Interferon-α Treatment of Hepatitis C Patients With Psychiatric Illness: Evidence-Based Risk-Benefit Assessment

Sir: The clinical management of individuals with comorbid chronic hepatitis C virus (HCV) infection and psychiatric illness is a substantial public health problem.1 At least 50% of patients with HCV suffer from at least 1 psychiatric illness.2,3 Furthermore, the prevalence of HCV in patients with psychiatric illness (10%–20%)1 is 5 to 10 times that in the general U.S. population (2%). Recent advances in the treatment of HCV and the introduction of interferon-α–based therapies in combination with ribavirin have resulted in viral clearance (complete eradication of HCV; absent HCV viral load 6 months after HCV treatment is completed) rates of 50% to 59% of patients with HCV genotype 1 (70% of the U.S. HCV-infected population) and 80% to 90% of patients with HCV genotypes 2 and 3 (20%–30% of the U.S. HCV-infected population).4,5 These viral clearance rates, however, may not be applicable to the HCV-infected population with comorbid psychiatric illness, since most large HCV treatment trials4,5 have excluded patients with any history of psychiatric or substance use disorders. The practice of excluding patients with HCV and psychiatric illness from interferon-α treatment is stigmatizing and will result in substantial morbidity and mortality for a vulnerable population no less deserving of treatment than HCV patients without psychiatric illness. Recently, gastroenterologists have started evaluating patients with HCV and comorbid psychiatric illness and making a risk-benefit assessment for interferon-α treatment. Fearing the precipitation or worsening of preexisting psychiatric illness with interferon-α treatment, gastroenterologists call upon consultant psychiatrists to assist in making a risk assessment regarding the probability of interferon-α–induced neuropsychiatric adverse effects. Several risk factors are thought to increase the probability of interferon-α–emergent neuropsychiatric adverse effects6: a history of any psychiatric illness, a history of substance abuse, a family history of psychiatric illness, and a history of suicidal ideation. The ability to predict the variable interferon-α–induced neuropsychiatric adverse effects, however, remains modest at best due to the lack of systematic large-scale data and the exclusion of patients with psychiatric illness from HCV clinical trials.7 In contrast to the variable influence of these psychiatric risk factors, the decreased likelihood of viral clearance in response to interferon-α is associated with several well-established predictive and additive factors including male gender, African American race, increased body mass index, advanced age (> 40 years), higher HCV viral load, coinfection with human immunodeficiency virus, and HCV genotype 1.8 I propose a comprehensive clinical risk-benefit model (Figure 1) integrating factors pertaining to the likelihood of viral clearance in response to interferon-α and the probable risk of interferon-α–induced neuropsychiatric adverse effects. Figure 1. Risk-Benefit Model for Interferon-α Treatment of Hepatitis C Patients Integrating the Risks of Neuropsychiatric Adverse Events and the Likelihood of Viral Clearance A 35-year-old slender white woman with no history of psychiatric illness who is infected with a low HCV viral load of either genotype 2 or 3 would be a candidate for interferon-α treatment (represented by case 1 in Figure 1). In the case of a 50-year-old obese African American man with a history of psychosis and a substance use disorder who is infected with a high viral load of HCV genotype 1 (represented by case 2 in Figure 1), interferon-α should be delayed in the absence of advancing cirrhosis. While these 2 cases present clinical scenarios at the opposite ends of the risk-benefit spectrum, the risk-benefit profile in the majority of patients with HCV and psychiatric comorbidities is in an intermediate zone. Prophylactic treatment with psychotropics might be offered if the woman in case 1 had a history of major depressive disorder and was infected with a low viral load of HCV genotype 1. Biopsy-demonstrated cirrhosis might be a compelling reason to attempt interferon-α treatment in case 2. Ongoing psychiatric follow-up is certainly indicated when a patient has 1 or more of the psychiatric risk factors listed above. In cases in which a low estimated likelihood of viral clearance of HCV is combined with an intermediate to low probability of psychiatric adverse effects, an evaluation incorporating the patient's interferon-α treatment preference and available psychosocial support can influence the treatment decision. Use of an evidence-based approach in selecting patients for interferon-α treatment is paramount when endeavoring to treat patients with HCV and comorbid psychiatric illness in order to minimize the morbidity and mortality associated with interferon-α (i.e., suicide). This model is intended to assist clinicians in making an individualized and balanced risk-benefit analysis incorporating HCV–disease specific factors as well the potential for psychiatric complications prior to offering interferon-α treatment.