Max Marquez

Normothermic ex vivo liver perfusion using steen solution as perfusate for human liver transplantation: First North American results.

The European trial investigating normothermic ex vivo liver perfusion (NEVLP) as a preservation technique for liver transplantation (LT) uses gelofusine, a non–US Food and Drug Administration–approved, bovine‐derived, gelatin‐based perfusion solution. We report a safety and feasibility clinical NEVLP trial with human albumin–based Steen solution. Transplant outcomes of 10 human liver grafts that were perfused on the Metra device at 37 °C with Steen solution, plus 3 units of erythrocytes were compared with a matched historical control group of 30 grafts using cold storage (CS) as the preservation technique. Ten liver grafts were perfused for 480 minutes (340‐580 minutes). All livers cleared lactate (final lactate 1.46 mmol/L; 0.56‐1.74 mmol/L) and produced bile (61 mL; 14‐146 mL) during perfusion. No technical problems occurred during perfusion, and all NEVLP‐preserved grafts functioned well after LT. NEVLP versus CS had lower aspartate aminotransferase and alanine aminotransferase values on postoperative days 1‐3 without reaching significance. No difference in postoperative graft function between NEVLP and CS grafts was detected as measured by day 7 international normalized ratio (1.1 [1‐1.56] versus 1.1 [1‐1.3]; P = 0.5) and bilirubin (1.5; 1‐7.7 mg/dL versus 2.78; 0.4‐15 mg/dL; P = 0.5). No difference was found in the duration of intensive care unit stay (median, 1 versus 2 days; range, 0‐8 versus 0‐23 days; P = 0.5) and posttransplant hospital stay (median, 11 versus 13 days; range, 8‐17 versus 7‐89 days; P = 0.23). Major complications (Dindo‐Clavien ≥ 3b) occurred in 1 patient in the NEVLP group (10%) compared with 7 (23%) patients in the CS group (P = 0.5). No graft loss or patient death was observed in either group. Liver preservation with normothermic ex vivo perfusion with the Metra device using Steen solution is safe and results in comparable outcomes to CS after LT. Using US Food and Drug Administration–approved Steen solution will avoid a potential regulatory barrier in North America. Liver Transplantation 22 1501–1508 2016 AASLD.

The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: A prospective validation study

The selection of liver transplant candidates with hepatocellular carcinoma (HCC) relies mostly on tumor size and number. Instead of relying on these factors, we used poor tumor differentiation and cancer‐related symptoms to exclude patients likely to have advanced HCC with aggressive biology. We initially reported similar 5‐year survival for patients whose tumors exceeded (M+ group) and were within (M group) the Milan criteria. Herein, we validate our original data with a new prospective cohort and report the long‐term follow‐up (10‐years) using an intention‐to‐treat analysis. The previously published study (cohort 1) included 362 listed (294 transplanted) patients from January 1996 to August 2008. The validation cohort (cohort 2) includes 243 listed (105 M+ group, 76 beyond University of California San Francisco criteria; 210 transplanted) patients from September 2008 to December 2012. Median follow‐up from listing was 59.7 (26.8‐103) months. For the validation cohort 2, the actuarial survival from transplant for the M+ group was similar to that of the M group at 1 year, 3 years, and 5 years: 94%, 76%, and 69% versus 95%, 82%, and 78% (P = 0.3). For the combined cohorts 1 and 2, there were no significant differences in the 10‐year actuarial survival from transplant between groups. On an intention‐to‐treat basis, the dropout rate was higher in the M+ group and the 5‐year and 10‐year survival rates from listing were decreased in the M+ group. An alpha‐fetoprotein level >500 ng/mL predicted poorer outcomes for both the M and M+ groups. Conclusion: Tumor differentiation and cancer‐related symptoms of HCC can be used to select patients with advanced HCC who are appropriate candidates for liver transplantation; alpha‐fetoprotein level limitations should be incorporated in the listing criteria for patients within or beyond the Milan criteria. (Hepatology 2016;64:2077‐2088)

Outcomes of patients with cirrhosis and hepatorenal syndrome type 1 treated with liver transplantation

