Coinfection

HCV Does Not Worsen Cognitive Impairment in HIV Positive People without Advanced Liver Damage

Coinfection with hepatitis C virus (HCV) does not appear to contribute to neurocognitive impairment in people with HIV who do not have advanced liver disease, according to results from the CHARTER study published in the December 10 online edition of Neurology.

David Clifford from Washington University School of Medicine and fellow investigators looked at the effect of HCV on neurocognitive performance among people with chronic HIV infection in the ongoing CHARTER (CNS HIV Antiretroviral Therapy Effects Research) study.

A total of 1582 CHARTER participants were tested for HCV antibodies; HCV RNA was measured in 346 people who tested positive. Neurocognitive test results were compared between 408 HIV/HCV coinfected participants and 1174 people with HIV alone. The researchers also analyzed a subset of 160 coinfected and 707 HIV monoinfected participants without serious comorbid neurological conditions that might impair performance.

They also controlled for potentially confounding factors including injection drug use, education level, and liver function that could influence cognitive performance. Severe liver dysfunction can lead to hepatic encephalopathy when the liver cannot filter out toxins such as ammonia, but this study focused on milder cognitive impairment revealed by neurocognitive testing.

The study found that a similar proportion of participants showed neurocognitive impairment in the HIV/HCV coinfected and HIV monoinfected groups. Participants with HCV showed a small advantage in verbal scores in a univariate analysis, but this was no longer significant in a multivariate analysis. Among the subset of participants without comorbidities, scores in all 7 neurocognitive function domains did not differ by HCV status.

"In HIV-infected patients, HCV coinfection does not contribute to neurocognitive impairment, at least in the absence of substantial HCV-associated liver damage, which was not evident in our cohort," the study authors concluded.

Below is an edited excerpt from a Washington University news release describing the study findings in more detail.

Hepatitis C Ruled Out as Cause of Mental Impairment In HIV Patients

December 11, 2014 -- Advances in treatment for human immunodeficiency virus (HIV) have made it possible for people with HIV to survive much longer. As they age, however, many experience impaired thinking, memory loss, mood swings and other evidence of impaired mental function. 

To stop these changes, scientists have to learn what is causing them. One possibility researchers are considering is that long-term infections with other pathogens, common in HIV-positive patients, are affecting the brain. But a new study has eliminated one of their prime suspects: the hepatitis C virus, which infects about one in every three HIV-positive patients in the United States.

The research, conducted by a team that includes scientists at Washington University School of Medicine in St. Louis, appeared Dec. 10 in Neurology.

"Hepatitis C infection has serious long-term side effects, such as damage to the liver, but our research indicates that it does not affect the brain," said lead author David Clifford, MD, of Washington University. 

The research was conducted as part of the CNS HIV Anti-retroviral Therapy Effects (CHARTER) study, a multicenter collaborative that is examining the long-term neurological effects of HIV infection.

Hepatitis C most commonly infects illicit drug users who share needles used to inject the drugs. Drug abuse can harm the brain, making it difficult to determine whether hepatitis C or problems caused by drug use contribute to brain impairment in patients with both HIV and hepatitis C.

To answer this question, Clifford and his colleagues studied 1,582 HIV patients, 408 of whom were also infected with hepatitis C. Each patient received a detailed neuropsychological exam devised by Clifford and other CHARTER researchers to detect signs of HIV-associated mental deficits.

The exam takes two to 2.5 hours, and includes written examinations taken by the patient and physical exams given by medical professionals. Patients are tested for their ability to express themselves, to make decisions, to learn and retain new information using multiple types of memory, and to move the body and control muscles. 

"In all, we looked at seven domains of mental function," said Clifford, who is the Melba and Forest Seay Professor of Clinical Neuropharmacology in Neurology. "We studied their overall performance and looked at each domain individually and found no evidence that the group with hepatitis C performed worse."

According to Clifford, this was particularly impressive because the participants in the group with hepatitis C were older, had less education and had lower scores on tests of reading, comprehension, spelling and math.

With hepatitis C eliminated, Clifford and his colleagues are turning their attention to the immune responses triggered by HIV in the brain and the bowel during the initial stages of infection. He and others believe these early responses, which include bursts of inflammation, lead to chronic inflammation that adversely affects the brain.

"If a hepatitis C infection gets to the point where it damages liver function, the resulting inflammation might well contribute to mental impairment," Clifford said. "Beyond that, though, it doesn’t seem to be an active collaborator in the harm HIV does to the brain."

12/17/14

Reference

DB Clifford, F Vaida, Y-T Kao, et al. Absence of neurocognitive effect of hepatitis C infection in HIV-coinfected people. Neurology. December 10, 2014 (Epub ahead of print).

Other Source

MC Purdy, Washington University School of Medicine. Hepatitis C Ruled Out as Cause of Mental Impairment In HIV Patients. News release. December 11, 2014.