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Variceal bleeding in non-cholestatic PBC: subgroup with improved prognosis
Category 9: Immunology, autoimmune liver disease (IA-2A) in 44 patients with autoimrnune hepatopathy. 16 of them had primary biliary cirrhosis (PBC), 28 autoimmune hepatitis (AIH). They have been diagnosed approximately 7.2 years ago. 27 patients with AIH were treated with immunosupresive therapy before the study started. We compared the results with 15 healthy controls. Results: There were 5 (11%) patients ICA positive (NS), 10 (22%) IAA postitive (p = 0.04), 9 (20%) GADA positive (p = 0.057), 2 (4.5%) IA-2A positive (NS) in the study group. 4 patients have had more than 1 marker positive. In the control group there were no patients with any positive marker for IDDM (p = 0.001). Condusious: We proved positive markers of IDDM in 20 (45%) patients with autoimmune hepatopathy. Even though the markers were positive, nobody has suffered from IDDM yet. All these patients will be further followed up and they will be tested by intravenous glucagon test.
~ 1 1 - ~ HUMORAL IMMUNE RESPONSE IN CHILDREN WITH BILARY ATRESIA SPLENIC MALFORMATION SYNDROME R.M. Taylor, E Cheeseman, D. Goldblatt, M. Davenport, G. Mieli-Vergani, A. Dhawan, A. Baker, N. Hadzic. Department of
Child Health, King's College Hospital, London, UK 10-15% of infants with biliary atresia (BA) have splenic malformations (BASM) and have worse long-term prognosis. Aims: to determine whether children with BASM mount the same immune response to immunisations as those without splenic abnormalities. Method: 20 children with BASM (median age at presentation 0.12 [range 0.02~3.3] months, 5 male) were studied. Age and sex matched control data were obtained from 20 children with BA and normal spleen. Data is presented as median [range] Results: Date of vaccination was known in 14 in the BASM group and 15 in the BA group. Tetanus antibody concentrations after the third DPT (n -- 14) were 1.174 [0.129->2.33] iu/ml in the BASM group compared to 0.849 [0.116->2.30] iu/ml in BA, p = NS. After the pre-school booster (n -- 5) antibody levels were 0.332 [0.054->2.33] iu/ml and 2.3 [0.642->2.30] iu/ml respectively, (p --- 0.04). The total number of hospital admissions in the BASM group were 46 [range 0-8 per patient] and 28 [range 0--4 per patient] in the BA group, p = NS. Cholangitis occurred 13 times in each group and respiratory infection in 20 with BASM versus 9 with BA, p = NS. 3 children with BASM died (2 with sepsis) but none with BA. Conclusion: Splenic abnormalities in children with biliary atresia are not associated with altered humoral immune response in the first year of life but there is diminished response by 5 years. This does not appear to predispose to serious infections, while the effect on minor infection is unknown.
was 59.4 years + 2 (F/M: 22/4) which was not significantly different from those >34 μmol/1 (n = 76) but ALP was lower (476 U/1-4- 52 v. 630 U/I -4- 50, p = 0.035) and no difference in albumin values, but a longer survival mean 59 months q- 9 v. 26 -4- 4 of the others 76 patients (p < 0.0001). Condusious: There is a subgroup of PBC patients with near normal bilirubin levels who have significant portal hypertension and present with variceal bleeding as the first sign of PBC (i.e. no previous cholestatic symptoms) whilst having stage 4 histology. This group represents a different clinical expression of the disease and would not conform to current prognostic models.
