Use of interferon for prevention of hepatocellular carcinoma in cirrhotic patients with hepatitis B or hepatitis C virus infection.

The incidence of hepatocellular carcinoma in North America is increasing. Current debate focuses on whether interferon administered to cirrhotic patients-with or without biochemical or virologic response-delays or prevents cancer of the liver. Review of the literature revealed several studies that showed improvement in or delay in progression of histologic fibrosis in patients with hepatitis C virus (HCV) infection. In patients with hepatitis B virus (HBV) infection, conversion to the nonreplicative stage may be associated with histologic improvement. However, only 11 studies (6 of HCV, 3 of HBV, and 2 of HCV and HBV) compared development of hepatocellular carcinoma in interferon-treated patients with cirrhosis and cirrhotic patients who were not treated with interferon. Although no firm statistical conclusions could be drawn, the literature suggests that interferon therapy may prevent hepatocellular carcinoma in patients with cirrhosis, particularly those infected with HCV. Interferon treatment cannot be recommended for all persons with cirrhosis and HBV or HCV infection because the current evidence is only suggestive. Long-term randomized, controlled trials may provide definitive data; however, it will be difficult, if not impossible, to conduct such trials because of the improved efficacy of combination therapy with interferon and ribavirin in patients with chronic HCV infection and the development of new therapies for patients with HBV infection.

Interleukin-15 signals T84 colonic epithelial cells in the absence of the interleukin-2 receptor beta-chain.

Interleukin-15 (IL-15) shares many biological functions with interleukin-2 (IL-2) due to common receptor components. IL-15 binds to the IL-2 receptor (IL-2R) beta-chain and the common gamma-chain receptor in addition to one other IL-15 binding receptor protein (IL-15R alpha). Both IL-2R beta- and gamma-chains are required to promote cell growth in hematopoietic cells. The colonic cryptlike epithelial cell line T84 contains the common gamma-chain but lacks the IL-2R beta-chain. We report IL-15R alpha-chain mRNA in T84 cells with the use of reverse transcriptase-polymerase chain reaction. T84 and normal colonic epithelial cells bind a FLAG-IL-15 fusion protein in immunoperoxidase and flow cytometric experiments. In addition, IL-15, but not IL-2, accelerates and enhances the development of transepithelial resistance across T84 monolayers in a dose-dependent fashion. We conclude that normal and T84 colonic epithelial cells express IL-15R alpha and are able to bind IL-15. IL-15 can deliver a nonproliferative functional signal in the absence of IL-2R beta-chain in T84 cells.