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Risk factors and outcomes in post orthotopic liver transplantation bile duct stones: A case control study
2857
Table#1: DaclizumabInductionand HCV TreatmentResults Results
Induction
Control
p Value
Number Recurrent HCV Days to HCV Biopsy Score Biochemical Resp Drop out Viral Clearance Pro Tx Quant
31 15 (48.4%) 254 (± 302) 4.2 (:t: 0.8) 12 (80.(P/o) 7 (46.7%) 0 4.6 (_+1.4) MC
33 17 (51.5%) 237 (+ 325) 4.4 (:1:0.4) 15 (88.2%) 8 (47 %) 3 3.8 (+ 1.6) MC
NS NS NS NS NS NS NS
Dystipidemia And Other Major Coronary Risk Factors In Liver Transplant Recipients Sanjay Ramrakhiani, Alex S. 6efeler, Bruce R. Bacon, Saint Louis Univ, St. Louis, MO
2855 incidence and Outcome of New Onset Oiabutes Mellitus After Liver TraecplaMagu: A Case-Control Study. Preeti R. John, Paul J. Thuluvath, Johns Hopkins Univ Sch of Medicine, Baltimore, MO Studies published to date have shown a 4 to 20% incidence of new onset diabetes maltitus (NODM) following solid organ transplantation.Long-term complicationsin patientswith NODM following orthotopic liver transplantation (OLT) remain unknown. Objective:To determine the outcome in patients who developNODM comparedto those with normal blood sugar. Patients and Methods: BetweenOctober 1986 and August 2000, a total of 492 adult OLT ware done at Johns Hopkins Hospital and of these 46 patients (female 14, mean age 47.2 _+ 11.1 yr) developedNODMfollowing OLT. For each case,two contemporaryage, sex and race-roatc~ controls (N=92) who had OLT, but did not have DM, were selected.Mean duration of followup was 60.2 _+ 36.2 months for the diabetic group and 50.9 _ 39.6 months for the control group. Results: The incidence of NODM was 9.3%. Mean time to detection of DM after transplant was 11.6 _+ 23.3 months. 76.7% of diabetics were on tacrolimus compared to 46.9% of case-controla(P=O.O01). Mean dose of tacrolimus, cyclosporine and prednisooe (1 month after OLT) was similar in both groups. Age, sex, race, body mass index, severe obesity and cold ischemia time were similar in both groups. Duration of hospital stay, cost of hospitalization,incidence of rejection and re-transplantation,graft survival and one-, twoand five-year patient survival were not significantly different in the two groups. Kaplan-Meler survival analysisdid not show a significant differencein overall survival (P = 0.21). However, post OLT complications were significantly higher in the diabetics compared to the easecontrols as shown in the table. Conclusions:New onset of DM occuring after OLT is associated with a very high morbidity. Organ System
PostNon-Diabetics P, value Transplant (n=92) DU (n=46)
Odds Ratio
Cardiovascular Gaatroenterologic al Nearologicul Major infections Minor infecUons New Onset Malignandes Respiratory
26 (56.5%) 26 (56.5%)
24 (26.1%) 24 (26.1%)
0 0005 0.0005
3.7 3.7
13 (28.3%) 35 (76.1%) 15 (32.6%) 12 (26.1%)
8 (6.7%) 24 (26.1%) 5 (5.4%) 6 (6.5%)
0.005 < 0.0001 < 0.0001 0.003
4.t 9.0 8.4 5.1
9 (19.6°,o)
6 (6.5%)
0.04
3.5
2856 Persistent Hyperglycemia in Pediatric Liver Transplant Recipients, Rene Romero, Karen J. Melde, Todd J. Pillen, Gregory A. Smallwood, Colleen M O'Neill, Jill M. Depaolo,Thomas G. Heffron, Emory Univ, Atlanta, GA Introduction: Hyperglycemiais a common complication of organ transplantation in adult liver transplant recipients and chronic hepatitis C infection appears to be a significant risk factor. Risk factors for persistent hyperglycemia(PH) in the pediatric liver transplant population are unknown. We set out to determineif certain children were predisposedto PH after transplantation. Methods: Medical records of all pediatric liver transplant recipients from 1-97 to 12-00 were reviewed. Parametersabstracted included patient age, diagnoses, family history, pretransplantation hyperglycemia,type of immunosuppression, and rejection episodes. Patients with serum glucose determinationsof > 200 mg/dl, occurnng more than 2 weeks after initial steroid induction cycle, and persisting for more than 2 weeks, were defined as having PH. For continuous data, a two-tailed student s t test was used. For nominal data Fisher s exact test was utilized. Results: 78 patients underwent transplants during the study period. PH occurred in 11 patients (14%). Older children more commonly developedPH (12.3 + / - 4.6 yrs vs. 5.3 +/-5.6 yrs, p = <0.001). Additionally, children with autoimmuoe hepatitis (AH) accounted for 5/11(45%) patients with PH, p= 0.002 with a RR 8.07; 95%CI 2.55, 25.5. No episodes of PH occurred in children initially started on Cyclosporioe-basedimmunosuppressign. All 11 children with PH were initially managed with tacrolimus, p
Background: Coronary artery disease (CAD) is the major cause of death following cardiac or renal transplantation, improvements in surgical technique and immunosuppressiun have led to increased survival in fiver transplant recipients and focussed attention on the prevalence of risk factors for CAD in this population. Aims: We assessed the prevalence and nature of dyslipidemia and other major coronary risk in liver transplant recipients. Patients and Methods:Retrospaofivechart reviewwas performedto collect information about demographics, etiology of liver disease, body mass index, immunosuppressivetherapy and lipid profiles on 87 patients who underwent orthotopic liver transplantation from 1992 to 1999. Results:The mean age of the patients was 53 yrs and 48 were male. Patients were maintained on irnmunosuppressivetherapy with either Prograf (n = 54) or Neural (n = 48). All pts received prednisoneinitially but only 38 ware still on prednisoneat the time of the study. Dyslipidemia was defined as presence of either serum cholesterol > 240 mg/dL, serum LDL > 160 mg/ dL, serum triglyceride levels > 200 mgJdL, or serum HDL < 35 mg/dL. Hypedipidemiawas present in 42 patients; 14 patents had elevated total cholesterol; 10 patients had elevated LDL levels; hypeddgly~emia was present in 38 patients. In addition, 9 patients had serum HDL concentrations < 35 rng/dL that has been identified as an independentrisk factor for developmentof CAD. Majority of the patients had hypertension(n = 56) while diabetesmellitus was present in a smaller proportion of patients (n = 28). Most of the patientswere overweight with a body mass index greater than 25 (n=66); of these, 33 patients were obese with a BMI of greater than 30. The maintenance dose of prodnisone was much higher in patients who ware overweight or had diabetes mellitus, hypertension or dyslipidemia. The proportion of patients with major cardiovascular risk factors is as follows: 19 pts had 2, 22 pts had 3, and 21 pts had 4 or more major risk factors. Therewas no significant difference in prevalence of coronary risk factors among pts on Prograf or Neural.Conclusions:1)Completelipid profile should be obtained in liver transplant recipients to recognizedyslipidemia that is common in these patients 2)Use of higher doses of prednisone is associated with risk for development of obesity, hypertensionand diabetesmellltus and 3)Majority of the liver transplant recipients have multiple,potentially modifiable risk factors for cardiovascular morbidity and mortality.
