Combined lung-liver-pancreas transplantation in a recipient with cystic fibrosis.

Cystic fibrosis (CF) affects multiple organs including the lung, liver, and pancreas. Lung transplant, liver transplant, and combined lung-liver transplant have become well-established therapies for CF patients with end-stage organ failure. Thus far, however, there has been limited experience with pancreas transplantation in CF. In this report, we detail the clinical history, transplant procedure, and post-operative recovery of a patient who underwent combined lung-liver-pancreas transplant for advanced CF.

Donor BMI >30 Is Not a Contraindication for Live Liver Donation.

The increased prevalence of obesity worldwide threatens the pool of living liver donors. Although the negative effects of graft steatosis on liver donation and transplantation are well known, the impact of obesity in the absence of hepatic steatosis on outcome of living donor liver transplantation (LDLT) is unknown. Consequently, we compared the outcome of LDLT using donors with BMI <30 versus donors with BMI ≥30. Between April 2000 and May 2014, 105 patients received a right-lobe liver graft from donors with BMI ≥30, whereas 364 recipients were transplanted with grafts from donors with BMI <30. Liver steatosis >10% was excluded in all donors with BMI >30 by imaging and liver biopsies. None of the donors had any other comorbidity. Donors with BMI <30 versus ≥30 had similar postoperative complication rates (Dindo-Clavien ≥3b: 2% vs. 3%; p = 0.71) and lengths of hospital stay (6 vs. 6 days; p = 0.13). Recipient graft function, assessed by posttransplant peak serum bilirubin and international normalized ratio was identical. Furthermore, no difference was observed in recipient complication rates (Dindo-Clavien ≥3b: 25% vs. 20%; p = 0.3) or lengths of hospital stay between groups. We concluded that donors with BMI ≥30, in the absence of graft steatosis, are not contraindicated for LDLT.

First-Degree Living-Related Donor Liver Transplantation in Autoimmune Liver Diseases.

Liver transplantation (LT) is the treatment of choice for end-stage autoimmune liver diseases. However, the underlying disease may recur in the graft in some 20% of cases. The aim of this study is to determine whether LT using living donor grafts from first-degree relatives results in higher rates of recurrence than grafts from more distant/unrelated donors. Two hundred sixty-three patients, who underwent a first LT in the Toronto liver transplant program between January 2000 and March 2015 for autoimmune liver diseases, and had at least 6 months of post-LT follow-up, were included in this study. Of these, 72 (27%) received a graft from a first-degree living-related donor, 56 (21%) from a distant/unrelated living donor, and 135 (51%) from a deceased donor for primary sclerosing cholangitis (PSC) (n = 138, 52%), primary biliary cholangitis (PBC) (n = 69, 26%), autoimmune hepatitis (AIH) (n = 44, 17%), and overlap syndromes (n = 12, 5%). Recurrence occurred in 52 (20%) patients. Recurrence rates for each autoimmune liver disease were not significantly different after first-degree living-related, living-unrelated, or deceased-donor LT. Similarly, time to recurrence, recurrence-related graft failure, graft survival, and patient survival were not significantly different between groups. In conclusion, first-degree living-related donor LT for PSC, PBC, or AIH is not associated with an increased risk of disease recurrence.

Live donor liver transplantation: a valid alternative for critically ill patients suffering from acute liver failure.