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VARICEAL BLEEDING IN NON-CHOLESTATIC PBC: SUBGROUP WITH IMPROVED PROGNOSIS
J. Vlachogiannakos, M.L. Raimondo, J. Goulis, M. Feudjo 1, J. Carpenter l, D. Patch, A.K. Burroughs. Liver Transplantation Unit,
Royal Free Hospital; ~L.S.T.M.H. (Medical Statistics), UCL, London, UK Background: Varices are a late complication in PBC and have been used as a surrogate marker of progression. However, individual PBC patients without clinical or biochemical cholestasis have been noted to bleed from varices. It is not known if this represents a different clinical expression of the disease. Aim: Using our PBC data base (n = 370) for characteristics of variceal bleeding to evaluate patients with bilirubin < 34 μmol/l at time of bleeding. Patients/Results: 102 variceal bleeders: 26 (25%) had bilirubin < 34 μmol/1. They all had stage 4 histologically and only 4 had ascites; for 13 variceal bleeding was the first presentation of PBC. The mean age
EARLY PRIMARY BILIARY CIRRHOTICS DEMONSTRATE HYPERCOAGULABILITY BY THROMBOELASTOGRAPHY
J. Vlachogiannakos, P. Montalto, M.L. Raimondo, D. Cox 1, D. Patch, A.K. Burroughs. Liver Transplantation Unit; 1Anaesthesia
Department, Royal Free Hospital, London, UK Background: We previously showed, advanced PBC patients are hypercoagulable with no thrombophilic factors compared to non-cholestatic cirrhotics (J Hepatol 1997; 26: 554). Aim: Assess hypercoagulability in early stage PBC. Methods: 34 early PBC patients [median age: 57.5 (33-71), stage 1/2, median bilirubin: 16.5 μ mol/l (5-58), no evidence of portal hypertension] and 40 healthy controls (median age: 51 (28-72), from a previous study were evaluated with thromboelastography (TEG), FBC, PT, APTT and LFFs. Hypercoagulability defined by TEG values > 2SD over controls (r < 19 mm, MA > 60 rnm, alpha angle > 43). Results: All three TEG parameters were abnormal in 10/34 (29.4%) PBC but 0% in controls (p < 0.001). The median values of r and alpha angle between PBC and controls were not different but the MA was significantly greater in the PBC group [63.8 mm (48.5-83.5) v 52 mm (48-56), p < 0.001] reflecting hypercoagulability. No differences in serum bilirubin (p = 0.42) and albumin (p -- 0.36) between PBC with or without hypercoagulability. PT and APTF were not significantly different between PBC and controls and not correlated with r values (p = 0.10 and p = 0.30 respectively) which were abnormal in 13 PBC (38%). MA was increased in 22 (64.7%) PBC but 0 controls (p < 0.001). alpha angle was abnormal in 17 (50%) PBC patients versus 10 (25%) controls (p = 0.025). MA had no correlation with bilirubin (p = 0.37) or albumin (p = 0.65). Conclusions: Hypercoagulability detected by TEG occurs in early stage PBC. The implications of these findings in clinical practice need to be evaluated.
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215
IL-2 INDUCED IMMUNOCOMPETENCE IN HIV/HCV OR HIV/I-IBV COINFECTED PATIENTS UNDER ANTIRETROVIRAL THERAPY
A. Barreiros, J. Schlaak, C. Schramm, E. Bayer, P. Galle, H. Jaeger,
H. Loehr. L Department, Universityof Mainz, Germany HIV patients coinfected with HCV or HBV presented oftenly with progressive liver disease, liver cirrhosis and its complications. The efficacy of the antiretroviral regime, however, is decisive for their overall prognosis. In this study it was analysed whether interleukin-2 (IL-2) has antiviral or immunomodulating activities with respect to the HIV and HCV or HBV replication and the absolute CD4+ T cell counts. IL-2 was administered s.c. daily in increasing dosages for 6 months (2-3-4 miu/die for two months). Furthermore, these patients received an effective HAART and presented with a stable viral load of < 104 HIV copies/ml. Neither HIV nor HCV or HBV replication was significantly influenced by the daily low-dose IL-2 coadministration, however, in five patients IL-2 treatment had to be stopped of adverse side-effects or worsening
~ 1 1 - ~ HUMORAL IMMUNE RESPONSE IN CHILDREN WITH BILARY ATRESIA SPLENIC MALFORMATION SYNDROME R.M. Taylor, E Cheeseman, D. Goldblatt, M. Davenport, G. Mieli-Vergani, A. Dhawan, A. Baker, N. Hadzic. Department of
Child Health, King's College Hospital, London, UK 10-15% of infants with biliary atresia (BA) have splenic malformations (BASM) and have worse long-term prognosis. Aims: to determine whether children with BASM mount the same immune response to immunisations as those without splenic abnormalities. Method: 20 children with BASM (median age at presentation 0.12 [range 0.02~3.3] months, 5 male) were studied. Age and sex matched control data were obtained from 20 children with BA and normal spleen. Data is presented as median [range] Results: Date of vaccination was known in 14 in the BASM group and 15 in the BA group. Tetanus antibody concentrations after the third DPT (n -- 14) were 1.174 [0.129->2.33] iu/ml in the BASM group compared to 0.849 [0.116->2.30] iu/ml in BA, p = NS. After the pre-school booster (n -- 5) antibody levels were 0.332 [0.054->2.33] iu/ml and 2.3 [0.642->2.30] iu/ml respectively, (p --- 0.04). The total number of hospital admissions in the BASM group were 46 [range 0-8 per patient] and 28 [range 0--4 per patient] in the BA group, p = NS. Cholangitis occurred 13 times in each group and respiratory infection in 20 with BASM versus 9 with BA, p = NS. 3 children with BASM died (2 with sepsis) but none with BA. Conclusion: Splenic abnormalities in children with biliary atresia are not associated with altered humoral immune response in the first year of life but there is diminished response by 5 years. This does not appear to predispose to serious infections, while the effect on minor infection is unknown.
was 59.4 years + 2 (F/M: 22/4) which was not significantly different from those >34 μmol/1 (n = 76) but ALP was lower (476 U/1-4- 52 v. 630 U/I -4- 50, p = 0.035) and no difference in albumin values, but a longer survival mean 59 months q- 9 v. 26 -4- 4 of the others 76 patients (p < 0.0001). Condusious: There is a subgroup of PBC patients with near normal bilirubin levels who have significant portal hypertension and present with variceal bleeding as the first sign of PBC (i.e. no previous cholestatic symptoms) whilst having stage 4 histology. This group represents a different clinical expression of the disease and would not conform to current prognostic models.
