Changes in ultrastructure of hepatocytes and liver test results before, during, and after treatment with interferon-? in patients with HBeAg-positive chronic active hepatitis

Abstract

We studied the histological and ultrastructural changes in the liver and alterations in the liver test results before, during, and after treatment with human interferon-beta from five patients with hepatitis B e antigen-positive chronic active hepatitis. A daily dose of 3 x 10(6) to 6 x 10(6) units of interferon-beta was given intravenously for four weeks. The total index of periportal and portal inflammation, intralobular degeneration, and focal necrosis before treatment was decreased significantly six months after treatment (P less than 0.05). Ultrastructurally, the structure of endoplasmic reticulum was irregularly shaped or fragmentally decreased during treatment, but these disappeared six or 12 months after treatment. Glycogen particles diminished greatly during treatment. The alanine aminotransferase concentrations in these patients increased during treatment. Serum albumin and cholinesterase levels decreased significantly at the fourth week of treatment (P less than 0.01) and at the third day (P less than 0.01) to the second week (P less than 0.05) of treatment, respectively. These results suggest that interferon-beta injures endoplasmic reticulum and glycogen areas and damages the cholinesterase activity in the early stage of treatment and protein synthesis in patients with hepatitis B e antigen-positive chronic active hepatitis.

Acute Hepatitis Induced by Alpha-Interferon in a Patient with Chronic Hepatitis C

“…Itoh et al (11) showed the ultrastructural change of hepatocytes in patients receiving interferon for chronic hepatitis B. A marked decrease in the number of mitochondria, as well as alterations of endoplasmic reticulum and fat vacuoles, were seen in their patients.…”

Presentation and Outcomes with Clinically Apparent Interferon Beta Hepatotoxicity

“…The 3 commercially available interferon beta products are recombinant, parenterally administered polypeptides. Interferon beta-1a has direct effects on hepatocytes acting through cell surface receptors and leading to changes in gene expression and protein synthesis and hepatocyte ultrastructure (31). Interferon beta can depress the activity of inducible and constitutive cytochrome P-450 isoenzymes that may alter the metabolism of other drugs (3233).…”

Macrovesicular steatosis induced by interferon alfa therapy for chronic myelogenous leukaemia

“…IFN-a also decreases the transcription of mitochondrial DNA and could thereby impair fatty acid p oxidation (9). Indeed, in patients treated with IFN-a for chronic hepatitis B, ultrastructural modifications of the liver, including fat vacuoles, suggesting decreased fatty acid oxidation have been reported (10). However, this mechanism remains hypothetical in the case of our patient, as microvesicular steatosis, a characteristic lesion when fatty acid p oxidation is inhibited (1 l), was not evidenced on both liver specimens.…”