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Association of HLA antigens wit posttransplant diabetes mellitus in recipients of liver transplants
434A
AASLD ABSTRACTS
1309 CHRONIC REJECTION FOLLOWING PRIMARY ADULT LIVER TRANSPLANTATION UNDER TACROLIMUS. AB Jain*, A Sin~hal, JJ Fung, AC Tsamandas, S Todo. TE Starzl, J Demetris. Pittsburgh Transplantation Institute, University of Pittsburgh, Pittsburgh, PA.
1310
Tacrulimus is a potent inmmnosuppression and has statistically significant reduced incidence and severity of acute rejection following liver transplantation (LTx). It also has an ability to halt and reverse the chronic rejection of liver allograft under cyclosporine. However, little is known about development of chronic rejection under tacrolimus following LTx. We reviewed 834 consecutive primary LTx at our center, perfomled between August 1989 to December 1992. Mean age was 51.0+12.7 (range 18-74) years with mean follow-up of 39.5 (range 19-59) mouths. All the primary graft losses either requiring retransplantation or as a result of death were evaluated to determine the cause of graft loss. Results: 288 (35%) primary grafts were lost either as a result of death or retransplantation during the mean follow-up period of 40 months. Only 9 (1%) patients lost their primary graft purely due to chronic rejection after mean interval of 18.6 months. Eight patients had more than two episodes of acute rejection. Three patients (37%) were noncompliant to take their medications. in 3(37%) patient's inmmnosuppression was held for cytomegalovirus (n=2), in association of fungal sepsis (n=2), and bacterial infection (n=l). Two patients had recurrent of hepatitis C with chronic rejection and another two had recurrent hepatitis B infection (t of them also had CMV and candida infection). In conclusion, while incidence of chronic rejection under cyclosporine has been described from 2.4 to 16.8%, chronic rejections under tecrolimus based immunosuppression is comparatively low and usually associated with other risk factors.
1311
ASSOCIATION OF HLA ANTIGEN8 WITH POaTTR~NaPLANT DIABETES MELLITUS IN RECIPIENT8 OF LIVER TP.ANBPLANT8.
RM Jindal0 D Huuhes. MD Pescovitz. LL Lumenq, SB LeaDman. RS File. Z Brahmi. Departments of Surgery and Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. HLA antigens (Ag) may be associated with diabetes mellitus (DM). We analyzed the association of r e c i p i e n t - H L A a n d for donor-liver on posttransplant diabetes mellitus (PTDM) in 200 liver transplant recipients. After excluding deaths, re-transplants, and preexisting DM, 72 patients were analyzed. HLA typing was done serologically and by DNA. Recipients who developed PTDM (54.2%, n=39) were divided in 4 groups (gr): Gr 1 had at least 1 DM-protective Ag (DR2, DQwl), gr 2 had at least 1 DM-risk Ag (DR3, DR4, DRwlt, DQw8, A28, B8, BIS, B18). Gr 3 had none of above Ag, while gr 4 had at least 1 risk and 1 protective Ag. Gr were compared using the Chi square test, p<.05 was considered significant. The incidence of PTDM when analyzed by recipient HLA was 50% (gr 1), 53.3% (gr 2), 65% (gr 3) and 44.4% (gr 4). The effect of HLA carried by the donor-liver on PTDM was 58.82% (gr i), 66.67% (gr 2), 70% (gr 3) and 38.1% (gr 4). The combination of risk-Ag in both the recipient and donor-liver was also not a significant factor. H L A w a s not a predictive marker for PTDM in recipients of liver transplants.
