Hepatitis C can worsen cognitive deficits caused by HIV infection and methamphetamine abuse

Infection with hepatitis C virus can worsen the deficits in brain function caused by HIV and by abuse of methamphetamine (‘crystal meth’), according to the results of a cross-sectional study presented in the 26^th April edition of Neurology.

The study suggests that when all three factors are combined in one individual, there is an enhanced risk of psychological impairment.

Investigators from San Diego recruited 430 men and women for their study of the effects of HIV and methamphetamine use on psychological impairment. After finding that many of their cohort were also infected with hepatitis C, particularly among those who had a history of methamphetamine abuse, they extended their analysis to include this co-infection.

“Observations from the current study are consistent with the hypothesis that hepatitis C virus infection has an independent adverse effect on neuropsychiatric performance,” conclude the researchers. “The effects of hepatitis C virus, HIV and methamphetamine use are additive.”

The researchers used a range of neuropsychiatric tests to assess the participants’ learning, recall, attention and working memory, speeded information processing, verbal fluency, abstraction and problem solving, and motor ability. They combined the results of these tests into a ‘global deficit score’, reflecting the degree of cognitive impairment in each participant.

They compared the numbers of patients with cognitive deficit against the number of risk factors, finding that the more risk factors a participant had, the greater their chance of having a deficit (p

When they divided the global score into its components, they found a significant relationship between the number of risk factors and deficits in learning, recall, motor skills and abstraction and problem solving (all p

The investigators also broke down their analysis by risk factor using 'multivariate regression'. All other things being equal, hepatitis C infection was significantly associated with global cognitive deficits (p

The investigators did not find any link between the stage of liver damage and cognitive deficits, although this was assessed by measuring the blood levels of liver enzymes and not by the more accurate method of taking a liver biopsy.

HIV infection was independently associated with global deficit scores (p

Similarly, methamphetamine dependence was linked to global deficits (p

Study participants with more risk factors also tended to drink more alcohol (p

Since the study did not set out to assess hepatitis C infection, the numbers of patients without hepatitis C virus infection was unevenly distributed. Only two participants had hepatitis C but did not have HIV or a history of methamphetamine abuse, while only eight were co-infected with hepatitis C and HIV but did not have methamphetamine abuse as a risk factor.

As noted in an accompanying editorial, “while the authors used statistical methods to control for an examine these effects, different methods are needed: a sufficient number of participants per cell and equivalent alcohol consumption by group. The authors note that a prospective study is needed.”

The investigators speculate that hepatitis C virus may cause damage to brain cells and bring about cognitive impairment, by infecting cells within the brain itself. Alternatively, the virus could infect cells that move into the brain from the blood, such as monocytes, where it could increase the rate of HIV replication. They do not offer a hypothesis for the additional effect of methamphetamine abuse.

The editorial concludes: “It is evident that hepatitis C virus may cause major cognitive impairment among those infected. However, because the majority of hepatitis C virus-infected adults have additional risk factors for cognitive impairment such as drug or alcohol abuse or HIV infection, the prevalence of cognitive impairment among these persons may be disconcertingly high.”