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ABSTRACT: BACKGROUND: Blood loss during liver transplantation is not incorporated into the dominant models for post-transplant survival. Our objective was to investigate blood transfusion requirement as a risk factor for mortality after liver transplantation, and to further analyze risk factors for intraoperative blood transfusion requirement and hepatectomy time. STUDY DESIGN: We conducted a retrospective analysis of 233 consecutive liver transplant recipients over a span of 3 years by a single experienced surgeon. Mean follow-up was 2.5 years. Independent risk factors for patient survival after liver transplantation were identified using Cox proportion hazard regression. Independent risk factors for intraoperative blood transfusion requirement and hepatectomy time were identified using logistic regression. RESULTS: Two factors were identified as significant predictors in multivariate analysis for survival after liver transplantation: hepatocellular carcinoma (hazard ratio [HR] 1.9, 95% CI 1.1 to 3.2) and intraoperative blood transfusion requirement per unit (HR 1.01, 95% CI 1.0 to 1.02). Threshold analysis revealed that intraoperative blood transfusion volume ≥28 units or 85th percentile (HR 2.5, 95% CI 1.3 to 4.7) was a significant risk factor for patient survival. Four covariates were identified as significant risk factors for intraoperative blood requirement: warm ischemia time (odds ratio [OR] 1.12, 95% CI 1.06 to 1.18), bilirubin (OR 1.04, 95% CI 1.02 to 1.08), previous surgery (OR 1.7, 95% CI 1.02 to 2.9), and hepatectomy time (OR 1.01, 95% CI 1.00 to 1.02). The only risk factor for prolonged hepatectomy time was previous major abdominal surgery (OR 4.0, 95% CI 1.7 to 9.5). CONCLUSIONS: Intraoperative blood transfusion requirement is an important risk factor for mortality after liver transplantation. The strongest risk factors for intraoperative blood transfusion requirement are warm ischemia time and bilirubin levels. Intraoperative blood loss and its risk factors should be incorporated into models to predict survival after liver transplantation.
Journal of the American College of Surgeons 03/2013; · 4.55 Impact Factor
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Vatche G Agopian,
Fady M Kaldas,
Johnny C Hong,
Meredith Whittaker,
Curtis Holt,
Abbas Rana,
Ali Zarrinpar,
Henrik Petrowsky, Douglas Farmer,
Hasan Yersiz,
Victor Xia,
Jonathan R Hiatt,
Ronald W Busuttil
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ABSTRACT: : To analyze incidence, outcomes, and utilization of health care resources in liver transplantation (LT) for nonalcoholic steatohepatitis (NASH).
: With the epidemic of obesity and metabolic syndrome in nearly 33% of the US population, NASH is projected to become the leading indication for LT in the next several years. Data on predictors of outcome and utilization of health care resources after LT in NASH is limited.
: We conducted an analysis from our prospective database of 144 adult NASH patients who underwent LT between December 1993 and August 2011. Outcomes and resource utilization were compared with other common indications for LT. Independent predictors of graft and patient survival were identified.
: The average Model for End-Stage Liver Disease score was 33. The frequency of NASH as the primary indication for LT increased from 3% in 2002 to 19% in 2011 to become the second most common indication for LT at our center behind hepatitis C. NASH patients had significantly longer operative times (402 vs 322 minutes; P < 0.001), operative blood loss (18 vs 14 packed red blood cell units; P = 0.001), and posttransplant length of stay (35 vs 29 days; P = 0.032), but 1-, 3-, and 5-year graft (81%, 71%, 63%) and patient (84%, 75%, 70%) survival were comparable with other diagnoses. Age greater than 55 years, pretransplant intubation, dialysis, hospitalization, presence of hepatocellular carcinoma on explant, donor age greater than 55 years, and cold ischemia time greater than 550 minutes were significant independent predictors of survival for all patients, whereas body mass index greater than 35 was a predictor in NASH patients only.
: We report the largest single institution experience of LT for NASH. Over a 10-year period, the frequency of LT for NASH has increased 5-fold. Although outcomes are comparable with LT for other indications, health care resources are stressed significantly by this new and increasing group of transplant candidates.
