- Email: [email protected]
Liver metastases and procollagen mRNAs expression
101 LIVER
METASTASES
Mlani,
AND
PROCOLLAGEN
nRNAs
EXPRESSION.
H.
Herbsr, D. Schuppa”, M.R. Blagini, S. Vigan6, C. Surrenci. Gnstroenterology Unit, CliU”iV. of Florence, nical Pathophysiology Dept., Italy and Pathology and Castroenterology Depts., Free Univ. of Berlin, West: Germany. S.
The growth and diffusion of metastases in the liver is associated with their ability to interact with the hepatic extracellular matrix. nowever. little is know” about their influence on the reguWe have stulation of hepatic collage” synthesis. died the expression of procollagen I, III, and IV ,&NAs by in situ hybridization with (35)-S RNA probes and the immunohistochemical distribution of the corresponding procollagens and of desmin-positive cells in 4 iiver aetastasrs iron poorly differentiated colon adenocarcinomas. Procollagen I. III, and IV nRSAs were found highly expressed in sinusoidal cells adjacent to neoplastic cells and in nesenchynal cells of tumor stroma. Increased deposition of collagens and number of desmin-positive cells were observed in some sinusoids invaded by neoplastic cells and in t”mor stroma. We conclude that metastatic cells may induce an abnormal recruireent and/or differentiation of liver stromal cells and activate procoilagen gene expression in the tuF.or stro”a and the surrounding liver parenchyma. 103
184
R. Miiller, G. Gubernatis, H. Farle, C. Wittekind,
LONG-TERM TREATMEN WITH LDU OOSES ff INTERFERON ALFA-20 (rIFNaZbI IN PATIENTS WITH CWONIC NON-A, NON-B (NAN91 HEPATITIS : OATA OF A HULTICENTER RANDDMIZED PRDSPECTIVELV CDfllROLLED TRIAL.
LIVER TRANSPLIINTATION IN HSsAg POSITIVE GRAFT RECIPIENTS: PREVENTION OF HB" RECURRENCE BY PASSIVE IMHUNIZATION K. Btiker,
schule Hannover, FRG. Orthotopic liver transplantation has become the treatmeilt of choice for irreversible end-stage liver disease. However itS use $" patients With HGV infection remains controversial due to the high risk of HBV recurrence with associated liver diSease In the graft after surgery. In the present study the course of 34 HBsAg p"Sitive liver transplant recipients is reported. 23 received long-term passive imwnizatio" with a polyvalent HGIg preparation obtained from anti-deltfi negative donor sera after native NBV infection (Hepstect , Biotest Ltd., Frankfurt a.H., FRG 1. Anti-IlE% serum levels of >lOO III/l were maintained in 11 patients for 6 nanths and in 12 patients for 12 months after transplantation. In six patients HBIg was only given during the anhepatic phase of the operation. Five patients underwent liver grafting uithout any HGIg prophylaxis. The rate of recurrent HBV infections was found in less than 201 of individuals receiving long-term passive inuniration, whereas all 11 patients who had not bee" treated with gamnaglobulin or had received HBIg only once had experienced 4 reinfection within 15 nwnths after transplantation. The preoperative HBV marker profile in the Serum was 4 crucical indicator for HEY recurrence. Definite disappearence of HBSR9 from the serum was only observed in HIJV-ONA negative graft recipients after long-ten HBIg substitution. The mwtality rate of transplant reclpients with recurrent PBV infections was significantly higher than in patients without w-infection. HBV recurrence ~4s associated with Subclinical hepatitis runntng a chronic course. In patients, recurrent cirrhosis 1" the graft was show" on biopsy 20 and 31 months after surgery. Accordingly. long-term passive irnnunization with Ml9 sppearf to be a successful treatment procedure for prevention of recurrent HEY infection after liver transplantation and should be offered to HBsAg positive graft reclsQie"tS with S low replicative state of HGv.
