Utility of glutamine synthetase immunohistochemistry in identifying features of regressed cirrhosis.

The prevailing view that cirrhosis is irreversible has been challenged. It has been proposed that varying degrees of fibrosis regression can be achieved if the injurious agent is removed. In the normal liver, glutamine synthetase immunostaining is present around central veins. In regressed cirrhosis, although fibrous bands between portal tracts and central veins may largely be resorbed, the abnormal portal tract-central vein adherence often remains. Hence, we hypothesized that aberrant glutamine synthetase positivity adjacent to portal tracts would help identify regressed cirrhosis. We performed glutamine synthetase immunohistochemistry on 49 liver specimens (16 regressed cirrhosis, 18 cirrhotic, and 15 normal livers). Qualification for regressed cirrhosis required the following histologic features: curved, delicate incomplete septa, portal tract-central vein adhesions, and portal tract "remnants" (portal tracts with no venous branch). Out of 16, 14 regressed cirrhosis cases had baseline cirrhosis established based on previous biopsy or signs of cirrhosis based on physical exam, laboratory, and radiological findings. All regressed cirrhosis cases (100%) had areas of aberrant glutamine synthetase positivity adjacent to portal tracts, indicating that portal tract-central vein approximation had occurred (p < 0.001 compared to all other categories). No normal cases had glutamine synthetase positivity adjacent to portal tracts, and half of cirrhosis cases had areas showing features of regression, with focal glutamine synthetase positivity adjacent to portal tracts. Overall, glutamine synthetase expression showed highly significant differences among the three categories (p < 0.001). This study shows that aberrant glutamine synthetase positivity adjacent to portal tracts is present in regressed cirrhosis and can be useful in identifying regressed cirrhosis when it is histologically suspected.