IlvINMmmoq~mmda In Liver Trasplaut Recipleuts Adil Habib, Bruce R. Bacon, Sanjay Ramrakhiani, Saint Louis Univ, St, Louis, MO Sackground:Cardiovasculardisease (CAD) is the leading cause of morbidity and mortality in patients undergoingcardiac or renaltransplantation. Hyperhomocysteinemiahas been recognized as an independentrisk factor for developmentof CAD. Aim:We assessedthe prevalence and risk factors for hyperhomocyeteinemiain liver transplant (OLT) recipients. The effect of folic acid supplementation on plasma total homocysteioe levels (tHcy) was also studied, Patients and Methods:FastingplasmatHcy ware measuredin 98 OLT recipientsusing Fluorescence Polarization Immunoassay. Baseline plasma folate and vitamin B12 levels were also measured in some pts. A tHee level < 9 umol/L was defined as normal; 9-14.9 as mildly elevated; 15-19.9 as moderately elevated; and > 20 umol/L as severely elevated. Pts with elevatedtHcy levels were started on folic acid (lmg/d) supplementationand had repeattHcy levels checked after 4 weeks. If tHee was elevated on repeat determination, the folic acid dose increasedto 4 mg]d and vitamin B6 and 812 supplementsadded.RepeattHee determination was performed after 4 weeks. Results: The mean age of the pts was 54 years (range 23-72). The mean creatinioe was 1.45 mg/dl (range 0.6-2.9 mg/di) with a cr. clearance of 67.6 mg/dl. Only 5 (5%) pts had normal tHee levels. Others had mild (n =41, 42%), moderate (n=29, 31%) or severe (n=22, 22%) elevations of tHcy levels. The mean tHcy level was 15.9 umol/L (range 5.7-29 umol/L). Serum folic acid and vitamin B12 levels were normal in all pts in whom the measurementwas performed.Therewas no significant correlation between tHee level and age, body mass index, vitamin B 12 or folic acid level. Plasma tHee levels after folic acid supplementation correlated strongly with serum creatinine level (R=0.65). Folic acid supplementation(1 rag/d) was associatedwith a statistically significant mean decline in tHcy level by 1 umol/L (p <0.02). The increase in the dose of folic acid and vitamin B6 and B12 supplementationled to a further decline in tHcy levels (mean 0.9 umol/L, p <0.02). Only two patientstaking 4 mg/d of folic acid with Vitamin B6 and B12 supplementationreported side effects of nausea and abdominal bloating. Conclusions: 1) Hyperbomocysteinemiais common in liver transplant recipientsand may be associatedwith increasedrisk for cardiovascular morbidity and mortality. 3) Renalfunction is the most important determinant of plasma thee levels 2) Folic acid supplementation is well tolerated and leads to a decline in serum tHee levels ragardless of baseline serum folate and vitamin B12 levels. 2859 Risk Factors and Outcomes in Post Orthutopi¢ Liver Transplantation Bile Duct Stones : A Case Control Study Adnan Said, Alexandru I. Musat, Munci Kalayoglu, Univ of Wisconsin Hosp and Clinics, Madison, Wl; Bora Gumustop, Medical Univ of South Carolina, Charleston, SC Background: Post Orthotopic Liver Transplant (OLT) bile duct stones (BDS) are associated with significant morbidity. Risk factors and efficacy of treatment in OLT patients with BDS have not been explored. Methods: We report analysis of pro and post OLT risk factors for endoscopic retrograde choiaogiogram (ERC) pmvan BDS and efficacy of therapeutic interventions derived from a case-control study based on 672 consecutive OLT patients performed in the University of Wisconsin Hospital Clinics between 1/89 and 8/O0. Cases include all OLT patients with BDS excluding those with t-tubes and biliary stents. Controls were chosen randomly from the total population of OLT patients with a case : control ratio of 1 : 2.5. A series of pro and post OLT risk factors were analyzed using univariate and multivariate analysis. Data for cases and controls was obtained through a prospectively constructed OLT database.Results: 28 cases with post OLT BDS and 70 OLT controls were included in the analysis. On presentation, 8 ( 29% ) of the cases had abdominal pain, 10 ( 36% ) had jaundice, all had cholestatic liver enzyme abnormalities of which 19 ( 68% ) had
A-562
hepatocellular enzyme elevation and 14 ( 52% ) had an imaging study that was suggestive of 8DS. Recipients pre OLT history of gallstones/ BDS was significantly associatedwith risk of post OLT BDS ( OR : 3.8, p < 0.005 ) and ursodiol use was associated with marked protective effect ( OR : 0.25, p < 0.005 ) on both the univadeteand the multivariateanalysis. Age, gender, body mass index, cyclospodn use, donor stone status and presenceof diabetes were not significantly different between cases and controls. In our series therapeutic ERC of stones provided pain relief ( 7/8 ) and marked improvementor normalizationof liver enzymes ( 20/28 ). None of the patients had post ERCcomplications. Conclusions: Pre OLT gallstone/ BDS history in the recipient despite a new liver is a significant risk factor for the development of post OLT BDS. Whereas a donor's gallstone and BDS history is not a risk factor. Drsodiol has a significant protective effect for BOSformation. ERC managementof BDS post transplant is effective, safe and helps avoid major morbidity.