two
R. Hiiller. R. Baumgerten. R. Harkus, KH. Beckh. K. Loeschke. P. Hcd. "ochschul.? H4""ove~. Stadt. Krhs. Qrenzlauer Bero. berlin. DDR. Med. Uniklinik i!arburg. Med. Uniklinik 1"ne;itadt &hen; Med. Unikllnik DiIsseldorf, t&d. Uniklinik TUbingen. In 4 phase I trial 5 out of 11 patients with chronic NAN8 hepatitis revealed e C.wnplete response ICR = normal All) to treatment with rlFN4Zb llntron A ESSEY-Pharm4lSchering-Plough) at 4 dose of 1 Megaunit &rice weekly for one year. Only one of these individuals experienced a relrpse upon discontinuation of IFN therapy. To verify these promising findings I Swlticcnter randomized controlled tri41 ~4s initiated in 93 patients with chronic NAN8 hepatitis of at least one year duration and without evidence of chronic hepatitis 9. eutoimnune or drug-Induced' liver disease. Anti-HCV testing end two liver btopsles taken at a" interval of least li lnonths duration were performed. 46 patients received 1 Hu of rlFNa2b according to the phase 1 trial protocol. patients served es untreated controls. Presently 14 patients treated and 17 centrals have canpleted the trials protocol. Another 39 individuals rre followed for more than 6 months. So far e CR waf see" in 6 (:32) and a partill response (reduction of AL1 >5011 in 10 13221 p4tients. Nom out of the patients with CR relapsed during follow-up. In responders liver biopsies befort Md after treatment showed e Pronounced reduction in i"flnn4tion. Side-effects were mild and well tolerated. Antimicrosolrl antibodies against thyroid tissue in the Serum were observed in tug femtle patients with hypcrthyreadism in one of them. These preliminary findings indiCe& e beneficial effect of e low-dose rIFNaZb therapy with chronic NAN9 hepatitis md suggest that frequent relapses observed et discontinuation of short-term IFN medication may be woidcd by long-term treatment.
at
47
METASTASES
Mlani,
AND
PROCOLLAGEN
nRNAs
EXPRESSION.
H.
Herbsr, D. Schuppa”, M.R. Blagini, S. Vigan6, C. Surrenci. Gnstroenterology Unit, CliU”iV. of Florence, nical Pathophysiology Dept., Italy and Pathology and Castroenterology Depts., Free Univ. of Berlin, West: Germany. S.
The growth and diffusion of metastases in the liver is associated with their ability to interact with the hepatic extracellular matrix. nowever. little is know” about their influence on the reguWe have stulation of hepatic collage” synthesis. died the expression of procollagen I, III, and IV ,&NAs by in situ hybridization with (35)-S RNA probes and the immunohistochemical distribution of the corresponding procollagens and of desmin-positive cells in 4 iiver aetastasrs iron poorly differentiated colon adenocarcinomas. Procollagen I. III, and IV nRSAs were found highly expressed in sinusoidal cells adjacent to neoplastic cells and in nesenchynal cells of tumor stroma. Increased deposition of collagens and number of desmin-positive cells were observed in some sinusoids invaded by neoplastic cells and in t”mor stroma. We conclude that metastatic cells may induce an abnormal recruireent and/or differentiation of liver stromal cells and activate procoilagen gene expression in the tuF.or stro”a and the surrounding liver parenchyma. 103
184
R. Miiller, G. Gubernatis, H. Farle, C. Wittekind,
LONG-TERM TREATMEN WITH LDU OOSES ff INTERFERON ALFA-20 (rIFNaZbI IN PATIENTS WITH CWONIC NON-A, NON-B (NAN91 HEPATITIS : OATA OF A HULTICENTER RANDDMIZED PRDSPECTIVELV CDfllROLLED TRIAL.
