Hepatitis C in asymptomatic British blood donors with indeterminate seropositivity

BMJ 1994; 309 doi: (Published 01 October 1994) Cite this as: BMJ 1994;309:847
  1. D J Mutimer,
  2. R F Harrison,
  3. K B O'Donnell,
  4. J Shaw,
  5. B A B Martin,
  6. H Atrah,
  7. F A Ala,
  8. S Skidmore,
  9. S G Hubscher,
  10. J M Neuberger,
  11. E Elias
  1. Liver Unit, Queen Elizabeth Hospital, Birmingham B15 2TH Departments of Pathology and Infection, University of Birmingham, Birmingham West Midlands Regional Health Authority Blood Transfusion Service Regional Virology Laboratories, East Birmingham
  1. Correspondence to: Dr Mutimer.
  • Accepted 22 June 1994

False positive results are common when low risk populations, such as volunteer British blood donors, are screened for antibodies to hepatitis C virus. In this setting a confirmatory assay is required, but an indeterminate result may still be obtained. This regional blood transfusion service uses a second generation recombinant immunoblot assay (RIBA HCV, Ortho diagnostics) to confirm positive results on enzyme linked immunosorbent assay (ELISA). Donors with indeterminate results in the confirmatory assay are excluded from the donor pool and advised that the use of their blood may not be safe.

We examined 61 such donors for evidence of hepatitis C and liver disease.

Patients, methods, and results

Consecutive patients referred to this liver unit were interviewed and examined. Liver function was checked, and serum was stored at - 70°C. Liver biopsy was performed, and histology was scored according to a modified Knodell activity index (maximum possible score 13). Part of the biopsy specimen was snap frozen and stored at - 70°C. Stored serum samples and biopsy specimens were examined for hepatitis C virus RNA (assay detection sensitivity 0.4-4 copies of target complementary DNA).

Six donors had had blood transfusions, and 55 had no overt risk factor for hepatitis C. All were asymptomatic, with no physical signs of liver disease. One obese donor had raised serum alanine transaminase activity (45 U/l, normal <41), and the remainder (including the six donors who had had transfusions) had normal results. All serum samples were negative for hepatitis C virus RNA.

Fifty nine liver biopsies were performed. Histological abnormalities were mild, and most specimens (49/59) had an activity index of 0 (table). The most commonly observed abnormality was steatosis, sometimes accompanied by an inflammatory infiltrate. Of six patients with a history of transfusion, four had an index of 0 and the two others scored 1. Significant abnormality was observed in a single biopsy specimen (mild chronic active hepatitis, activity index 5). This donor had persistently normal serum transaminase activity during two years' follow up. Twenty biopsy specimens, selected to represent a range of histological changes (table), were negative for hepatitis C virus RNA.

Results for 59 liver biopsy specimens from asymptomatic blood donors with indeterminate seropositivity for hepatitis C virus

View this table:


When the confirmatory assay for antibodies to hepatitis C virus is positive, British blood donors are nearly always viraemic with histological evidence of liver disease.1 They should be excluded from blood donation and referred for investigation and management of chronic hepatitis.

Interpretation of indeterminate results on recombinant immunoblot assay is more difficult and is principally dependent on the clinical context. Patients with such indeterminate results with known or suspected liver disease probably have hepatitis C, and viral RNA will usually be detected in their serum.2 Blood donors with such indeterminate results, however, usually have no known risk factor for hepatitis C.3 In other studies a minority of such donors in Britain (about 5%) were serum positive for hepatitis C virus RNA.4

In our cohort risk factors for parenteral exposure were uncommon and liver function was normal (except for an obese man with slightly increased serum alanine transaminase activity). All 61 serum samples and a representative selection of liver biopsy specimens, were negative for hepatitis C virus RNA.

The interpretation of minor histological abnormalities in this context is a challenge. None is pathognomonic of hepatitis C, but lymphoid aggregates (common in chronic hepatitis C5) were observed in a single biopsy specimen (activity index 5). Our patients would not have undergone biopsy outside the context of this study, and the prevalence of minor histological abnormalities in a comparable unselected population is not known.

In conclusion, British blood donors with normal liver function and an indeterminate result on second generation recombinant immunoblot assay should be reassured that covert liver disease is most unlikely. Further investigation, including liver biopsy, is not indicated. Normal transaminase activities were a feature of our cohort. Viraemia and liver disease may be more likely when liver function tests give abnormal results.


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