Recent outcomes of liver transplantation for Budd-Chiari syndrome: A study of the European Liver Transplant Registry (ELTR) and affiliated centers.

BACKGROUND AND AIMS: Management of Budd-Chiari syndrome (BCS) has improved over the last decades. The main aim was to evaluate the contemporary post-liver transplant (post-LT) outcomes in Europe. APPROACH AND RESULTS: Data from all patients who underwent transplantation from 1976 to 2020 was obtained from the European Liver Transplant Registry (ELTR). Patients < 16 years, with secondary BCS or HCC were excluded. Patient survival (PS) and graft survival (GS) before and after 2000 were compared. Multivariate Cox regression analysis identified predictors of PS and GS after 2000. Supplemental data was requested from all ELTR-affiliated centers and received from 44. In all, 808 patients underwent transplantation between 2000 and 2020. One-, 5- and 10-year PS was 84%, 77%, and 68%, and GS was 79%, 70%, and 62%, respectively. Both significantly improved compared to outcomes before 2000 ( p < 0.001). Median follow-up was 50 months and retransplantation rate was 12%. Recipient age (aHR:1.04,95%CI:1.02-1.06) and MELD score (aHR:1.04,95%CI:1.01-1.06), especially above 30, were associated with worse PS, while male sex had better outcomes (aHR:0.63,95%CI:0.41-0.96). Donor age was associated with worse PS (aHR:1.01,95%CI:1.00-1.03) and GS (aHR:1.02,95%CI:1.01-1.03). In 353 patients (44%) with supplemental data, 33% had myeloproliferative neoplasm, 20% underwent TIPS pre-LT, and 85% used anticoagulation post-LT. Post-LT anticoagulation was associated with improved PS (aHR:0.29,95%CI:0.16-0.54) and GS (aHR:0.48,95%CI:0.29-0.81). Hepatic artery thrombosis and portal vein thrombosis (PVT) occurred in 9% and 7%, while recurrent BCS was rare (3%). CONCLUSIONS: LT for BCS results in excellent patient- and graft-survival. Older recipient or donor age and higher MELD are associated with poorer outcomes, while long-term anticoagulation improves both patient and graft outcomes.

Fully automated preoperative liver volumetry incorporating the anatomical location of the central hepatic vein.

The precise preoperative calculation of functional liver volumes is essential prior major liver resections, as well as for the evaluation of a suitable donor for living donor liver transplantation. The aim of this study was to develop a fully automated, reproducible, and quantitative 3D volumetry of the liver from standard CT examinations of the abdomen as part of routine clinical imaging. Therefore, an in-house dataset of 100 venous phase CT examinations for training and 30 venous phase ex-house CT examinations with a slice thickness of 5 mm for testing and validating were fully annotated with right and left liver lobe. Multi-Resolution U-Net 3D neural networks were employed for segmenting these liver regions. The Sørensen-Dice coefficient was greater than 0.9726 ± 0.0058, 0.9639 ± 0.0088, and 0.9223 ± 0.0187 and a mean volume difference of 32.12 ± 19.40 ml, 22.68 ± 21.67 ml, and 9.44 ± 27.08 ml compared to the standard of reference (SoR) liver, right lobe, and left lobe annotation was achieved. Our results show that fully automated 3D volumetry of the liver on routine CT imaging can provide reproducible, quantitative, fast and accurate results without needing any examiner in the preoperative work-up for hepatobiliary surgery and especially for living donor liver transplantation.

Normal Primary Graft Function Despite Early Hepatic Artery Thrombosis After Living-Donor Liver Transplant.

