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Hepatitis C viral (HCV) infection and liver transplantation (LT) — relation of outcome to posttransplant steroid use
HEFATOLOGY Vol. 22, No. 4, P t . 2, 1995
AASLD ABSTRACTS
1 3 6 1 HEPATITIS
447A
C VIRAL (HCV) INFECTION AND LIVER TRANSPLANTATION (LT) - RELATION OF OUTCOME TO POSTTRANSPLANT STEROID USE: L Lerut M. Donatacdo. O. Ci¢¢arelli. Ch. Comu*. P.F. Laterre**, LB. Otte - Depts of Digestive Surgery, Virology*, Intensive Care** - Univ. Hospital St-Luc - Catholic Univ. of Louvain - Brussels - Belgium
1 3 6 2 PREVALENCE,AND RISK FACTORS FOR GALLSTONE DISEASE IN FRANCE: A
During the period february 1984-december 1993, fifty seven (20.6 %) of 276 adults underwent LT because of posthepatitis C cirrhosis (priorHCV pat.); thirteen (4.7%) patients acquired HCV-infection following LT (post-HCV pat.). Clinical and histological outcome of HCV (re)infection in 67 long-term survivors were analyzed in relation to steroid use. Nine (12.8 %) pat. died during late (> 3 mo.) post-LT period. One post HCV patient died because of HCV-allograft reinfection; two prior-HCV and one post-HCV patients died of fungal infection following severe HCV-infection. None of the pat. got antiviral therapy during post'transplant period. All patients had CyA based IS. "High dose steroid pat/' (HD-ster Group I) had a total first week dose of methyl-prednisolone (MP) of at least 1650 mgr and all continued steroids throughout follow-up. "Low dose steroid pat." (LD-ster Group II) had a first week MP dose of 300 mgr and all, but one, discontinued steroids within one post-LT year. Group I contained 33 prior-HCV and 13 post-HCV pat.; group II 21 prior-HCV patients. Inddences of rejection (34/46 pat-73.9 % i n group I and 17/21 pat-80.9 % in group II) as well as use of antilymphocytic serum (33/46 pat-71.7 % in group I and 12/21 pat.-57.1% in group II) were not significantly different.
OBJECTIVE: The prevalence of gallstone disease is still unknown in France. Therefore, to investigate the prevalence and associated factors of gallstone disease in an unselected population, we carried out a prospective survey on gallstone disease using ultrasonography. PATIENTS AND METHODS: A random sample of 437 volunteers (mean age 37, range 17-64), members of the hospital staff, entered the study and were screened by a gallbladder ultrasonography performed after an overnight fast. To assess risk factors for gallstone disease, they answered a preceded questionnaire and had a blood sample taken in the fasting condition which included blood glucose, creatinin, urea, uric acid, cholesterol and triglycerides. RESULTS: Prevalence of gallstone disease was 9.3% (10.4% for women and 6% for men). After adjustement with the Sirmione sludy (1), the 2 population samples were statistically comparable. Statistically significant associations (p<0.05) with cholelithiasis were observed for the following items: age, personal previous history of bilary pain in the preceding 5 years, familial history of cholecystectomy and, in women only, a body mass index greater than 25 kg/(m) 2. A positive, but not significant, association was observed with sex and parity. Oral contraceptives, alcohol consumption or cigarettes smoking, diabetes, hypercholesterolemia, hypertriglyceridemia were not risk factors in our study. In women, a cumulative association was observed belween the prevalence of cholelithiasis and the number of risk factors. CONCLUSIONS: This ongoing study reports a gallstone prevalence of 9.3% in France. This prevalence seems to be similar to that estimated in most Western European countries and to remain stable in Europe since 10 years.
High dose steroids (gI) Low dose steroids (gII) HCV prior post LT HCV prior LT median follow-up 1550d (134 to 3497) 546 d (122 to 892) hepatitis - acute 6 2 (2 +) 9 (1 +) - chronic 16 (1 +) 8 9 cirrhosis 5° 2 1 39/46 pat. (84.8 %) 19/21 pat. (90.5 %)
Total 17 (25.4 %) 33 (49.5 %) 8 (11.9 %) 58 (86.6 %)
There was no difference between LD and HD steroid use in relation to the histoloKical evolution of HCV allograft (re)infection.