2862 Immediate Complications of T-Tube Removal After Liver Trensplantion. Atul B. Vachhani, Karl T. Esrason, Fred A, Simmons, Jeftery A. Kahn, Khaled SeUm,John A. Donovan, Southern CA Permanenfe Medical Group, Los Angeles, CA Background:Choledocotomyand intra-operativeT-tube (Tt) placementduring liver transplantation (LT) allows post-operativebiliary tract accessbut mandateslaterTt removal.Complications of Tt removal, including bile leak, prolong the length of hospital stay (LOS) for observation, evaluation, or other therapies. AIM: To describe a single center experienceof Tt removal after LT with attention to immediatecomplications of the procedure.Methods: Retrospectivereview of consecutive Tt removal (2/93 to 9/00) from adult recipients of cadaveric LT. All Tt were withdrawn over guidewire using flouroscopic guidancefollowed by temporary biliary catheter drainage of Tt tract. Removal was considered uncomplicated if confinement for observation was less than 24 hours and there was no need for bile leak treatment by other interventions (ERCP/drainage).Results: One hundred two (102) patients had It removal performed 5.8 to 36.7 (average22 wk) after LT. Eighty-ninepatients were studied by this analysis (13 excluded; prior Tt migration = 4, Tt removed at another institution = 2, accidental extraction = 1, incompletedata = 5). Sixty-eight patients(76%) had an uncomplicatedTt removal.Tt removal was complicated in 21 (33%) patients. Time interval from LT to Tt removal was equivalent in both groups ( 22.2 vs. 21.6 wk). Seven(33%) patients with a related complication required extendedconfinement for more than 24 hr. (average2.7d; range 2-5d); fever = 2, analgesia = 4, initial high output via temporary Tt tract stent = 1. Fourteen (66%) patients with complication required ERCPfor treatment of a documented bile leak (stenf = 12, nasobiliary = 1, stent + percutaneousdrainage = 1). Average LOS for these patients with bile leak requiring intervention was 6d (range 1-33d). Conclusion: 1-1 removal after LT can be a cause of significant morbidity that is most often due to bile leak. Indicated therapies may result in extended hospital confinement and continued utilization of medical resources.
2860 Biliary Casts Following Adult Orthotopic Liver Transplantation (OLT): Clinical Factors and Biochemical Analysis Janak N. Shah, Univ of Pennsylvania, Philadelphia,PA; W Geoffrey Haigh, Sum P. Lee, Univ of Washington, Seattle, WA; Michael R. Lucey, Gregory G. Ginsberg, Univ of Pennsylvania, Philadelphia,PA BACKGROUND:Biliary casts develop in up to 10% of recipients of OLT. Cast formation is associated with morbidity, graft failure, need for retransplantation, and mortality (6-27%). Proposedetiologic mechanisms includeacute cellular rejection, ischemia,infection, and biliary obstruction. AIM: To identify clinical features associated with biliary cast formation and to analyzethe biochemicalcomposition of casts following OLT. METHODS:Castspecimenswere retrieved at ERCPfrom 60LT recipients (4M/2F; mean age=47 years, R 22-61) with biliary cast syndrome. Patients'records were reviewedretrospectively,and clinical datawere collected with attention to ischemia, rejection, biliary obstruction, and infection. The casts were analyzed biochemically using high performance liquid, gas, and thin layer chromatography.RESULTS: The meancold ischemiatime was 547 minutes (R 415-749). Time from transplant to diagnosis of biliary cast syndrome was 7,52,6,16,10, and 351 weeks in subjects A-F, respectively. Ischemic factors were noted in 5 (see table): cardiogenic shock-3(ADF), non-hearf beating donor-2(A8), hepatic artery stenosis-l(E). Extrahepatic biliary obstruction was seen in 3. Acute cellular rejection was recognizedand treated in 2. Cholangitis was documented in 2. Four casts (ABDE)were in satisfactorycondition for analysis. Bilirubin was the main constituent (-10-50%). Bile acid synthesis products and cholesterol comprised smaller percentages,and protein composed only 5-10%. CONCLUSION:Ischemia was the most uniform clinical factor assoc'latedw ~ biliary cast formation. Cast specimenswere primarily composed of bilirubin, with only a small protein component. This favors an ischemia related dysmotility mechanism rather than biliary tract necrosis/sloughingas a cause of biliary cast formation following OLT.