We report the outcome of live donor liver transplantation (LDLT) for patients suffering from acute liver failure (ALF). From 2006 to 2013, all patients with ALF who received a LDLT (n = 7) at our institution were compared to all ALF patients receiving a deceased donor liver transplantation (DDLT = 26). Groups were comparable regarding pretransplant ICU stay (DDLT: 1 [0-7] vs. LDLT: 1 days [0-10]; p = 0.38), mechanical ventilation support (DDLT: 69% vs. LDLT: 57%; p = 0.66), inotropic drug requirement (DDLT: 27% vs. LDLT: 43%; p = 0.64) and dialysis (DDLT: 2 vs. LDLT: 0 patients; p = 1). Median evaluation time for live donors was 24 h (18-72 h). LDLT versus DDLT had similar incidence of overall postoperative complications (31% vs. 43%; p = 0.66). No difference was detected between LDLT and DDLT patients regarding 1- (DDLT: 92% vs. LDLT: 86%), 3- (DDLT: 92% vs. LDLT: 86%), and 5- (DDLT: 92% vs. LDLT: 86%) year graft and patient survival (p = 0.63). No severe donor complication (Dindo-Clavien ≥3 b) occurred after live liver donation. ALF is a severe disease with high mortality on liver transplant waiting lists worldwide. Therefore, LDLT is an attractive option since live donor work-up can be expedited and liver transplantation can be performed within 24 h with excellent short- and long-term outcomes.

Benefit of Treating Hepatocellular Carcinoma Recurrence after Liver Transplantation and Analysis of Prognostic Factors for Survival in a Large Euro-American Series.

PURPOSE: To identify prognostic factors after hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). METHODS: We retrospectively reviewed the combined experience at Toronto General Hospital and Hospital Vall d'Hebron managing HCC recurrence after LT (n = 121) between 2000 and 2012. We analyzed prognostic factors by uni- and multi-variate analysis. Median follow-up from LT was 29.5 (range 2-129.4) months. Median follow-up from HCC recurrence was 12.2 (range 0.1-112.5) months. RESULTS: At recurrence, 31.4 % were treated with curative-intent treatments (surgery or ablation), 42.1 % received palliative treatment, and 26.4 % received best supportive care. The 1-, 3-, and 5-year survivals, respectively, after HCC recurrence were 75, 60, and 31 %, vs. 60, 19, and 12 %, vs. 52, 4, and 5 % (p < 0.001). By multivariate analysis, not being amenable to a curative-intent treatment [hazard ratio (HR) 4.7, 95 % confidence interval (CI) 2.7-8.3, p < 0.001], α-fetoprotein of ≥100 ng/mL at the time of HCC recurrence (HR 2.1, 95 % CI 1.3-2.3, p = 0.002) and early recurrence (<12 months) after LT (HR 1.6, 95 % CI 1.1-2.5, p = 0.03) were found to be poor prognosis factors. A prognostic score was devised on the basis of these three independent variables. Patients were divided into three groups, as follows: good prognosis, 0 points (n = 22); moderate prognosis, 1 or 2 points (n = 84); and poor prognosis, 3 points (n = 15). The 1-, 3-, and 5-year actuarial survival for each group was 91, 50, and 50 %, vs. 52, 7, and 2 %, vs. 13, 0, and 0 %, respectively (p < 0.001). CONCLUSIONS: Patients with HCC recurrence after transplant amenable to curative-intent treatments can experience significant long-term survival (~50 % at 5 years), so aggressive management should be offered. Poor prognosis factors after recurrence are not being amenable to a curative-intent treatment, α-fetoprotein of ≥100 ng/mL, and early (<1 year) recurrence after LT.

Living vs. deceased donor liver transplantation provides comparable recovery of renal function in patients with hepatorenal syndrome: a matched case-control study.

Outcomes of living versus deceased donor liver transplantation in patients with chronic liver disease and hepatorenal syndrome (HRS) was compared using a matched pair study design. Thirty patients with HRS receiving a live donor liver transplantation (LDLT) and 90 HRS patients receiving a full graft deceased donor liver transplantation (DDLT) were compared. LDLT versus DDLT of patients with HRS was associated with decreased peak aspartate aminotransferase levels (339 ± 214 vs. 935 ± 1253 U/L; p = 0.0001), and similar 7-day bilirubin (8.42 ± 7.89 vs. 6.95 ± 7.13 mg/dL; p = 0.35), and international normalized ratio levels (1.93 ± 0.62 vs. 1.78 ± 0.78; p = 0.314). LDLT vs. DDLT had a decreased intensive care unit (2 [1-39] vs. 4 [0-93] days; p = 0.004), and hospital stay (17 [4-313] vs. 26 [0-126] days; p = 0.016) and a similar incidence of overall postoperative complications (20% vs. 27%; p = 0.62). No difference was detected between LDLT and DDLT patients regarding graft survival at 1 (80% vs. 82%), at 3 (69% vs. 76%) and 5 years (65% vs. 76%) (p = 0.63), as well as patient survival at 1 (83% vs. 82%), 3 (72% vs. 77%) and 5 years (72% vs. 77%) (p = 0.93). The incidence of chronic kidney disease post-LT (10% vs. 6%; p = 0.4) was similar between both groups. LDLT results in identical long-term outcome when compared with DDLT in patients with HRS.

