Difficult-to-Treat Hepatitis C Patients Respond to Pegylated Interferon-Alpha/Ribavirin


ESSEN, Germany, Dec. 5 -- Pre-existing psychiatric comorbidities -- including depression and schizophrenia -- did not worsen when hepatitis C patients were treated with pegylated interferon-alpha and ribavirin.
Action Points --->
Explain to interested patients that this report suggests that patients with hepatitis C who have psychiatric comorbidities respond well to standard antiviral therapy.
Explain, too, that this study suggests that a special interdisciplinary approach that allows for close monitoring is important when treating patients who have both hepatitis C and psychiatric diagnoses.
Moreover, those comorbidities did not adversely affect sustained virological response to treatment, according to Martin Schaefer, M.D., of Essen Hospitals, and colleagues.
But the key to success in this difficult-to-treat population was a multidisciplinary approach in which hepatologists worked closely with psychiatrists, the researchers said. They strongly recommended "offering interdisciplinary treatment units in order to optimize adherence and response rates and to manage effects."
The study enrolled 70 patients with chronic hepatitis C infection; 22 of them had psychiatric disorders, 18 were on methadone maintenance, 13 were former drug users, and 17 were free of psychiatric or substance abuse diagnoses.
All patients received pegylated interferon-alpha subcutaneously (57 received 1.5 mg/kg per week and 13 received 180 mg/kg per week) plus ribavirin 800 to 1,200 mg/day orally according to body weight. Genotypes 2 and 3 received antiviral treatment for 24 weeks; genotypes 1 and 4 were treated for 48 weeks.
Depression was measured at baseline and during treatment using the Montgomery-Asberg Depression Rating Scale (MADRS), which defines mild depression as a score between 7 and 19, moderate depression as 20 to 33, and more than 33 as severe depressive syndrome.
Psychotic symptoms were evaluated with the Brief Psychiatric Rating Scale (BPRS) -- a 7-point severity scale that rates individual symptoms from 0 to 7, with 7 indicating extremely severe.
Sustained virological response was found in 58.6% of all patients, with the individual rates breaking down this way: 50% of psychiatric patients, 72.2% of those taking methadone, 53.8% of former drug users, and 58.8% of controls, according to findings published in the October issue of Hepatology.
Not surprisingly, the methadone patients and the former drug users had higher dropout rates -- 27.8% in the methadone group and 15.4% among former drug users versus 9.1% for psychiatric patients and 5.9% among controls. Of the 70 patients enrolled in the study, only ten dropped out.
During treatment, MADRS scores increased significantly for all patients, except those on methadone (P<0.001 compared with baseline for controls, P=0.006 for psychiatric patients, and P=0.039 for former drug users).
Methadone patients and former drug users had the highest BPRS scores at baseline and during treatment. However, only those in the control group had psychiatric changes during treatment that approached significance (P=0.055).
Dr. Schaefer said the study was limited by its small size and by the exclusion of homeless patients, those with dementia and other organic brain diseases, and those with ongoing drug or alcohol abuse.
Nonetheless, in an editorial that accompanied the study, Cynthia M.A. Geppert, M.D., Ph.D., M.P.H., and Sanjeev Arora, M.D., both of the University of New Mexico, said it was a pivotal study.
They wrote that close to 20% of patients with severe mental illness are believed to be HCV-positive, yet hepatologists have been reluctant to treat these patients because of concerns that interferon would exacerbate depression as well as anxiety, suicidality, mania, and psychosis.
The study by Schaefer et al, as the first prospective study in this population, supports the "development of evidence-based thinking regarding whether mental health disorders should continue to be considered as exclusions for therapy with pegylated interferon and ribavirin," Drs. Geppert and Arora wrote.
Dr. Schaeffer reported no potential conflicts of interest but a co-author disclosed that he is a consultant for Pfizer and AstraZeneca and received grants from Janssen-Cilag, Bristol-Myers Squibb, and Lilly. They did not disclose a funding source for the study.
Primary source: HepatologySource reference:Schaefer M, et al "Hepatitis C treatment in 'difficult-to-treat' psychiatric patients with pegylated interferon-alpha and ribavirin: response and psychiatric side effects" Hepatology 2007; 46: 991-998. Additional source: HepatologySource reference: Geppert C, Arora S, "Widening the door: the evolution of hepatitis C treatment in patients with psychiatric disorders" Hepatology 2007; 46: 957-959.