Rejection lschemia Obstruction Infection
A
B
+ +
+
C
Subjects D
+
+ + +
E + +
+
2863 Etiology Of Ascites After Liver transplant. Claudio R. Tombazzi,Suhas L. Dcshmukh, Bradford Waters, M. Hosein Shokouh-Amiri, Jacqueline F. Fleckenstein,Mark A. Levstik, Rene Davila, Santiago R. Vera, Hani P. Grewal, Osama Gaher, Tanci Payne, CarolineA. Riely, Univ of Tennessee,Memphis, TN Ascites after liver transplantation is a complication which is difficult to manage and is said to carry a bad prognosis.Objectives:To evaluate outcome and possible factors related to ascites formation after fiver transplantation. Methods: The charts of patiens that underwent liver transplantation during the last four years were reviewed. The demographic aspects, surgical technique (cava preservationor cava replacement)and the outcome after transplantation were considered.Severeascites was defined if the patient requiedat least one therapeutic paracentesis. Results: 176 orthotopic liver transplantations (OLT)were performed during this period. Twelve pediatric and 3 combined liver/kidney transplantation were excluded. Of 161 patients, 64 underwent OLT with cava preservation technique and 97 underwent OLT with cava replacement technique. The group of cava preservation included 16 adult to adult living related liver transplantation. The group of cava replacement included 3 split liver transplantations. Eleven patients developed severe ascites (6.83%), 5M/6F; mean age 43.5 (range: 18-57).The etiology of the liver disease was hepatitis C in five and in one patient each: Hepatitis C with hepatocellularcarcinoma, sarcoidosis, primary sclerosing cho(angitis, primary biliary cirrhosis, Budd-Chiadand non-alcoholic steatohepatitis.Seven patients developed ascites during the first month, two between one to three months, one between three months and one year and one after one year. The etiology was retroperitoneal lymphatic leak with chilous ascites (1), portal vein thrombosis (1), portal vein anastomosis stricture (1), and late cava stricture with ascites after one year of transplant (1). In 7 patients the etiology was possibly related to early complication of the surgical technique. Four of these patients undergone cava preservation,piggy-backtechnique and three cava replacementtechnique (p value: 0.216). Cavogram in two of these seven patients showed stenosis of the vena cava in one patient and outflow obstruction with caval compression in other patient. All patients improved, nine after medical treatment, two (one in each group of surgical technique)after angioplasty and one after surgical correction of lymphatic leak. Conclusion: Ascites is an infrequent comptication after liver transplantation. The possible etiologies are multiples. We did not find a significant difference betweenthe technique of caval anastomosis. Most of the patients improved with medical treatment.
F + +
2861 BUiary Strictures after Pediatric Liver Transplantation: Clinical Spectrum and Outcome. David L. Suskind, John P. Roberts, Philip Rosenthal, UCSF,San Francisco, CA With improved survival rates, liver transplanfation(LTx) has become the accepted method of treatment for children with end-stage liver disease.With this success, attention has focused on complications & their treatment. The small size of ducts & the indications for LTx in children do not often permit standardbiliary reconstruction. In cadaverictransplants,depending upon size disparity, a duct-to-duct anastomosis may he attempted. In many cadaveric & all living-related or split transplants, recontruction is through a choledocho- jejunostomy. Biliary strictures(BSt)are one of the complications associated with the bilary tract. The aim of this study was to review the clinical spectrum, laboratory findings & outcomes of children who underwent LTx & developed6St. METHODS:The medicalrecordsof all children who underwent LTx at UCSFbetween 1988 & 2000 were reviewed retrospectively.Clinical & laboratory data was collected & compared between children who did or did not develop BSt. RESULTS:Of 175 eligible pediatric LTx recipients, 12(6.0%) developedBSt. Ages ranged from 5 month to 17 years, with 7 children <3.5 years & 5 children >12 years of age. Four children developed 2 strictures. Nine children received cadavedc orthotopic LTx(6 whote;3 splits) & 3 children receivedliving related LTx(left-lateralsegment).The majority of strictures were at anastomotic sites(78%) whereasfew were intrahepatic or high BSt(22%). BSt were diagnosed between 1 month-ll years post-LTx with 4 <2months following LTx, 7 between 5-8 months post-LTx, & 5 >2 years post-LTx.Clinically, presentationsvaried considerablywith 4 children presenting with cholangltis & 3 being asymptomatic. Normal or only minimally elevated serum total hiliruhin values(O.5-1.3 mg/dl) were observed in 11 BSt. Hyperbilirubinemia (2.3-18.3 mg/ dl) was observed in 5 BSt. Serum alkaline phosphatasevaluesshowed elevationfrom baseline values in all children with BSt(252-872U/L). Six children were treated with interventional radiology & stent placement,four of whom restrictured & requiredre-stenting.Six had surgical correction of the stricture & required no further treatment. CONCLUSIONS:Biliary strictures can be seen with all forms of pediatric LTx. A wide variety of clinical presentations was observed. Elevationof serum alkaline phosphataseabove baseline & not bilirubin appearsto be an important laboratoryfinding. Surgical repair(cholcdochojejunostomy)is a more effective treatment for BSt in children post LTx then stent placement.
2864 Fibrosing Cholestatic Hepatitis: Clinical Features, Outcome And Response To Interferon And Ribavirin. Mohammad K. Ismail, Isam Daboul, Bradford Waters, Jaquelyn F. Fleckenstein,Santiago R. Vera, CarolineA. Riely, Univ of Tennessee,Memphis, TN AIMS: To review the etiology, clinical features and outcome in all patients with fibrosing cholestatic hepatitis (FCH) and response to treatment with interferon and ribavirin in liver transplant recipients with FCH and hepatitis C. METHODS: Retrospective chart review of patients (pts) with pathologic diagnosis of FCH. RESULTS:Between 8-93 and 2-00 thirteen pts with FCH were identified with median age of 40 yr (15-73 yr). M/F ratio was 11:2. Ten pts had received liver transplantation (OLT) for end stage hepatitis C (HCV-8), hepatitis 8 (HBV-1), and autoimmune hepatitis with post-OLT acquired HBV (1). One was a renal TX with HBV. Two other pts were HCV positive with acute lymphocytic leukemia (ALL) (1) and end stage HIV (1). OLT Group: Medianonset of FCHfrom OLT was 10 months (1-72 months). Minimizing immunosuppressionwas undertaken in all these pts. Four out of 80LT pts with RCV(HCV+ OLT) were treatedwith interferon and dbavirin (I/R rx). I/R rx (HCV+ OLT) (n = 4). Treatment was discontinued in all 4 pts due to side effects after a median of 8 wks (4-16 wks). Two of these pts died of worsening graft function after a median of 8 months postFCH diagnosis. One pt showed improvement following 16 wks of I/R rx although I/R had to be discontinued due to side effects, while the another pt was re-TX but died following IX with intracranial bleed. No-I/R rx (HCV+OLT) (n=4). In this group one pt died 8 months following the onset of FCH,one was re-TXand treated immediatelywith combinationtreatment