1 3 6 3 STUDY OF "HEPATOTROIMIlC" SUBSTANCES AFTER PORTAL BRANCHES UGATION IN THE RAT. B LL X Havaux. L ~ . Lab. of Experimental S ~ , Univemk,y of Louvaut, Brussels, Belgium. In order to study the complex aUvphy-hypertrophyreaction following the ligation of portalbra~es, m occluding PE catheterwas insmtod in the branch feed~the l d latoral and ~ lobm of Wmmr r ~ md ] mi saline infused for 24 hr. At tha~time, in comperison with sham operatedrats, a 30% atrophy of the lis~mr~lobes (LL) is observed : nxlucfion of the ratio LL weight/body weight (LL/BW) ~ ambacreasein the DNA ¢ ¢ m ~ h ~ . The DNA contmt remainsm ~ n s e d ; this, in absence of sips of DNA symbesis and at histology of leukocy~ infiluafion, susgests a reductionof ceil volume. There am only a few minor aress of necrosis and no s i ~ of apoptosis. On sel electrcpho~is, fmgmem~m of DNA do~ n ~ appem before 24 hr. ~ ~mte of tlw rek~ively minor ,~,~-e~_ in the LL, in the non-ligted lobes (HI.L), the 3-1-1thynud~ uptake in D N A (TdrU) at itspeak at 24 hr isthreethnes greatertlum a0.era 1/3 paff~d bq~__,~_~,~myaml only 50% less than a~er a 2/3PH. Wbm 4 units of insulin are addedm salin~ infusion, the nxhc~ion of cell voh.ne is Ires marked : higher DNA/g and LL/BW; the weisbt of the NLL also incrases with no dum~ in T(h'U. The additionofEOF (30p~)to inmdmdoes not modify these results (n~ drown), whereas S~ucason (30pg) decrmses the tropic effect of insulin on LL and on NLL~where the TdrU is reduced. ...... [ Sham (4) Saline (8) I InsuUn(4) Ins+GlucigG) L U.~N(g/100g) I 2.20",1:0.09 1.51~'0.05" 11.83"~.09"+ 1.4300.04* mgDNNgiver I 2.35,0.01 3.50~.12" 12.9!*0.15 + 3.44:1:0.42" ON~,,~ooaew)i 5.15:1:026 5.30"*0.33 J 5.35~0.6 4.87*0.57 1.1&I:0.02 1.38:kO.03" [ t55.0.03"+ 1.2210.04 + TdrU(Om~ON~i 0,70.1.44 139.15.6" ~127.11.6" 74.6.11 *÷ p <0.05 compared to sham * to saline .,, In conclusion, the proliferative n~pnem M the NLL occum in p r m m ~ of a slig~y redm:edliver mass and of an um:ba~ed DNA com~m~. The atrophyof LL is only p~dy re~_,_e~_ by ~d~m, the effect of wtdd~ is ~ by gluca$on. Thi~ ~-w mt model i~ ~ ~ t i v e to d~e Eck fmtul~ currmfly p ~ r m e d m dos ~ t h e study ofhe'~r;~.~c subsmaces.
l~u..u.,,mv(~oo~I
PROSPECTIVE ULTRASOUND STUDY - PREUMINARY RESULTS S. L6vv (1L D. Canron (1L R. Delcenserie (1L JP. Jolv (l't. J. Li~nard (2L JP. CaDron (1). (1)Dept ef Hepato-Gastroenterology, (2) Dept. of Health Care Medecine. Amiens Hospital. 80054 Amiens, France.
(1)Barbara L, Sama C, Morselli-Labate AM, Taroni F, Rusticalli AG, Festi D, et al. Hepatology 1987; 7: 913-7.