1312
HEPATOLOGYOctober 1995
I N VITRO PROTON (1H) MAGNETIC RESONANCE SPECTROSCOPY
OF THE PLASMA IN CIRRHOSIS AND CHANGES FOLLOWING THE TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC STENTSHUNT (TEPSS). R.Jalaa, Y.L.CI~ung, ^D.N.Redhead, *P.C.E[ayes, J.D.Beil. R.E. Steiner MR Unit, Hammersmith Hospital and Dept. of *Medicine aad ^Radiology, Royal l~firmary, Edinburgh. Background and Ahns In vitro hydragen-1 magnetic resonance spectroscopy (IH MRS) is a non invasive, multicomponent analytical technique of assessing changes in the biochemical profile nf bedy fluids and tissue. The aim of this study was to assess (1) changes in the 1H MR spectrum of plasma in patients with cirrhosis and its relationship to the severity of liver disease and portal hypertension, and (2) changes in the spectrum following TIPSS. Methods Seventeen patients undergoing TIPSS (M:F-13:4, age-51.8 (+-10.4), Child A-3, B-7 and C-7) and six matched controls were studied using IH MRS. Plasma was collected prior to and 3 months after TIPSS when the patients attended for routine portography. ]H MR spectra were acquired in a 11.5 Teala, 500 Mhz vertical superconducting magnet (Jenl) using spin echo technique and 128 averages. The spectra were analysed on NMRI® spectral processing program and results mialysed using Wilcoxon signed ranks and linear regression. Results Mean portal pressure gradient (PPG, portal pressure*inferlur vena cave pressure) prior to TIPSS was 18.1 (+-5.3) and at 3 months was 8.2 (+2.9) mmHg. Three patients became encephalopathic following TIPSS. Patients with cirrhosis had significantly higher levels of I3-OH butyrate, lactate, acetone, dimethylamine, trimethylamine oxide (TMAO), glyci'ne, tyrnsine and histidine. Significant correlation was observed between the Pugh score and lactate (p<0.04), acetone (p<0.04) and glycine (p<0.04). Lactate (p<0.04) and TMAO (<0.05) correlated with the PPG. The only significant change in the IH MRS profile following TI]?SS was an increase in tyrosine (p<0.01). Conclusions (1) 1H MR spectra is significantly different in patients with cirrhosis and the changes correlate with disease severity (2) significant correlation between TMAO (reflects renal dysfunction) and PPG suggests a relationship between these parameters in cirrhosis ~3) except for an increase in tyrosine, no significant change was noted in the ~H MR specman following TIPSS. This method may provide clues to the further understanding of the biochemical basis nf liver disease and its complications.
DETECTION OF PNEUMOC¥aTI8 C A R I N I I (PC) DNA I N BIOPSY SPECIMEN8 OF TR~NaPL~.NT R E C I P I E N T 8 USING P O L Y M E R A a E C H A I N R E A C T I O N _(PCR}. I
Rahul M. Jindal 1. Ronald S. File . Lawrence Lumenu ~. Chao-Hunu Lee 3. Departments of Surgery1~ Medicine ~, Pathology and Laboratory M e d i c i n e % Indiana University School of Medicine, Indianapolis, IN, USA. Pneumocvstis carinii pneumonia (PCP) is a significant cause for morbidity and mortality in immunosuppressed recipients of organ transplants. We investigated the occurence of PC DNA in biospy specimens from liver and kidney allografts. We have earlier described an accurate method for diagnosis of P C P b y d e t e c t i o n of PC DNA from sera and sputum by the PC-ITS-PeR which uses nested PeR to amplify the internal transcribed spacers (ITS) of the rRNA genes of P.carinii. We applied this technique to needle core biopsy specimens obtained from 6 liver and 6 kidney transplant recipients. Controls were kidney and liver specimens obtained from non-immunosuppressed patients. A patient who had chronic rejection of kidney transplant showed positive PCP-ITS-PCR in the biopsy specimen, despite prophylactic Septra. H i s serum was negative for PC DNA. Specimens from non-immunosuppressed patients (n=12) were negative for PC DNA. PC may remain dormant in some patients, and may be reactivated during stress. This finding may explain why some patients develop PCP despite anti-PCP prophylactic therapy. Our findings suggest that recipients of organ transplants should remain on long-term anti-PeP therapy, and may require increased dosing of anti-PeP medications during stress.