Hepatorenal syndrome type 1 (HRS1) is acute renal failure in the setting of advanced cirrhosis, and it results from hemodynamic derangements, which should be fully reversible after liver transplantation. However, the rate of hepatorenal syndrome (HRS) reversal and factors predicting renal outcomes after transplantation have not been fully elucidated. The aim of this study was to assess outcomes of HRS1 patients after liver transplantation and factors predicting HRS reversal. A chart review of all liver transplant patients with HRS1 (according to International Ascites Club criteria) at Toronto General Hospital from 2001 to 2010 was conducted. Patient demographic data, pretransplant and posttransplant laboratory data, and the presence of and time to posttransplant HRS reversal (serum creatinine < 1.5 mg/dL) were extracted from the centers transplant electronic database. Patients were followed until death or the end of the 2011 calendar year. Sixty‐two patients (mean age, 54.7 ± 1.2 years; mean Model for End‐Stage Liver Disease score, 35 ± 1) with HRS1 (serum creatinine, 3.37 ± 0.13 mg/dL) at liver transplant were enrolled. Thirty‐eight patients received midodrine, octreotide, and albumin without success and subsequently received renal dialysis. One further patient received dialysis without pharmacotherapy. After liver transplantation, HRS1 resolved in 47 of 62 patients (75.8%) at a mean time of 13 ± 2 days. Patients without HRS reversal had significantly higher pretransplant serum creatinine levels (3.81 ± 0.34 versus 3.23 ± 0.14 mg/dL, P = 0.06), a longer duration of HRS1 {25 days [95% confidence interval (CI), 16‐42 days] versus 10 days (95% CI, 10‐18 days), P = 0.02}, a longer duration of pretransplant dialysis [27 days (95% CI, 13‐41 days) versus 10 days (95% CI, 6‐14 days), P = 0.01], and increased posttransplant mortality (P = 0.0045) in comparison with those whose renal function recovered. The only predictor of HRS1 nonreversal was the duration of pretransplant dialysis with a 6% increased risk of nonreversal with each additional day of dialysis. In conclusion, our study suggests that patients with HRS1 should receive a timely liver transplant to improve their outcome. Liver Transpl 21:300–307, 2015.

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.

Thymoglobulin versus basiliximab induction therapy for simultaneous kidney-pancreas transplantation: impact on rejection, graft function, and long-term outcome.

Background. Thymoglobulin (ATG) and basiliximab induction therapies are used by the majority of centers for pancreas transplantation today. Although both strategies have different mechanisms, there is a paucity of studies comparing them. We compared the efficacy and side effects of both methods in simultaneous pancreas-kidney (SPK) transplantation. Methods. We analyzed 128 SPKs at our institution between January 2001 and August 2008. Forty-nine patients received basiliximab (40 mg), whereas 79 patients had ATG (5 mg/kg). Graft function, complications, rejection, and survival rates were analyzed. Results. ATG versus basiliximab therapy was associated with decreased 3-month (6% vs. 21%; P=0.01) and 1-year (14% vs. 27%; P=0.049) rejection rate. Steroid-resistant rejections were decreased with ATG (3%) vs. basiliximab (14%) (P=0.01). In a univariate regression analysis, basiliximab induction was a risk factor for rejection (HR, 7.1; CI, 3.8–13). No differences were observed regarding complications and graft function up to 5 years. ATG versus basiliximab therapy resulted in identical 1-year (90% vs. 93%), 3-year (87% vs. 89%), and 5-year (78% vs. 83%) pancreas survival (P=0.7). No difference was observed in kidney survival after 1 year (99% vs. 98%), 3 years (97% vs. 98%), and 5 years (95% vs. 95%) (P=0.4). Conclusions. ATG versus basiliximab induction therapy results in decreased acute cellular rejection in the first year after SPK with similar side effects. Long-term graft function and survival are not affected by induction regimen.

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.

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.

Pancreas-after-kidney versus synchronous pancreas-kidney transplantation: comparison of intermediate-term results.

