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. 1996 Nov;39(5):679–683. doi: 10.1136/gut.39.5.679

Combination thymosin alpha 1 and lymphoblastoid interferon treatment in chronic hepatitis C.

G Rasi 1, D DiVirgilio 1, M G Mutchnick 1, F Colella 1, P Sinibaldi-Vallebona 1, P Pierimarchi 1, B Valli 1, E Garaci 1
PMCID: PMC1383391  PMID: 9026482

Abstract

BACKGROUND: Monotherapy for chronic hepatitis C using interferon (IFN) results in a very small proportion of patients exhibiting a sustained response. Clinical trials assessing the benefit of combination drug therapy may provide evidence of improved treatment response over that seen with single drug treatment. AIM: To assess the response in patients with chronic hepatitis C to one year of combination treatment: thymosin alpha 1 (T alpha 1), 1 mg twice weekly, and lymphoblastoid (L)-IFN, 3 MU thrice weekly. PATIENTS AND METHODS: Fifteen patients with serum HCV RNA positive chronic hepatitis C were studied. Eleven patients were treatment naive and four had failed previous standard IFN therapy. Thirteen patients were HCV RNA serotype 1b. All patients were given combination T alpha 1 and L-IFN therapy for one year with a six month follow up period. RESULTS: Six months after initiation of treatment seven patients (47%) were sera HCV RNA negative and at completion of the one year treatment 11 (73%), including two who had failed previous standard IFN treatment, had negative serum HCV RNA. Six months after treatment, six patients (40%), including five with HCV type 1b, showed a sustained response characterized by a negative serum HCV RNA. CONCLUSIONS: The results of this open label trial suggest that there may be a potential benefit to combining an immune modulator (T alpha 1) with an antiviral (IFN) in the treatment of chronic hepatitis C. Verification of the observations in this study require completion of a randomised controlled study.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alter M. J., Margolis H. S., Krawczynski K., Judson F. N., Mares A., Alexander W. J., Hu P. Y., Miller J. K., Gerber M. A., Sampliner R. E. The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic non-A, non-B Hepatitis Study Team. N Engl J Med. 1992 Dec 31;327(27):1899–1905. doi: 10.1056/NEJM199212313272702. [DOI] [PubMed] [Google Scholar]
  2. Boucher E., Jouanolle H., Andre P., Ruffault A., Guyader D., Moirand R., Turlin B., Jacquelinet C., Brissot P., Deugnier Y. Interferon and ursodeoxycholic acid combined therapy in the treatment of chronic viral C hepatitis: results from a controlled randomized trial in 80 patients. Hepatology. 1995 Feb;21(2):322–327. [PubMed] [Google Scholar]
  3. Brillanti S., Garson J., Foli M., Whitby K., Deaville R., Masci C., Miglioli M., Barbara L. A pilot study of combination therapy with ribavirin plus interferon alfa for interferon alfa-resistant chronic hepatitis C. Gastroenterology. 1994 Sep;107(3):812–817. doi: 10.1016/0016-5085(94)90131-7. [DOI] [PubMed] [Google Scholar]
  4. Burstein Y., Buchner V., Pecht M., Trainin N. Thymic humoral factor gamma 2: purification and amino acid sequence of an immunoregulatory peptide from calf thymus. Biochemistry. 1988 May 31;27(11):4066–4071. doi: 10.1021/bi00411a024. [DOI] [PubMed] [Google Scholar]
  5. Causse X., Godinot H., Chevallier M., Chossegros P., Zoulim F., Ouzan D., Heyraud J. P., Fontanges T., Albrecht J., Meschievitz C. Comparison of 1 or 3 MU of interferon alfa-2b and placebo in patients with chronic non-A, non-B hepatitis. Gastroenterology. 1991 Aug;101(2):497–502. doi: 10.1016/0016-5085(91)90030-o. [DOI] [PubMed] [Google Scholar]