Annals of surgery 09/2012; 256(4):624-33. · 7.90 Impact Factor
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ABSTRACT: One of the current ultimate goals of orthotopic liver transplantation (OLT) is the improvement of patients' health-related quality of life (HRQOL). The purpose of this study was to look at the effects of socioeconomic and demographic differences on the short-term and long-term HRQOL outcomes of OLT recipients. Three hundred three adult OLT recipients who were seen at the University of California Los Angeles were administered the Medical Outcomes Study Short Form 36 (SF-36), the Chronic Liver Disease Questionnaire (CLDQ), and a demographic survey. A parsimonious model of 12 socioeconomic and demographic predictors was identified. Their simultaneous influence on each SF-36 and CLDQ HRQOL domain score was evaluated with multivariate linear regression and backward selection. Hepatitis C virus impaired HRQOL; this was shown in the SF-36 Vitality and Bodily Pain domains and in most CLDQ domains. Females experienced more HRQOL impairment only within the CLDQ Abdominal Symptoms domain. OLT recipients who were married had better SF-36 Role-Emotion domain scores. OLT recipients with more than 12 years of education had better SF-36 Physical Functioning scores. Employed OLT recipients had less HRQOL impairment; this was evidenced by better scores in multiple domains of the SF-36 and the CLDQ. OLT patients with health maintenance organization or preferred provider organization insurance had higher HRQOL scores within almost all SF-36 and CLDQ domains. Patients with a mix of public and private insurance had significantly higher HRQOL scores in comparison with those with only public insurance. Identifying patients at higher risk for worse HRQOL scores, less satisfaction with OLT results, and greater problems with fatigue or mental health stressors will assist transplant centers in using their medical teams to develop early interventions and multidisciplinary approaches to improve HRQOL outcomes after OLT.
Liver Transplantation 05/2011; 17(5):580-90. · 3.39 Impact Factor
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ABSTRACT: Infants (<12 months) who require liver transplantation (LTx) represent a particularly challenging and understudied group of patients.
This retrospective study aimed to describe a large single-center experience of infants who received isolated LTx, illustrate important differences in infants versus older children, and identify pretransplant factors which influence survival. More than 25 pre-LTx demographic, laboratory, and operative variables were analyzed using the Log-rank test and Cox proportional hazards model.
Between 1984 and 2006, 216 LTx were performed in 186 infants with a mean follow-up time of 62 months. Median age at LTx was 9 months, the majority had cholestatic liver disease, were hospitalized pre-LTx, and received whole grafts. Leading indications for re-LTx (n=30) included vascular complications (43%) and graft nonfunction (40%), whereas leading causes of death were sepsis and multiorgan failure. One-, 5-, and 10-year graft and patient survivals were 75%/72%/68% and 79%/77%/75%, respectively. Relative to older pediatric recipients, infants had worse overall patient survival (P=0.05). The following were significant univariate predictors of graft loss: age less than 6 months and reduced cadaveric grafts; and of patient loss: age less than 6 months, calculated CrCl less than 90, pre-LTx hospitalization, pre-LTx mechanical ventilation, repeat LTx, infants transplanted for reasons other than cholestatic liver disease, and patients transplanted between 1984 and 1994.
Long-term outcomes for infants undergoing LTx are excellent and have improved over time. As the largest, single-center analysis of LTx in infants, this study elucidates a unique set of predictors that can aid in medical decision making.
Transplantation 12/2009; 89(5):600-5. · 4.00 Impact Factor
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ABSTRACT: Although renal dysfunction (RD) has been commonly associated with poor outcome after other solid organ transplants, it has not been studied in detail after intestinal transplantation (ITx). Here we provide a detailed analysis of renal function after ITx, and identify predictors of post-ITx RD.
A retrospective analysis of patients undergoing ITx from 1991 to 2006 was performed. For each patient, the estimated glomerular filtration rate (eGFR) was compared with the normal GFR for age and gender to obtain the percent of normal eGFR. Chi-square analysis and log-rank tests were used to identify categorical variables associated with RD (eGFR <75% of normal) and to determine if RD was predictive of post-ITx survival.
