0
Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

1
Letter to the Editor   |    
Interferon for Hepatitis C Patients With Psychiatric Disorders
MUHAMAD ALY RIFAI, M.D.; BAHMAN BOZORG, M.D.; DONALD L. ROSENSTEIN, M.D.
Am J Psychiatry 2004;161:2331-2332. doi:10.1176/appi.ajp.161.12.2331

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-α) treatment of patients with chronic hepatitis C virus infection. Reluctance to treat patients with hepatitis C virus and psychiatric illnesses with IFN-α 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-α had been made, Dr. Onyike et al. appropriately raised the question of whether he should be offered yet another trial of IFN-α in the future despite neuropsychiatric toxicity associated with his first two courses of IFN-α. 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-α with ribavirin achieves sustained virological response (i.e., complete eradication of hepatitis C virus; absent hepatitis C virus viral load 6 months after IFN-α 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 (35) 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-α treatment (79). 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 (35). 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-α-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-α difficult to justify.

The practice of excluding patients with hepatitis C virus and psychiatric illnesses from IFN-α 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-α treatment. Despite the absence of a consensus regarding when IFN-α 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-α treatment.

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
[PubMed]
[CrossRef]
 
Poynard T, Yuen M-F, Ratziu V, Lung Lai C: Viral hepatitis C. Lancet  2003; 362:2095–2100
[PubMed]
[CrossRef]
 
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-α2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med  2004; 140:346–355
[PubMed]
 
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
[PubMed]
[CrossRef]
 
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
[PubMed]
[CrossRef]
 
Strader D: Understudied populations with hepatitis C. Hepatology 2002; 36:S226-S236
 
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
[PubMed]
[CrossRef]
 
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
[PubMed]
[CrossRef]
 
Fried MW: Side effects of therapy of hepatitis C and their management. Hepatology 2002; 36(suppl 1):S237-S244
 
+

References

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
[PubMed]
[CrossRef]
 
Poynard T, Yuen M-F, Ratziu V, Lung Lai C: Viral hepatitis C. Lancet  2003; 362:2095–2100
[PubMed]
[CrossRef]
 
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-α2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med  2004; 140:346–355
[PubMed]
 
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
[PubMed]
[CrossRef]
 
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
[PubMed]
[CrossRef]
 
Strader D: Understudied populations with hepatitis C. Hepatology 2002; 36:S226-S236
 
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
[PubMed]
[CrossRef]
 
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
[PubMed]
[CrossRef]
 
Fried MW: Side effects of therapy of hepatitis C and their management. Hepatology 2002; 36(suppl 1):S237-S244
 
+
+

CME Activity

There is currently no quiz available for this resource. Please click here to go to the CME page to find another.
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe



Web of Science® Times Cited: 5

Related Content
Books
The American Psychiatric Publishing Textbook of Substance Abuse Treatment, 4th Edition > Chapter 41.  >
APA Practice Guidelines > Chapter 4.  >
The American Psychiatric Publishing Textbook of Substance Abuse Treatment, 4th Edition > Chapter 41.  >
The American Psychiatric Publishing Textbook of Substance Abuse Treatment, 4th Edition > Chapter 41.  >
The American Psychiatric Publishing Textbook of Substance Abuse Treatment, 4th Edition > Chapter 41.  >
Topic Collections
Psychiatric News
APA Guidelines
PubMed Articles