  6. Chemello L., Bonetti P., Cavalletto L., Talato F., Donadon V., Casarin P., Belussi F., Frezza M., Noventa F., Pontisso P. Randomized trial comparing three different regimens of alpha-2a-interferon in chronic hepatitis C. The TriVeneto Viral Hepatitis Group. Hepatology. 1995 Sep;22(3):700–706. doi: 10.1002/hep.1840220303. [DOI] [PubMed] [Google Scholar]
  7. Cianciara J., Laskus T. Thymic factor X treatment of chronic hepatitis B. Hepatology. 1992 Dec;16(6):1507–1508. doi: 10.1002/hep.1840160635. [DOI] [PubMed] [Google Scholar]
  8. Daniels H. M., O'Toole A., Hussein M. J., Corridori S., Alexander G. J., Williams R. THF gamma 2 stimulates cytokine release by peripheral blood mononuclear cells of patients with chronic hepatitis B virus infection. J Hepatol. 1994 Mar;20(3):370–375. doi: 10.1016/s0168-8278(94)80010-3. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Esteban J. I., López-Talavera J. C., Genescà J., Madoz P., Viladomiu L., Muñiz E., Martin-Vega C., Rosell M., Allende H., Vidal X. High rate of infectivity and liver disease in blood donors with antibodies to hepatitis C virus. Ann Intern Med. 1991 Sep 15;115(6):443–449. doi: 10.7326/0003-4819-115-6-443. [DOI] [PubMed] [Google Scholar]
  11. Farhat B. A., Marinos G., Daniels H. M., Naoumov N. V., Williams R. Evaluation of efficacy and safety of thymus humoral factor-gamma 2 in the management of chronic hepatitis B. J Hepatol. 1995 Jul;23(1):21–27. doi: 10.1016/0168-8278(95)80306-8. [DOI] [PubMed] [Google Scholar]
  12. Garson J. A., Brillanti S., Whitby K., Foli M., Deaville R., Masci C., Miglioli M., Barbara L. Analysis of clinical and virological factors associated with response to alpha interferon therapy in chronic hepatitis C. J Med Virol. 1995 Mar;45(3):348–353. doi: 10.1002/jmv.1890450320. [DOI] [PubMed] [Google Scholar]
  13. Gonzalez-Peralta R. P., Davis G. L., Lau J. Y. Pathogenetic mechanisms of hepatocellular damage in chronic hepatitis C virus infection. J Hepatol. 1994 Aug;21(2):255–259. doi: 10.1016/s0168-8278(05)80405-2. [DOI] [PubMed] [Google Scholar]
  14. Knodell R. G., Ishak K. G., Black W. C., Chen T. S., Craig R., Kaplowitz N., Kiernan T. W., Wollman J. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology. 1981 Sep-Oct;1(5):431–435. doi: 10.1002/hep.1840010511. [DOI] [PubMed] [Google Scholar]
  15. Koziel M. J., Dudley D., Wong J. T., Dienstag J., Houghton M., Ralston R., Walker B. D. Intrahepatic cytotoxic T lymphocytes specific for hepatitis C virus in persons with chronic hepatitis. J Immunol. 1992 Nov 15;149(10):3339–3344. [PubMed] [Google Scholar]
  16. Liaw Y. F., Lee C. S., Tsai S. L., Liaw B. W., Chen T. C., Sheen I. S., Chu C. M. T-cell--mediated autologous hepatocytotoxicity in patients with chronic hepatitis C virus infection. Hepatology. 1995 Nov;22(5):1368–1373. [PubMed] [Google Scholar]
  17. Marcellin P., Pouteau M., Martinot-Peignoux M., Degos F., Duchatelle V., Boyer N., Lemonnier C., Degott C., Erlinger S., Benhamou J. P. Lack of benefit of escalating dosage of interferon alfa in patients with chronic hepatitis C. Gastroenterology. 1995 Jul;109(1):156–165. doi: 10.1016/0016-5085(95)90281-3. [DOI] [PubMed] [Google Scholar]
  18. Martinot-Peignoux M., Marcellin P., Pouteau M., Castelnau C., Boyer N., Poliquin M., Degott C., Descombes I., Le Breton V., Milotova V. Pretreatment serum hepatitis C virus RNA levels and hepatitis C virus genotype are the main and independent prognostic factors of sustained response to interferon alfa therapy in chronic hepatitis C. Hepatology. 1995 Oct;22(4 Pt 1):1050–1056. [PubMed] [Google Scholar]
  19. Mutchnick M. G., Appelman H. D., Chung H. T., Aragona E., Gupta T. P., Cummings G. D., Waggoner J. G., Hoofnagle J. H., Shafritz D. A. Thymosin treatment of chronic hepatitis B: a placebo-controlled pilot trial. Hepatology. 1991 Sep;14(3):409–415. [PubMed] [Google Scholar]
