LETTERS
TO THE EDITOR
419
infectious pathogens acts as an endogenous immunosuppressant, which further aggravates the imm~~odeficie~cy state of these patients. We are indebted to Miss G. Schijnhuber for her excellent technical assistance. This work was financially supported by a grant of the Austrian Research Fund ‘Zur Fiirderung der wissenschaftlichen Forschung’, project No. 7475.
. Tllg’, U. Westhop, W. Vogel’, W.E. Aulitzkf, M. Herold’, R. argreiter4, C. I&be? and H. Grosse-Wilde’ I Divisions of Ciinicai Immunobioiopy and Gastroenterology, Department of Internal Medicine, Innsbruck University Hospital, Intwbruck, Austria, 2rs apartment of Immunogenedcs, University Hospital of Essen, Essen, Federal Republic of Germany, ‘Department of Hemaiology, Johannes Gutenberg University, Mainz, Federal Republic of Germany and ‘Division of Transplant Surgery, First Department of Surgery, Innsbruck Hospital, Innsbruck, Austria
RePerences
bent assay. Blut 1989; 59: 449-54. Tilg H, Vogel W, Aulitzky WE, et al. Evaluation cytokine-induced secondary messages in sera liver transplantation. Transplantation 1990; 49: Suminoto RS, Kamada N. Specific suppression jection by soluble class I antigen and complexes antibody. Transplantation 1990; 50: 678-82.
1 Davies HS, Pollard SG, Caine RY. Soluble HLA antigens in the circulation of liver graft recipients. Transplantation 1989; 47: 524-9. 2 Doxiadis I, Westhoff U, Grosse-Wilde H. Quantification of soluble HLA class I gene products by an enzyme linked immunosor-
of cytokines and of patients after 1074-80. of allograft rewith monoclonal
HEPAT 01062
Interferon is effective in treating both B- and C-type chronic active hepatitis (CAM) (l-3). However, a number of patients do not respond to this treatment, and criteria for the identification of responders and nonresponders have yet to be established (4). Here we report the preliminary findings of a study in which ten C-virus CAH patients, who failed to respond to recombinant interferon-a treatment (Roferon-Roche. 3 MU three times a week for 4 months and 6 MU three times a week for a further 2 months), were treated,, after a with lymphoblastoid interferon 4-month interval, (Wellferon-Wellcome. 6 MU three times a week for 2
months followed by 3 MU three times a week for 4 months). All subjects had elevated serum enzyme activity (alanine transaminase, ALT, 4-6-times above norma!). Patient sera were not checked for neutralising antibodies against the recombinant interferon alpha (5). As shown in Table 1, ALT values reverted to normal in live patients within 2 months of treatment, and remained normal for the follow-up period of 6 months after discontinuation of therapy. Liver biopsy performed in three of these five patients showed improved histology. The statistical analysis by the McNemar test tends towards significancy of results @ < 0.1 > 0.05).
TABLE 1 Alanine transaminase (ALT) values before and after interferon t.epatitis patients ‘non-responders’ to recombinant IFN-a No.
1 2 3 4 5 6 7 8 9 10
Sex
M M M F M F F M F F
treatments
(rIFN-a
and lymphoblastoid-IFN,
Age
ALT (U/l) (nr rmal value ~40)
(years)
rIFN-a
47 46 42 60 48 62 53 32 67 55
respectively)
in ten chronic
lymphoblastoid-IFN
before
alrer
before
after
226 173 205 135 284 570 210 392 40.5 142
129 297 185 108 104 138 I62 289 108 113
154 275 153 120 135 270 139 179 121 114
36 44 20 118 153 23 28 502 186 97
420 The improvement obtained in our five patients is probably related to the change in interferon preparation and dosage schedule. Recently, lymphoblastoid interferon has been shown to be very effective in HCV hepatitis (6,7). The small number of patients in the present study prevents us from drawing any final conclusion; however, it appears that a second course of treatment with a different interferon preparation can be useful in some CAH
References 1 Alexander GJM, Brahm J, Fagan EA, et al. Loss of HBsAg with interferon therapy in chronic hepatitis B virus infection. Lancet 1987; ii: 66-8. 2 Saracco G, Mazzella G, Rosina F, et al. A controlled trial of human lymphoblastoid interferon in chronic hepatitis B in Italy. Hepatology 1989; 10: 336-41. 3 Davis GL, Balart LA, Schiff ER, et al. Treatment of chronic hepatitis C with recombinant interferon alfa. Multicenter randomized, controlled trial. N Engl J Med 1989; 321: 1501-6. 4 Eddleston ALWF. The natural history of hepatitis B virus infections. Chemioterapia 1988; 7 (S3): 5-8.