OBJECTIVES: Early hepatic artery thrombosis is rare but devastating in living-donor liver transplant recipients. In this study, our aim was to evaluate the results of all patients with early hepatic artery thrombosis at our center. MATERIALS AND METHODS: Between October 2004 and November 2015, 841 patients underwent liver transplant for end-stage liver disease at our center. All recipients with early hepatic artery thrombosis were identified and retrospectively analyzed. Early hepatic artery thrombosis was defined in our study as its occurrence within the first postoperative week. RESULTS: Early hepatic artery thrombosis was seen in 12 patients (1.8%). Seven of these 12 patients developed hepatic artery thrombosis on postoperative day 1 after intraoperative dissection of the hepatic artery with necessity of repeated reconstruction. However, the primary liver function of these patients was excellent, with nearly normal serum liver panel results. The other 5 patients were diagnosed after sudden significant increases of liver values followed by graft dysfunction within the first postoperative week. All patients were listed as high urgent and underwent retransplant. Two patients died perioperatively due to primary nonfunction, and 2 other patients died due to liver cirrhosis based on recurrent autoimmune hepatitis 29 and 106 months after retransplant. The remaining patients were alive with good liver function after a median time of 18 months (interquartile range, 13-45 mo). CONCLUSIONS: Early hepatic artery thrombosis is not always associated with graft dysfunction. Retransplant is still necessary due to ischemic cholangiopathy in the long-term follow-up. However, an elective retransplant, which could mean better outcomes, should be preferred instead of an emergency retransplant.

Combined liver transplantation and off-pump coronary artery bypass grafting: a report of two cases.

INTRODUCTION: Liver transplantation (LT) is the most effective treatment modality in patients with end-stage liver disease (ESLD). With the increased prevalence of diabetes and non-alcoholic fatty liver disease (NAFLD), coupled with a steady increase in the age of transplant population, liver transplant candidates are at increased risk for coronary artery disease (CAD). Improvements in anesthesia, surgical experiences, and increased effectiveness of drugs have facilitated concurrent surgical interventions in transplantation, allowing for orthotopic LT to be performed in elderly patients with a high incidence of coexisting diseases, especially those of the cardiovascular system. In this study, we present two cases of combined off-pump coronary artery bypass surgery and living donor liver transplantation. CASE PRESENTATION: A 68-year-old male patient with ESLD due to chronic hepatitis C infection and multi-vessel CAD, and a 65-year-old female patient with NAFLD cirrhosis and multi-vessel CAD were referred to our institution for an LT evaluation. We performed combined living donor LT and off-pump coronary artery bypass surgery in both patients. Both the first and second patients were alive with good liver and cardiac function at the 25 and 15 months after surgery, respectively. CONCLUSION: Combined off-pump coronary artery bypass surgery and living donor LT are an alternative treatment for patients with severe CAD and ESLD. We consider that combined coronary artery bypass graft surgery and LT can be safely performed by experienced anesthesia and surgical teams in selected patients.

Living Donor Liver Transplantation: The Optimal Curative Treatment for Hepatocellular Carcinoma Even Beyond Milan Criteria.

INTRODUCTION: Liver transplantation offers the most reasonable expectation for curative treatment for hepatocellular carcinoma. Living-donor liver transplantation represents a treatment option, even in patients with extended Milan criteria. This study aimed to evaluate the outcomes of hepatocellular carcinoma patients, particularly those extended Milan criteria. MATERIALS AND PATIENTS: All HCC patients who received liver transplant for HCC were included in this retrospective study. Clinical characteristics including perioperative data and survival data (graft and patient) were extracted from records. Univariate and multivariate analyses was performed to identify significant prognostic factors for survival, postoperative complications and recurrence. RESULTS: Two-hundred and two patients were included. The median age was 54.8 years (IQR 53-61). Fifty-one patients (25.3%) underwent deceased donors liver transplantation and 151 patients (74.7%) underwent living donor liver transplantation. Perioperative mortality rate was 5.9% (12 patients). Recurrent disease occurred in 43 patients (21.2%). The overall 1-year and 5-year survival rates were 90.7% and 75.6%, respectively. Significant differences between patients beyond Milan criteria compared to those within Milan criteria were not found. Alpha-fetoprotein level >300 ng/mL, vascular invasion, and bilobar tumor lesions were independent negative prognostic factors for survival. CONCLUSION: Liver transplantation is the preferred treatment for hepatocellular carcinoma and it has demonstrated an excellent potential to cure even in patients with beyond Milan criteria. This study shows that the Milan criteria alone are not sufficient to predict survival after transplantation. The independent parameters for survival prediction are Alpha-Fetoprotein-value and status of vascular invasion.

