Histological changes in HCV antibody–positive, HCV RNA–negative subjects suggest persistent virus infection

✍ Scribed by Matthew Hoare; William T. H. Gelson; Simon M. Rushbrook; Martin D. Curran; Tracy Woodall; Nicholas Coleman; Susan E. Davies; Graeme J. M. Alexander

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 377 KB
• Volume: 48
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.22484

✦ Synopsis

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 RNAnegative 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.