Hepaticojejunostomy in Orthotopic Liver Transplant: A Retrospective Case Control Study.

The reported biliary morbidity rate for deceased donor full-size orthotopic liver transplantation is up to 30%. The technique used may be influenced by multiple factors, and in some situations, biliary reconstruction must be carried out through Roux-en-Y hepaticojejunostomy. The aim of our study was to determine the results of the orthotopic liver transplantation according to the technique used in the biliary reconstruction. A retrospective study was performed with the first 1000 orthotopic liver transplants (951 patients) carried out consecutively (1996-2013) with follow-up until 2017. A matched case-control study was designed in 1:3 ratio (47/136) to compare the reconstruction by hepaticojejunostomy vs the end-to-end coledoco-coledocostomy. Hepaticojejunostomy was associated with patients with cholestatic (44.7% vs 3.7%) and ischemic disease (14.9% vs 0%; P < .001) and previous transplant (29.8% vs 1.5%; P = .003). The mean biliary duct reconstruction, surgery, and cold ischemia times were also higher. Vascular complications were significantly more frequent in the hepaticojejunostomy group (36.1% vs 10.4%; P < .001), mainly because of differences in early arterial complications. Nevertheless, there were no differences in the total biliary complication (21.2% vs 16.9%; P = .5). The biliary leakage rate and the biliary stricture rate were also similar. Hepaticojejunostomy in orthotopic liver transplantation presented longer biliary reconstruction, surgery, and cold ischemia times when compared with end-to-end coledoco-coledocostomy. In addition, it was followed by a higher incidence of arterial complications but had similar biliary complication rate and graft survival. Differences could be explained by the fact that hepaticojejunostomy was used more often in cholestatic or ischemic diseases and in retransplant procedures.

Manejo perioperatorio en el trasplante hepático en los centros españoles: resultados de una encuesta / Perioperative management of liver transplantation in Spanish hospitals: results of a survey

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Octogenarian Donors in Liver Transplantation.

INTRODUCTION: Due to the disparity between the number of patients on the list for liver transplantation and the availability of organs, the use of older donors has become necessary. The aim of this study was to investigate the outcomes of liver transplantation using octogenarian donors. METHODS: From December 2003 to February 2016, 777 liver transplantations were performed at our institution, 33 of them (4.2%) with donors 80 years old and above. Our policy for the acceptance of these donors is based on preoperative liver function tests, donor hemodynamic stability, and intraoperative normal gross aspect. Octogenarian grafts were deliberately not assigned to retransplantations or to recipients with multiple previous surgical procedures or extensive portal thrombosis. RESULTS: Mean donor age was 82.7 ± 2.1 years, with a range between 80 and 88. Only 12.1% suffered hemodynamic instability during the intensive care unit stay. Three donors (9.1%) had a history of diabetes mellitus. The mean Model for End-Stage Liver Disease score among recipients was 14.7 ± 5.6. Mean cold ischemia time was 302 ± 61 minutes. After a median follow-up of 18.5 months (range 7.5 to 47.5), no graft developed primary nonfunction. We observed hepatic artery thrombosis in 1 patient (3%) and biliary complications in 4 patients (12.5%). There was 1 case of ischemic-type biliary lesion, although it was related to hepatic artery thrombosis. Patient survival at 1 and 3 years was 90.3%, whereas graft survival was 92.6% and 86.4%, respectively. CONCLUSIONS: Excellent mid-term results can be obtained after liver transplantation with octogenarian donors with strict donor selection and adequate graft allocation.

Intraoperative Portal Flow of Less Than 1 Liter per Minute After Orthotopic Liver Transplantation Is Not Associated Per Se With an Increased Rate of Early Graft Dysfunction.

OBJECTIVE: The aim of this study was to determine whether a portal flow of <1,000 mL/min in orthotopic liver transplantation (OLT) is associated with a higher incidence of early graft dysfunction (EGD) and graft loss. METHODS: A retrospective study was performed of 540 OLTs carried out consecutively from December 2004 to December 2013. Patients were divided into 2 groups: group A, portal flow <1,000 mL/min; and group B, portal flow >1,000 mL/min. We studied the incidence of EGD and graft survival. A subanalysis was performed to define the minimum acceptable portal flow/100 g of liver weight to reduce the development EGD and graft loss. RESULTS: Group A included 29 patients and group B, 511 patients. Group A had significantly lower-weight donors and recipients, female recipients with cholestatic disease, lower MELD scores, and lower hepatic artery flow. EGD occurred in 7 patients in group A (24.1%) versus 101 patients in group B (19.8%; P = .43). No significant differences were found in 1- and 5-year graft survival. A portal flow of <80 mL/min/100 g of liver weight was related to a significantly higher risk of developing EGD (odds ratio, 4.35; 95% confidence interval [CI], 1.46-12.91; P = .008) and graft loss (hazard ratio, 4.05; 95% CI, 1.32-12.42; P = .014). CONCLUSIONS: Intraoperative portal flow of <1,000 mL/min in OLT was not related per se with a higher incidence of EGD or graft loss. Significantly higher risk of developing EGD and graft loss was associated with a portal flow of <80 mL/min/100 g of liver weight.

