Clinical

Prolonged low-dose peginterferon does not harm brain function: study

Last Updated: 2010-02-05 12:46:48 -0400 (Reuters Health)

By Megan Brooks

NEW YORK (Reuters Health) - In patients with advanced chronic hepatitis C, long-term low-dose peginterferon does not impair cognition, according to a cognitive substudy from the HALT-C trial.

Clinicians have long suspected that interferon causes dose-dependent neuropsychiatric side effects, including mood changes, emotional distress and difficulty thinking, HALT-C investigator Dr. Robert J. Fontana of the University of Michigan, Ann Arbor, noted in a telephone interview with Reuters Health.

Therefore, Dr. Fontana and his colleagues looked for such patterns in 129 of their HALT-C participants. Overall, the HALT-C trial (Hepatitis C Antiviral Long-Term treatment against Cirrhosis) had included 1050 patients with advanced chronic hepatitis C virus (HCV) infection who were randomized to receive low-dose peginterferon alfa-2a (90 micrograms/week) or no treatment for 3.5 years after failing to respond to standard peginterferon/ribavirin therapy. The trial showed that long-term low-dose peginterferon does not prevent disease progression. (See Reuters Health Report, Dec. 4, 2008.)

"Based on this finding, along with several other studies, it is no longer being proposed as a way to treat hepatitis C patients who did not clear virus," Dr. Fontana said in the interview.

The analysis of mood and cognitive disturbances involved 66 patients assigned to maintenance low-dose interferon and 63 patients in the control group. All of them completed a battery of neuropsychological tests and the Beck Depression Inventory (BDI) before treatment and at 12 months (61 treated, 56 untreated), 24 months (57 treated, 49 untreated), 36 months (47 from each group), and 48 months (41 from each group).

Patients averaged 51.2 years of age; 67% were male and 42% had cirrhosis. The mean pretreatment global deficit score (GDS) was 0.68. In 28%, the GDS score was 1.0 or greater, indicating cognitive impairment. The mean BDI score was 6.4, and 25.6% of patients met criteria for mild depression.

After accounting for baseline GDS scores, the overall mean GDS scores did not change significantly with time (p = 0.46) or with treatment group (p = 0.49), nor did the proportion of subjects with cognitive impairment, the researchers note in an advance online issue of the American Journal of Gastroenterology.

Furthermore, the authors add, "The frequency and severity of cognitive impairment did not increase in subjects with and without baseline impairment and were also not influenced by treatment."

"What we found was that there was not a decline in cognitive function in either group," Dr. Fontana added.

There was also "no discernible relationship between the cumulative exposure to peginterferon and cognitive function," the report indicates.

Likewise, and "contrary to expectations," Beck Depression scores did not significantly increase over time (p = 0.60), nor did they vary by treatment assignment (p = 0.74).

These findings, Dr. Fontana said, "are reassuring in that if there are the occasional patients that doctors need to use long-term interferon -- for whatever the clinical circumstances are -- that it's going to be okay from a cognitive and brain perspective."

Along with their interest in the effects of maintenance therapy with interferon, the authors also wanted to analyze how progression of liver disease would affect cognition. "As patients with liver disease get sicker and develop signs of liver failure, for many years, physicians have believed that their cognition and speed of mental processing declined in parallel with liver function," Dr. Fontana added.

But in fact, the frequency and severity of cognitive impairment did not differ between patients with and without objective worsening of their liver disease.

"This really is an important finding," Dr. Fontana said. "If confirmed in other longitudinal studies, further clarification of the definition of minimal hepatic encephalopathy and other cognitive disorders associated with chronic liver disease may be warranted."

It's possible, they add, that the association between liver disease progression and cognitive decline is "better represented by a tipping point rather than by a linear function. In other words, cognitive decline may be precipitous at a certain stage of liver failure, rather than continuously declining as the disease progresses."

Am J Gastroenterol 2010.