Portal venous versus systemic venous drainage of pancreas grafts: impact on long-term results.

Portal venous (PV) and systemic venous (SV) drainage methods are used in pancreas transplantation. The impact of the reconstruction technique on long-term outcome remains unclear. We compared the efficacy and side effects of both methods in 192 recipients who received synchronous pancreas kidney transplants between November 1995 and November 2007. SV and PV drainage were used in 147 and 45 cases, respectively. Pancreas function was determined by hemoglobin A1c levels and annual oral glucose tolerance test. Serum creatinine assessed kidney function. Serum lipid (low-density lipoprotein, high-density lipoprotein and cholesterol) levels and body mass index were measured annually. Patient and graft survival were calculated by log-rank analysis. Pancreas survival for SV versus PV patients was similar after 5 years (81.8% vs. 75.5%) and 10 years (65.1% vs. 60%; p = NS). Similarly, no difference was detected between the groups regarding kidney survival after 5 years (92.9% vs. 84.4%) and 10 years (81.6% vs. 75.5%; p = NS). Patient survival did not differ at 5 years (94.3% vs. 88.8%) and 10 years (85.1% vs. 84.4%; p = NS). Pancreas and kidney function and the lipid profiles were similar in both groups. SV and PV drainage of pancreas grafts offer similar long-term graft survival and function and choice of method should remain the preference of the surgeon.

Adult living liver donors have excellent long-term medical outcomes: the University of Toronto liver transplant experience.

Right lobe living donor liver transplantation is an effective treatment for selected individuals with end-stage liver disease. Although 1 year donor morbidity and mortality have been reported, little is known about outcomes beyond 1 year. Our objective was to analyze the outcomes of the first 202 consecutive donors performed at our center with a minimum follow-up of 12 months (range 12-96 months). All physical complications were prospectively recorded and categorized according to the modified Clavien classification system. Donors were seen by a dedicated family physician at 2 weeks, 1, 3 and 12 months postoperatively and yearly thereafter. The cohort included 108 males and 94 females (mean age 37.3 +/- 11.5 years). Donor survival was 100%. A total of 39.6% of donors experienced a medical complication during the first year after surgery (21 Grade 1, 27 Grade 2, 32 Grade 3). After 1 year, three donors experienced a medical complication (1 Grade 1, 1 Grade 2, 1 Grade 3). All donors returned to predonation employment or studies although four donors (2%) experienced a psychiatric complication. This prospective study suggests that living liver donation can be performed safely without any serious late medical complications and suggests that long-term follow-up may contribute to favorable donor outcomes.

Reduced mortality with right-lobe living donor compared to deceased-donor liver transplantation when analyzed from the time of listing.

Right lobe living donor liver transplantation (RLDLT) is not yet a fully accepted therapy for patients with end-stage liver failure in the Western hemisphere because of concerns about donor safety and inferior recipient outcomes. An outcome analysis from the time of listing for all adult patients who were listed for liver transplantation (LT) at our center was performed. From 2000 to 2006, 1091 patients were listed for LT. One hundred fifty-four patients (LRD; 14%) had suitable live donors and 153 (99%) underwent RLDLT. Of the remaining patients (DD/Waiting List; n = 937), 350 underwent deceased donor liver transplant (DDLT); 312 died or dropped off the waiting list; and 275 were still waiting at the time of this analysis. The LRD group had shorter mean waiting times (6.0 months vs. 9.8 months; p < 0.001). Although medical model for end-stage liver disease (MELD) scores were similar at the time of listing, MELD scores at LT were significantly higher in the DD/Waiting List group (15.4 vs. 19.5; p = 0.002). Patients in Group 1 had a survival advantage with RLDLT from the time of listing (1-year survival 90% vs. 80%; p < 0.001). To our knowledge, this is the first report to document a survival advantage at time of listing for RLDLT over DDLT.