1364 ~
~ c ~ oF ~ C".~.T.TK,b~ ~
~ ~ v A~4ESICN MOt~CU/~ C~ ZN VI'VO 1~SKIblSEg '1'0 ~ C IG~.~X:C"~.
Jiaslm/n Li, Ginny B t m ~ e r Division of Transplantation, Department of Surgery, The Ohio State University, Col~mlbus, ohio. The adhesion molecule ~ IC~M-I is inportant in graft rejection in a cardiac allograft model. However, the role of AM in the stimulation of an alloimmune response to hepatocytes [HC] in vivo has not been defined. The purpose of this study was to canpax~ the role of MHC class I and ICa_M~I in host T cell responses to allogeneic [ALLO] HC using the hepatocyte-sponge matrix allograft model (HCSMA). In _A C3H(H2k) hosts transplanted (TX) with sponge grafts bearing 2 x 106 C57BL/6 (B6) (H2b) HC received IgG isotype control (ctrl) or anti-ICAM-i mAb on days i-i0 after TX. In _B sponge grafts bearing ICAM-I deficient (ICAM-I def), YHC class I deficient ( ~ C I def), or normal B6 HC were grafted into C3H host mice. After 12 days, host cells infiltrating HC-SMA were tested for the development of allospecific cytotc~ic cells (allo-CThs) in a SiCr release assay at various effector to target (E:T) ratios using allospecific EL4 (H2b) or P815 "third party" (H2d) tu~nor targets. Host Donor % CytotuKicity (E:T) (H2k) (H2b) Target: ~ P815 (H2a) i00 1 50:1 100:1 A: IgG ctrl N-~4 55 49 15.0 anti- ICAM-I N=6 10 7 3.5 B__t:C3H B6 N=4 63 67 23.0 C3H IC7~4-Idef N=5 42 43 ii.0 C3H ~ C I def N=6 3 2 0 In conclusion, the e~pression of Y~{C Class I, but not IC7¢41 on donor HC, is critical to the development of allo-CYI~s in HC-~t~A. ICAM-I appears to be more inl~ortant in the interaction between host cells rather than between host cells and donor HC since ICTkM-I clef HC stimulated significant @llospecific cytotc~icity in }{C-SMA.
AASLD ABSTRACTS
1 3 6 1 HEPATITIS
447A
C VIRAL (HCV) INFECTION AND LIVER TRANSPLANTATION (LT) - RELATION OF OUTCOME TO POSTTRANSPLANT STEROID USE: L Lerut M. Donatacdo. O. Ci¢¢arelli. Ch. Comu*. P.F. Laterre**, LB. Otte - Depts of Digestive Surgery, Virology*, Intensive Care** - Univ. Hospital St-Luc - Catholic Univ. of Louvain - Brussels - Belgium
1 3 6 2 PREVALENCE,AND RISK FACTORS FOR GALLSTONE DISEASE IN FRANCE: A
During the period february 1984-december 1993, fifty seven (20.6 %) of 276 adults underwent LT because of posthepatitis C cirrhosis (priorHCV pat.); thirteen (4.7%) patients acquired HCV-infection following LT (post-HCV pat.). Clinical and histological outcome of HCV (re)infection in 67 long-term survivors were analyzed in relation to steroid use. Nine (12.8 %) pat. died during late (> 3 mo.) post-LT period. One post HCV patient died because of HCV-allograft reinfection; two prior-HCV and one post-HCV patients died of fungal infection following severe HCV-infection. None of the pat. got antiviral therapy during post'transplant period. All patients had CyA based IS. "High dose steroid pat/' (HD-ster Group I) had a total first week dose of methyl-prednisolone (MP) of at least 1650 mgr and all continued steroids throughout follow-up. "Low dose steroid pat." (LD-ster Group II) had a first week MP dose of 300 mgr and all, but one, discontinued steroids within one post-LT year. Group I contained 33 prior-HCV and 13 post-HCV pat.; group II 21 prior-HCV patients. Inddences of rejection (34/46 pat-73.9 % i n group I and 17/21 pat-80.9 % in group II) as well as use of antilymphocytic serum (33/46 pat-71.7 % in group I and 12/21 pat.-57.1% in group II) were not significantly different.