LETTERS TO THE EDITOR
patients who failed to respond to an earlier course of interferon treatment.
Lucia Cimino, Cinzia Citarella, Gerard0 Gabriele Budillon
Nardone and
Cattedra di Gastroenterologia 2, II Facolta’ di Medicina, Universita’ di Napoli Federico II, Naples, Italy
5 Antonelli G, Currenti M, Turriziani 0, Dianzani F. Neutralizing antibodies to interferon alpha: relative frequency in patients treated with different interferon preparation. J Infect Dis 1991; 163: 882-5. 6 Ideo G, Bellati G, Pedraglio E, Alfieri G. Recombinant alpha 2a interferon, lymphoblastoid alpha interferon or no treatment for nAnb chronic active hepatitis: a prospective randomized controlled trial. Abstract: 40th Meeting of American Association for liver disease. Chicago, 1989. 7 Mazzella G, Villanova N, Bazzoli F, et al. Preliminary results of a randomized controlled trial with human lymphoblastoid interferon in chronic non-a, non-b hepatitis. Abstract: International Symposium on Viral Hepatitis and Liver Disease, Houston, 1990.
TO THE EDITOR
419
infectious pathogens acts as an endogenous immunosuppressant, which further aggravates the imm~~odeficie~cy state of these patients. We are indebted to Miss G. Schijnhuber for her excellent technical assistance. This work was financially supported by a grant of the Austrian Research Fund ‘Zur Fiirderung der wissenschaftlichen Forschung’, project No. 7475.
. Tllg’, U. Westhop, W. Vogel’, W.E. Aulitzkf, M. Herold’, R. argreiter4, C. I&be? and H. Grosse-Wilde’ I Divisions of Ciinicai Immunobioiopy and Gastroenterology, Department of Internal Medicine, Innsbruck University Hospital, Intwbruck, Austria, 2rs apartment of Immunogenedcs, University Hospital of Essen, Essen, Federal Republic of Germany, ‘Department of Hemaiology, Johannes Gutenberg University, Mainz, Federal Republic of Germany and ‘Division of Transplant Surgery, First Department of Surgery, Innsbruck Hospital, Innsbruck, Austria
RePerences
bent assay. Blut 1989; 59: 449-54. Tilg H, Vogel W, Aulitzky WE, et al. Evaluation cytokine-induced secondary messages in sera liver transplantation. Transplantation 1990; 49: Suminoto RS, Kamada N. Specific suppression jection by soluble class I antigen and complexes antibody. Transplantation 1990; 50: 678-82.