A-563
Table#1: DaclizumabInductionand HCV TreatmentResults Results
Induction
Control
p Value
Number Recurrent HCV Days to HCV Biopsy Score Biochemical Resp Drop out Viral Clearance Pro Tx Quant
31 15 (48.4%) 254 (± 302) 4.2 (:t: 0.8) 12 (80.(P/o) 7 (46.7%) 0 4.6 (_+1.4) MC
33 17 (51.5%) 237 (+ 325) 4.4 (:1:0.4) 15 (88.2%) 8 (47 %) 3 3.8 (+ 1.6) MC
NS NS NS NS NS NS NS
Dystipidemia And Other Major Coronary Risk Factors In Liver Transplant Recipients Sanjay Ramrakhiani, Alex S. 6efeler, Bruce R. Bacon, Saint Louis Univ, St. Louis, MO
2855 incidence and Outcome of New Onset Oiabutes Mellitus After Liver TraecplaMagu: A Case-Control Study. Preeti R. John, Paul J. Thuluvath, Johns Hopkins Univ Sch of Medicine, Baltimore, MO Studies published to date have shown a 4 to 20% incidence of new onset diabetes maltitus (NODM) following solid organ transplantation.Long-term complicationsin patientswith NODM following orthotopic liver transplantation (OLT) remain unknown. Objective:To determine the outcome in patients who developNODM comparedto those with normal blood sugar. Patients and Methods: BetweenOctober 1986 and August 2000, a total of 492 adult OLT ware done at Johns Hopkins Hospital and of these 46 patients (female 14, mean age 47.2 _+ 11.1 yr) developedNODMfollowing OLT. For each case,two contemporaryage, sex and race-roatc~ controls (N=92) who had OLT, but did not have DM, were selected.Mean duration of followup was 60.2 _+ 36.2 months for the diabetic group and 50.9 _ 39.6 months for the control group. Results: The incidence of NODM was 9.3%. Mean time to detection of DM after transplant was 11.6 _+ 23.3 months. 76.7% of diabetics were on tacrolimus compared to 46.9% of case-controla(P=O.O01). Mean dose of tacrolimus, cyclosporine and prednisooe (1 month after OLT) was similar in both groups. Age, sex, race, body mass index, severe obesity and cold ischemia time were similar in both groups. Duration of hospital stay, cost of hospitalization,incidence of rejection and re-transplantation,graft survival and one-, twoand five-year patient survival were not significantly different in the two groups. Kaplan-Meler survival analysisdid not show a significant differencein overall survival (P = 0.21). However, post OLT complications were significantly higher in the diabetics compared to the easecontrols as shown in the table. Conclusions:New onset of DM occuring after OLT is associated with a very high morbidity. Organ System
PostNon-Diabetics P, value Transplant (n=92) DU (n=46)
Odds Ratio
Cardiovascular Gaatroenterologic al Nearologicul Major infections Minor infecUons New Onset Malignandes Respiratory
26 (56.5%) 26 (56.5%)
24 (26.1%) 24 (26.1%)
0 0005 0.0005
3.7 3.7
13 (28.3%) 35 (76.1%) 15 (32.6%) 12 (26.1%)
8 (6.7%) 24 (26.1%) 5 (5.4%) 6 (6.5%)
0.005 < 0.0001 < 0.0001 0.003
4.t 9.0 8.4 5.1
9 (19.6°,o)
6 (6.5%)
0.04
3.5
2856 Persistent Hyperglycemia in Pediatric Liver Transplant Recipients, Rene Romero, Karen J. Melde, Todd J. Pillen, Gregory A. Smallwood, Colleen M O'Neill, Jill M. Depaolo,Thomas G. Heffron, Emory Univ, Atlanta, GA Introduction: Hyperglycemiais a common complication of organ transplantation in adult liver transplant recipients and chronic hepatitis C infection appears to be a significant risk factor. Risk factors for persistent hyperglycemia(PH) in the pediatric liver transplant population are unknown. We set out to determineif certain children were predisposedto PH after transplantation. Methods: Medical records of all pediatric liver transplant recipients from 1-97 to 12-00 were reviewed. Parametersabstracted included patient age, diagnoses, family history, pretransplantation hyperglycemia,type of immunosuppression, and rejection episodes. Patients with serum glucose determinationsof > 200 mg/dl, occurnng more than 2 weeks after initial steroid induction cycle, and persisting for more than 2 weeks, were defined as having PH. For continuous data, a two-tailed student s t test was used. For nominal data Fisher s exact test was utilized. Results: 78 patients underwent transplants during the study period. PH occurred in 11 patients (14%). Older children more commonly developedPH (12.3 + / - 4.6 yrs vs. 5.3 +/-5.6 yrs, p = <0.001). Additionally, children with autoimmuoe hepatitis (AH) accounted for 5/11(45%) patients with PH, p= 0.002 with a RR 8.07; 95%CI 2.55, 25.5. No episodes of PH occurred in children initially started on Cyclosporioe-basedimmunosuppressign. All 11 children with PH were initially managed with tacrolimus, p
Background: Coronary artery disease (CAD) is the major cause of death following cardiac or renal transplantation, improvements in surgical technique and immunosuppressiun have led to increased survival in fiver transplant recipients and focussed attention on the prevalence of risk factors for CAD in this population. Aims: We assessed the prevalence and nature of dyslipidemia and other major coronary risk in liver transplant recipients. Patients and Methods:Retrospaofivechart reviewwas performedto collect information about demographics, etiology of liver disease, body mass index, immunosuppressivetherapy and lipid profiles on 87 patients who underwent orthotopic liver transplantation from 1992 to 1999. Results:The mean age of the patients was 53 yrs and 48 were male. Patients were maintained on irnmunosuppressivetherapy with either Prograf (n = 54) or Neural (n = 48). All pts received prednisoneinitially but only 38 ware still on prednisoneat the time of the study. Dyslipidemia was defined as presence of either serum cholesterol > 240 mg/dL, serum LDL > 160 mg/ dL, serum triglyceride levels > 200 mgJdL, or serum HDL < 35 mg/dL. Hypedipidemiawas present in 42 patients; 14 patents had elevated total cholesterol; 10 patients had elevated LDL levels; hypeddgly~emia was present in 38 patients. In addition, 9 patients had serum HDL concentrations < 35 rng/dL that has been identified as an independentrisk factor for developmentof CAD. Majority of the patients had hypertension(n = 56) while diabetesmellitus was present in a smaller proportion of patients (n = 28). Most of the patientswere overweight with a body mass index greater than 25 (n=66); of these, 33 patients were obese with a BMI of greater than 30. The maintenance dose of prodnisone was much higher in patients who ware overweight or had diabetes mellitus, hypertension or dyslipidemia. The proportion of patients with major cardiovascular risk factors is as follows: 19 pts had 2, 22 pts had 3, and 21 pts had 4 or more major risk factors. Therewas no significant difference in prevalence of coronary risk factors among pts on Prograf or Neural.Conclusions:1)Completelipid profile should be obtained in liver transplant recipients to recognizedyslipidemia that is common in these patients 2)Use of higher doses of prednisone is associated with risk for development of obesity, hypertensionand diabetesmellltus and 3)Majority of the liver transplant recipients have multiple,potentially modifiable risk factors for cardiovascular morbidity and mortality.