Thoracoabdominal Aortic Aneursym Accompanied by Leriche Syndrome in a Patient with Coronary Artery Disease: Management Strategy in a Single Case Experience.

Aneurysms and occlusive pathologies of the aorta are frequently associated with atherosclerosis; however, thoracoabdominal aortic aneurysm accompanied by Leriche syndrome is an extremely rare condition with challenging treatment strategy and without established surgical treatment protocols. In this report, we present our treatment strategy in a 64-year-old male patient with ischemic heart disease and type 5 thoracoabdominal aortic aneurysm accompanied by Leriche syndrome.

Splenic Artery Transposition for Arterial Reconstruction in Living Donor Liver Transplantation.

PURPOSE: In living donor liver transplantation, poor compatibility of the recipient hepatic artery remains a technical challenge. Here, we analyzed our 14 years of experience with extra-anatomic hepatic artery reconstruction. METHODS: Between July 2004 and December 2018, there were 1063 liver transplantations at our center. All patients with an extra-anatomic hepatic artery reconstruction were identified. The gastroduodenal artery and the transposed splenic artery were the primary options for extra-anatomic arterial reconstruction. Patient characteristics, operative data, and post-transplant outcome were reviewed retrospectively. RESULTS: There were 22 patients with extra-anatomic hepatic artery reconstruction, 6 with gastroduodenal artery, and 16 with splenic artery. There were 2 major complications: 1 patient underwent early reoperation due to bleeding from the splenic artery trunk and another had an iatrogenic injury to the transposed splenic artery during conversion hepaticojejunostomy. Both were treated successfully with surgery. One patient died perioperatively due to sepsis. The 1- and 3-year graft survival rates of these 16 patients were 93.7% and 87.5%. CONCLUSION: If the hepatic arteries are not suitable for anastomosis, then we consider the gastroduodenal artery and the splenic artery to be the conduits of choice for extra-anatomic arterial reconstruction. The transposed splenic artery is very consistent, easily accessible, and offers adequate length and diameter for successful arterial anastomosis.

Hand-assisted retroperitoneoscopic donor nephrectomy offers more liberal use of right kidneys: lessons learned from 565 cases - a retrospective single-center study.

The introduction of laparoscopic donor nephrectomy caused a shift toward' left donor nephrectomy. Some centers report a significantly low rate of endoscopic right donor nephrectomy. Hand-assisted retroperitoneoscopic donor nephrectomy (HARP-DN) was introduced as a novel surgical technique, which aims to avoid intra-abdominal complications. It was also reported to provide technical advantages for right-sided DN. In this retrospective single-center study, we evaluated the impact of HARP-DN technique on utilization of right-sided DNs. After the implementation of HARP-DN on February 2009, a total of 565 DNs were performed until December 2015. The introduction of HARP-DN technique resulted in an immediate increase in the utilization of right kidneys from 6.1% to an average of 19.6% annually. The donors 'outcome was similar to the left-sided and right-sided DN groups, excluding the increased incidence of incisional hernias in left kidney donors. None of the donors developed intra-abdominal complications. In conclusion, the implementation of HARP technique significantly increased the use of right-sided DNs, which enables a more liberal use of donors in LDKT.

The prognostic relationship between histopathological and immunohistochemical features of hepatocellular carcinoma, intrahepatic cholangiocarcinoma and mixed type.

Hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and combined hepatocellular and cholangiocarcinoma are the most common cancers of the liver. In this study, our first aim is to evaluate the relationship between prognosis and clinicopathological parameters. The second aim involves investigating the need for immunohistochemical staining and patterns of tumours to differentiate between them. Sixty-one cases were included in this study. For IHC, we used Hep par-1, CK7, CK19, CD56 and p53 staining, and the patterns of tumours were evaluated in haematoyxylin-eosin sections. No significant differences were found in Kaplan-Meier life analysis between the tumour types and OS and DFS values, but these values were greater in HCC than in ICC. There were no relationships between clinicopathologic parameters and OS and DFS. Although the multifocality, stage and grade of tumour were higher in HCC than in ICC, the perineural invasion and lymph node metastasis were more common in ICC than in HCC. The diagnosis was changed in 4 cases, from HCC to ICC in one case and to combined type in 3 cases after IHC. Pathologist should be alert to mixed patterns in terms of diagnosis and IHC, because it helps differential diagnosis in these cases.

