Fatigue does not correlate with the degree of hepatitis or the presence of autoimmune disorders in chronic hepatitis C infection

Eur J Gastroenterol Hepatol. 1999 Aug;11(8):833-8. doi: 10.1097/00042737-199908000-00004.


Background: Fatigue is probably the most commonly reported symptom in chronic hepatitis C virus (HCV) infection. It is unclear whether fatigue is related to the severity of underlying liver disease or other autoimmune disorders often described with chronic HCV infection.

Objective: To quantify fatigue in terms of its impact on quality of life in a homogeneous cohort and examine its relationship to the status of liver disease or associated autoimmunity.

Methods: The Fatigue Impact Scale (FIS) questionnaire (Fisk et al. Clin Infect Dis 1994; 18:S79-S83), a recently validated psychometric tool for assessing patients' perceptions of the functional limitations attributable to fatigue (40 statements; three subscales: physical, cognitive and psychological; maximum score = 160), was applied to a cohort of Irish women who were PCR-positive for HCV genotype 1b via inoculation with contaminated anti-D products in 1977. RIBA-positive, PCR-negative patients (n = 20) and healthy age-matched women (n = 50) served as controls. The degree of hepatitis was assessed using the Knodell histological activity index (HAI) score on previous liver biopsies. Clinical and laboratory evidence of cryoglobulinaemia, Sjogren's syndrome, connective tissue diseases, autoimmune thyroid disease and glomerulonephritis was sought.

Results: The mean FIS score of the 66 PCR-positive women (mean 78+/-36; range 7-153) was significantly higher than in age-matched controls (mean 31+/-24, range 0-78, P<0.001) but not statistically different from that of the RIBA-positive, PCR-negative group. The FIS score did not correlate with the HAI score (median HAI = 4; range 2-9; Pearson's correlation coefficient r=0.01, P=0.9). Significant levels of cryoglobulins were detected in 10 (15.2%). The sicca complex was diagnosed in six patients, three of whom had associated cryoglobulinaemia. Thyroid antibodies, anti-nuclear antibody, rheumatoid factor, antimitochondrial antibody and anti-smooth muscle antibody were detected in 15.2%, 6%, 4.5%, 4.5% and 1.5%, respectively. There was no significant difference in the FIS score between the groups with autoimmune diseases and those without. The FIS score of the nine patients previously treated with interferon was not statistically different from the untreated group (P=0.39).

Conclusion: The perceived functional impact of fatigue on quality of life is significantly higher in patients with chronic HCV genotype 1b infection compared to healthy controls. However, it is unrelated to the degree of hepatitis and cannot be accounted for by the co-existence of autoimmune disorders alone.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Autoimmune Diseases / complications*
  • Cohort Studies
  • Fatigue / complications*
  • Fatigue / diagnosis*
  • Female
  • Genotype
  • Hepacivirus / genetics
  • Hepacivirus / isolation & purification
  • Hepatitis C Antibodies / blood
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / diagnosis
  • Hepatitis C, Chronic / pathology
  • Hepatitis C, Chronic / virology
  • Humans
  • Inflammation / pathology
  • Liver / pathology
  • Middle Aged
  • Polymerase Chain Reaction
  • Quality of Life
  • RNA, Viral / blood
  • Severity of Illness Index
  • Surveys and Questionnaires


  • Hepatitis C Antibodies
  • RNA, Viral
  • Alanine Transaminase