IlvINMmmoq~mmda In Liver Trasplaut Recipleuts Adil Habib, Bruce R. Bacon, Sanjay Ramrakhiani, Saint Louis Univ, St, Louis, MO Sackground:Cardiovasculardisease (CAD) is the leading cause of morbidity and mortality in patients undergoingcardiac or renaltransplantation. Hyperhomocysteinemiahas been recognized as an independentrisk factor for developmentof CAD. Aim:We assessedthe prevalence and risk factors for hyperhomocyeteinemiain liver transplant (OLT) recipients. The effect of folic acid supplementation on plasma total homocysteioe levels (tHcy) was also studied, Patients and Methods:FastingplasmatHcy ware measuredin 98 OLT recipientsusing Fluorescence Polarization Immunoassay. Baseline plasma folate and vitamin B12 levels were also measured in some pts. A tHee level < 9 umol/L was defined as normal; 9-14.9 as mildly elevated; 15-19.9 as moderately elevated; and > 20 umol/L as severely elevated. Pts with elevatedtHcy levels were started on folic acid (lmg/d) supplementationand had repeattHcy levels checked after 4 weeks. If tHee was elevated on repeat determination, the folic acid dose increasedto 4 mg]d and vitamin B6 and 812 supplementsadded.RepeattHee determination was performed after 4 weeks. Results: The mean age of the pts was 54 years (range 23-72). The mean creatinioe was 1.45 mg/dl (range 0.6-2.9 mg/di) with a cr. clearance of 67.6 mg/dl. Only 5 (5%) pts had normal tHee levels. Others had mild (n =41, 42%), moderate (n=29, 31%) or severe (n=22, 22%) elevations of tHcy levels. The mean tHcy level was 15.9 umol/L (range 5.7-29 umol/L). Serum folic acid and vitamin B12 levels were normal in all pts in whom the measurementwas performed.Therewas no significant correlation between tHee level and age, body mass index, vitamin B 12 or folic acid level. Plasma tHee levels after folic acid supplementation correlated strongly with serum creatinine level (R=0.65). Folic acid supplementation(1 rag/d) was associatedwith a statistically significant mean decline in tHcy level by 1 umol/L (p <0.02). The increase in the dose of folic acid and vitamin B6 and B12 supplementationled to a further decline in tHcy levels (mean 0.9 umol/L, p <0.02). Only two patientstaking 4 mg/d of folic acid with Vitamin B6 and B12 supplementationreported side effects of nausea and abdominal bloating. Conclusions: 1) Hyperbomocysteinemiais common in liver transplant recipientsand may be associatedwith increasedrisk for cardiovascular morbidity and mortality. 3) Renalfunction is the most important determinant of plasma thee levels 2) Folic acid supplementation is well tolerated and leads to a decline in serum tHee levels ragardless of baseline serum folate and vitamin B12 levels. 2859 Risk Factors and Outcomes in Post Orthutopi¢ Liver Transplantation Bile Duct Stones : A Case Control Study Adnan Said, Alexandru I. Musat, Munci Kalayoglu, Univ of Wisconsin Hosp and Clinics, Madison, Wl; Bora Gumustop, Medical Univ of South Carolina, Charleston, SC Background: Post Orthotopic Liver Transplant (OLT) bile duct stones (BDS) are associated with significant morbidity. Risk factors and efficacy of treatment in OLT patients with BDS have not been explored. Methods: We report analysis of pro and post OLT risk factors for endoscopic retrograde choiaogiogram (ERC) pmvan BDS and efficacy of therapeutic interventions derived from a case-control study based on 672 consecutive OLT patients performed in the University of Wisconsin Hospital Clinics between 1/89 and 8/O0. Cases include all OLT patients with BDS excluding those with t-tubes and biliary stents. Controls were chosen randomly from the total population of OLT patients with a case : control ratio of 1 : 2.5. A series of pro and post OLT risk factors were analyzed using univariate and multivariate analysis. Data for cases and controls was obtained through a prospectively constructed OLT database.Results: 28 cases with post OLT BDS and 70 OLT controls were included in the analysis. On presentation, 8 ( 29% ) of the cases had abdominal pain, 10 ( 36% ) had jaundice, all had cholestatic liver enzyme abnormalities of which 19 ( 68% ) had
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hepatocellular enzyme elevation and 14 ( 52% ) had an imaging study that was suggestive of 8DS. Recipients pre OLT history of gallstones/ BDS was significantly associatedwith risk of post OLT BDS ( OR : 3.8, p < 0.005 ) and ursodiol use was associated with marked protective effect ( OR : 0.25, p < 0.005 ) on both the univadeteand the multivariateanalysis. Age, gender, body mass index, cyclospodn use, donor stone status and presenceof diabetes were not significantly different between cases and controls. In our series therapeutic ERC of stones provided pain relief ( 7/8 ) and marked improvementor normalizationof liver enzymes ( 20/28 ). None of the patients had post ERCcomplications. Conclusions: Pre OLT gallstone/ BDS history in the recipient despite a new liver is a significant risk factor for the development of post OLT BDS. Whereas a donor's gallstone and BDS history is not a risk factor. Drsodiol has a significant protective effect for BOSformation. ERC managementof BDS post transplant is effective, safe and helps avoid major morbidity.
