Valentina Serra

Multiple Ways to Manage Portal Thrombosis During Liver Transplantation: Surgical Techniques and Outcomes

BACKGROUND Portal vein thrombosis (PVT) is a well-recognized complication of chronic liver disease with a prevalence ranging from 1% to 16%. MATERIALS AND METHODS We performed a retrospective review of 447 consecutive patients who underwent liver transplantation (OLT) between October 2000 and December 2011 comparing 51 recipients with PVT (study group) with 399 without PVT (control group). The aim of this study was to determine the impact of pre-existent PVT on the surgical procedure, to identify specific preventable perioperative complications, and based on our studies and other works, to determine whether this group of patients are acceptable candidates for OLT. RESULTS Among the 51 patients with PVT, 44 showed partial and 7 complete thrombosis. In 47 cases, we performed a thromboendovenectomy. There were six anastomoses at the confluence of the superior mesenteric vein (SMV) and one, with a venous graft interposition. In four complete thrombosis recipients we performed an extra-anatomic by pass between the main trunk of the SMV and the donor portal vein. Compared with the control group, regarding preoperative characteristics, PVT patients were older at the time of transplantation (P = .001) and had a higher use of TIPS (P = .02). The operative characteristics showed a longer warm ischemia time in the PVT group (46.9 ± 22.5 vs 39.3 ± 15 min; P = .004). There were significant differences in postoperative evaluations, nor in the complication rates. Overall survivals at 10 years were similar: 61.7% versus 65.3%; (P = .9). CONCLUSION Although PVT was associated with greater operative complexity, it had no influence on postoperative complications or overall survival.

Early use of mammalian target of rapamycin inhibitors is an independent risk factor for incisional hernia development after liver transplantation

Incisional hernias (IHs) are common complications after liver transplantation (LT) with a reported incidence of 1.7% to 34.3%. The purpose of this retrospective study was to evaluate the risk factors for IH development after LT with a focus on the role of immunosuppressive therapy during the first month after LT. We analyzed 373 patients who underwent LT and divided them into 2 groups according to their postoperative course: an IH group (121 patients or 32.4%) and a no‐IH group (252 patients or 67.6%). A univariate analysis demonstrated that the following were risk factors related to IH development: male sex (P = 0.03), a body mass index ≥ 29 kg/m2 (P = 0.005), LT after 2004 (P = 0.02), a Model for End‐Stage Liver Disease (MELD) score ≥ 22 (P = 0.01), and hepatitis B virus infection (P = 0.01). The highest incidence of IHs was found in patients treated with mammalian target of rapamycin (mTOR) inhibitors (54.5%, P = 0.004). A multivariate analysis revealed male sex (P = 0.03), a pretransplant MELD score ≥ 22 (P = 0.04), and the use of mTOR inhibitors (P = 0.001) to be independent risk factors for IHs after LT. In conclusion, immunosuppressive therapy with mTOR inhibitors is an important independent risk factor for IH development after LT. To reduce the incidence of IHs, mTOR inhibitors should be avoided until the fourth month after LT unless their use is deemed to be strictly necessary. Liver Transpl 18:188–194, 2012.

University of Modena Experience in HIV-Positive Patients Undergoing Liver Transplantation

INTRODUCTION Highly effective antiretroviral therapy in the last decade has increased the survival rates of HIV-positive patients, yielding a greater number of HIV patients suffering from liver-related disease. Liver transplantation (LT) is the only curative treatment for end-stage liver disease (ESLD) associated or not with hepatocellular carcinoma (HCC). PATIENTS AND METHODS From June 2003 to September 2010, 23 patients underwent cadaveric donor LT for ESLD at our institution. Inclusion criteria followed the Italian Protocol for LT in HIV-positive patients. Immunosuppressive regimens were based on cyclosporine or tacrolimus, eventually switched to Rapamycin. RESULTS The median CD4 T-cell count was 275/mmc (range=119-924). All patients were affected by ESLD, which was associated with HCC in 14 cases. Ten patients were within the Milan criteria and four patients exceeded them but were within the San Francisco criteria. Conversion from calcineurin inhibitors (CNI) to rapamycin occurred in ten cases. Hepatitis C virus (HCV) recurrence occurred in 13/21 HCV-positive patients. Acute cellular rejection occurred in eight patients with one developing chronic cellular rejection. Overall patient and graft survivals at 80 months were 50% and 45% respectively. DISCUSSION LT in HIV-positive patients is a feasible procedure, even if in our experience was burdened by a greater incidence of complications including HCV recurrence and infection compared with HIV-negative patients.