Selective use of older adults in right lobe living donor liver transplantation.

Many centers are reluctant to use older donors (>44 years) for adult right-lobe living donor liver transplantation (RLDLT) due to concerns about possible increased morbidity in donors and poorer outcomes in recipients. Since 2000, 130 adult RLDLTs have been performed at our institution. Recipients were divided into those who received a right lobe graft from a donor 44 (n = 41, 32%; mean age 52). The two donor and recipient populations had similar demographic and operative profiles. With a median follow-up of 29 months, the severity and number of complications in older donors were similar to those in younger donors. No living donor died. Older donor allografts had initial allograft dysfunction compared to younger donors. Complication rates were similar among recipients in both groups but there was a higher bile duct stricture rate with older donor grafts (27% vs. 12%; p = 0.04). One-year recipient graft survival was 86% for older donors and 85% for younger donors (p = 0.95). Early experience with the use of selected older adults (>44 years) for RLDLT is encouraging, but may be associated with a higher rate of biliary complications in the recipient.

Biliary strictures in 130 consecutive right lobe living donor liver transplant recipients: results of a Western center.

Biliary strictures remain the most challenging aspect of adult right lobe living donor liver transplantation (RLDLT). Between 04/2000 and 10/2005, 130 consecutive RLDLTs were performed in our center and followed prospectively. Median follow-up was 23 months (range 3-67) and 1-year graft and patient survival was 85% and 87%, respectively. Overall incidence of biliary leaks (n = 19) or strictures (n = 22) was 32% (41/128) in 33 patients (26%). A duct-to-duct (D-D) or Roux-en-Y (R-Y) anastomosis were performed equally (n = 64 each) with no difference in stricture rate (p = 0.31). The use of ductoplasty increased the number of grafts with a single duct for anastomosis and reduced the biliary complication rate compared to grafts >/=2 ducts (17% vs. 46%; p = 0.02). Independent risk factors for strictures included older donor age and previous history of a bile leak. All strictures were managed nonsurgically initially but four patients ultimately required conversion from D-D to R-Y. Ninety-six percent (123/128) of patients are currently free of any biliary complications. D-D anastomosis is safe after RLDLT and provides access for future endoscopic therapy in cases of leak or stricture. When presented with multiple bile ducts, ductoplasty should be considered to reduce the potential chance of stricture.

Reconstruction of middle hepatic vein of a living-donor right lobe liver graft with recipient left portal vein.

Venous outflow problems in right lobe, living-donor liver transplantation are uncommon, but devastating when they occur. We describe the successful use of the recipient's left portal vein as an interposition graft to drain a dominant middle hepatic vein in a right lobe liver transplant. Two weeks after transplantation, the vein graft accounted for 56% of the total venous outflow of the liver.

The effect of systemic versus portal insulin delivery in pancreas transplantation on insulin action and VLDL metabolism.