Sixty-eight transplantations were performed in 62 patients. Overall patient survival at 1 and 5 years was 78% and 56%, respectively. Renal dysfunction was observed in 16% of patients post-ITx. The most frequent predictors of post-ITx RD were preoperative eGFR less than 75% of normal, pre-ITx location in the intensive care unit, and high-dose tacrolimus immunotherapy. An eGFR less than 75% of normal at days 7, 28, and 365 was predictive of poor patient survival (P<0.05).
This study provides the first detailed analysis of renal function after ITx. We identified specific risk factors for the development of RD in the first year post-ITx and found a significant association of RD with decreased long-term survival. Given the strong correlation of RD with poor outcome, preserving renal function may be key to improving long-term outcomes in ITx recipients.
Transplantation 07/2008; 86(1):117-22. · 4.00 Impact Factor
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Béatrice Bailly-Maitre,
Constantino Fondevila,
Fady Kaldas,
Nathalie Droin,
Fréderic Luciano,
Jean-Ehrland Ricci,
Rhonda Croxton,
Maryla Krajewska,
Juan M Zapata,
Jerzy W Kupiec-Weglinski, Douglas Farmer,
John C Reed
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ABSTRACT: Ischemia-reperfusion (IR) injury induces endoplasmic reticulum (ER) stress and cell death. Bax Inhibitor-1 (BI-1) is an evolutionarily conserved ER protein that suppresses cell death and that is abundantly expressed in both liver and kidney. We explored the role of BI-1 in protection from ER stress and IR injury by using bi-1 knockout mice, employing models of transient hepatic or renal artery occlusion. Compared to wild-type bi-1 mice, bi-1 knockout mice subjected to hepatic IR injury exhibited these characteristics: (i) increased histological injury; (ii) increased serum transaminases, indicative of more hepatocyte death; (iii) increased percentages of TUNEL-positive hepatocytes; (iv) greater elevations in caspase activity; and (v) more activation of ER stress proteins inositol-requiring enzyme 1 and activating transcription factor 6 and greater increases in expression of ER stress proteins C/EBP homologous protein and spliced XBP-1 protein. Moreover, hepatic IR injury induced elevations in bi-1 mRNA in wild-type liver, suggesting a need for bi-1 gene induction to limit tissue injury. Similar sensitization of kidney to ER stress and IR injury was observed in bi-1(-/-) mice. We conclude that bi-1 provides endogenous protection of liver and kidney from ER stress and IR injury. Analysis of components of the bi-1-dependent pathway for protection from IR injury may therefore reveal new strategies for organ preservation.
Proceedings of the National Academy of Sciences 03/2006; 103(8):2809-14. · 9.68 Impact Factor
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ABSTRACT: The intestine has been more difficult to transplant than other solid organs. We analyzed registry data to determine the scope and success of intestine transplantation in the current era.
All known intestinal-transplant programs participated. Patient- and graft-survival estimates were obtained using the Kaplan-Meier product limit method and were analyzed with the Wilcoxon statistic.
Sixty-one programs provided data on 989 grafts in 923 patients. Four patients were lost to follow-up. The short-gut syndrome was the most common primary indication for transplantation. Sixty-one percent of the recipients were < or =18 years. Proportionally more combined intestinal and liver transplants were performed in this group. More than 80% of all current survivors had stopped parenteral nutrition and resumed normal daily activities. A multivariate analysis of cases within the last 5 years revealed that transplantation of patients waiting at home, recipient age, antibody induction immune suppression, and center experience with at least 10 cases were associated with improved patient survival. One-year graft survival rates of 81% were achieved in patients who were induced with antithymocyte globulin and maintained on tacrolimus.
Transplantation is an effective therapy for the treatment of patients with end-stage intestine failure who cannot tolerate parenteral nutrition. With newer immune suppressive protocols, 1-year graft and patient survival rates approach the results of liver transplantation. Further improvement in survival are expected with early referral since suitable donor organs are scarce and survival rates are better when patients are well enough to wait at home for their transplant.