Reduced Transfusion During OLT by POC Coagulation Management and TEG Functional Fibrinogen: A Retrospective Observational Study.

Background Patients undergoing orthotopic liver transplantation are at high risk of bleeding complications. Several Authors have shown that thromboelastography (TEG)-based coagulation management and the administration of fibrinogen concentrate reduce the need for blood transfusion. Methods We conducted a single-center, retrospective cohort observational study (Modena Polyclinic, Italy) on 386 consecutive patients undergoing liver transplantation. We assessed the impact on resource consumption and patient survival after the introduction of a new TEG-based transfusion algorithm, requiring also the introduction of the fibrinogen functional thromboelastography test and a maximum amplitude of functional fibrinogen thromboelastography transfusion cutoff (7 mm) to direct in administering fibrinogen (2012-2014, n = 118) compared with a purely TEG-based algorithm previously used (2005-2011, n = 268). Results After 2012, there was a significant decrease in the use of homologous blood (1502 ± 1376 vs 794 ± 717 mL, P < 0.001), fresh frozen plasma (537 ± 798 vs 98 ± 375 mL, P < 0.001), and platelets (158 ± 280 vs 75 ± 148 mL, P < 0.005), whereas the use of fibrinogen increased (0.1 ± 0.5 vs 1.4 ± 1.8 g, P < 0.001). There were no significant differences in 30-day and 6-month survival between the 2 groups. Conclusions The implementation of a new coagulation management method featuring the addition of the fibrinogen functional thromboelastography test to the TEG test according to an algorithm which provides for the administration of fibrinogen has helped in reducing the need for transfusion in patients undergoing liver transplantation with no impact on their survival.

Pulmonary Hypertension as a Predictor of Postoperative Complications and Mortality After Liver Transplantation

Most transplant centers consider severe pulmonary hypertension (PHT) to be an absolute contraindication for orthotopic liver transplantation (OLT). We retrospectively examined the outcome of 24 patients with PHT (group 1) who underwent OLT compared with 24 matched patients (group 2) without PHT, who also underwent OLT. Based on right cardiac catheterization measurements made after the induction of anesthesia for OLT, PHT was defined as mild or moderate-to-severe if the mean pulmonary arterial pressure exceeded 25 or 35 mm Hg, respectively. The incidence of PHT was 9.8% (24/244); 21/24 PHT patients showed mild and 3/24 moderate PHT. Kaplan-Meier survival analysis did not show a significant difference between the two groups. The incidence of pulmonary infections was significantly greater in group 1 (P < .05). The duration of ventilation and intensive care unit stay was similar in the two groups. Echocardiography detected only the three moderate cases of PHT and not the twenty-one cases of mild PHT. Our analysis suggested that mild PHT was common and did not affect patient outcomes after OLT; moderate or severe PHT was uncommon. The two patients with moderate PHT survived OLT and did not succum to PHT during long-term follow-up.