Combined kidney-pancreas transplantation (KPT) with anastomosis of the pancreatic vein to the systemic circulation (KPT-S) or to the portal circulation (KPT-P) provides a human model in which the chronic effects of portal versus systemic insulin delivery on glucose and VLDL metabolism can be examined. Despite similar plasma glucose and C-peptide levels, KPT-S (n = 9) had an approximate twofold elevation of fasting and intravenous glucose-stimulated plasma insulin levels compared with both KPT-P (n = 7) and healthy control subjects (n = 15). The plasma free fatty acid (FFA) levels were elevated in both transplant groups versus control subjects, but the plasma insulin elevation necessary to lower plasma FFA by 50% was approximately two times higher in KPT-S versus KPT-P and control subjects. Endogenous glucose production was similar in KPT-S and KPT-P, despite approximately 35% higher hepatic insulin levels in the latter, and was suppressed to a greater extent during a euglycemic-hyperinsulinemic clamp in KPT-S versus KPT-P. Total-body glucose utilization during the euglycemic-hyperinsulinemic clamp was approximately 40% lower in KPT-S versus KPT-P, indicating peripheral tissue but not hepatic insulin resistance in KPT-S versus KPT-P. Both transplant groups had an approximate twofold elevation of triglyceride (TG)-rich lipoprotein apolipoprotein B (apoB) and lipids versus control subjects. Elevation of VLDL-apoB and VLDL-TG in both transplant groups was entirely explained by an approximately 50% reduction in clearance of VLDL compared with healthy control subjects. In the presence of increased FFA load but in the absence of hepatic overinsulinization and marked hepatic insulin resistance, there was no elevation of VLDL secretion in KPT-S versus KPT-P and control subjects. These findings suggest that chronic systemic hyperinsulinemia and peripheral tissue insulin resistance with the consequent elevation of plasma FFA flux are insufficient per se to cause VLDL overproduction and that additional factors, such as hepatic hyperinsulinemia and/or gross insulin resistance, may be an essential prerequisite in the pathogenesis of VLDL overproduction in the common form of the insulin resistance syndrome.

The hippurate ratio as an indicator of functional hepatic reserve for resection of hepatocellular carcinoma in cirrhotic patients.

Predicting the ability of the cirrhotic liver to withstand resection remains a challenge for the surgeon. This study evaluates the use of the hippurate ratio, a novel assessment of glycine conjugation of para-aminobenzoic acid by the liver, as a preoperative indicator of functional hepatic reserve. Between 1998 and 2000, sixty-one cirrhotic patients were prospectively assessed for hepatic resection using the hippurate ratio, indocyanine green retention at 15 minutes (ICG R-15), and other standard measures of liver function. Twenty-six patients were excluded as candidates for resection on the basis of inadequate functional hepatic reserve. Patients excluded from resection had significantly higher ICG R-15 values (29% +/- 9% vs. 16% +/- 12%, P = 0.001), higher Child-Pugh scores (5.9 +/- 0.9 vs. 5.3 +/- 0.4, P = 0.01), and lower hippurate ratios (30% +/- 14% vs. 45% +/- 15%, P = 0.005). There was a significant correlation between the hippurate ratio and ICG R-15. Other indicators of liver function such as factor V, factor VII, albumin, bilirubin, prothrombin time, and transaminases were no different between patients who did and those who did not undergo resection. Of the 35 patients resected, there were seven (20%) who developed varying degrees of liver failure with three perioperative deaths (8.5%). Patients who had some degree of liver failure had significantly lower hippurate ratios than patients who had no liver failure (29% +/- 10% vs. 48% +/- 14%, P = 0.002). There was no difference in ICG R-15 values between patients who had liver failure and those who did not. The hippurate ratio offers information on hepatocellular reserve that is not provided by other measures of liver function and may allow better selection of cirrhotic patients for liver resection.

Liver transplantation for hepatocellular carcinoma.