LIVER TRANSPLIINTATION IN HSsAg POSITIVE GRAFT RECIPIENTS: PREVENTION OF HB" RECURRENCE BY PASSIVE IMHUNIZATION K. Btiker,
schule Hannover, FRG. Orthotopic liver transplantation has become the treatmeilt of choice for irreversible end-stage liver disease. However itS use $" patients With HGV infection remains controversial due to the high risk of HBV recurrence with associated liver diSease In the graft after surgery. In the present study the course of 34 HBsAg p"Sitive liver transplant recipients is reported. 23 received long-term passive imwnizatio" with a polyvalent HGIg preparation obtained from anti-deltfi negative donor sera after native NBV infection (Hepstect , Biotest Ltd., Frankfurt a.H., FRG 1. Anti-IlE% serum levels of >lOO III/l were maintained in 11 patients for 6 nanths and in 12 patients for 12 months after transplantation. In six patients HBIg was only given during the anhepatic phase of the operation. Five patients underwent liver grafting uithout any HGIg prophylaxis. The rate of recurrent HBV infections was found in less than 201 of individuals receiving long-term passive inuniration, whereas all 11 patients who had not bee" treated with gamnaglobulin or had received HBIg only once had experienced 4 reinfection within 15 nwnths after transplantation. The preoperative HBV marker profile in the Serum was 4 crucical indicator for HEY recurrence. Definite disappearence of HBSR9 from the serum was only observed in HIJV-ONA negative graft recipients after long-ten HBIg substitution. The mwtality rate of transplant reclpients with recurrent PBV infections was significantly higher than in patients without w-infection. HBV recurrence ~4s associated with Subclinical hepatitis runntng a chronic course. In patients, recurrent cirrhosis 1" the graft was show" on biopsy 20 and 31 months after surgery. Accordingly. long-term passive irnnunization with Ml9 sppearf to be a successful treatment procedure for prevention of recurrent HEY infection after liver transplantation and should be offered to HBsAg positive graft reclsQie"tS with S low replicative state of HGv.
two
R. Hiiller. R. Baumgerten. R. Harkus, KH. Beckh. K. Loeschke. P. Hcd. "ochschul.? H4""ove~. Stadt. Krhs. Qrenzlauer Bero. berlin. DDR. Med. Uniklinik i!arburg. Med. Uniklinik 1"ne;itadt &hen; Med. Unikllnik DiIsseldorf, t&d. Uniklinik TUbingen. In 4 phase I trial 5 out of 11 patients with chronic NAN8 hepatitis revealed e C.wnplete response ICR = normal All) to treatment with rlFN4Zb llntron A ESSEY-Pharm4lSchering-Plough) at 4 dose of 1 Megaunit &rice weekly for one year. Only one of these individuals experienced a relrpse upon discontinuation of IFN therapy. To verify these promising findings I Swlticcnter randomized controlled tri41 ~4s initiated in 93 patients with chronic NAN8 hepatitis of at least one year duration and without evidence of chronic hepatitis 9. eutoimnune or drug-Induced' liver disease. Anti-HCV testing end two liver btopsles taken at a" interval of least li lnonths duration were performed. 46 patients received 1 Hu of rlFNa2b according to the phase 1 trial protocol. patients served es untreated controls. Presently 14 patients treated and 17 centrals have canpleted the trials protocol. Another 39 individuals rre followed for more than 6 months. So far e CR waf see" in 6 (:32) and a partill response (reduction of AL1 >5011 in 10 13221 p4tients. Nom out of the patients with CR relapsed during follow-up. In responders liver biopsies befort Md after treatment showed e Pronounced reduction in i"flnn4tion. Side-effects were mild and well tolerated. Antimicrosolrl antibodies against thyroid tissue in the Serum were observed in tug femtle patients with hypcrthyreadism in one of them. These preliminary findings indiCe& e beneficial effect of e low-dose rIFNaZb therapy with chronic NAN9 hepatitis md suggest that frequent relapses observed et discontinuation of short-term IFN medication may be woidcd by long-term treatment.
at
47