1 Davies HS, Pollard SG, Caine RY. Soluble HLA antigens in the circulation of liver graft recipients. Transplantation 1989; 47: 524-9. 2 Doxiadis I, Westhoff U, Grosse-Wilde H. Quantification of soluble HLA class I gene products by an enzyme linked immunosor-
of cytokines and of patients after 1074-80. of allograft rewith monoclonal
HEPAT 01062
Interferon is effective in treating both B- and C-type chronic active hepatitis (CAM) (l-3). However, a number of patients do not respond to this treatment, and criteria for the identification of responders and nonresponders have yet to be established (4). Here we report the preliminary findings of a study in which ten C-virus CAH patients, who failed to respond to recombinant interferon-a treatment (Roferon-Roche. 3 MU three times a week for 4 months and 6 MU three times a week for a further 2 months), were treated,, after a with lymphoblastoid interferon 4-month interval, (Wellferon-Wellcome. 6 MU three times a week for 2
months followed by 3 MU three times a week for 4 months). All subjects had elevated serum enzyme activity (alanine transaminase, ALT, 4-6-times above norma!). Patient sera were not checked for neutralising antibodies against the recombinant interferon alpha (5). As shown in Table 1, ALT values reverted to normal in live patients within 2 months of treatment, and remained normal for the follow-up period of 6 months after discontinuation of therapy. Liver biopsy performed in three of these five patients showed improved histology. The statistical analysis by the McNemar test tends towards significancy of results @ < 0.1 > 0.05).
TABLE 1 Alanine transaminase (ALT) values before and after interferon t.epatitis patients ‘non-responders’ to recombinant IFN-a No.
1 2 3 4 5 6 7 8 9 10
Sex
M M M F M F F M F F
treatments
(rIFN-a
and lymphoblastoid-IFN,
Age
ALT (U/l) (nr rmal value ~40)
(years)
rIFN-a
47 46 42 60 48 62 53 32 67 55
respectively)
in ten chronic
lymphoblastoid-IFN
before
alrer
before
after
226 173 205 135 284 570 210 392 40.5 142
129 297 185 108 104 138 I62 289 108 113
154 275 153 120 135 270 139 179 121 114
36 44 20 118 153 23 28 502 186 97
420 The improvement obtained in our five patients is probably related to the change in interferon preparation and dosage schedule. Recently, lymphoblastoid interferon has been shown to be very effective in HCV hepatitis (6,7). The small number of patients in the present study prevents us from drawing any final conclusion; however, it appears that a second course of treatment with a different interferon preparation can be useful in some CAH
References 1 Alexander GJM, Brahm J, Fagan EA, et al. Loss of HBsAg with interferon therapy in chronic hepatitis B virus infection. Lancet 1987; ii: 66-8. 2 Saracco G, Mazzella G, Rosina F, et al. A controlled trial of human lymphoblastoid interferon in chronic hepatitis B in Italy. Hepatology 1989; 10: 336-41. 3 Davis GL, Balart LA, Schiff ER, et al. Treatment of chronic hepatitis C with recombinant interferon alfa. Multicenter randomized, controlled trial. N Engl J Med 1989; 321: 1501-6. 4 Eddleston ALWF. The natural history of hepatitis B virus infections. Chemioterapia 1988; 7 (S3): 5-8.
LETTERS TO THE EDITOR
patients who failed to respond to an earlier course of interferon treatment.
Lucia Cimino, Cinzia Citarella, Gerard0 Gabriele Budillon
Nardone and
Cattedra di Gastroenterologia 2, II Facolta’ di Medicina, Universita’ di Napoli Federico II, Naples, Italy
5 Antonelli G, Currenti M, Turriziani 0, Dianzani F. Neutralizing antibodies to interferon alpha: relative frequency in patients treated with different interferon preparation. J Infect Dis 1991; 163: 882-5. 6 Ideo G, Bellati G, Pedraglio E, Alfieri G. Recombinant alpha 2a interferon, lymphoblastoid alpha interferon or no treatment for nAnb chronic active hepatitis: a prospective randomized controlled trial. Abstract: 40th Meeting of American Association for liver disease. Chicago, 1989. 7 Mazzella G, Villanova N, Bazzoli F, et al. Preliminary results of a randomized controlled trial with human lymphoblastoid interferon in chronic non-a, non-b hepatitis. Abstract: International Symposium on Viral Hepatitis and Liver Disease, Houston, 1990.
