Abstract
Interferon is currently considered to be the only accepted effective treatment for chronic viral hepatitis. A history of the treatment of chronic hepatitis B and C before the use of interferon is presented here. Hepatitis B virus does not seem to be directly cytopathic and the disease is known to be modulated largely by the host's immune response. Experience with immunosuppressant and immunostimulant drugs and a wide variety of antiviral agents, however, has indicated that none of these are of any benefit in patients with chronic hepatitis B, with the possible exception of adenine arabinoside. In view of the much more recent identification of the hepatitis C virus, studies of therapy for chronic hepatitis C are inevitably less extensive. A pilot study using acyclovir in patients with chronic non-A, non-B hepatitis did not show any benefit, although the treatment period may have been too short for the results to be conclusive. The only agent other than alpha interferon to be tried in chronic hepatitis C is ribavirin, which may have some activity. Many of the agents studied in chronic hepatitis B should also be investigated for the treatment of patients with chronic hepatitis C.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alexander G. J., Fagan E. A., Hegarty J. E., Yeo J., Eddleston A. L., Williams R. Controlled clinical trial of acyclovir in chronic hepatitis B virus infection. J Med Virol. 1987 Jan;21(1):81–87. doi: 10.1002/jmv.1890210111. [DOI] [PubMed] [Google Scholar]
- Bar-Meir S., Halpern Z., Gutman M., Shpirer Z., Baratz M., Bass D. Effect of (+)-cyanidanol-3 on chronic active hepatitis: a double blind controlled trial. Gut. 1985 Sep;26(9):975–979. doi: 10.1136/gut.26.9.975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bassendine M. F., Chadwick R. G., Salmeron J., Shipton U., Thomas H. C., Sherlock S. Adenine arabinoside therapy in HBsAg-positive chronic liver disease: a controlled study. Gastroenterology. 1981 May;80(5 Pt 1):1016–1022. [PubMed] [Google Scholar]
- Blumberg B. S., Gerstley B. J., Hungerford D. A., London W. T., Sutnick A. I. A serum antigen (Australia antigen) in Down's syndrome, leukemia, and hepatitis. Ann Intern Med. 1967 May;66(5):924–931. doi: 10.7326/0003-4819-66-5-924. [DOI] [PubMed] [Google Scholar]
- Brzosko W. J., Debski R., Derecka K. Immunostimulation for chronic active hepatitis. Lancet. 1978 Aug 5;2(8084):311–311. doi: 10.1016/s0140-6736(78)91707-5. [DOI] [PubMed] [Google Scholar]
- Caselmann W. H., Eisenburg J., Hofschneider P. H., Koshy R. Beta- and gamma-interferon in chronic active hepatitis B. A pilot trial of short-term combination therapy. Gastroenterology. 1989 Feb;96(2 Pt 1):449–455. doi: 10.1016/0016-5085(89)91570-9. [DOI] [PubMed] [Google Scholar]
- Davis G. L., Balart L. A., Schiff E. R., Lindsay K., Bodenheimer H. C., Jr, Perrillo R. P., Carey W., Jacobson I. M., Payne J., Dienstag J. L. Treatment of chronic hepatitis C with recombinant interferon alfa. A multicenter randomized, controlled trial. Hepatitis Interventional Therapy Group. N Engl J Med. 1989 Nov 30;321(22):1501–1506. doi: 10.1056/NEJM198911303212203. [DOI] [PubMed] [Google Scholar]
- Fattovich G., Brollo L., Pontisso P., Pornaro E., Rugge M., Alberti A., Realdi G. Levamisole therapy in chronic type B hepatitis. Results of a double-blind randomized trial. Gastroenterology. 1986 Sep;91(3):692–696. doi: 10.1016/0016-5085(86)90640-2. [DOI] [PubMed] [Google Scholar]