Safety and Efficacy of Early Everolimus When Calcineurin Inhibitors Are Not Recommended in Orthotopic Liver Transplantation.

Our aim was to study the safety and efficacy of immunosuppression with everolimus (EVL) within the 1st month after orthotopic liver transplantation (LT) when calcineurin inhibitors are not recommended. For this purpose, 28 recipients who had been treated with EVL within the 1st month after adult LT were eligible to enter in a retrospective multicenter study. Patients were followed up for 12 months after LT. EVL therapy was initiated at a median of 14 days (range, 4-24) after LT. The reason for early EVL was neurotoxicity in 14 cases, renal dysfunction in 12, and acute cellular rejection combined with renal impairment in 2. In 23 patients, immunosuppression was EVL + mycophenolate mofetil/mycophenolate sodium + steroids, and EVL + tacrolimus + steroids/mycophenolate sodium was used in 4 cases. Neurotoxicity disappeared in all patients. Renal function in patients with renal impairment improved from a median of 32 mL/min/1.73 m2 at the moment of implementation of EVL to 62 mL/min/1.73 m2 at 1 year. Four patients (14.3%) developed acute cellular rejection. We observed incisional hernia in 4 patients (14.3%), hematologic complications in 6 (21.4%), proteinuria in 2 (7.1%), edema and/or effusions in 8 (28.6%), and dyslipidemia in 12 (42.8%). No arterial complications were observed. EVL was withdrawn in 5 patients during the 1st year after LT. One-year patient survival was 92.7%. In conclusion, use of EVL within the 1st month after LT when calcineurin inhibitors are not recommended seems to be an effective therapeutic option with an acceptable safety profile.

Liver Retransplantation in Patients With HIV-1 Infection: An International Multicenter Cohort Study.

Liver retransplantation is performed in HIV-infected patients, although its outcome is not well known. In an international cohort study (eight countries), 37 (6%; 32 coinfected with hepatitis C virus [HCV] and five with hepatitis B virus [HBV]) of 600 HIV-infected patients who had undergone liver transplant were retransplanted. The main indications for retransplantation were vascular complications (35%), primary graft nonfunction (22%), rejection (19%), and HCV recurrence (13%). Overall, 19 patients (51%) died after retransplantation. Survival at 1, 3, and 5 years was 56%, 51%, and 51%, respectively. Among patients with HCV coinfection, HCV RNA replication status at retransplantation was the only significant prognostic factor. Patients with undetectable versus detectable HCV RNA had a survival probability of 80% versus 39% at 1 year and 80% versus 30% at 3 and 5 years (p = 0.025). Recurrence of hepatitis C was the main cause of death in the latter. Patients with HBV coinfection had survival of 80% at 1, 3, and 5 years after retransplantation. HIV infection was adequately controlled with antiretroviral therapy. In conclusion, liver retransplantation is an acceptable option for HIV-infected patients with HBV or HCV coinfection but undetectable HCV RNA. Retransplantation in patients with HCV replication should be reassessed prospectively in the era of new direct antiviral agents.

Risk factors for biliary complications after orthotopic liver transplantation with T-tube: a single-center cohort of 743 transplants.

