Neuropsychiatric Symptoms in Hepatitis C Patients Resemble Those of Patients With Autoimmune Liver Disease but Are Different From Those in Hepatitis B Patients

Meike Dirks; Kim Haag; Henning Pflugrad; Anita B. Tryc; Ramona Schuppner; Heiner Wedemeyer; Andrej Potthoff; Hans L. Tillmann; Kajetan Sandorski; Hans Worthmann; Xiaoqi Ding; Karin Weissenborn


J Viral Hepat. 2019;26(4):422-431. 

In This Article

Abstract and Introduction


Chronic fatigue, mood alterations and cognitive impairment are frequent accessory symptoms of HCV infection. Fatigue and mood alterations have also been observed in autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC), but not in hepatitis B virus (HBV)-infection, thus indicating an autoimmune response as possible cause of HCV infection-associated encephalopathy. Data, however, are sparse. This study aimed to prove that HCV patients feature similar to those with autoimmune liver disease but contrary to HBV patients regarding neuropsychiatric symptoms. A total of 132 noncirrhotic patients (HCV: 46, HBV: 22, AIH: 27, PBC: 29, AIH/PBC: 8) completed questionnaires addressing the domains mentioned above. Eighty-eight underwent a comprehensive neuropsychological assessment. Patient groups were compared among each other and to 33 healthy controls. Fatigue, anxiety and depression scores were significantly increased, and the SF-36 mental score significantly decreased in all patient groups compared to controls. Fatigue was significantly more pronounced in HCV than in HBV patients. HCV patients scored significantly worse than HBV patients but not AIH and PBC patients in the SF-36. HCV, AIH and PBC but not HBV patients did significantly worse than controls in word learning. Recognition of words was impaired in HCV, AIH and PBC patients and recognition of figures in HCV patients, exclusively (P ≤ 0.002). HCV patients did also worse than controls and HBV patients concerning alertness and working memory (P ≤ 0.001). The neuropsychiatric profiles of HCV patients are similar to those of AIH and PBC patients but differ from those of HBV patients, suggesting an autoimmune response as a possible cause for these differences.


About 50% of the patients with hepatitis C virus (HCV) infection complain about chronic fatigue, mood alterations and cognitive dysfunction.[1] The symptoms are independent of the grade of liver disease, PCR-status and virus replication rate.[2,3] Recently, it has been shown that the virus is able to infect human brain endothelial cells, and in addition, negative strand HCV-RNA has been detected in microglia in human brain samples as well as in cerebrospinal fluid of HCV-infected patients proving HCV replication within the brain.[4–7] Nevertheless, the cause of neuropsychiatric symptoms in HCV patients remains unclear. Several hypotheses have been discussed: chronic HCV infection of the brain resulting in brain damage similar to HIV encephalitis, induction of an autoimmune response within the brain or an unspecific activation of neuroinflammatory pathways via increased levels of mediators of inflammation accompanying chronic progressive hepatitis. Clinicians often refer to unspecific alterations of well-being and mental state in patients with chronic liver disease in general—irrespective of the underlying cause—and thereby also put into question that neuropsychiatric symptoms in HCV-infected patients might be different. Fatigue, for example, was reported in patients with autoimmune hepatitis (AIH)[8] and primary biliary cholangitis (PBC),[9] and patients with PBC were shown to have significantly impaired cognitive function compared to controls.[10] Recent data revealing a low prevalence of fatigue in HBV patients, however, indicate that chronic liver disease per se is not the source of fatigue.[11] Differences in frequency and presentation of neuropsychiatric symptoms between various liver diseases can be expected considering the differences in aetiology, pathology and course of the disease. This study aimed to describe and compare frequency, extent and characteristics of neuropsychiatric symptoms in noncirrhotic patients with hepatitis C, hepatitis B, autoimmune hepatitis and primary biliary cholangitis. Since HCV infection is frequently associated with dysregulation of the cytokine/chemokine network and the development of autoimmune diseases,[12,13] we hypothesize that the pattern of neuropsychiatric symptoms in HCV patients differs significantly from that of HBV patients, while it resembles that of AIH and PBC, two frequent autoimmune liver diseases.