Annals of Surgery 04/2005; 241(4):607-13. · 7.49 Impact Factor
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Fasiha Kanwal,
David Chen,
Lena Ting,
Jeffrey Gornbein,
Sammy Saab,
Francisco Durazo,
Hasan Yersiz, Douglas Farmer,
R Mark Ghobrial,
Ronald W Busuttil,
Steven-Huy Han
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ABSTRACT: Postoperative mental status changes are common after liver transplantation (LT). A clear cause of these mental status changes cannot be identified in a significant proportion of patients. In adult liver transplant recipients, our goals are to: (1) identify independent predictors for the development of post-LT mental status changes of unclear cause and (2) derive a practical formula to predict the risk for developing this complication by using simple clinical parameters. Eligible patients had documented mental status changes of at least 3 days' duration, occurring within 1 month of LT. Exclusion criteria were known structural brain disorders, major organ dysfunction, or metabolic causes of altered mentation. Age- and sex-matched controls were liver transplant recipients without post-LT neurological sequelae. Data were collected on preoperative, intraoperative, and postoperative variables. Univariate and multivariate analyses were performed to detect factors predictive of the development of post-LT mental status of unclear cause. There were 40 cases and 40 controls. Independent predictors of mental status changes of unclear cause included alcoholic and metabolic liver diseases; pre-LT mechanical ventilation; Model for End-Stage Liver Disease (MELD) score greater than 15; and nonelective LT. Using these four preoperative factors, a simple predictive rule was developed. Risk for developing altered mental status of unclear cause after LT was 78% to 89% if all four predictors were present versus 0.8% to 2.4% if no predictors were present. In conclusion, alcoholic and metabolic liver diseases, pre-LT mechanical ventilation, MELD score greater than 15, and nonelective LT are independent predictive factors for post-LT altered mental status changes of unclear cause. A simple model can be used to calculate the risk for developing altered mental status post-LT.
Liver Transplantation 01/2004; 9(12):1312-9. · 3.39 Impact Factor
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Rafik M. Ghobrial,
Sammy Saab,
Charles Lassman,
David S.K. Lu,
Steven Raman,
Piyagorn Limanond,
Greg Kunder,
Karyn Marks,
Farin Amersi,
Dean Anselmo,
Pauline Chen, Douglas Farmer,
Steven Han,
Francisco Durazo,
Leonard I. Goldstein,
PhD Ronald W. Busuttil MD
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ABSTRACT: Severe donor organ shortage has provided the impetus for adult living donor liver transplantation (ALDLT). Despite rapid implementation and expansion of the procedure, outcome analysis of ALDLT is still incomplete. This study analyzed both donor and recipient outcomes after ALDLT at a single center. ALDLT performed at UCLA between August 1999 and November 2001 were reviewed retrospectively. Twenty recipients (14 men and 6 women) with a mean age of 48.8 ± 9.7 (29 to 66) years underwent right lobe ALDLT. By computed tomograpy (CT), graft/recipient weight ratio (GRWR) was 1.3 ± 0.3 (1 to 2.2). Overall 1-year patient and graft survival rates were 95% and 85%, respectively. One recipient died of heart failure with normal liver function 5 months after transplantation. Three grafts (14%) were lost and all three patients underwent successful cadaveric retransplantation. Complications were classified according to the Clavien grading system with all but 3 recipients encountering at least one complication. Nine (45%) had grade 1 (minor), 10 (50%) had grade 2 (potentially life threatening without residual disease/disability), 3 (14%) had grade 4A (retransplantation) and one grade 4B (death). Right lobectomy for living donation was performed in 20 patients (12 men, 8 women). Residual left lobe volumes were 36 ± 5.3 (23.9 to 47.9)% of total donor liver volume. No donor required intensive care unit admission and median hospital stay was 7.5 (6 to 14) days. One donor was aborted after intraoperative biopsy showed > 50% macrovesicular steatosis. No donor mortality or long-term complications were encountered. Five grade 1 minor complications, by Clavien Classification, occurred in 4 of 20 (20%) donors. ALDLT using right lobe grafts is an effective procedure to expand a severely depleted donor, but is associated with a high complication rate despite good survival outcomes. Continuous standardized reporting of ALDLT outcomes is required to allow successful and safe implementation of the procedure.
