Skip to main content
Log in

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

  • Original Articles
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

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-β from five patients with hepatitis B e antigen-positive chronic active hepatitis. A daily dose of 3×106 to 6×106 units of interferon-β 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<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<0.01) and at the third day (P<0.01) to the second week (P<0.05) of treatment, respectively. These results suggest that interferon-β 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Greenberg HB, Pollard RB, Lutwick LI, Gregory PB, Robinson WS, Merigan TG: Effect of human leukocyte on hepatitis B virus infection in patients with chronic active hepatitis. N Engl J Med 295:517–522, 1976

    Google Scholar 

  2. Caselmann WH, Eisenburg J, Hofschneider PH, Rajen K: α-and β-Interferon in chronic active hepatitis B. A pilot trial of short-term combination therapy. Gastroenterology 96:449–455, 1989

    Google Scholar 

  3. Hoofnagle JH, Peters M, Mulien KD, Jones B, Rustigi V, Di Bisceglie A, Hallahan C, Park Y, Meschievitz C, Jones A: Randomized controlled trial of recombinant human α-interferon in patients with chronic hepatitis B. Gastroenterology 95:1318–1325, 1988

    Google Scholar 

  4. Weimer W, Heijtink RA, Schalm SW, Masurel N, Schellekens H: Double-blind study of leukocyte interferon administration in chronic HBeAg positive hepatitis. Lancet 1:336–338, 1980

    Google Scholar 

  5. Dooley JS, Davis GL, Peters M, Waggner JG, Goodman Z, Hoofnagle JH: Pilot study of recombinant human α-interferon for chronic type B hepatitis. Gastroenterology 90:150–157, 1986

    Google Scholar 

  6. Dusheiko GM, Di Bisceglie A, Bowyer S, Sacks E, Kew MG: Prolonged recombinant leukocyte interferon treatment of chronic hepatitis B. Hepatology 5:556–560, 1985

    Google Scholar 

  7. Scullard GH, Pollard RB, Smith JL, Sacks SL, Gregory PB, Robinson WS, Merigan TC: Antiviral treatment of chronic hepatitis B virus infection. I. Changes in viral markers with interferon combined with adenine arabinoside. J Infect Dis 143:772–783, 1981

    Google Scholar 

  8. Itoh S, Matsuo S, Shimoji K, Oda T, Sasaki I: The effect of α-interferon on the liver in a patient with hairy cell leukemia: light and electron microscopic studies. Am J Gastroenterol 84:942–947, 1989

    Google Scholar 

  9. Kaplan PM, Greeman RL, Gerin JL, Purcell RH, Robinson WS: DNA polymerase associated with human hepatitis B antigen. J Biol 12:995–1005, 1973

    Google Scholar 

  10. DeGroote J, Desmet VJ, Gedick P, Korb G, Popper H, Poulsen H, Scheuer PJ, Schmid M, Thaler H, Uelinger E, Wepler W: A classification of chronic hepatitis. Lancet 2:626–628, 1968

    Google Scholar 

  11. Knodell RG, Ishak KG, Black WC, Chen TS, Craig R, Kaplowitz N, Kiernan TW, Wollman J: Formation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1:431–435, 1981

    Google Scholar 

  12. Moochhala SM, Renton KW, Stebbing N: Induction and depression of cytochrome P-450-dependent mixed-function oxidase by a cloned consensus α-interferon (INF-αCON1) in the hamster. Biochem Pharmacol 38:439–447, 1989

    Google Scholar 

  13. Marutani K: Changes in hepatic function and ultrastructures of hepatocytes during treatment with interferon β and a streptococcal preparation (OK-432) in patients with HBeAg-positive chronic hepatitis. Saitama Med J 18:279–292, 1991

    Google Scholar 

  14. Saito M, Ebina T, Koi M, Yamaguchi T, Kawade Y, Ishida N: Induction of interferon-γ in mouse spleen cells by OK-432, a preparation ofstreptococcus pyogenes. Cell Immunol 68:187–192, 1982

    Google Scholar 

  15. Matsubara S, Suzuki F, Ishida N: Induction of immune interferon in mice treated with a bacterial immunopotentiator, OK-432. Cancer Immunol Immunother 6:41–45, 1979

    Google Scholar 

  16. Uchida A, Nicksche M:In vitro augmentation of natural killing activity by OK-432. Int J Immunopharmacol 3:365–375, 1981

    Google Scholar 

  17. Gooderham NJ, Mannering GJ: Depression of cytochrome P-450 and alterations of protein metabolism in mice treated with the interferon inducer polyriboinosinic acid · polyribocytidylic acid. Arch Biochem Biophys 250:418–425, 1986

    Google Scholar 

  18. Mannering GJ, Deloria LB, Abbott V: Role of xanthine oxidase in the interferon-mediated depression of the hepatic cytochrome P-450 system in mice. Cancer Res 48:2107–2112, 1988

    Google Scholar 

  19. Williams SJ, Farrel GC: Inhibition of antipyrine metabolism by interferon. Br J Clin Pharmacol 22:610–612, 1986

    Google Scholar 

  20. Jonkman JHG, Nicholson KG, Farrow PR, Eckert M, Grasmeijer G, Oosterhuis B, De Noord OE, Guentert TW: Effects of α-interferon on theophylline pharmacokinetics and metabolism. Br J Clin Pharmacol 27:795–802, 1989

    Google Scholar 

  21. Itabashi M: Clinical utility of13C-aminopyrine breath test in patients with chronic liver diseases. Saitama Med J 18:261–268, 1991

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Itoh, S., Marutani, K. & Matsuo, S. Changes in ultrastructure of hepatocytes and liver test results before, during, and after treatment with interferon-β in patients with HBeAg-positive chronic active hepatitis. Digest Dis Sci 37, 1260–1267 (1992). https://doi.org/10.1007/BF01296570

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01296570

Key Words

Navigation