Neuropsychiatric Impairment in Patients With HCV Despite Virus Clearance

Disabling chronic fatigue is reported in approximately 60% of patients with confirmed hepatitis C virus (HCV) infection,^1,2 as well as decreased quality of life (QoL)^3,4 and cognitive dysfunction (eg, deficits in attention and verbal learning).^5,6 While these neuropsychiatric symptoms may be expected in patients with ongoing HCV infection, it is questionable whether these effects are also present in HCV-exposed patients who currently are cured of the infection (polymerase chain reaction-negative [PCR-]). 

A study⁷ recently published in the Journal of Viral Hepatitis found no evidence linking the presence of HCV infection with these neuropsychiatric symptoms. Instead, researchers suggest that the fatigue and impairment in health-related quality of life (HRQoL) and cognitive and mental function commonly found in HCV-exposed patients may be explained by either an HCV infection-triggered autoimmune response persisting beyond virus clearance or the development of a virus variant in the brain.⁷

In this study, researchers recruited 159 anti-HCV-positive individuals without advanced liver disease from an outpatient clinic for viral hepatitis at Hannover Medical School in Germany and an HCV patient support group. Patients were excluded if they had a comorbidity that could confound the study results (eg, drug addiction, neurologic or psychiatric disorders, liver disease from conditions other than HCV infection, HIV co-infection, or hypothyreoidism). Patients answered a series of HRQoL, fatigue, and depression questionnaires, and underwent a battery of attention and memory tests. In addition, patients were divided into 4 groups according to their viremia status and interferon/ribavirin (IFN) treatment history ([1] successful [PCR-/IFN+] IFN therapy; [2] unsuccessful (PCR+/IFN+) IFN therapy; [3] never treated and PCR+ (PCR+/IFN-); and [4] spontaneous virus clearance (PCR-/IFN-). Their responses were examined against norms based on test manuals and compared with those of 33 age-matched health controls.

Of the 159 patients, 122 (77%) were PCR+ at the time of the study, with 59 (48%) not responding to antiviral therapy (PCR+/IFN+) and 63 (52%) not treated with antiviral therapy (PCR+/IFN-). In the 37 PCR- patients, 22 (60%) cleared the virus with IFN therapy (PCR-/IFN+) and 15 (40%) cleared the virus spontaneously (PCR-/IFN-). Liver function was normal in all patients, and age was similar among patients and controls (mean age 48.5 to 53.3 years).

The researchers found the following: (1) PCR+ and PCR- HCV-afflicted patients with only mild liver disease but neuropsychiatric symptoms did not differ with regard to the features and extent of these symptoms; (2) chronic fatigue was the most frequent neuropsychiatric symptom and had the most significant impact on the patients’ HRQoL; and (3) significant cognitive dysfunction was present in approximately one-third of the patients with neuropsychiatric symptoms and was not affected by the presence of depression.

According to the investigators, “Our study included patients with mild liver disease, exclusively, thereby even further eliminating the confounding [effect] of advanced liver disease on brain function. Nevertheless, we found deficits in the recognition of words or figures in 45% and attention deficits in 30% of the patients. About 77% showed chronic fatigue, and 50%-60% mild-to-moderate anxiety and depression. Health-related quality of life correlated negatively with fatigue, as did the patients’ attention ability. Of note, the patients’ cognitive function was independent from their mood status.”

This study was potentially limited by a “selection bias” that resulted in the greater impairment in the PCR- patients compared with PCR+ patients. This can be explained by the greater likelihood of PCR- patients with symptoms rather than their counterparts without symptoms to seek the services of the hepatitis outpatient clinic or patient support group from which the study participants were recruited.

References

1. Poynard T, Cacoub P, Ratziu V, et al; Multivirc group. Fatigue in patients with chronic hepatitis C. J Viral Hepatitis. 2002;9:295-303. doi:10.1046/j.1365-2893.2002.00364
2. Hassoun Z, Willems B, Deslauriers J, Nguyen BN, Huet PM. Assessment of fatigue in patients with chronic hepatitis C using the Fatigue Impact Scale. Dig Dis Sci. 2002;47:2674-2681.
3. Carithers RL, Sugano D, Bayliss M. Health assessment for chronic HCV infection: results of quality of life. Dig Dis Sci. 1996;41:75S-80S.
4. Rodger AJ, Jolley D, Thompson SC, Lanigan A, Crofts N. The impact of diagnosis of hepatitis c virus on quality of life. Hepatology. 1999;30:1299-1301. doi:10.1002/hep.510300504
5. Forton DM, Thomas HC, Murphy CA, et al. Hepatitis C and cognitive impairment in a cohort of patients with mild liver disease. Hepatology. 2002;35:433-439. doi:10.1053/jhep.2002.30688
6. Forton DM, Allsop JM, Main J, Foster GR, Thomas HC, Taylor-Robinson SD. Evidence for a cerebral effect of the hepatitis C virus. Lancet. 2001;358:38-39. doi:10.1016/S0140-6736(00)05270-3
7. Dirks M, Pflugrad H, Haag K, et al. Persistent neuropsychiatric impairment in HCV patients despite clearance of the virus?! [published online January 24, 2017] J Viral Hepat. doi:10.1111/jvh.12674