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Effect of interferon-free therapy on cognition in HCV and HCV/HIV infection: A pilot study
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- SVR in HCV & HCV/HIV Coinfected Shows Improved Cognitive Function 12 weeks After Treatment Followup
"trial with HCV and HCV/HIV coinfected patients andplanned HCV treatment.....all patients were HCV-RNA-negative at week 12 aftertreatment completion....Our first
follow-up data support this assumption, showing animprovement in those cognitive domains that wereimpaired before HCV eradication......At baseline, thepatient group showed significantly poorerperformance in the domains of visual and workingmemory, processing speed, attention, and executivefunctioning (table).We did not observe a differencebetween monoinfected and coinfected patients......significant (p <0.05)improvement in the domains visual memory, processingspeed, attention, and executive functioning. Inaddition, we observed a significant (p =0.022)decline in self-reported fatigue severity. There wasno significant change in the level of depression, butan increase in self-reported quality of life.”
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Effect of interferon-free therapy on cognition in HCV and HCV/HIV infection: A pilot study
Neurology
Published Ahead of Print on December 21, 2016
Felix Kleefeld, Sophie Heller, Heiko Jessen, et al.
Approval of direct-acting antivirals against the hepatitis C virus (HCV) has dramatically changed the management of HCV infection due to high cure rates and a favorable safety profile. Their influence on neurologic aspects is notably relevant, as studies demonstrated active HCV replication within the CNS1 and alterations in cerebral metabolism consistent with neuroinflammatory conditions.2 These findings may be causative for cognitive deficits in HCV-infected patients.3 Similar impairment has been demonstrated in patients coinfected with HIV, with a prevalence as high as 60%.4 Therefore, these patients may particularly benefit from HCV eradication. To date, studies addressing the issue of reversibility of cognitive deficits after HCV therapy are based on interferon treatment, which itself can cause continuing cognitive impairment.5 The important question whether these deficits are indeed reversible after HCV eradication remains unsolved to date.
Methods. We conducted an open observational trialwith HCV and HCV/HIV coinfected patients andplanned HCV treatment. Patients with liver cirrhosis
(defined as fibroscan >12.5 kPa), a history of substancedependence, or cerebral diseases were excluded.HIV-infected patients had to have undetectable
plasma HIV levels for at least 6 months. We assesseda comparison group of healthy controls (n =30)for baseline, but not for follow-up. Theneuropsychological test battery included standardizedtests and—to minimize practice effects—alternateversions for follow-up testing, covering 7 domains(table). We used age-corrected norms. To test forbaseline and longitudinal differences, we used t testsfor dependent and independent samples, respectively.Participants completed self-report assessments ofcognitive symptoms, instrumental activities of dailyliving, fatigue, depression, and quality of life. Testingsessions took place at baseline and at the earliest 12weeks after the end of HCV treatment.
Results. We have seen 25 HCV-positive outpatientsbetween 2015 and 2016 before treatment. Fifteenwere coinfected with HIV. All but one participantwere male. Groups did not differ significantly in ageor years of education (patients [mean age 43.8 years(SD 11.7); mean education 15.1 years (SD 2.1)];controls [mean age 39.5 years (SD 9.9); meaneducation 16.1 years (SD 2.0)]). Mean nadir CD4of the coinfected group was 328 cells/mL (SD 215);baseline CD4 cell count was 846 cells/mL (SD 242)and remained stable over time.
At baseline, thepatient group showed significantly poorerperformance in the domains of visual and workingmemory, processing speed, attention, and executivefunctioning (table). We did not observe a differencebetween monoinfected and coinfected patients.
To date, 12 participants have completed therapyand undergone follow-up. Treatment regimens werewell-tolerated and included the following: ombitasvir/paritaprevir/ritonavir 1 ribavirin (n =2), ledipasvir/sofosbuvir (n =9), or sofosbuvir 1 ribavirin (n =1).
Mean therapy duration was 10 weeks (8–12 weeks); allpatients were HCV-RNA-negative at week 12 aftertreatment completion.
At follow-up assessment, patients did not showcognitive decline in any domains compared tobaseline; neither did any patient report subjectiveimpairment during or after the therapy.
On the contrary,2-tailed t tests indicate a significant (p <0.05)improvement in the domains visual memory, processingspeed, attention, and executive functioning. Inaddition, we observed a significant (p =0.022)decline in self-reported fatigue severity. There wasno significant change in the level of depression, butan increase in self-reported quality of life.
Discussion. In this study, we investigate the effect ofan interferon-free treatment on cognitive function inHCV-monoinfected and HCV/HIV coinfected
patients. Our data show that HCV-infected patientswithout comorbidities had significantly poorercognitive performance than controls. Against ourexpectations, HIV coinfection did not increase theextent of cognitive deficits. These findings partiallycontradict conclusions made by other studies. Arecent study6 showed that HCV coinfection did nothave an effect on cognitive function in a cohort ofHIV-infected patients, which led the authors toquestion an influence of HCV on cognition per se.
In contrast, our data suggest a significant influenceof HCV infection on cognitive function, which seemsto outweigh that caused by HIV infection. Our first
follow-up data support this assumption, showing animprovement in those cognitive domains that wereimpaired before HCV eradication. Our study wasexplicitly designed to detect differences attributableto HCV eradication. In contrast to thecross-sectionalapproach of most previous studies, we thereforechose a longitudinal approach.
Nevertheless, these first data have to be interpretedcarefully due to small sample size. Practice effectsmight partially contribute to the observed improvements.
However, reported effect sizes are relativelysmall (Cohen d 5 0.00–0.24)7 compared to the onesseen in our cohort (d 5 0.20–1.79). To verify animprovement, more follow-up data need to be consideredusing a reliable change index approach8 todifferentiate between practice effects andtreatment relatedcognitive changes.
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