title: The natural course of hepatitis C virus infection after 22 years in a unique homogenous cohort: spontaneous viral clearance and chronic HCV infection.
abstract: OBJECTIVE
  The cohort of Irish women infected with hepatitis C virus (HCV) genotype 1b via contaminated anti-D immunoglobulin in 1977 represent a unique homogenous group to investigate the natural course of HCV infection.
  
  
  METHODS
  The clinical status of 87 polymerase chain reaction (PCR) positive and 68 PCR negative women was investigated at diagnosis (1994/95) and after 4-5 years of follow up (21/22 years after inoculation). Other features investigated included: histological status/progression, psychosocial impact of HCV infection, extrahepatic manifestations, and HLA class II associations.
  
  
  RESULTS
  The most common symptoms reported were fatigue and arthralgia. Furthermore, 77% of women fell within the clinical range for psychological distress. A history of icteric hepatitis was reported in 20.6% of PCR negative and 3.4% of PCR positive women after inoculation (p=0.002). The mean histological activity index/fibrosis scores of PCR positive and negative women were 4.1 (1.4)/1.1 (1.3) and 2.1 (1.5)/0.15 (0.36) at diagnosis and 4.1 (1.2)/1.0 (1.0) in 44 PCR positive women after five years of follow up. Cirrhosis or hepatocellular carcinoma was not observed. The DRB1*01 allele was present in 28.8% of PCR negative and 8.7% of PCR positive women (p=0.004). The prevalence rates of mixed cryoglobulinaemia, sicca complex, positive thyroid autoantibodies, antinuclear antibody, rheumatoid factor, and antimitochondrial antibody in PCR positive women were 12.7%, 7.6%, 13.9%, 5.1%, 3.8%, and 3.8%.
  
  
  CONCLUSIONS
  A benign course of HCV infection with lack of disease progression was observed in women with chronic HCV, 22 years after inoculation. Acute icteric hepatitis and the HLA DRB1*01 allele were associated with viral clearance. Despite this favourable outcome, high levels of psychological distress and poor quality of life were present.
authors.affiliation: Centre for Liver Diseases, Mater Misericordiae Hospital, Eccles St, Dublin 7, Ireland.
authors.forename: S
authors.initials: S
authors.lastname: Barrett
authors.forename: J
authors.initials: J
authors.lastname: Goh
authors.forename: B
authors.initials: B
authors.lastname: Coughlan
authors.forename: E
authors.initials: E
authors.lastname: Ryan
authors.forename: S
authors.initials: S
authors.lastname: Stewart
authors.forename: A
authors.initials: A
authors.lastname: Cockram
authors.forename: J C
authors.initials: JC
authors.lastname: O'Keane
authors.forename: J
authors.initials: J
authors.lastname: Crowe
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D015331:Cohort Studies; D003449:Cryoglobulinemia / Q000097:blood / Q000209:etiology; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D011581:Psychological Tests; D011788:Quality of Life; D012075:Remission, Spontaneous; D013967:Thyroiditis, Autoimmune / Q000097:blood / Q000209:etiology; D019562:Viral Load
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000410:Alanine Transaminase