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VARICEAL BLEEDING IN NON-CHOLESTATIC PBC: SUBGROUP WITH IMPROVED PROGNOSIS
J. Vlachogiannakos, M.L. Raimondo, J. Goulis, M. Feudjo 1, J. Carpenter l, D. Patch, A.K. Burroughs. Liver Transplantation Unit,
Royal Free Hospital; ~L.S.T.M.H. (Medical Statistics), UCL, London, UK Background: Varices are a late complication in PBC and have been used as a surrogate marker of progression. However, individual PBC patients without clinical or biochemical cholestasis have been noted to bleed from varices. It is not known if this represents a different clinical expression of the disease. Aim: Using our PBC data base (n = 370) for characteristics of variceal bleeding to evaluate patients with bilirubin < 34 μmol/l at time of bleeding. Patients/Results: 102 variceal bleeders: 26 (25%) had bilirubin < 34 μmol/1. They all had stage 4 histologically and only 4 had ascites; for 13 variceal bleeding was the first presentation of PBC. The mean age
EARLY PRIMARY BILIARY CIRRHOTICS DEMONSTRATE HYPERCOAGULABILITY BY THROMBOELASTOGRAPHY
J. Vlachogiannakos, P. Montalto, M.L. Raimondo, D. Cox 1, D. Patch, A.K. Burroughs. Liver Transplantation Unit; 1Anaesthesia
Department, Royal Free Hospital, London, UK Background: We previously showed, advanced PBC patients are hypercoagulable with no thrombophilic factors compared to non-cholestatic cirrhotics (J Hepatol 1997; 26: 554). Aim: Assess hypercoagulability in early stage PBC. Methods: 34 early PBC patients [median age: 57.5 (33-71), stage 1/2, median bilirubin: 16.5 μ mol/l (5-58), no evidence of portal hypertension] and 40 healthy controls (median age: 51 (28-72), from a previous study were evaluated with thromboelastography (TEG), FBC, PT, APTT and LFFs. Hypercoagulability defined by TEG values > 2SD over controls (r < 19 mm, MA > 60 rnm, alpha angle > 43). Results: All three TEG parameters were abnormal in 10/34 (29.4%) PBC but 0% in controls (p < 0.001). The median values of r and alpha angle between PBC and controls were not different but the MA was significantly greater in the PBC group [63.8 mm (48.5-83.5) v 52 mm (48-56), p < 0.001] reflecting hypercoagulability. No differences in serum bilirubin (p = 0.42) and albumin (p -- 0.36) between PBC with or without hypercoagulability. PT and APTF were not significantly different between PBC and controls and not correlated with r values (p = 0.10 and p = 0.30 respectively) which were abnormal in 13 PBC (38%). MA was increased in 22 (64.7%) PBC but 0 controls (p < 0.001). alpha angle was abnormal in 17 (50%) PBC patients versus 10 (25%) controls (p = 0.025). MA had no correlation with bilirubin (p = 0.37) or albumin (p = 0.65). Conclusions: Hypercoagulability detected by TEG occurs in early stage PBC. The implications of these findings in clinical practice need to be evaluated.
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215
IL-2 INDUCED IMMUNOCOMPETENCE IN HIV/HCV OR HIV/I-IBV COINFECTED PATIENTS UNDER ANTIRETROVIRAL THERAPY
A. Barreiros, J. Schlaak, C. Schramm, E. Bayer, P. Galle, H. Jaeger,
H. Loehr. L Department, Universityof Mainz, Germany HIV patients coinfected with HCV or HBV presented oftenly with progressive liver disease, liver cirrhosis and its complications. The efficacy of the antiretroviral regime, however, is decisive for their overall prognosis. In this study it was analysed whether interleukin-2 (IL-2) has antiviral or immunomodulating activities with respect to the HIV and HCV or HBV replication and the absolute CD4+ T cell counts. IL-2 was administered s.c. daily in increasing dosages for 6 months (2-3-4 miu/die for two months). Furthermore, these patients received an effective HAART and presented with a stable viral load of < 104 HIV copies/ml. Neither HIV nor HCV or HBV replication was significantly influenced by the daily low-dose IL-2 coadministration, however, in five patients IL-2 treatment had to be stopped of adverse side-effects or worsening