Liver Transplantation 12/2003; 8(10):901 - 909. · 3.39 Impact Factor
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Angeles Baquerizo,
Dean Anselmo,
Christopher Shackleton,
Teng-Wei Chen,
Carlos Cao,
Michael Weaver,
Jeffrey Gornbein,
Sunil Geevarghese,
Nicholas Nissen, Douglas Farmer,
Achilles Demetriou,
Ronald W Busuttil
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ABSTRACT: This study analyzes the prognostic significance of serum phosphorus in patients with acute liver failure (ALF).
We performed a retrospective analysis of 112 patients with ALF. Univariate and bivariate analyses based on Kaplan-Meier recovery curves and a multivariate Classification Tree Structure Survival Analysis were performed to identify independent predictors of outcome. The variables analyzed were age, gender, race, ABO blood group, etiology of liver disease, grade of encephalopathy, serum bilirubin, prothrombin time, creatinine, serum phosphorus, phosphorus administered, phosphorus binders, and hemodialysis.
The median follow-up time was 5 days, the median age was 28 years, and 62% of the patients were female. The patients' outcomes were as follows: 28% recovered, 52% required orthotopic liver transplantation, and 20% died. White patients showed the best prognosis (58% recovered in the first week), and Hispanics showed the worst prognosis (0.3% recovered at 1 week) (P=0.0001). Encephalopathy and bilirubin were significant predictors of recovery (P<0.0001 and P=0.004). The analysis of the serum phosphorus showed a statistically significant better prognosis in patients with low phosphorus (P<0.001). The recovery rate at 1 week was 74% in patients with serum phosphorus less than 2.5 mg/dL, 45% if phosphorus ranged between 2.5 to 5 mg/dL, and 0% if phosphorus was more than 5 mg/dL. The bivariate analysis on the effects of phosphorus administration showed that phosphorus replacement was associated with a significant improvement in recovery in patients with low (P<0.004) or normal serum phosphorus levels (P<0.017)
Hypophosphatemia and early phosphorus administration are associated with a good prognosis in ALF, whereas hyperphosphatemia is predictive of poor recovery.
Transplantation 07/2003; 75(12):2007-14. · 4.00 Impact Factor
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Steven-Huy Han,
Paul Martin,
Marc Edelstein,
Rena Hu,
Gregg Kunder,
Curtis Holt,
Sammy Saab,
Francisco Durazo,
Leonard Goldstein, Douglas Farmer,
Rafik M Ghobrial,
Ronald W Busuttil
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ABSTRACT: Recurrent hepatitis B infection after liver transplantation was previously frequent and associated with significant allograft failure and mortality. Recurrence rates of hepatitis B were improved with the use of passive immunoprophylaxis with hepatitis B immune globulin, and later, lamivudine monotherapy. Combination prophylaxis with intravenous hepatitis B immune globulin and lamivudine substantially decreased rates of hepatitis B recurrence, but intravenous administration of hepatitis B immune globulin was expensive and associated with significant adverse effects. In the current study, 59 patients receiving primary liver transplantation for chronic hepatitis B infection were prospectively followed up after converting from intravenous to intramuscular hepatitis B immune globulin in combination with lamivudine. All patients tolerated intramuscular hepatitis B immune globulin well. At a median follow-up of 511 days after conversion to intramuscular hepatitis B immune globulin, 58 of 59 patients (98.3%) were hepatitis B surface antigen-negative. Twenty-one patients (35.6%) required a median of one supplemental intravenous hepatitis B immune globulin infusion to maintain therapeutic antibody levels. Economic analysis showed an average cost-effectiveness ratio for combination intramuscular hepatitis B immune globulin plus lamivudine of $52,600 per recurrence prevented, which was far below the cost of lamivudine monotherapy and of intravenous hepatitis B immune globulin alone or in combination with lamivudine. These results suggest that intramuscular administration of hepatitis B immune globulin in combination with lamivudine offers a safe, effective, and cost-effective approach to preventing hepatitis B recurrence after orthotopic liver transplantation.