BACKGROUND: Despite recent advances in organ preservation, surgical procedures, and immunosuppression, biliary reconstruction after orthotopic liver transplantation (OLT) remains as a major source of morbidity. The purpose of this study was to identify risk factors for the development of biliary complications (BCs) after end-to-end choledochocholedochostomy (EE-CC) with a T-tube as the standard technique for biliary reconstruction after OLT. METHODS: A total of 833 consecutive liver transplantations that took place from February 1996 to April 2010 were retrospectively reviewed. Patients with concomitant hepatic artery complications were excluded, as were those who underwent urgent retransplantation or died within 1 week after transplantation. Finally, the study group comprised 743 patients. RESULTS: The overall BC rate was 9.8% (73 patients), including stricture in 19 patients (2.6%) and bile leakage in 39 patients (5.2%). After univariate analysis, significant risk factors for BCs were surgery time >5 hours, arterial ischemia time >30 minutes, use of a classic transplant technique, transfusion of red blood cells ≥5 units, anti-cytomegalovirus treatment, and period of transplantation between 1996 and 2002. Stepwise logistic regression study was performed, including those variables with a value of P <.200. Multivariate analysis showed that pretransplant serum creatinine (odds ratio = 1.27; 95% confidence interval [CI], 1.03-1.57; P = .025) and arterial ischemia time >30 minutes (odds ratio = 2.44; 95% CI, 1.45-4.12; P = .001) were the only independent risk factors related to the development of BCs after biliary reconstruction with the T-tube. CONCLUSIONS: The performance of different variables in predicting occurrence of BCs was assessed with the use of receiver operating characteristic analysis. The area under the receiver operating characteristic curve of our model was 0.637 (95% CI, 0.564-0.710), and therefore we must conclude that other variables not included in our model may have influence in the development of BCs after OLT with an EE-CC with a T-tube as the procedure for biliary reconstruction.

"Very early" intrahepatic cholangiocarcinoma in cirrhotic patients: should liver transplantation be reconsidered in these patients?

A retrospective cohort multicenter study was conducted to analyze the risk factors for tumor recurrence after liver transplantation (LT) in cirrhotic patients found to have an intrahepatic cholangiocarcinoma (iCCA) on pathology examination. We also aimed to ascertain whether there existed a subgroup of patients with single tumors ≤2 cm ("very early") in which results after LT can be acceptable. Twenty-nine patients comprised the study group, eight of whom had a "very early" iCCA (four of them incidentals). The risk of tumor recurrence was significantly associated with larger tumor size as well as larger tumor volume, microscopic vascular invasion and poor degree of differentiation. None of the patients in the "very early" iCCA subgroup presented tumor recurrence compared to 36.4% of those with single tumors >2 cm or multinodular tumors, p = 0.02. The 1-, 3- and 5-year actuarial survival of those in the "very early" iCCA subgroup was 100%, 73% and 73%, respectively. The present is the first multicenter attempt to ascertain the risk factors for tumor recurrence in cirrhotic patients found to have an iCCA on pathology examination. Cirrhotic patients with iCCA ≤2 cm achieved excellent 5-year survival, and validation of these findings by other groups may change the current exclusion of such patients from transplant programs.

Intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma in patients undergoing liver transplantation: a Spanish matched cohort multicenter study.

OBJECTIVE: To evaluate the outcome of patients with hepatocellular-cholangiocarcinoma (HCC-CC) or intrahepatic cholangiocarcinoma (I-CC) on pathological examination after liver transplantation for HCC. BACKGROUND: Information on the outcome of cirrhotic patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study is limited. METHODS: Multicenter, retrospective, matched cohort 1:2 study. STUDY GROUP: 42 patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study; and control group: 84 patients with a diagnosis of HCC. I-CC subgroup: 27 patients compared with 54 controls; HCC-CC subgroup: 15 patients compared with 30 controls. Patients were also divided according to the preoperative tumor size and number: uninodular tumors 2 cm or smaller and multinodular or uninodular tumors 2 cm or larger. Median follow-up: 51 (range, 3-142) months. RESULTS: The 1-, 3-, and 5-year actuarial survival rate differed between the study and control groups (83%, 70%, and 60% vs 99%, 94%, and 89%, respectively; P < 0.001). Differences were found in 1-, 3-, and 5-year actuarial survival rates between the I-CC subgroup and their controls (78%, 66%, and 51% vs 100%, 98%, and 93%; P < 0.001), but no differences were observed between the HCC-CC subgroup and their controls (93%, 78%, and 78% vs 97%, 86%, and 86%; P = 0.9). Patients with uninodular tumors 2 cm or smaller in the study and control groups had similar 1-, 3-, and 5-year survival rate (92%, 83%, 62% vs 100%, 80%, 80%; P = 0.4). In contrast, patients in the study group with multinodular or uninodular tumors larger than 2 cm had worse 1-, 3-, and 5-year survival rates than their controls (80%, 66%, and 61% vs 99%, 96%, and 90%; P < 0.001). CONCLUSIONS: Patients with HCC-CC have similar survival to patients undergoing a transplant for HCC. Preoperative diagnosis of HCC-CC should not prompt the exclusion of these patients from transplant option.

Biliary complications after orthotopic liver transplantation: a review of incidence and risk factors.

