 1 (6).

Similarly, several risk factors are thought to increase the probability of emergent psychiatric comorbidity during IFN- treatment (7–9). Those factors include the following: a previous history of any psychiatric illness, a history of substance abuse, a family history of psychiatric illnesses, and a history of suicidal ideation (8). Although these factors are not well validated, they were used as exclusion criteria in several large hepatitis C virus clinical trials (3–5). The patient described by Dr. Onyike et al. would have had an estimated 50%–60% chance of achieving sustained virological response if infected with genotypes 2 or 3 but only a 10%–20% chance of achieving sustained virological response if infected with genotype 1. These predictions factor in the lower remission rates for an African American man and for patients with a higher body mass index (6). Furthermore, this patient would have had a greater likelihood of developing psychiatric complications because of his previous and family psychiatric histories (7, 9). The high probability of IFN--induced psychiatric comorbidity coupled with a hepatitis C virus genotype 1 and a high viral load would make the case for a future course of IFN- difficult to justify.

The practice of excluding patients with hepatitis C virus and psychiatric illnesses from IFN- treatment is stigmatizing (8) and will result in substantial morbidity and mortality for a vulnerable population no less deserving of treatment than patients with hepatitis C virus without psychiatric illnesses. Nonetheless, evidence-based patient selection is paramount when endeavoring to treat patients with comorbid psychiatric illnesses and hepatitis C virus to minimize the morbidity and mortality associated with IFN- treatment. Despite the absence of a consensus regarding when IFN- treatment should be withheld (either because of the low estimated likelihood of sustained virological response and/or the high probability of psychiatric morbidity), clinicians must still make an individualized and balanced risk-benefit analysis incorporating hepatitis C virus disease-specific factors as well the potential for psychiatric complications before offering IFN- treatment.

References

1. Onyike CU, Bonner JO, Lyketsos CG, Treisman GJ: Mania during treatment of chronic hepatitis C with pegylated interferon and ribavirin (clin case conf). Am J Psychiatry 2004; 161:429–435[Free Full Text]
2. Poynard T, Yuen M-F, Ratziu V, Lung Lai C: Viral hepatitis C. Lancet 2003; 362:2095–2100[CrossRef][Medline]
3. Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, Ramadori G, Bodenheimer H Jr, Bernstein D, Rizzetto M, Zeuzem S, Pockros PJ, Lin A, Ackrill AM: Peginterferon-2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004; 140:346–355[Abstract/Free Full Text]
4. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M-H, Albrecht JK: Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001; 358:958–965[CrossRef][Medline]
5. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Haussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J: Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002; 347:975–982[Abstract/Free Full Text]
6. Strader D: Understudied populations with hepatitis C. Hepatology 2002; 36:S226-S236
7. Dieperink E, Ho SB, Thuras P, Willenbring ML: 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]
8. Edlin BR, Seal KH, Lorvick J, Kral AH, Ciccarone DH, Moore LD, Lo B: Is it justifiable to withhold treatment for hepatitis C from illicit-drug users? N Engl J Med 2001; 345:211–214[Free Full Text]
9. Fried MW: Side effects of therapy of hepatitis C and their management. Hepatology 2002; 36(suppl 1):S237-S244

This article has been cited by other articles:

				M. A. Rifai Ethical Impasses in the Care of Patients With Hepatitis C Psychosomatics, December 1, 2006; 47(6): 540 - 541. [Full Text] [PDF]

				M. A. Rifai and D. L. Rosenstein Hepatitis C and Psychiatry Focus, April 1, 2005; 3(2): 194 - 202. [Abstract] [Full Text] [PDF]

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