- Ferenci P., Dragosics B., Dittrich H., Frank H., Benda L., Lochs H., Meryn S., Base W., Schneider B. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol. 1989 Jul;9(1):105–113. doi: 10.1016/0168-8278(89)90083-4. [DOI] [PubMed] [Google Scholar]
- Garcia G., Smith C. I., Weissberg J. I., Eisenberg M., Bissett J., Nair P. V., Mastre B., Rosno S., Roskamp D., Waterman K. Adenine arabinoside monophosphate (vidarabine phosphate) in combination with human leukocyte interferon in the treatment of chronic hepatitis B. A randomized, double-blinded, placebo-controlled trial. Ann Intern Med. 1987 Sep;107(3):278–285. doi: 10.7326/0003-4819-107-2-278. [DOI] [PubMed] [Google Scholar]
- Guarascio P., De Felici A. P., Migliorini D., Alexander G. J., Fagan E. A., Visco G. Treatment of chronic HBeAg-positive hepatitis with acyclovir. A controlled trial. J Hepatol. 1986;3 (Suppl 2):S143–S147. doi: 10.1016/s0168-8278(86)80113-1. [DOI] [PubMed] [Google Scholar]
- Hoofnagle J. H., Hanson R. G., Minuk G. Y., Pappas S. C., Schafer D. F., Dusheiko G. M., Straus S. E., Popper H., Jones E. A. Randomized controlled trial of adenine arabinoside monophosphate for chronic type B hepatitis. Gastroenterology. 1984 Jan;86(1):150–157. [PubMed] [Google Scholar]
- Hoofnagle J. H., Mullen K. D., Jones D. B., Rustgi V., Di Bisceglie A., Peters M., Waggoner J. G., Park Y., Jones E. A. Treatment of chronic non-A,non-B hepatitis with recombinant human alpha interferon. A preliminary report. N Engl J Med. 1986 Dec 18;315(25):1575–1578. doi: 10.1056/NEJM198612183152503. [DOI] [PubMed] [Google Scholar]
- Lange J., Schumacher K., Witscher H. P. Die Behandlung der chronisch-aggressiven Hepatitis mit D-Penicillamin. Dtsch Med Wochenschr. 1971 Jan 22;96(4):139–passim. doi: 10.1055/s-0028-1108216. [DOI] [PubMed] [Google Scholar]
- Loke R. H., Anderson M. G., Coleman J. C., Tsiquaye K. N., Zuckerman A. J., Murray-Lyon I. M. Suramin treatment for chronic active hepatitis B--toxic and ineffective. J Med Virol. 1987 Jan;21(1):97–99. doi: 10.1002/jmv.1890210113. [DOI] [PubMed] [Google Scholar]
- Nair P. V., Tong M. J., Stevenson D., Roskamp D., Boone C. A pilot study on the effects of prednisone withdrawal on serum hepatitis B virus DNA and HBeAg in chronic active hepatitis B. Hepatology. 1986 Nov-Dec;6(6):1319–1324. doi: 10.1002/hep.1840060616. [DOI] [PubMed] [Google Scholar]
- Onji M., Kondoh H., Horiike N., Yamaguchi S., Ogawa Y., Kumon I., Ohta Y. Effect of recombinant interleukin 2 on hepatitis B e antigen positive chronic hepatitis. Gut. 1987 Dec;28(12):1648–1652. doi: 10.1136/gut.28.12.1648. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perrillo R. P., Regenstein F. G., Bodicky C. J., Campbell C. R., Sanders G. E., Sunwoo Y. C. Comparative efficacy of adenine arabinoside 5' monophosphate and prednisone withdrawal followed by adenine arabinoside 5' monophosphate in the treatment of chronic active hepatitis type B. Gastroenterology. 1985 Mar;88(3):780–786. doi: 10.1016/0016-5085(85)90151-9. [DOI] [PubMed] [Google Scholar]
- Perrillo R. P., Regenstein F. G., Peters M. G., DeSchryver-Kecskemeti K., Bodicky C. J., Campbell C. R., Kuhns M. C. Prednisone withdrawal followed by recombinant alpha interferon in the treatment of chronic type B hepatitis. A randomized, controlled trial. Ann Intern Med. 1988 Jul 15;109(2):95–100. doi: 10.7326/0003-4819-109-2-95. [DOI] [PubMed] [Google Scholar]
