Cognitive function does not worsen during long-term low-dose peginterferon therapy in patients with chronic hepatitis C.
OBJECTIVE
Neuropsychiatric toxicity is a common dose-limiting side effect of interferon therapy. The primary aim of this study was to determine whether patients receiving long-term low-dose peginterferon therapy had a higher incidence of cognitive side effects compared with untreated patients enrolled in the Hepatitis C Antiviral Long-Term treatment against Cirrhosis (HALT-C) Trial.


METHODS
A total of 129 patients with chronic hepatitis C and advanced fibrosis completed a battery of 10 neuropsychological tests and the Beck Depression Inventory at pretreatment baseline and at months 12, 24, 36, and 48 while receiving long-term peginterferonalpha2a (90 microg/week) or no therapy during the randomized phase of the HALT-C Trial. Cognitive impairment was defined as a global deficit score (GDS) > or = 1.0.


RESULTS
The mean age was 51.2 years, 67% were male, and 42% had cirrhosis. After accounting for baseline GDS scores, the mean GDS scores did not significantly change over time (P=0.46) nor with treatment group (P=0.49). Cognitive function was also not influenced by medication adherence in the 66 patients receiving maintenance peginterferon (P=0.14) after controlling for baseline GDS scores and time. Beck Depression scores did not significantly increase over time (P=0.60), nor did they vary by treatment group (P=0.74). Although 32% of patients experienced objective worsening of their liver disease during follow-up, the frequency and severity of cognitive impairment did not differ in those with and without disease progression (P=0.71).


CONCLUSIONS
Measures of cognitive function were neither influenced by low-dose peginterferon treatment nor with objective evidence of liver disease progression in patients with advanced chronic hepatitis C prospectively followed up for 3.5 years.
Fontana
Robert J
RJ
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, 3912 Taubman Center, Ann Arbor, MI 48109-0362, USA. rfontana@med.umich.edu
Bieliauskas
Linas A
LA
Back-Madruga
Carla
C
Lindsay
Karen L
KL
Litman
Heather J
HJ
Lok
Anna Sf
AS
Kronfol
Ziad
Z
D000704:Analysis of Variance; D000998:Antiviral Agents / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects*; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000523:psychology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000150:complications; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011994:Recombinant Proteins
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a