Hepatic inclusions during interferon therapy in chronic viral hepatitis

✍ Scribed by Zsuzsa Schaff; Jay H. Hoofnagle; Philip M. Grimley

• Publisher: John Wiley and Sons
• Year: 1986
• Tongue: English
• Weight: 638 KB
• Volume: 6
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840060526

✦ Synopsis

Two types of cytomembranous abnormalities were identified for the first time in liver biopsies from patients with chronic active type B hepatitis during treatment with recombinant a-interferon. Tubuloreticular inclusions were present in the hepatic endothelial cells, Kupffer cells and perisinusoidal cells of liver biopsies from both patients, and they were absent in liver biopsies obtained before treatment. Cylindrical confronting lamellae, having "test tube" or "ring-shape" forms were observed in the cytoplasm both of Kupffer cells and macrophages in the second liver biopsy of one of the patients. The findings suggest that interferon can be involved in the pathogenesis of both cytomembranous abnormalities, but that additional biological factors may play a role in formation of the cylindrical confronting lamellae.

a-or P-interferons can induce characteristic electron microscopic changes within the endoplasmic reticulum of some cell populations (1-4). Treatment of lymphocytes in uitro with natural or recombinant a-interferon leads to the development of cytoplasmic tubuloreticular inclusions (TRI). The TRI also are detected in mononuclear cells of patients with high endogenous levels of serum a-interferon (5). Furthermore, treatment of patients with chronic type B hepatitis using recombinant, human a-interferon is consistently followed by the appearance of TRI in 1 to 10% of circulating lymphocytes within 1 to 2 days of starting therapy (4). These inclusions disappear within 5 to 16 days of stopping interferon treatment. The ultrastructural effect of interferon on cells in the livers of such patients had not been analyzed. Recent availability of liver biopsy tissue from two patients who were received systemic a-interferon (Hoofnagle, J. H. et al., Gastroenterology 1985; 88:1665, Abstract) allowed us to investigate the presence and distribution of interferon-associated ultrastructural changes.