  20. Mutchnick M. G., Ehrinpreis M. N., Kinzie J. L., Peleman R. R. Prospectives on the treatment of chronic hepatitis B and chronic hepatitis C with thymic peptides and antiviral agents. Antiviral Res. 1994 Jul;24(2-3):245–257. doi: 10.1016/0166-3542(94)90071-x. [DOI] [PubMed] [Google Scholar]
  21. Nousbaum J. B., Pol S., Nalpas B., Landais P., Berthelot P., Bréchot C. Hepatitis C virus type 1b (II) infection in France and Italy. Collaborative Study Group. Ann Intern Med. 1995 Feb 1;122(3):161–168. doi: 10.7326/0003-4819-122-3-199502010-00001. [DOI] [PubMed] [Google Scholar]
  22. Okamoto H., Kurai K., Okada S., Yamamoto K., Lizuka H., Tanaka T., Fukuda S., Tsuda F., Mishiro S. Full-length sequence of a hepatitis C virus genome having poor homology to reported isolates: comparative study of four distinct genotypes. Virology. 1992 May;188(1):331–341. doi: 10.1016/0042-6822(92)90762-e. [DOI] [PubMed] [Google Scholar]
  23. Poynard T., Bedossa P., Chevallier M., Mathurin P., Lemonnier C., Trepo C., Couzigou P., Payen J. L., Sajus M., Costa J. M. A comparison of three interferon alfa-2b regimens for the long-term treatment of chronic non-A, non-B hepatitis. Multicenter Study Group. N Engl J Med. 1995 Jun 1;332(22):1457–1462. doi: 10.1056/NEJM199506013322201. [DOI] [PubMed] [Google Scholar]
  24. Rasi G., Mutchnick M. G., Di Virgilio D., Sinibaldi-Vallebona P., Pierimarchi P., Colella F., Favalli C., Garaci E. Combination low-dose lymphoblastoid interferon and thymosin alpha 1 therapy in the treatment of chronic hepatitis B. J Viral Hepat. 1996 Jul;3(4):191–196. doi: 10.1111/j.1365-2893.1996.tb00094.x. [DOI] [PubMed] [Google Scholar]
  25. Reichard O., Foberg U., Frydén A., Mattsson L., Norkrans G., Sönnerborg A., Wejstål R., Yun Z. B., Weiland O. High sustained response rate and clearance of viremia in chronic hepatitis C after treatment with interferon-alpha 2b for 60 weeks. Hepatology. 1994 Feb;19(2):280–285. [PubMed] [Google Scholar]
  26. Saito I., Miyamura T., Ohbayashi A., Harada H., Katayama T., Kikuchi S., Watanabe Y., Koi S., Onji M., Ohta Y. Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6547–6549. doi: 10.1073/pnas.87.17.6547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Simmonds P. Variability of hepatitis C virus. Hepatology. 1995 Feb;21(2):570–583. doi: 10.1002/hep.1840210243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Tinè F., Magrin S., Craxì A., Pagliaro L. Interferon for non-A, non-B chronic hepatitis. A meta-analysis of randomised clinical trials. J Hepatol. 1991 Sep;13(2):192–199. doi: 10.1016/0168-8278(91)90814-r. [DOI] [PubMed] [Google Scholar]
  29. Tsubota A., Chayama K., Ikeda K., Yasuji A., Koida I., Saitoh S., Hashimoto M., Iwasaki S., Kobayashi M., Hiromitsu K. Factors predictive of response to interferon-alpha therapy in hepatitis C virus infection. Hepatology. 1994 May;19(5):1088–1094. [PubMed] [Google Scholar]
  30. Yamada G., Takatani M., Kishi F., Takahashi M., Doi T., Tsuji T., Shin S., Tanno M., Urdea M. S., Kolberg J. A. Efficacy of interferon alfa therapy in chronic hepatitis C patients depends primarily on hepatitis C virus RNA level. Hepatology. 1995 Nov;22(5):1351–1354. [PubMed] [Google Scholar]
  31. Yoshioka K., Kakumu S., Wakita T., Ishikawa T., Itoh Y., Takayanagi M., Higashi Y., Shibata M., Morishima T. Detection of hepatitis C virus by polymerase chain reaction and response to interferon-alpha therapy: relationship to genotypes of hepatitis C virus. Hepatology. 1992 Aug;16(2):293–299. doi: 10.1002/hep.1840160203. [DOI] [PubMed] [Google Scholar]
  32. Zeldis J. B., Jensen P. Hepatitis C virus pathogenicity: the corner pieces of the jigsaw puzzle are found. Gastroenterology. 1994 Apr;106(4):1118–1120. [PubMed] [Google Scholar]

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