AASLD ABSTRACTS
1309 CHRONIC REJECTION FOLLOWING PRIMARY ADULT LIVER TRANSPLANTATION UNDER TACROLIMUS. AB Jain*, A Sin~hal, JJ Fung, AC Tsamandas, S Todo. TE Starzl, J Demetris. Pittsburgh Transplantation Institute, University of Pittsburgh, Pittsburgh, PA.
1310
Tacrulimus is a potent inmmnosuppression and has statistically significant reduced incidence and severity of acute rejection following liver transplantation (LTx). It also has an ability to halt and reverse the chronic rejection of liver allograft under cyclosporine. However, little is known about development of chronic rejection under tacrolimus following LTx. We reviewed 834 consecutive primary LTx at our center, perfomled between August 1989 to December 1992. Mean age was 51.0+12.7 (range 18-74) years with mean follow-up of 39.5 (range 19-59) mouths. All the primary graft losses either requiring retransplantation or as a result of death were evaluated to determine the cause of graft loss. Results: 288 (35%) primary grafts were lost either as a result of death or retransplantation during the mean follow-up period of 40 months. Only 9 (1%) patients lost their primary graft purely due to chronic rejection after mean interval of 18.6 months. Eight patients had more than two episodes of acute rejection. Three patients (37%) were noncompliant to take their medications. in 3(37%) patient's inmmnosuppression was held for cytomegalovirus (n=2), in association of fungal sepsis (n=2), and bacterial infection (n=l). Two patients had recurrent of hepatitis C with chronic rejection and another two had recurrent hepatitis B infection (t of them also had CMV and candida infection). In conclusion, while incidence of chronic rejection under cyclosporine has been described from 2.4 to 16.8%, chronic rejections under tecrolimus based immunosuppression is comparatively low and usually associated with other risk factors.
1311
ASSOCIATION OF HLA ANTIGEN8 WITH POaTTR~NaPLANT DIABETES MELLITUS IN RECIPIENT8 OF LIVER TP.ANBPLANT8.
RM Jindal0 D Huuhes. MD Pescovitz. LL Lumenq, SB LeaDman. RS File. Z Brahmi. Departments of Surgery and Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. HLA antigens (Ag) may be associated with diabetes mellitus (DM). We analyzed the association of r e c i p i e n t - H L A a n d for donor-liver on posttransplant diabetes mellitus (PTDM) in 200 liver transplant recipients. After excluding deaths, re-transplants, and preexisting DM, 72 patients were analyzed. HLA typing was done serologically and by DNA. Recipients who developed PTDM (54.2%, n=39) were divided in 4 groups (gr): Gr 1 had at least 1 DM-protective Ag (DR2, DQwl), gr 2 had at least 1 DM-risk Ag (DR3, DR4, DRwlt, DQw8, A28, B8, BIS, B18). Gr 3 had none of above Ag, while gr 4 had at least 1 risk and 1 protective Ag. Gr were compared using the Chi square test, p<.05 was considered significant. The incidence of PTDM when analyzed by recipient HLA was 50% (gr 1), 53.3% (gr 2), 65% (gr 3) and 44.4% (gr 4). The effect of HLA carried by the donor-liver on PTDM was 58.82% (gr i), 66.67% (gr 2), 70% (gr 3) and 38.1% (gr 4). The combination of risk-Ag in both the recipient and donor-liver was also not a significant factor. H L A w a s not a predictive marker for PTDM in recipients of liver transplants.