2862 Immediate Complications of T-Tube Removal After Liver Trensplantion. Atul B. Vachhani, Karl T. Esrason, Fred A, Simmons, Jeftery A. Kahn, Khaled SeUm,John A. Donovan, Southern CA Permanenfe Medical Group, Los Angeles, CA Background:Choledocotomyand intra-operativeT-tube (Tt) placementduring liver transplantation (LT) allows post-operativebiliary tract accessbut mandateslaterTt removal.Complications of Tt removal, including bile leak, prolong the length of hospital stay (LOS) for observation, evaluation, or other therapies. AIM: To describe a single center experienceof Tt removal after LT with attention to immediatecomplications of the procedure.Methods: Retrospectivereview of consecutive Tt removal (2/93 to 9/00) from adult recipients of cadaveric LT. All Tt were withdrawn over guidewire using flouroscopic guidancefollowed by temporary biliary catheter drainage of Tt tract. Removal was considered uncomplicated if confinement for observation was less than 24 hours and there was no need for bile leak treatment by other interventions (ERCP/drainage).Results: One hundred two (102) patients had It removal performed 5.8 to 36.7 (average22 wk) after LT. Eighty-ninepatients were studied by this analysis (13 excluded; prior Tt migration = 4, Tt removed at another institution = 2, accidental extraction = 1, incompletedata = 5). Sixty-eight patients(76%) had an uncomplicatedTt removal.Tt removal was complicated in 21 (33%) patients. Time interval from LT to Tt removal was equivalent in both groups ( 22.2 vs. 21.6 wk). Seven(33%) patients with a related complication required extendedconfinement for more than 24 hr. (average2.7d; range 2-5d); fever = 2, analgesia = 4, initial high output via temporary Tt tract stent = 1. Fourteen (66%) patients with complication required ERCPfor treatment of a documented bile leak (stenf = 12, nasobiliary = 1, stent + percutaneousdrainage = 1). Average LOS for these patients with bile leak requiring intervention was 6d (range 1-33d). Conclusion: 1-1 removal after LT can be a cause of significant morbidity that is most often due to bile leak. Indicated therapies may result in extended hospital confinement and continued utilization of medical resources.
2860 Biliary Casts Following Adult Orthotopic Liver Transplantation (OLT): Clinical Factors and Biochemical Analysis Janak N. Shah, Univ of Pennsylvania, Philadelphia,PA; W Geoffrey Haigh, Sum P. Lee, Univ of Washington, Seattle, WA; Michael R. Lucey, Gregory G. Ginsberg, Univ of Pennsylvania, Philadelphia,PA BACKGROUND:Biliary casts develop in up to 10% of recipients of OLT. Cast formation is associated with morbidity, graft failure, need for retransplantation, and mortality (6-27%). Proposedetiologic mechanisms includeacute cellular rejection, ischemia,infection, and biliary obstruction. AIM: To identify clinical features associated with biliary cast formation and to analyzethe biochemicalcomposition of casts following OLT. METHODS:Castspecimenswere retrieved at ERCPfrom 60LT recipients (4M/2F; mean age=47 years, R 22-61) with biliary cast syndrome. Patients'records were reviewedretrospectively,and clinical datawere collected with attention to ischemia, rejection, biliary obstruction, and infection. The casts were analyzed biochemically using high performance liquid, gas, and thin layer chromatography.RESULTS: The meancold ischemiatime was 547 minutes (R 415-749). Time from transplant to diagnosis of biliary cast syndrome was 7,52,6,16,10, and 351 weeks in subjects A-F, respectively. Ischemic factors were noted in 5 (see table): cardiogenic shock-3(ADF), non-hearf beating donor-2(A8), hepatic artery stenosis-l(E). Extrahepatic biliary obstruction was seen in 3. Acute cellular rejection was recognizedand treated in 2. Cholangitis was documented in 2. Four casts (ABDE)were in satisfactorycondition for analysis. Bilirubin was the main constituent (-10-50%). Bile acid synthesis products and cholesterol comprised smaller percentages,and protein composed only 5-10%. CONCLUSION:Ischemia was the most uniform clinical factor assoc'latedw ~ biliary cast formation. Cast specimenswere primarily composed of bilirubin, with only a small protein component. This favors an ischemia related dysmotility mechanism rather than biliary tract necrosis/sloughingas a cause of biliary cast formation following OLT.