- Pollard R. B., Smith J. L., Neal A., Gregory P. B., Merigan T. C., Robinson W. S. Effect of vidarabine on chronic hepatitis B virus infection. JAMA. 1978 Apr 21;239(16):1648–1650. [PubMed] [Google Scholar]
- Price J. S., France A. J., Moaven L. D., Welsby P. D. Foscarnet in fulminant hepatitis B. Lancet. 1986 Nov 29;2(8518):1273–1273. doi: 10.1016/s0140-6736(86)92694-2. [DOI] [PubMed] [Google Scholar]
- Reichard O., Andersson J., Schvarcz R., Weiland O. Ribavirin treatment for chronic hepatitis C. Lancet. 1991 May 4;337(8749):1058–1061. doi: 10.1016/0140-6736(91)91707-2. [DOI] [PubMed] [Google Scholar]
- Sagnelli E., Manzillo G., Maio G., Pasquale G., Felaco F. M., Filippini P., Izzo C. M., Piccinino F. Serum levels of hepatitis B surface and core antigens during immunosuppressive treatment of HBsAg-positive chronic active hepatitis. Lancet. 1980 Aug 23;2(8191):395–397. doi: 10.1016/s0140-6736(80)90442-0. [DOI] [PubMed] [Google Scholar]
- Schalm S. W., Heytink R. A., van Buuren H. R., de Man R. A. Acyclovir enhances the antiviral effect of interferon in chronic hepatitis B. Lancet. 1985 Aug 17;2(8451):358–360. doi: 10.1016/s0140-6736(85)92498-5. [DOI] [PubMed] [Google Scholar]
- Schalm S. W., Summerskill W. H., Gitnick G. L., Elveback L. R. Contrasting features and responses to treatment of severe chronic active liver disease with and without hepatitis BS antigen. Gut. 1976 Oct;17(10):781–786. doi: 10.1136/gut.17.10.781. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sheron N., Lau J. Y., Daniels H. M., Webster J., Eddleston A. L., Alexander G. J., Williams R. Tumour necrosis factor to treat chronic hepatitis B virus infection. Lancet. 1990 Aug 4;336(8710):321–322. doi: 10.1016/0140-6736(90)91866-9. [DOI] [PubMed] [Google Scholar]
- Steroids in chronic B-hepatitis. A randomized, double-blind, multinational trial on the effect of low-dose, long-term treatment on survival. A trial group of the European Association for the Study of the Liver. Liver. 1986 Aug;6(4):227–232. [PubMed] [Google Scholar]
- Suzuki H., Yamamoto S., Hirayama C., Takino T., Fujisawa K., Oda T. Cianidanol therapy for HBe-antigen-positive chronic hepatitis: a multicentre, double-blind study. Liver. 1986 Feb;6(1):35–44. doi: 10.1111/j.1600-0676.1986.tb00266.x. [DOI] [PubMed] [Google Scholar]
- Thyagarajan S. P., Subramanian S., Thirunalasundari T., Venkateswaran P. S., Blumberg B. S. Effect of Phyllanthus amarus on chronic carriers of hepatitis B virus. Lancet. 1988 Oct 1;2(8614):764–766. doi: 10.1016/s0140-6736(88)92416-6. [DOI] [PubMed] [Google Scholar]
- Trépo C., Ouzan D., Fontanges T., Chevallier M., Chossegros P., Degos F., Chevallier P., Hantz O. Therapeutic activity of vidarabine in symptomatic chronic active hepatitis related to HBV. J Hepatol. 1986;3 (Suppl 2):S97–105. doi: 10.1016/s0168-8278(86)80106-4. [DOI] [PubMed] [Google Scholar]
- Venkateswaran P. S., Millman I., Blumberg B. S. Effects of an extract from Phyllanthus niruri on hepatitis B and woodchuck hepatitis viruses: in vitro and in vivo studies. Proc Natl Acad Sci U S A. 1987 Jan;84(1):274–278. doi: 10.1073/pnas.84.1.274. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wright E. C., Seeff L. B., Berk P. D., Jones A., Plotz P. H. Treatment of chronic active hepatitis. An analysis of three controlled trials. Gastroenterology. 1977 Dec;73(6):1422–1430. [PubMed] [Google Scholar]
- de Man R. A., Berk L., Schalm S. W., Stijnen T. Treatment of chronic viral hepatitis. Dig Dis. 1991;9(1):17–35. doi: 10.1159/000171290. [DOI] [PubMed] [Google Scholar]