OBJECTIVE: To analyze patient and tumor characteristics that influence patient survival to select patients who would most benefit from liver transplantation. SUMMARY BACKGROUND DATA: The selection of patients with hepatocellular carcinoma (HCC) for liver transplantation remains controversial. METHODS: One hundred twelve patients with nonfibrolamellar HCC who underwent a liver transplant from 1985 to 2000 were reviewed. Survival was calculated using the Kaplan-Meier method, with differences in outcome assessed using the log-rank procedure. Multivariate analysis was then performed using a Cox regression model. RESULTS: Overall patient survival rates were 78%, 63%, and 57% at 1, 3, and 5 years, respectively. Patients infected with the hepatitis B virus had a worse 5-year survival than those who were not (43% vs. 64%), with most deaths being attributed to recurrent hepatitis B. However, patients with hepatitis B virus who underwent more recent transplants using antiviral therapy fared as well as those who were negative for the virus, showing a 5-year survival rate of 77%. Patients with vascular invasion by tumor had a worse 5-year survival than patients without vascular invasion (33% vs. 68%). Vascular invasion, tumor size greater than 5 cm, and poorly differentiated tumor grade were predictors of tumor recurrence by univariate analysis; however, only vascular invasion remained significant on multivariate analysis: the rate of tumor recurrence at 5 years was 65% in patients with vascular invasion and only 4% for patients without vascular invasion. CONCLUSIONS: For well-selected patients with HCC, liver transplantation in the current era can achieve equivalent results to transplantation for nonmalignant indications. Vascular invasion is an indicator of high risk of tumor recurrence but is difficult to detect before transplantation.

Portal venous and enteric exocrine drainage versus systemic venous and bladder exocrine drainage of pancreas grafts: clinical outcome of 40 consecutive transplant recipients.

OBJECTIVE: To test the hypothesis that pancreas transplantation using the more physiologic method of portal venous-enteric (PE) drainage could be performed without compromising patient and graft outcome, compared with the standard method of systemic venous-bladder (SB) drainage. METHODS: Between November 1995 and November 1998, the authors prospectively followed up 20 consecutive patients with SB drainage followed by 20 consecutive patients with PE drainage. All patients underwent simultaneous pancreas-kidney transplantation, and all were immunosuppressed with antilymphocyte serum, cyclosporin, azathioprine, and steroids. RESULTS: The actuarial patient survival rate at 1 year was 95% in the SB group and 100% in the PE group. Death-censored kidney graft survival was 100% in both groups; pancreas graft survival was 95% in the SB group and 100% in the PE group. The mean initial hospital stay was 15 days for both groups. However, during the first 6 months after transplantation, the SB group required more medical day-unit visits, mostly for treatment of metabolic acidosis and dehydration. The incidence of urinary tract infections was similar in both groups. The incidence of cytomegalovirus infections was significantly less in the PE group. The incidence of acute rejection was 37% in the SB group and 15% in the PE group. Mean serum creatinine levels 6 months after transplantation were significantly lower in the PE group than in the SB group. Glycemic control was excellent in both groups, but fasting serum insulin levels were significantly lower in the PE group. CONCLUSIONS: The PE method of pancreas transplantation can be performed with excellent patient and graft outcomes.

Hepatitis C-related cirrhosis: a predictor of diabetes after liver transplantation.

Hepatitis C virus (HCV) infection has recently been suggested to be a risk factor for the development of diabetes mellitus. The aim of our study was to investigate whether the prevalence of diabetes is increased among liver transplant recipients infected with HCV. We compared the prevalence of diabetes among 278 liver transplant recipients whose original cause of liver failure was HCV infection (110 patients), hepatitis B virus infection (HBV; 53 patients), and cholestatic liver disease (CLD; 115 patients). The pretransplantation prevalence of diabetes was higher in the HCV group (29%) compared with the HBV (6%) and CLD (4%) groups (P <.001). The prevalence of diabetes remained higher in the HCV group 1 year after transplantation: 37%, 10%, and 5% in the HCV, HBV, and CLD groups, respectively (P <.001). The cumulative steroid dose during the first year of transplantation was significantly lower in the HCV group compared with the CLD group. Multivariate analysis revealed that HCV-related liver failure (P =.002), pretransplantation diabetes (P <.0001), and male sex (P =.019) were independent predictors of the presence of diabetes 1 year after transplantation. The high prevalence of diabetes persisted in the HCV group, with 41% diabetic at 5 years. The majority of patients with diabetes mellitus (89%) required insulin therapy after transplantation. Patient and graft survival rates were similar among patients with and without diabetes. In conclusion, our study shows that there is a high prevalence of diabetes among liver transplant recipients infected with HCV both before and after transplantation.