Rejection lschemia Obstruction Infection
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2863 Etiology Of Ascites After Liver transplant. Claudio R. Tombazzi,Suhas L. Dcshmukh, Bradford Waters, M. Hosein Shokouh-Amiri, Jacqueline F. Fleckenstein,Mark A. Levstik, Rene Davila, Santiago R. Vera, Hani P. Grewal, Osama Gaher, Tanci Payne, CarolineA. Riely, Univ of Tennessee,Memphis, TN Ascites after liver transplantation is a complication which is difficult to manage and is said to carry a bad prognosis.Objectives:To evaluate outcome and possible factors related to ascites formation after fiver transplantation. Methods: The charts of patiens that underwent liver transplantation during the last four years were reviewed. The demographic aspects, surgical technique (cava preservationor cava replacement)and the outcome after transplantation were considered.Severeascites was defined if the patient requiedat least one therapeutic paracentesis. Results: 176 orthotopic liver transplantations (OLT)were performed during this period. Twelve pediatric and 3 combined liver/kidney transplantation were excluded. Of 161 patients, 64 underwent OLT with cava preservation technique and 97 underwent OLT with cava replacement technique. The group of cava preservation included 16 adult to adult living related liver transplantation. The group of cava replacement included 3 split liver transplantations. Eleven patients developed severe ascites (6.83%), 5M/6F; mean age 43.5 (range: 18-57).The etiology of the liver disease was hepatitis C in five and in one patient each: Hepatitis C with hepatocellularcarcinoma, sarcoidosis, primary sclerosing cho(angitis, primary biliary cirrhosis, Budd-Chiadand non-alcoholic steatohepatitis.Seven patients developed ascites during the first month, two between one to three months, one between three months and one year and one after one year. The etiology was retroperitoneal lymphatic leak with chilous ascites (1), portal vein thrombosis (1), portal vein anastomosis stricture (1), and late cava stricture with ascites after one year of transplant (1). In 7 patients the etiology was possibly related to early complication of the surgical technique. Four of these patients undergone cava preservation,piggy-backtechnique and three cava replacementtechnique (p value: 0.216). Cavogram in two of these seven patients showed stenosis of the vena cava in one patient and outflow obstruction with caval compression in other patient. All patients improved, nine after medical treatment, two (one in each group of surgical technique)after angioplasty and one after surgical correction of lymphatic leak. Conclusion: Ascites is an infrequent comptication after liver transplantation. The possible etiologies are multiples. We did not find a significant difference betweenthe technique of caval anastomosis. Most of the patients improved with medical treatment.
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2861 BUiary Strictures after Pediatric Liver Transplantation: Clinical Spectrum and Outcome. David L. Suskind, John P. Roberts, Philip Rosenthal, UCSF,San Francisco, CA With improved survival rates, liver transplanfation(LTx) has become the accepted method of treatment for children with end-stage liver disease.With this success, attention has focused on complications & their treatment. The small size of ducts & the indications for LTx in children do not often permit standardbiliary reconstruction. In cadaverictransplants,depending upon size disparity, a duct-to-duct anastomosis may he attempted. In many cadaveric & all living-related or split transplants, recontruction is through a choledocho- jejunostomy. Biliary strictures(BSt)are one of the complications associated with the bilary tract. The aim of this study was to review the clinical spectrum, laboratory findings & outcomes of children who underwent LTx & developed6St. METHODS:The medicalrecordsof all children who underwent LTx at UCSFbetween 1988 & 2000 were reviewed retrospectively.Clinical & laboratory data was collected & compared between children who did or did not develop BSt. RESULTS:Of 175 eligible pediatric LTx recipients, 12(6.0%) developedBSt. Ages ranged from 5 month to 17 years, with 7 children <3.5 years & 5 children >12 years of age. Four children developed 2 strictures. Nine children received cadavedc orthotopic LTx(6 whote;3 splits) & 3 children receivedliving related LTx(left-lateralsegment).The majority of strictures were at anastomotic sites(78%) whereasfew were intrahepatic or high BSt(22%). BSt were diagnosed between 1 month-ll years post-LTx with 4 <2months following LTx, 7 between 5-8 months post-LTx, & 5 >2 years post-LTx.Clinically, presentationsvaried considerablywith 4 children presenting with cholangltis & 3 being asymptomatic. Normal or only minimally elevated serum total hiliruhin values(O.5-1.3 mg/dl) were observed in 11 BSt. Hyperbilirubinemia (2.3-18.3 mg/ dl) was observed in 5 BSt. Serum alkaline phosphatasevaluesshowed elevationfrom baseline values in all children with BSt(252-872U/L). Six children were treated with interventional radiology & stent placement,four of whom restrictured & requiredre-stenting.Six had surgical correction of the stricture & required no further treatment. CONCLUSIONS:Biliary strictures can be seen with all forms of pediatric LTx. A wide variety of clinical presentations was observed. Elevationof serum alkaline phosphataseabove baseline & not bilirubin appearsto be an important laboratoryfinding. Surgical repair(cholcdochojejunostomy)is a more effective treatment for BSt in children post LTx then stent placement.
2864 Fibrosing Cholestatic Hepatitis: Clinical Features, Outcome And Response To Interferon And Ribavirin. Mohammad K. Ismail, Isam Daboul, Bradford Waters, Jaquelyn F. Fleckenstein,Santiago R. Vera, CarolineA. Riely, Univ of Tennessee,Memphis, TN AIMS: To review the etiology, clinical features and outcome in all patients with fibrosing cholestatic hepatitis (FCH) and response to treatment with interferon and ribavirin in liver transplant recipients with FCH and hepatitis C. METHODS: Retrospective chart review of patients (pts) with pathologic diagnosis of FCH. RESULTS:Between 8-93 and 2-00 thirteen pts with FCH were identified with median age of 40 yr (15-73 yr). M/F ratio was 11:2. Ten pts had received liver transplantation (OLT) for end stage hepatitis C (HCV-8), hepatitis 8 (HBV-1), and autoimmune hepatitis with post-OLT acquired HBV (1). One was a renal TX with HBV. Two other pts were HCV positive with acute lymphocytic leukemia (ALL) (1) and end stage HIV (1). OLT Group: Medianonset of FCHfrom OLT was 10 months (1-72 months). Minimizing immunosuppressionwas undertaken in all these pts. Four out of 80LT pts with RCV(HCV+ OLT) were treatedwith interferon and dbavirin (I/R rx). I/R rx (HCV+ OLT) (n = 4). Treatment was discontinued in all 4 pts due to side effects after a median of 8 wks (4-16 wks). Two of these pts died of worsening graft function after a median of 8 months postFCH diagnosis. One pt showed improvement following 16 wks of I/R rx although I/R had to be discontinued due to side effects, while the another pt was re-TX but died following IX with intracranial bleed. No-I/R rx (HCV+OLT) (n=4). In this group one pt died 8 months following the onset of FCH,one was re-TXand treated immediatelywith combinationtreatment
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