Incidental Intra-Hepatic Cholangiocarcinoma and Hepatocholangiocarcinoma in Liver Transplantation: A Single-Center Experience

BACKGROUND Cholangiocarcinoma (CCA) is an aggressive malignancy of the biliary tract that is a challenging issue for the medical community, with increasing incidence. Risk factors for CCA are similar to those known for hepatocellular carcinoma (HCC), such as cirrhosis, chronic hepatitis B and C, obesity, diabetes, and alcohol. We describe the outcome and the management of patients who underwent liver transplantation (LT) with an incidental diagnosis of intrahepatic (iCCA) or hepatocholangiocarcinoma (CHC). METHODS From 2000 to May 2015, 655 LT were performed LT at the Liver Transplant Center in Modena, Italy. We retrospectively reviewed the pathological data of the explanted livers, finding 5 cases of iCCA or CHC. The pathological examination of the explanted livers showed 1 case of iCCA; 1 case of multifocal HCC associated with a nodule of iCCA; 2 cases of CHC associated with nodules of HCC; and 1 case of CHC associated with iCCA. Mean disease-free survival (DFS) was 15.49 months (1.55-42.04) and mean overall survival (OS) was 24.76 months (3.91-75.49). All patients died of recurrent tumor progression. RESULTS iCCA incidental finding after LT affects patient outcomes, massively causing OS and DFS reduction. We stress the necessity of a more accurate selection of the candidates whenever an augmented risk of iCCA or CHC is present. CONCLUSIONS Further investigations are required to better understand the role of LT in these patients and to define the best management for them once they have been transplanted and the histological examination reveals the presence of iCCA or CHC.

Perioperative effects of high doses of intraoperative thymoglobulin induction in liver transplantation.

AIM To describe our single-centre experience in liver transplantation (LT) with the infusion of high perioperative thymoglobulin doses. The optimal dosage and timing of thymoglobulin(®) [antithymocyte globulin (ATG)] administration during LT remains controversial. Cytokine release syndrome, haemolytic anaemia, thrombocytopenia, neutropenia, fever and serum sickness are potential adverse effects associated with ATG infusion. METHODS Between December 2009 and December 2010, 16 adult non-randomized patients (ATG group), receiving a liver graft from a deceased donor, received an intraoperative infusion (4-6 h infusion) of thymoglobulin (3 mg/kg, ATG: Thymoglobuline(®)). These patients were compared (case control approach) with 16 patients who had a liver transplant without ATG treatment (control group) to evaluate the possible effects of intraoperative ATG infusion. The matching parameters were: Sex, recipient age (± 5 years), LT indication including viral status, MELD score (± 5 points), international normalized ratio and platelet count (as close as possible). The exclusion criteria for both groups included the following: Multi-organ or living donor transplant, immunosuppressive therapy before transplantation, contraindications to the administration of any thymocyte globulin, human immunodeficiency virus seropositivity, thrombocytopenia [platelet < 50000/μL] or leukopenia [white blood cells < 1000/μL]. The perioperative side effects (haemodynamic alterations, core temperature variations, colloids and crystalloids requirements, and surgical time) possibly related to ATG infusion and the thromboelastographic (TEG) evaluation of the ATG effects on coagulation, blood loss and blood product transfusion were analysed during the operation and the first three postoperative days. RESULTS Intraoperative ATG administration was associated with longer surgical procedures [560 ± 88 min vs 480 ± 83 min (control group), P = 0.013], an intraoperative core temperature more than 37 °C (50% of ATG patients vs 6.2% of control patients, P = 0.015), major intraoperative blood loss [3953 ± 3126 mL vs 1419 ± 940 mL (control group), P = 0.05], higher red blood cell [2092 ± 1856 mL ATG group vs 472 ± 632 mL (control group), P = 0.02], fresh frozen plasma [671 ± 1125 mL vs 143 ± 349 mL (control group), P = 0.015], and platelet [374 ± 537 mL vs 15.6 ± 62.5 mL (control group), P = 0.017] transfusion, and a higher requirement for catecholamines (0.08 ± 0.07 μg/kg per minutes vs 0.01 ± 0.38 μg/kg per minutes, respectively, in the ATG and control groups) for haemodynamic support. The TEG tracings changed to a straight line during ATG infusion (preanhepatic and anhepatic phases) in 81% of the patients from the ATG group compared to 6.25% from the control group (P < 0.001). Patients from the ATG group compared to controls had higher post-op core temperatures (38 °C ± 1.0 °C vs 37.3 °C ± 0.5 °C; P = 0.02), an increased need of noradrenaline (43.7% vs 6.25%, P = 0.037), received more platelet transfusions (31.5% vs 0%, P = 0.04) and required continuous renal replacement therapy (4 ATG patients vs none in the control group; P = 0.10). ATG infusion was considered the cause of a fatal anaphylactic shock and of a suspected adverse reaction that led to intravascular haemolysis and acute renal failure. CONCLUSION The side effects and the coagulation imbalance observed in patients receiving a high dosage of ATG suggest caution in the use of thymoglobulin during LT.

