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Objective: Depression is a frequent side effect of interferon therapy in patients with chronic hepatitis C (CHC). The aim of this study was to identify baseline and on-treatment predictors of depression in CHC patients receiving peginterferon and ribavirin., Methods: In total, 201 prior nonresponders with advanced fibrosis were treated with peginterferon alfa-2a and ribavirin for 24 wk in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis trial. Of these, 74 continued on antiviral therapy through week 48. Mood states were assessed with the Beck Depression Inventory II and the Composite International Diagnostic Interview. Plasma cortisol and whole blood serotonin levels were measured in 101 subjects at weeks 0, 4, 24, 48, and 72., Results: The incidence of interferon-induced depression was 23% and 42% at weeks 24 and 48, respectively. Although 22% of patients had baseline depression, the absence of a week 20 virological response was the only independent predictor of interferon-induced depression at week 24 (P = 0.0009). Plasma cortisol levels did not change during treatment nor correlate with depression. In contrast, whole blood serotonin/platelet levels significantly decreased during treatment, but did not correlate with interferon-induced depression through week 24 (P = 0.35), nor through week 48 (P = 0.51)., Conclusion: Depression during peginterferon and ribavirin therapy was associated with a lower antiviral response. The significant reduction in whole blood serotonin levels over time suggest that further studies of the serotonergic pathway are warranted to identify the mediators of interferon-induced depression.

Unlabelled: Treatment of chronic hepatitis C with pegylated interferon (peginterferon) and ribavirin can cause or exacerbate depression but its effects on cognitive function are largely unknown. The aim of this study was to determine whether treatment with peginterferon and ribavirin adversely impacts cognitive function in patients with chronic hepatitis C. Prior nonresponders to interferon were retreated with peginterferon alfa-2a and ribavirin for 24 (n=177) or 48 weeks (n=57) in the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis trial. Cognitive function was prospectively assessed using a battery of 10 standardized neuropsychological tests at weeks 0, 24, 48, and 72. Cognitive impairment was defined based upon a global deficit score. The Beck Depression Inventory and Brief Symptom Inventory were used to assess mood status. The 57 subjects who completed 48 weeks of antiviral therapy reported significant increases in difficulty concentrating, emotional distress, and symptoms of depression, all of which improved after cessation of therapy [P<0.0001, analysis of variance (ANOVA)]. Nonetheless, the frequency of cognitive impairment did not increase during the first 24 weeks of treatment in 177 patients (34% versus 32%, P=0.64) nor in the 57 patients completing 48 weeks of treatment (P=0.48, ANOVA)., Conclusion: Retreatment of prior non-responders with peginterferon and ribavirin was not associated with objective evidence of cognitive impairment as measured by a comprehensive battery of neuropsychological tests. The lack of cognitive impairment is reassuring and suggests that self-reported symptoms of cognitive dysfunction are more likely related to the systemic and psychiatric side effects of antiviral treatment rather than measurable changes in cognition.

Background & Aims: Hepatic steatosis often is observed in patients with chronic hepatitis C and has been reported to be associated with hepatic fibrosis and impaired treatment response in some studies. Our aim was to determine the prevalence of and risk factors for hepatic steatosis among Hepatitis C Antiviral Long-term Treatment against Cirrhosis patients, and to determine the relationship between steatosis, fibrosis, and sustained virologic response (SVR) to re-treatment with pegylated interferon and ribavirin., Methods: Baseline data from 1143 Hepatitis C Antiviral Long-term Treatment against Cirrhosis patients, with a mean body mass index of 30, 5% with genotype 3, 38% with cirrhosis, and 24% with diabetes were analyzed., Results: Steatosis scores of 0, 1, 2, 3, and 4 were observed in 19%, 42%, 30%, 8%, and 1% of patients, respectively. High body mass index, triglyceride and alanine aminotransferase levels, and genotype 3 were associated with higher grades of steatosis. Among nondiabetic patients, steatosis scores of 0-2 but not scores of 3-4 were associated significantly with cirrhosis. For diabetic patients, there was no association between steatosis and cirrhosis. Similarly, steatosis scores of 2-4 were associated with a lack of SVR among nondiabetic but not among diabetic patients., Conclusions: In this cohort with predominantly hepatitis C virus genotype 1 infection, steatosis was associated strongly with metabolic factors that contribute to nonalcoholic fatty liver disease. Steatosis correlated with increasing stages of fibrosis up to but not including cirrhosis. Steatosis had a negative impact on SVR among nondiabetic but not diabetic patients. The discordant findings between nondiabetic and diabetic patients indicate that these 2 groups should be considered separately when analyzing metabolic factors and liver disease outcomes.