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 (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-α 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-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.