Background Controversy persists over the safety and efficacy of pancreas transplantation in patients with insulin-dependent diabetes mellitus who have received a prior kidney transplant. Methods We compared the outcomes of recipients who received either Synchronous-Pancreas Kidney-Transplantation (SPK, n=123) or Pancreas-After-Kidney-Transplants(n=49)at our institution between August 2002 to January 2010. Results Donor and recipient demographics were similar. Time interval between kidney and pancreas transplantation was 5.9 ± 3.8 (4.8 [1.6–12.2]) years. The majority of kidney-recipients in PAK group were transplanted at outside institutions and referred to us for PAK. Most patients received thymoglobulin induction and were maintained on tacrolimus, MMF, and prednisone. For SPK versus PAK recipients, there was no difference in median of length of hospital stay or incidence of overall complications. All PAK recipients are alive with functioning kidney grafts, whereas the 1-, 3-, and 5-year SPK patient survival rates were 98%,96%,and 94%, P=0.09. The 1-,3-, and 5-yr uncensored pancreas survival rates for SPK versus PAK were 93% vs. 90%, 90% vs. 90%, and 82% versus 85%, respectively (P=0.4). Conclusion Glycemic control and intermediate survival outcomes were similar in both groups. Pancreas-graft outcomes in SPK and PAK were equivalent in our study, but our specific population entailed among other factors a long K to PAK time interval; PAK could be a comparable option to SPK for patients with access to kidney grafts.

Duodenal leaks after pancreas transplantation with enteric drainage - characteristics and risk factors

Pancreas–kidney transplantation with enteric drainage has become a standard treatment in diabetic patients with renal failure. Leaks of the graft duodenum (DL) remain a significant complication after transplantation. We studied incidence and predisposing factors of DLs in both simultaneous pancreas–kidney (SPK) and pancreas after kidney (PAK) transplantation. Between January 2002 and April 2013, 284 pancreas transplantations were performed including 191 SPK (67.3%) and 93 PAK (32.7%). Patient data were analyzed for occurrence of DLs, risk factors, leak etiology, and graft survival. Of 18 DLs (incidence 6.3%), 12 (67%) occurred within the first 100 days after transplantation. Six grafts (33%) were rescued by duodenal segment resection. Risk factors for a DL were PAK transplantation sequence (odds ratio 3.526, P = 0.008) and preoperative immunosuppression (odds ratio 3.328, P = 0.012). In the SPK subgroup, postoperative peak amylase as marker of preservation/reperfusion injury and recipient pretransplantation cardiovascular interventions as marker of atherosclerosis severity were associated with an increased incidence of DLs. CMV‐mismatch constellations showed an increased incidence in the SPK subgroup, however without significance probability. Long‐term immunosuppression in PAK transplantation is a major risk factor for DLs. Early surgical revision offers the chance of graft rescue.

The long-term efficacy of nucleos(t)ide analog plus a year of low-dose HBIG to prevent HBV recurrence post-liver transplantation

Hepatitis B immunoglobulin (HBIG), given in combination with nucleos(t)ide therapy, has reduced the rate of recurrent hepatitis B virus (HBV) following liver transplantation (LT), although the most effective protocol is unknown. We have retrospectively evaluated the use of long‐term nucleos(t)ide analog in combination with one yr of low‐dose HBIG. One hundred and fifty‐two adults with HBV‐related liver disease underwent LT in our center from January 1999 to August 2009; of these, 132 patients who received one yr of HBIG combined with long‐term nucleos(t)ide analogs (largely on lamivudine [LAM] alone, n = 97) afterward were included for the purposes of this study. Median follow‐up post‐transplantation was 1752 d. Patient survival was 93.9%, 86.9% and 84.1% at 1, 5, and 10 yr, respectively; none of the 17 deceased patients had recurrent HBV. HBV recurrence was observed in nine patients (all received LAM+HBIG), yielding recurrence rates of 2.3%, 5.1%, and 8.6% at 1, 3, and 5/10 yr, respectively. All recurrences were successfully managed, usually with additional antiviral treatment. In conclusion, this study, with its long‐term follow‐up, demonstrates that short course of low‐dose HBIG (without anti‐HBs monitoring) combined with the use of long‐term nucleos(t)ide analog is effective and less cumbersome than many protocols in current use.