These authors contributed equally to this work.
Histological changes in HCV antibody–positive, HCV RNA–negative subjects suggest persistent virus infection†
Article first published online: 19 JUN 2008
Copyright © 2008 American Association for the Study of Liver Diseases
Volume 48, Issue 6, pages 1737–1745, December 2008
How to Cite
Hoare, M., Gelson, W. T. H., Rushbrook, S. M., Curran, M. D., Woodall, T., Coleman, N., Davies, S. E. and Alexander, G. J. M. (2008), Histological changes in HCV antibody–positive, HCV RNA–negative subjects suggest persistent virus infection. Hepatology, 48: 1737–1745. doi: 10.1002/hep.22484
Potential conflict of interest: As a transplant centre, we state explicitly that no donor organs are or have been obtained from executed prisoners or other institutionalized persons.
- Issue published online: 24 NOV 2008
- Article first published online: 19 JUN 2008
- Accepted manuscript online: 19 JUN 2008 12:00AM EST
- Manuscript Accepted: 9 JUN 2008
- Manuscript Received: 30 APR 2008
- Clinical research training fellowship from the Wellcome Trust
- British Transplantation Society
It is unclear whether hepatitis C virus (HCV) has been eradicated or persists at a low level in HCV antibody–positive HCV RNA–negative individuals. The natural history and liver histology are not well characterized. One hundred seventy-two HCV antibody–positive, serum HCV RNA–negative patients underwent diagnostic liver biopsy between 1992 and 2000 and were followed a median 7 years (range, 5–12). Patients with any possible cause of liver injury other than HCV were excluded. A single histopathologist scored sections using Ishak criteria. Characterization of the inflammatory infiltrate in selected cases used a novel semiquantitative technique and compared with HCV RNA–positive patients and healthy controls. One hundred two patients were excluded because of a risk factor for liver injury other than HCV. Seventy patients met the study criteria; four (5.7%) became HCV RNA–positive during follow-up. Sixty-six cases remained HCV RNA–negative; five (7.5%) had a normal liver biopsy; 54 (82%) had fibrosis (stage 2 or 3 in 16 (24%)). Nonviremic cases revealed expanded portal tracts (P < 0.05), with fewer CD4+ (P < 0.05) and more CD8+ cells (P < 0.05) than healthy controls, but were indistinguishable from HCV RNA–positive cases for these parameters. Lobular CD4 staining, absent in healthy controls, was noted in both HCV RNA–negative and –positive cases and was more marked in the latter (P < 0.05) with a sinusoidal lining cell distribution. Conclusion: Nonviremic HCV antibody–positive patients have a liver biopsy that is usually abnormal. Fibrosis was present in most with similar inflammatory infiltrate to viremic cases. The presence of a CD8+ rich inflammatory infiltrate suggests an ongoing immune response in the liver, supporting the view that HCV may persist in the liver in the majority of HCV RNA–negative cases. (HEPATOLOGY 2008;48;1737-1745.)