Liver Transplantation 03/2003; 9(2):182-7. · 3.39 Impact Factor
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Rafik M Ghobrial,
Sammy Saab,
Charles Lassman,
David S k Lu,
Steven Raman,
Piyagorn Limanond,
Greg Kunder,
Karyn Marks,
Farin Amersi,
Dean Anselmo,
Pauline Chen, Douglas Farmer,
Steven Han,
Francisco Durazo,
Leonard I Goldstein,
Ronald W Busuttil
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ABSTRACT: Severe donor organ shortage has provided the impetus for adult living donor liver transplantation (ALDLT). Despite rapid implementation and expansion of the procedure, outcome analysis of ALDLT is still incomplete. This study analyzed both donor and recipient outcomes after ALDLT at a single center. ALDLT performed at UCLA between August 1999 and November 2001 were reviewed retrospectively. Twenty recipients (14 men and 6 women) with a mean age of 48.8 +/- 9.7 (29 to 66) years underwent right lobe ALDLT. By computed tomograpy (CT), graft/recipient weight ratio (GRWR) was 1.3 +/- 0.3 (1 to 2.2). Overall 1-year patient and graft survival rates were 95% and 85%, respectively. One recipient died of heart failure with normal liver function 5 months after transplantation. Three grafts (14%) were lost and all three patients underwent successful cadaveric retransplantation. Complications were classified according to the Clavien grading system with all but 3 recipients encountering at least one complication. Nine (45%) had grade 1 (minor), 10 (50%) had grade 2 (potentially life threatening without residual disease/disability), 3 (14%) had grade 4A (retransplantation) and one grade 4B (death). Right lobectomy for living donation was performed in 20 patients (12 men, 8 women). Residual left lobe volumes were 36 +/- 5.3 (23.9 to 47.9)% of total donor liver volume. No donor required intensive care unit admission and median hospital stay was 7.5 (6 to 14) days. One donor was aborted after intraoperative biopsy showed > 50% macrovesicular steatosis. No donor mortality or long-term complications were encountered. Five grade 1 minor complications, by Clavien Classification, occurred in 4 of 20 (20%) donors. ALDLT using right lobe grafts is an effective procedure to expand a severely depleted donor, but is associated with a high complication rate despite good survival outcomes. Continuous standardized reporting of ALDLT outcomes is required to allow successful and safe implementation of the procedure.
Liver Transplantation 10/2002; 8(10):901-9. · 3.39 Impact Factor
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Rafik M. Ghobrial,
Chung-Bao Hsieh,
Susan Lerner,
Sharon Winters,
Nicholas Nissen,
Sherfield Dawson,
Farin Amersi,
Pauline Chen, Douglas Farmer,
Hasan Yersiz,
PhD Ronald W. Busuttil MD
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ABSTRACT: A right lobe graft that is drained by the right hepatic vein (RHV) is obtained by transecting the liver on the right side of the middle hepatic vein (MHV). On occasion, a small RHV that only drains a portion of the right lobe, with the predominant outflow achieved by the MHV, is encountered. If such variation is not recognized while performing right lobe liver transplantation and the RHV only is used for reconstruction, venous outflow obstruction with subsequent graft congestion and eventual graft failure will occur. Additionally, preservation of the main MHV and its branch drainage of the left lobe is crucial to avoid outflow blockage to the remaining segment 4 in the donor. We report 4 cases showing a variant type of small RHV and large MHV branch that drain not only segments 5 and 8, but also segments 6 and 7. These variations were simultaneously associated with a large-caliber inferior RHV that also required reconstruction. The methods used to diagnose such anatomic variations and the techniques for reconstruction in the donor and recipient are described.
Liver Transplantation 05/2001; 7(6):551 - 555. · 3.39 Impact Factor
