Adherence and mental side effects during hepatitis C treatment with interferon alfa and ribavirin in psychiatric risk groups

Abstract

Chronic HCV infection is the leading cause of chronic liver disease, including cirrhosis and cancer, and the most common indication for liver transplantation. 3 Interferon alfa (IFN-␣) was the first effective treatment of this disease, and the combination with ribavirin increased sustained virologic response rates from 10% to more than 40%. 4,5 The most frequent routes of HCV infection are contaminated human blood products and needle-sharing by individuals with an intravenous drug addiction. 1 Between 36% and 95% of intravenous drug users are infected with HCV before 40 years of age, mostly with genotype 2 and 3. 6-8 Young age and genotype 2 or 3 are regarded as positive predictors of response to IFN-␣ therapy, 4 but former or current drug use as well as mental disorders are considered risk factors for IFN-␣-induced severe psychiatric side effects such as depression, suicidality, or relapse in drug use. [9][10][11][12] In particular, reports of suicide attempts during IFN-␣ therapy and the risk of reinfection led to the Abbreviations: HCV, hepatitis C virus; IFN, interferon; ALT, alanine aminotransferase. From the

Difficulties with interferon treatment in former intravenous drug users

“…Five patients dropped out for unknown reasons; four received antiviral combination therapy while in prison, while the fifth patient reported itching and loss of appetite. Similar dropout rate (31%) was found by Seal et al, 17 and the corresponding figure was even higher (43%) in a German report 13 than the 28% seen in this study. A possible explanation for the lower dropout rate could be that in our hepatology center only 28% of the HCVinfected IDU patients received antiviral treatment, as opposed to 89% in Schaefer et al's study which included non-IDU patients as well.…”

“…12 Both active and former IDUs have a significantly higher dropout rate compared to HCV-infected patients without a history of illicit drug use. 13 Table 2 shows the comparison between IDUs and controls with respect to treatment. Two IDU patients were on methadone maintenance, another two on buprenorphin+naloxon maintenance while undergoing antiviral treatment; none of these four IDUs dropped out.…”

Review article: depression and the use of antidepressants in patients with chronic liver disease or liver transplantation

“…Mild to moderate depression has been reported to develop in 45-60% of HCV patients treated with IFN-a, moderate to severe depression in 15-40%, and major depression in 15-45%. 27,[32][33][34][35] The type of interferon used (pegylated or standard interferon) does not appear to have any differential impact on the prevalence of IFN-a-related depression; however, it does appear to be sensitive to dosage and duration of treatment as well as pre-morbid patient-related risk factors, including a previous history of psychiatric disorders and female sex. 33,36 This phenomenon has an increasingly well-characterised biological basis, with activation of a pro-inflammatory cytokine network and alterations in serotonin and dopamine neurotransmitter metabolism being postulated to exert the mood changes associated with IFN-a.…”

Trained innate immunity: a salient factor in the pathogenesis of neuroimmune psychiatric disorders

“…Although several studies reported that a history of past psychiatric disturbance significantly increased the risk of depression during IFN-α therapy, 18 on the other hand other studies did not find that a past history of depression significantly increases the risk of neuropsychiatric disturbance. 74,[77][78][79] This suggests that having a blunted response is also plausible and that the release of DAMP in presence of (neuro)inflammation could theoretically result in tolerance. However, whether tolerance or training occurs may well be dependent on the nature, doses, duration and frequency of immunostimulatory events.…”