Biliary complications (BCs) are a common source of morbidity after liver transplantation, leading to long-term and repeated therapies. The incidence of BCs currently ranges from 5% and 25%. Biliary strictures and leaks are the most common complications after deceased donor liver transplantation (DDLT), occurring in 9%-12% and 5%-10% of cases, respectively. Hepatic artery complications are recognized as the major risk factor for BCs; however, other circumstances such as advanced donor age, prolonged cold and warm ischemia times, grafts from donors after cardiac death, occurrence of a previous bile leak, T-tube use, cytomegalovirus infection, or graft steatosis have also been reported to be potential risk factors. Use of various preservation solutions has not significantly improved the biliary complication rate after DDLT. Technical modifications in biliary reconstruction have been proposed to improve outcomes after DDLT; the use of a T-tube for biliary reconstruction continues to be controversial. Non anastomotic strictures (NAS) are recognized to be different from anastomotic strictures. Although they have been associated with ischemic or immunological mechanisms, bile salt toxicity has recently been recognized as a potential factor for NAS. Donation after cardiac death is a significant source of organs that has been associated with decreased graft survival due to the increased BCs.

Biliary complications in orthotopic liver transplantation using choledochocholedochostomy with a T-tube.

Despite significant advances in orthotopic liver transplantation (OLT), biliary tract reconstruction is still a major source of complications. Choledochocholedochostomy with a T-tube used to be the standard procedure for biliary reconstruction after OLT. However, many centers currently avoid use of the T-tube because of the high incidence of complications. Our aim was to study the biliary complications occurring at our center when end-to-end choledochocholedochostomy (EE-CC) over a T-tube was used as the standard procedure for biliary reconstruction. A retrospective review was conducted of all patients who underwent liver transplantation from February 1, 1996, to April 30, 2010. Only patients requiring any therapy to treat biliary complications were considered, whereas those with concomitant hepatic artery complications were excluded. The study cohort consisted of 743 patients who had EE-CC with a T-tube. Of these, 73 patients (9.8%) experienced any biliary complication. Anastomotic strictures occurred in 17 patients (2.3%), and non-anastomotic strictures in 2 (0.3%). Fifteen patients with anastomotic strictures were successfully treated by dilatation and stenting. Bile leakage was diagnosed in 39 patients (5.2%). Leakage occurred at the anastomosis in 15 patients (2%), and at the exit site of the T-tube in 24 patients (3.2%). Tube opening was the only treatment used in 30 patients with bile leakage (76.9%). Seven patients experienced leaks after elective T-tube removal (1%). Overall, repeat surgery to manage biliary complications was needed in 9 patients (1.2%). The mortality rate from biliary complications was 0.13%. In conclusion, EE-CC with a T-tube was followed by a low incidence of biliary complications. The complication rate after elective T-tube removal and the repeat surgery rate were extremely low. These results might challenge the current trend to avoid T-tube stenting in OLT.

Liver retransplantation in HIV-infected patients: a prospective cohort study.

Information regarding liver retransplantation in HIV-infected patients is scant. Data from 14 HIV-infected patients retransplanted between 2002 and 2011 in Spain (6% retransplantation rate) were analyzed and compared with those from 157 matched HIV-negative retransplanted patients. In HIV-infected patients, early (≤30 days) retransplantation was more frequently indicated (57% vs. 29%; p = 0.057), and retransplantation for HCV recurrence was less frequently indicated (7% vs. 37%; p = 0.036). Survival probability after retransplantation in HIV-positive patients was lower than in HIV-negative patients, 42% versus 64% at 3 years, although not significantly (p = 0.160). Among HIV-infected patients, those with undetectable HCV RNA at retransplantation and those with late (>30 days) retransplantation showed better 3-year survival probability (80% and 67%, respectively), similar to that in their respective HIV-negative counterparts (72% and 70%). In HIV-infected and HIV-negative patients, 3-year survival probability in those with positive HCV RNA at retransplantation was 22% versus 65% (p = 0.008); in those with early retransplantation, 3-year survival probability was 25% versus 56% (p = 0.282). HIV infection was controlled with antiretroviral therapy after retransplantation. In conclusion, HIV-infected patients taken as a whole have unsatisfactory survival after liver retransplantation, although patients with undetectable HCV RNA at retransplantation or undergoing late retransplantation show a more favorable outcome.

Advagraf de novo in liver transplantation: a single-center experience.