Liver transplantation and combined hepatocellular-cholangiocarcinoma: Feasibility and outcomes

INTRODUCTION Combined hepatocellular-cholangiocarcinoma (CHC or cHCC-CC) is a rare primary liver tumor displaying histological features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Most patients are not suitable for surgery because of the advanced stage of the disease at the moment of diagnosis. We decided to review the literature in order to identify the outcomes after liver transplantation for CHC and to clarify which is the most appropriate treatment. MATERIAL AND METHODS A systematic literature search was performed. Studies reporting outcomes of liver transplantation (LT) for CHC and studies comparing oncologic outcomes after LT versus liver resection (LR) for CHC were included in this review. RESULTS The mean 5-y Disease Free Survival (DFS) reported in literature is 45.4%, while the mean 5-y overall survival (OS) is 41.8%, analyzing a cohort of 418 cases. The mean DSF in our series after LT was 7.97 months, while the mean OS was 11.7 months. CONCLUSIONS LT should be avoided for the treatment of CHC, in order to allocate organs for more appropriate diseases. Moreover, surgical resections, and in particular major hepatectomies, seem to be associated with acceptable outcomes. An accurate preoperative management is needed, and the use of PET-CT when differential diagnosis is difficult should be considered.

Liver Transplantation Due to Iatrogenic Injuries: Two Case Reports

The transjugular intrahepatic portosystemic shunt (TIPS) is an acceptable procedure that has proven benefits in the treatment of patients who have complications from portal hypertension due to liver cirrhosis. In the literature few reports have described complications after TIPS placement. Initial surgery and local hemostasis have been needed to manage abdominal bleeding: if this treatment is insufficient, it may be necessary to perform a liver transplantation. This report describes the role of liver transplantation to manage dangerous complications in 2 patients after TIPS placement, when surgical procedures and hemostasis were unable to stop the bleeding.

The impact of a multidisciplinary team on alcohol recidivism and survival after liver transplantation for alcoholic disease

BACKGROUND Alcohol use disorders have a prevalence of 10% among the population of the United States and Europe and are one of the most frequent causes of liver cirrhosis in the Western world. Currently, alcohol-related liver cirrhosis represents one of the most frequent indications to liver transplant (LT), both as independent cause or associated with hepatitis C virus or hepatitis B virus infections. Starting from 2014, a multidisciplinary team involving surgeons, gastroenterologists, clinical toxicologists, psychiatrists, and psychologists was developed within the Modena Liver Transplant Center. METHODS We retrospectively reviewed our prospectively maintained institutional database of liver transplants in order to identify cirrhotic patients eligible for LT with a diagnosis of alcohol use disorder. RESULTS A total of 756 liver transplants were performed at Policlinico University Hospital, University of Modena, and Reggio Emilia, MO, Italy, between November 2000 and November 2017; 102 patients who underwent LT were considered eligible for inclusion in the study. CONCLUSIONS The multidisciplinary approach, together with blood, urinary, and hair tests, allows identification of early recurrences and improves survival. Further studies are necessary to understand how multidisciplinary teams can change the 6-month rule in patient selection.