THYROID DYSFUNCTION FOLLOWING ALPHA-INTERFERON TREATMENT FOR CHRONIC HEPATITIS C

In order to evaluate the influnces of IFNα on thyroid function, thyroid-stimulating hormone (TSH), total thyroxine (T4), free T4, tri-iodothyronine (T3), and thyroxine-binding globulin were examined in IFNα-treated 351 patients with chronic hepatitis C before and during therapy. As therapy, either 3 million units (MU) of human lymphoblastoid IFNα or 9MU of recombinant IFNα2a was administrated daily for the initial two weeks followed by three times a week for 22 weeks. There were nine patients showing thyroid dysfunction during IFNα therapy. They consist of one relapse of Graves' disease, one relapse of Hashimoto thyroiditis, one development of apparent thyroid insufficiency from subclinical hypothyroidism, five cases with transient hyperthyroidism and one case with transient hypothyroidism. T4 and T3 levels in most patients who transiently developed thyroid dysfunction were normalized spontaneously after the discontinuation of IFNα. Thyroid-related autoantibodies were positive in 4 patients before IFNα therapy and newly developed in one patient during therapy. Attention should be paid first to the previous histories of autoimmune thyroid diseases and the existence of thyroid-related autoantibodies for the prediction of development of thyroid dysfunction during IFNα therapy. In addition, serial examinations of TSH, T3 and T4 should be also necessary for early detection of transient thyroid dysfunction during IFNα therapy

Combination of Interferon-β and the Angiotensin-Converting Enzyme Inhibitor, Perindopril, Attenuates Murine Hepatocellular Carcinoma Development and Angiogenesis.

PURPOSE: Angiogenesis is now recognized as a crucial step in the development of tumors, including hepatocellular carcinoma (HCC). The aim of this study was to elucidate the combined effect of the clinically used angiotensin I-converting enzyme (ACE) inhibitor, perindopril (PE), and IFN-beta on the development and angiogenesis of murine HCC at clinically comparable low doses. EXPERIMENTAL DESIGN: PE and IFN were administered at doses of 2 mg/kg/day and 1 x 10(4) IU/twice a week, respectively. RESULTS: Both PE and IFN significantly suppressed HCC development and inhibited neovascularization in the tumor, although the effect of low-dose IFN was weaker than that of PE. A combination regimen of PE plus IFN was effective; IFN significantly augmented the tumoricidal effect of PE. These inhibitory effects of PE plus IFN could be detected even on established tumors. The potent angiogenic factor, vascular endothelial growth factor, was markedly suppressed by combined treatment with PE and IFN, whereas these agents produced a marked increase of apoptosis in the tumor. The in vitro studies exhibited that PE and IFN inhibited endothelial cell tubular formation. IFN also suppressed endothelial cell proliferation, whereas neither IFN nor PE showed any inhibitory effect on proliferation of HCC cells. CONCLUSION: The combination treatment of PE and IFN at clinically comparable low doses could inhibit HCC development and angiogenesis and suppress vascular endothelial growth factor as well. Because both agents are widely used in clinical practice, this combination regimen may represent a potential new strategy for HCC therapy in the future.The definitive version is available at " http://clincancerres.aacrjournals.org/content/9/16/6038