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Chronic hepatitis in United Kingdom blood donors infected with hepatitis C virus

BMJ 1994; 308 doi: (Published 12 March 1994) Cite this as: BMJ 1994;308:695
  1. W L Irving,
  2. K R Neal,
  3. J C E Underwood,
  4. P N Simmonds,
  5. V James
  1. University Hospital, Queen's Medical Centre, Nottingham NG7 2UH Royal Hallamshire Hospital, Sheffield S10 2JF Medical School, University of Edinburgh, Edinburgh EH8 9AG Trent Regional Blood Transfusion Centre, Sheffield S5 7JN
  1. Correspondence to: Dr Irving.
  • Accepted 17 February 1994

Routine screening for antibodies to hepatitis C virus in blood donations was introduced in Britain in 1991. It showed that 1 in 2000 donors was positive for antibodies. The natural course and importance of hepatitis C virus infection in apparently healthy people are unclear. We assessed the value of clinical and laboratory data in predicting the need for liver biopsy in blood donors with antibodies to hepatitis C virus.

Patients, methods, and results

Blood donors in the Trent region are screened for antibodies to hepatitis C virus by second generation enzyme linked immunosorbent assay, and results are confirmed by a four antigen recombinant immunoblot assay. Donors with positive results are interviewed and referred to a consultant for further management. We studied all 52 donors who had had a liver biopsy by 1 May 1993 (30 men, 22 women; aged 21-57 (mean 35) years).

We collected data on risk factors for hepatitis C virus infection, duration of infection (assuming that infection was acquired on the first exposure to a risk factor), and alcohol intake. Alanine aminotransferase concentrations (three measurements), GOR antibodies,1 hepatitis C virus RNA,2 and hepatitis C virus serotype3 were measured. Biopsy specimens were scored blind by the Knodell and Sheffield4 schemes; the Sheffield scheme includes assessment of histological features characteristic of hepatitis C. We used the statistical package SPSS-PC to analyse data with Spearman rank correlation, Mann-Whitney, and logistic regression analyses. Predictive values for severe liver disease (chronic active hepatitis or cirrhosis) were calculated by using the standard definition and 95% confidence intervals by the program Confidence Interval Analysis.

The histological diagnoses were cirrhosis (four patients), chronic active hepatitis (13), chronic persistent hepatitis (32), fatty change (one), and normal (two). Hepatitis C virus RNA was detected in sera from 51 donors. The biopsy specimen from the donor without viral RNA was normal. Hepatitis C virus RNA was assayed twice in 31 donors: 28 had positive results in both samples, one had negative results in both, and two had a positive result in the first sample but a negative second result. The biopsy specimens from the donors with discordant results were reported as normal in one and chronic persistent hepatitis with features of (alpha)1 antitrypsin deficiency in the other. A negative test result was significantly associated with lower severity scores for biopsy specimens (Knodell score P=0.006; Sheffield score P=0.005).

Peak alanine aminotransferase concentration was correlated with both severity scores (Knodell score rs=0.59, P<0.001; Sheffield score rs=0.66, p<0.001, figure). The predictive value for chronic active hepatitis or cirrhosis was 0.42 (13/31 donors, 95% confidence interval 0.25 to 0.61) for an alanine aminotransferase concentration above 60 IU/l and 0.47 (9/19, 0.24 to 0.71) for a concentration above 100 IU/l. The predictive value of an alanine aminotransferase concentration under 60 IU/l for chronic persistent hepatitis, fatty change, or a normal biopsy result was 0.81 (17/21, 0.58 to 0.95).

Liver damage was more severe in men than women (median Knodell score 4 v 2, P=0.03; Sheffield score 5 v 3, P=0.02). Logistic regression models found no other significant predictor for histological change.


Correlation between Sheffield score of severity of disease in liver biopsy specimen and peak alanine aminotransferase concentration. (???)=Chronic hepatitis or normal, (???)=cirrhosis, (???)=chronic active hepatitis


Fifty of 52 biopsy specimens from apparently healthy blood donors infected with hepatitis C virus were abnormal, with a third having evidence of chronic active hepatitis or cirrhosis. Although peak alanine aminotransferase concentration and biopsy scores were strongly correlated, alanine aminotransferase concentration was a poor predictor of serious liver disease.

Possible explanations for the discordant results with the test for hepatitis C virus RNA include intermittent viraemia,5 low level viraemia, false positive or negative results, and clearance of viraemia between sampling. Larger studies are needed to determine whether variable results for viral RNA are associated with less severe liver disease.

We found no useful predictors of the severity of liver disease. Our estimates of age at, and duration of, infection, however, had obvious limitations. Our data suggest that donors who have repeated positive results for hepatitis C virus RNA require liver biopsy as a large proportion will have serious liver disease that cannot be predicted by measuring alanine aminotransferase concentration.

Members of the Trent Regional Hepatitis C Virus Study Group were D A Jones, P Nuttall (Trent Regional Blood Transfusion Service); S Day (Nottingham University); D Bennett, R P Eglin (Leeds Public Health Laboratory); R G Finch, R Read (Nottingham City Hospital); M McKendrick, D R Triger, D Williams (Royal Hallamshire Hospital, Sheffield); B B Scott (Lincoln County Hospital); K G Nicholson, M Wiselka (Leicester Royal Infirmary); J Freeman (Derby Royal Infirmary), and K Rose (Department of Microbiology, University of Edinburgh).


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