UNLABELLED: Advagraf, a prolonged release formulation of tacrolimus, is administered once daily in the morning. The aim of this study was to show the results obtained in our center, analyzing the safety, efficacy, blood trough levels, and drug doses. METHODS: We analyzed 50 consecutive recipients of a first liver transplantation with 6 months follow-up. Efficacy and safety variables were collected as the incidence of acute rejection episodes, patient and graft survivals, kidney function as well as incidences of diabetes mellitus and arterial hypertension de novo. RESULTS: The incidence of biopsy proven acute rejection episodes was 10% (n = 5), none 7 of which were steroid resistant and all resolved favorably. The rate of diabetes mellitus de novo was 22% (n = 11), 7 of whom required insulin. Hypertension developed in 9 patients (18%), all of whom were treated with a single drug. The mean serum creatinine level was 1.08 ± 0.25 mg/dL, with 3 patients (6%) displaying a value ≥ 1.5 mg/dL. Patient and graft survivals were 100%. CONCLUSION: Advagraf is an effective immunosuppressant in liver transplantation with a low incidence of biopsy-confirmed acute rejection episodes. The good results for patient and graft survival with few side effects make it a useful drug for de novo liver transplantation.

Management of hepatocellular carcinoma recurrence after liver transplantation.

UNLABELLED: Management of patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation (OLT) is not well established. We conducted a retrospective analysis of our results in the treatment of HCC recurrence after OLT Patients. The 23 HCC recurrences developed after 182 OLT performed for HCC within Milan criteria, had an average follow-up of 60 months. RESULTS: The median time to recurrence was 23.4 months. Surgical resection of the recurrence was possible in 11 patients, but an R-0 resection was obtained in 8 patients. Four of these 8 patients developed another recurrence, with 3 succumbing due to tumor recurrence and 1 alive at 12 months with recurrence. The other 4 patients without recurrences, include 3 who are alive at 19, 31, and 86 months and 1 who died at 32.6 months due to hepatitis C recurrence. The 3 patients with palliative resections developed recurrences. Twelve patients were rejected for surgery: 8 were treated symptomatically, 2 with systemic chemotherapy, and 2 with everolimus and sorafenib. This last treatment was also prescribed for 2 patients after R-0 surgery who are alive at 19 and 31 months and for 1 patient after R-1 surgery who is alive at 19 months. Of 15 patients who died, 13 succumbed to HCC recurrence. The average survival from transplantation was 61.7 +/- 37.5 and 48 +/- 34.3 months for patients without and with recurrence, respectively (P < .001). The survival from the recurrence was significantly higher among patients with R-0 surgery: 32.3 +/- 21.5 versus 11.9 +/- 6.9 months (P = .006). CONCLUSIONS: HCC recurrence after OLT of patients within Milan criteria was low but had a great impact on survival. Few cases are amenable to R-0 resection, but when possible it was associated with a significantly increased survival, although with an high incidence of a new recurrence. There is a rationale for the use of sorafenib and mammalian target of rapamycin based immunosuppression, which warrants randomized studies.

Incidence and clinical relevance of bacterial contamination in preservation solution for liver transplantation.

OBJECTIVE: Postoperative infection is considered one of the most important causes of morbidity and mortality after liver transplantation. We prospectively studied the incidence and significance of infections in preservation solutions for liver transplantation. MATERIALS AND METHODS: From March 2007 to March 2008, we cultured the University of Wisconsin preservation solution for 60 consecutive liver transplantations. Fluid samples were obtained at the beginning and at the end of the back table procedure. Our posttransplant infection prophylactic protocol consisted of ampicillin and cefotaxime for 48 hours. RESULTS: Cultures were positive in 59 patients (98.4%). Seventy-five percent of the isolates were superficial saprophytic flora (SSF; Staphylococcus coagulase negative, Streptococcus viridans, and Corynebacterium), nevertheless in 15 cases (25.1%) we isolated high virulence pathogens (Staphylococcus aureus, Klebsiella, Escherichia coli, Enterobacter, and Pseudomonas aeruginosa). There were neither anaerobic nor fungal isolates. Sixteen patients (36%) from the group with SSF developed postoperative fever, including 12 with negative posttransplant cultures, while 4 patients showed positive cultures for various microorganisms distinct from those isolated from the preservation solution. Five patients (30%) with high virulence pathogens in the preservation solution developed posttransplant fever, although no pathogen was isolated. CONCLUSIONS: Positive cultures of preservation fluids were observed in 98% of patients, although most of them (75%) were SSF. Microorganisms isolated from posttransplant cultures did not match the ones obtained from the preservation solution. Our results did not support routine culturing of the preservation solution provided that one administrator an adequate posttransplant antibiotic prophylactic regimen.