OBJECTIVE: The prevalence of gallstone disease is still unknown in France. Therefore, to investigate the prevalence and associated factors of gallstone disease in an unselected population, we carried out a prospective survey on gallstone disease using ultrasonography. PATIENTS AND METHODS: A random sample of 437 volunteers (mean age 37, range 17-64), members of the hospital staff, entered the study and were screened by a gallbladder ultrasonography performed after an overnight fast. To assess risk factors for gallstone disease, they answered a preceded questionnaire and had a blood sample taken in the fasting condition which included blood glucose, creatinin, urea, uric acid, cholesterol and triglycerides. RESULTS: Prevalence of gallstone disease was 9.3% (10.4% for women and 6% for men). After adjustement with the Sirmione sludy (1), the 2 population samples were statistically comparable. Statistically significant associations (p<0.05) with cholelithiasis were observed for the following items: age, personal previous history of bilary pain in the preceding 5 years, familial history of cholecystectomy and, in women only, a body mass index greater than 25 kg/(m) 2. A positive, but not significant, association was observed with sex and parity. Oral contraceptives, alcohol consumption or cigarettes smoking, diabetes, hypercholesterolemia, hypertriglyceridemia were not risk factors in our study. In women, a cumulative association was observed belween the prevalence of cholelithiasis and the number of risk factors. CONCLUSIONS: This ongoing study reports a gallstone prevalence of 9.3% in France. This prevalence seems to be similar to that estimated in most Western European countries and to remain stable in Europe since 10 years.
High dose steroids (gI) Low dose steroids (gII) HCV prior post LT HCV prior LT median follow-up 1550d (134 to 3497) 546 d (122 to 892) hepatitis - acute 6 2 (2 +) 9 (1 +) - chronic 16 (1 +) 8 9 cirrhosis 5° 2 1 39/46 pat. (84.8 %) 19/21 pat. (90.5 %)
Total 17 (25.4 %) 33 (49.5 %) 8 (11.9 %) 58 (86.6 %)
There was no difference between LD and HD steroid use in relation to the histoloKical evolution of HCV allograft (re)infection.
1 3 6 3 STUDY OF "HEPATOTROIMIlC" SUBSTANCES AFTER PORTAL BRANCHES UGATION IN THE RAT. B LL X Havaux. L ~ . Lab. of Experimental S ~ , Univemk,y of Louvaut, Brussels, Belgium. In order to study the complex aUvphy-hypertrophyreaction following the ligation of portalbra~es, m occluding PE catheterwas insmtod in the branch feed~the l d latoral and ~ lobm of Wmmr r ~ md ] mi saline infused for 24 hr. At tha~time, in comperison with sham operatedrats, a 30% atrophy of the lis~mr~lobes (LL) is observed : nxlucfion of the ratio LL weight/body weight (LL/BW) ~ ambacreasein the DNA ¢ ¢ m ~ h ~ . The DNA contmt remainsm ~ n s e d ; this, in absence of sips of DNA symbesis and at histology of leukocy~ infiluafion, susgests a reductionof ceil volume. There am only a few minor aress of necrosis and no s i ~ of apoptosis. On sel electrcpho~is, fmgmem~m of DNA do~ n ~ appem before 24 hr. ~ ~mte of tlw rek~ively minor ,~,~-e~_ in the LL, in the non-ligted lobes (HI.L), the 3-1-1thynud~ uptake in D N A (TdrU) at itspeak at 24 hr isthreethnes greatertlum a0.era 1/3 paff~d bq~__,~_~,~myaml only 50% less than a~er a 2/3PH. Wbm 4 units of insulin are addedm salin~ infusion, the nxhc~ion of cell voh.ne is Ires marked : higher DNA/g and LL/BW; the weisbt of the NLL also incrases with no dum~ in T(h'U. The additionofEOF (30p~)to inmdmdoes not modify these results (n~ drown), whereas S~ucason (30pg) decrmses the tropic effect of insulin on LL and on NLL~where the TdrU is reduced. ...... [ Sham (4) Saline (8) I InsuUn(4) Ins+GlucigG) L U.