Persistent Neuropsychiatric Impairment in HCV Patients Despite Clearance of the Virus?!

M. Dirks; H. Pflugrad; K. Haag; H. L. Tillmann; H. Wedemeyer; D. Arvanitis; H. Hecker; A. Tountopoulou; A. Goldbecker; H. Worthmann; K. Weissenborn


J Viral Hepat. 2017;24(7):541-550. 

In This Article

Abstract and Introduction


One of the most disabling symptoms of hepatitis C virus (HCV) infection is chronic fatigue. While this is accepted for HCV polymerase chain reaction (PCR)-positive patients, a relationship between HCV infection and chronic fatigue is questioned after successful virus eradication. As fatigue is a subjective criterion, we aimed to evaluate in addition mood alterations and cognitive function in HCV-exposed patients with only mild liver disease and to assess a) possible interrelationships between these factors and health-related quality of life and b) the impact of viremia and former interferon treatment. One hundred and fifty-nine anti-HCV-positive individuals without advanced liver disease answered health-related quality of life (HRQoL), fatigue and depression questionnaires and underwent a battery of attention and memory tests. Accompanying diseases which could distort the results of the study such as HIV co-infection or drug addiction were exclusion criteria. The patients were subdivided into four groups according to their viremia status and interferon treatment history. Patients' data were evaluated with respect to norms given in the respective test manuals and in addition compared to those of 33 age-matched healthy controls. Eighty-five per cent of the patients had chronic fatigue, 50–60% mild depression or anxiety, 45% memory deficits and 30% attention deficits, irrespective of their HCV viremia status or treatment history. HRQoL correlated negatively with chronic fatigue (P<.001), while cognitive deficits—especially memory function—were independent from fatigue and depression. HCV infection may cause long-standing cerebral dysfunction that significantly impairs HRQoL and may even persist after clearance of the virus.


About 80 million people worldwide are thought to be infected with the hepatitis C virus (HCV).[1] Most of them remain asymptomatic with regard to the liver. Thus, the diagnosis is frequently made by chance if a patient shows slightly elevated liver enzymes and carries a risk for HCV acquisition, or complains about decreased mental and physical efficiency. Of those patients with confirmed HCV infection, about 60% report disabling chronic fatigue.[2,3]

Impairment of quality of life was described in HCV-infected patients for the first time about 20 years ago.[4] Since then psychological and physiological causes have been discussed.[5,6] Importantly, Rodger et al.[7] showed that even subjects who were not aware of their HCV infection displayed decreased quality of life scores compared to controls. Shortly afterwards the presence of cognitive dysfunction—especially deficits in attention and verbal learning—has been detected in HCV-infected patients with only mild liver disease and has thereafter repeatedly been reported.[8–10] Increasing evidence suggests that exposure to HCV may result in long-term cerebral dysfunction in some of the patients. While this is more and more accepted for patients with ongoing virus replication, it is doubted for polymerase chain reaction (PCR)-negative patients who are actually considered to be cured. Indeed, several studies have shown that sustained response to antiviral treatment in HCV-infected patients is accompanied by an increase in health-related quality of life (HRQOL)[11–16] and cognitive improvement.[17] However, improvement does not occur in all treatment responders: about half of the patients with sustained viral response have been shown, for example, to continue suffering from chronic fatigue.[18]

This study compares features and extent of neuropsychiatric symptoms in PCR-positive and PCR-negative anti-HCV-positive patients with only mild liver disease and analyses interrelationships between HRQOL, fatigue and mood alterations as more subjective complaints on the one hand and cognitive function on the other, while considering also the interferon/ribavirin (IFN) treatment history.