Hepatic giant cells in hepatitis C virus (HCV) mono-infection and HCV/HIV co-infection

Background: The clinical and biological significance of syncytial giant cell change of hepatocytes in hepatitis C viral (HCV) infection is poorly understood. Aim: To investigate the clinical and histological correlates of giant cell transformation in the setting of HCV mono-infection and co-infection with HCV and HIV. Methods: The prevalence of hepatocyte giant cell transformation was determined and serological, biochemical and histological findings examined. Results: Among 856 liver biopsy specimens, 22 cases (2.6%) showed giant cell transformation, representing 18 individuals. The median serum ALT was 37 IU/l, AST 49 IU/l, and alkaline phosphatase 97 IU/l. Eleven cases had HCV RNA loads available, with a median HCV RNA of 5.52 log IU/ml. Twelve of 17 individuals with available test results were also HIV positive (71%), compared to 46% of controls (p = 0.08). Giant cell transformation was found exclusively in zone 3 hepatocytes; the accompanying histological findings were otherwise typical of chronic HCV. The hepatic giant cells typically had a cytoplasmic appearance that resembled smooth endoplasmic reticulum proliferation. Most cases had only mild inflammation and fibrosis, with a median modified hepatic activity index (MHAI) grade of 3/18 and a median MHAI stage of 1/6. Three individuals had follow-up biopsies; all continued to have giant cell change. Conclusion: Giant cell transformation occurs most commonly in the setting of HCV/HIV co-infection, but can also be seen in chronic HCV infection alone. Histologically, giant cells were located in zone 3 hepatocytes, were persistent over time, and do not appear to be a marker of aggressive hepatitis.