~N(g/100g) I 2.20",1:0.09 1.51~'0.05" 11.83"~.09"+ 1.4300.04* mgDNNgiver I 2.35,0.01 3.50~.12" 12.9!*0.15 + 3.44:1:0.42" ON~,,~ooaew)i 5.15:1:026 5.30"*0.33 J 5.35~0.6 4.87*0.57 1.1&I:0.02 1.38:kO.03" [ t55.0.03"+ 1.2210.04 + TdrU(Om~ON~i 0,70.1.44 139.15.6" ~127.11.6" 74.6.11 *÷ p <0.05 compared to sham * to saline .,, In conclusion, the proliferative n~pnem M the NLL occum in p r m m ~ of a slig~y redm:edliver mass and of an um:ba~ed DNA com~m~. The atrophyof LL is only p~dy re~_,_e~_ by ~d~m, the effect of wtdd~ is ~ by gluca$on. Thi~ ~-w mt model i~ ~ ~ t i v e to d~e Eck fmtul~ currmfly p ~ r m e d m dos ~ t h e study ofhe'~r;~.~c subsmaces.
l~u..u.,,mv(~oo~I
PROSPECTIVE ULTRASOUND STUDY - PREUMINARY RESULTS S. L6vv (1L D. Canron (1L R. Delcenserie (1L JP. Jolv (l't. J. Li~nard (2L JP. CaDron (1). (1)Dept ef Hepato-Gastroenterology, (2) Dept. of Health Care Medecine. Amiens Hospital. 80054 Amiens, France.
(1)Barbara L, Sama C, Morselli-Labate AM, Taroni F, Rusticalli AG, Festi D, et al. Hepatology 1987; 7: 913-7.
1364 ~
~ c ~ oF ~ C".~.T.TK,b~ ~
~ ~ v A~4ESICN MOt~CU/~ C~ ZN VI'VO 1~SKIblSEg '1'0 ~ C IG~.~X:C"~.
Jiaslm/n Li, Ginny B t m ~ e r Division of Transplantation, Department of Surgery, The Ohio State University, Col~mlbus, ohio. The adhesion molecule ~ IC~M-I is inportant in graft rejection in a cardiac allograft model. However, the role of AM in the stimulation of an alloimmune response to hepatocytes [HC] in vivo has not been defined. The purpose of this study was to canpax~ the role of MHC class I and ICa_M~I in host T cell responses to allogeneic [ALLO] HC using the hepatocyte-sponge matrix allograft model (HCSMA). In _A C3H(H2k) hosts transplanted (TX) with sponge grafts bearing 2 x 106 C57BL/6 (B6) (H2b) HC received IgG isotype control (ctrl) or anti-ICAM-i mAb on days i-i0 after TX. In _B sponge grafts bearing ICAM-I deficient (ICAM-I def), YHC class I deficient ( ~ C I def), or normal B6 HC were grafted into C3H host mice. After 12 days, host cells infiltrating HC-SMA were tested for the development of allospecific cytotc~ic cells (allo-CThs) in a SiCr release assay at various effector to target (E:T) ratios using allospecific EL4 (H2b) or P815 "third party" (H2d) tu~nor targets. Host Donor % CytotuKicity (E:T) (H2k) (H2b) Target: ~ P815 (H2a) i00 1 50:1 100:1 A: IgG ctrl N-~4 55 49 15.0 anti- ICAM-I N=6 10 7 3.5 B__t:C3H B6 N=4 63 67 23.0 C3H IC7~4-Idef N=5 42 43 ii.0 C3H ~ C I def N=6 3 2 0 In conclusion, the e~pression of Y~{C Class I, but not IC7¢41 on donor HC, is critical to the development of allo-CYI~s in HC-~t~A. ICAM-I appears to be more inl~ortant in the interaction between host cells rather than between host cells and donor HC since ICTkM-I clef HC stimulated significant @llospecific cytotc~icity in }{C-SMA.