1312
HEPATOLOGYOctober 1995
I N VITRO PROTON (1H) MAGNETIC RESONANCE SPECTROSCOPY
OF THE PLASMA IN CIRRHOSIS AND CHANGES FOLLOWING THE TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC STENTSHUNT (TEPSS). R.Jalaa, Y.L.CI~ung, ^D.N.Redhead, *P.C.E[ayes, J.D.Beil. R.E. Steiner MR Unit, Hammersmith Hospital and Dept. of *Medicine aad ^Radiology, Royal l~firmary, Edinburgh. Background and Ahns In vitro hydragen-1 magnetic resonance spectroscopy (IH MRS) is a non invasive, multicomponent analytical technique of assessing changes in the biochemical profile nf bedy fluids and tissue. The aim of this study was to assess (1) changes in the 1H MR spectrum of plasma in patients with cirrhosis and its relationship to the severity of liver disease and portal hypertension, and (2) changes in the spectrum following TIPSS. Methods Seventeen patients undergoing TIPSS (M:F-13:4, age-51.8 (+-10.4), Child A-3, B-7 and C-7) and six matched controls were studied using IH MRS. Plasma was collected prior to and 3 months after TIPSS when the patients attended for routine portography. ]H MR spectra were acquired in a 11.5 Teala, 500 Mhz vertical superconducting magnet (Jenl) using spin echo technique and 128 averages. The spectra were analysed on NMRI® spectral processing program and results mialysed using Wilcoxon signed ranks and linear regression. Results Mean portal pressure gradient (PPG, portal pressure*inferlur vena cave pressure) prior to TIPSS was 18.1 (+-5.3) and at 3 months was 8.2 (+2.9) mmHg. Three patients became encephalopathic following TIPSS. Patients with cirrhosis had significantly higher levels of I3-OH butyrate, lactate, acetone, dimethylamine, trimethylamine oxide (TMAO), glyci'ne, tyrnsine and histidine. Significant correlation was observed between the Pugh score and lactate (p<0.04), acetone (p<0.04) and glycine (p<0.04). Lactate (p<0.04) and TMAO (<0.05) correlated with the PPG. The only significant change in the IH MRS profile following TI]?SS was an increase in tyrosine (p<0.01). Conclusions (1) 1H MR spectra is significantly different in patients with cirrhosis and the changes correlate with disease severity (2) significant correlation between TMAO (reflects renal dysfunction) and PPG suggests a relationship between these parameters in cirrhosis ~3) except for an increase in tyrosine, no significant change was noted in the ~H MR specman following TIPSS. This method may provide clues to the further understanding of the biochemical basis nf liver disease and its complications.
DETECTION OF PNEUMOC¥aTI8 C A R I N I I (PC) DNA I N BIOPSY SPECIMEN8 OF TR~NaPL~.NT R E C I P I E N T 8 USING P O L Y M E R A a E C H A I N R E A C T I O N _(PCR}. I
Rahul M. Jindal 1. Ronald S. File . Lawrence Lumenu ~. Chao-Hunu Lee 3. Departments of Surgery1~ Medicine ~, Pathology and Laboratory M e d i c i n e % Indiana University School of Medicine, Indianapolis, IN, USA. Pneumocvstis carinii pneumonia (PCP) is a significant cause for morbidity and mortality in immunosuppressed recipients of organ transplants. We investigated the occurence of PC DNA in biospy specimens from liver and kidney allografts. We have earlier described an accurate method for diagnosis of P C P b y d e t e c t i o n of PC DNA from sera and sputum by the PC-ITS-PeR which uses nested PeR to amplify the internal transcribed spacers (ITS) of the rRNA genes of P.carinii. We applied this technique to needle core biopsy specimens obtained from 6 liver and 6 kidney transplant recipients. Controls were kidney and liver specimens obtained from non-immunosuppressed patients. A patient who had chronic rejection of kidney transplant showed positive PCP-ITS-PCR in the biopsy specimen, despite prophylactic Septra. H i s serum was negative for PC DNA. Specimens from non-immunosuppressed patients (n=12) were negative for PC DNA. PC may remain dormant in some patients, and may be reactivated during stress. This finding may explain why some patients develop PCP despite anti-PCP prophylactic therapy. Our findings suggest that recipients of organ transplants should remain on long-term anti-PeP therapy, and may require increased dosing of anti-PeP medications during stress.