Value of Intravoxel Incoherent Motion for Hepatocellular Carcinoma Grading.

BACKGROUND: To evaluate the diagnostic accuracy of intravoxel incoherent motion (IVIM) parameters in estimation of hepatocellular carcinoma (HCC) grading. MATERIALS AND METHODS: Twenty-nine patients with histopathologically diagnosed as 42 HCC at explant were included in this retrospective study. All patients were examined by 1.5T magnetic resonance imaging with the use of 4-channel phased array body coil. In addition to routine pre- and postcontrast sequences, IVIM (16 different b factors varying from 0 to 1300 s/mm2) and conventional diffusion-weighted imaging (3 different b factors of 50, 400, 800 s/mm2) were obtained with single-shot echo planar spin echo sequence. Apparent diffusion coefficient (ADC) and IVIM parameters including mean D (true diffusion coefficient), D* (pseudo-diffusion coefficient associated with blood flow), and f (perfusion fraction) values were calculated. Histopathologically, HCC was classified as low (grade 1, 2) and high (grade 3, 4) grade in accordance with the Edmondson-Steiner score. Quantitatively, ADC, D, D*, and f values were compared between the low- and high-grade groups by Student t test. The relationship between the parameters and histologic grade was analyzed using the Spearman's correlation test. To evaluate the diagnostic performance of the parameters, receiver operating characteristic analysis was performed. RESULTS: High-grade HCCs had significantly lower ADC and D values than low grade groups (P = .005 and P = .026, retrospectively); ADC and D values were inversely correlated with tumor grade (r = -0.519, P = .011, r = -0.510, P = .026, respectively). High-grade HCCs had significantly higher f values when compared with the low-grade group (P = .005). The f values were positively correlated with tumor grade (r = 0.548, P = .007). The best discriminative parameter was f value. Cut-off value of 32% of f values showed sensitivity of 75.6% and a specificity of 73.5%. CONCLUSION: ADC values and IVIM parameters such as f values appear to reflect the grade of HCCs.

Role of pre-transplant 18F-FDG PET/CT in predicting hepatocellular carcinoma recurrence after liver transplantation.

The last two decades have seen a paradigm shift in the selection of patients with hepatocellular carcinoma (HCC) for liver transplantation. Microvascular invasion and differentiation have been the most significant factors affecting post-transplant recurrence; however, because of inherent disadvantages of pre-transplant biopsy, histological criteria never gained popularity. Recently, the selection criteria evolved from morphological to biological criteria, such as biomarkers and response to loco-regional therapy. With the introduction of multimodality imaging, combination of computed tomography with nuclear medicine imaging, particularly, 18F-fluorodeoxyglucose positron emission tomography fulfilled an unmet need and rapidly became a critical component of HCC management. This review article will focus on the use of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography in the pre-transplant evaluation of HCC patients with special discussion on its ability to predict HCC recurrence after liver transplantation.

Living Donor Liver Transplantation.

In 50 years after the first liver transplantation, the medical world has witnessed the liver transplantation to become one of the widely recognized and leading branches of surgery. In this period, liver transplantation combined with surgical technique, patient selection, advancements in anesthesia and postoperative care and increased experience has become the most effective treatment option in treatment of several acute and chronic liver diseases. Yet, the worldwide organ restriction and associated high mortality rates in organ transplantation waiting list has compelled referring to living donors in order to expand the donor pool. This paper explains liver transplantation indications from living donors, the surgical technique involved, the complications of the procedure and the medical treatments used.

The long-term efficacy of combining nucleos(t)ide analog and low-dose hepatitis B immunoglobulin on post-transplant hepatitis B virus recurrence.

BACKGROUND: The aim of this study was to determine the long-term efficacy of nucleos(t)ide analog (NA) and low-dose hepatitis B immunoglobulin (HBIG) combination treatment for preventing post-transplant hepatitis B virus (HBV) recurrence. METHODS: A total of 296 patients with HBV-associated liver disease who underwent liver transplantation (LT) were enrolled. A combination of a daily NA and low-dose HBIG was used after LT. RESULTS: The median follow-up period was 46 months. HBV recurrence occurred in eight patients. The cumulative probability of HBV recurrence at 1, 3, 5, and 7 years was 1%, 3%, 3%, and 4%, respectively. Seven were on lamivudine (LMV) or adefovir dipivoxil (ADV), or LMV and ADV and HBIG combination treatment and one entecavir (ETV) and HBIG. With Cox regression analysis, HBV recurrence was determined to be associated with the presence of hepatocellular cancer (HCC) prior to LT (HR: 12.3, P=.02). Overall, 44 patients died. Survival was significantly better in the ETV or tenofovir disoproxil fumarate (TDF) and HBIG group than the other group (P<.001). CONCLUSION: The combination of ETV or TDF and low-dose HBIG achieved a more favorable prophylaxis against HBV recurrence after LT. The presence of HCC prior to LT was associated with post-transplant HBV recurrence.

Liver transplantation for homozygote familial hypercholesterolemia: the only curative treatment.

FH is an autosomal dominant genetic disorder characterized by increased TC and LDL level, which leads to xanthomas, atherosclerosis, and cardiac complications even in childhood. The treatment options are diet, medical treatment, lipid apheresis, and LT. The aim of our study was to analyze our data of patients with FH. Between 2004 and 2015, there were 51 patients who underwent pediatric LT at our center. All patients with FH were identified, and the data were retrospectively analyzed. There were eight patients with homozygous FH in the median age of 10 years (IQR 6-12) who underwent LT. The median pre-operative TC and LDL levels were 611 mg/dL (IQR: 460-844) and 574 mg/dL (IQR: 398-728) and decreased to normal levels 1 week after LT (TC: 193 mg/dL and LDL: 141 mg/dL). Two patients died two and 18 months after LT due to sudden cardiac arrest. Both patients were diagnosed with cardiovascular disease pre-operatively. The LT is the only curative treatment for this disease. To achieve an excellent outcome, it should be performed before the development of cardiovascular disease, because the regression of severe cardiovascular disease after transplantation is limited.

The evolution of anterior sector venous drainage in right lobe living donor liver transplantation: does one technique fit all?

In living donor liver transplantation (LDLT), an adequate hepatic venous outflow constitutes one of the basic principles of a technically successful procedure. The issue of whether the anterior sector (AS) of the right lobe (RL) graft should or should not be routinely drained has been controversial. The aim of this 10-year, single-center, retrospective cohort study was to review the evolution of our hepatic venous outflow reconstruction technique in RL grafts and evaluate the impact of routine AS drainage strategy on the outcome. The study group consisted of 582 primary RL LDLT performed between July 2004 and December 2014. The cases were divided into 3 consecutive periods with different AS venous outflow reconstruction techniques, which included middle hepatic vein (MHV) drainage in Era 1 (n=119), a more selective AS drainage with cryopreserved homologous grafts in Era 2 (n=391), and routine segment 5 and/or 8 oriented AS drainage with synthetic grafts in Era 3 (n=72). Intraoperative portal flow measurement with routine splenic artery ligation (SAL) technique (in RL grafts with a portal flow of ≥ 250 mL/min/100 g liver tissue) was added later in Era 3. These 3 groups were compared in terms of recipient and donor demographics, surgical characteristics and short-term outcome. The rate of AS venous drainage varied from 58.8% in Era 1 and 35.0% in Era 2 to 73.6% in Era 3 (P<0.001). Perioperative mortality rate of recipients significantly decreased over the years (15.1% in Era 1 and 8.7% in Era 2 vs. 2.8% in Era 3, P=0.01). After the addition of SAL technique in the 45 cases, there was only 1 graft loss and no perioperative mortality. One-year recipient survival rate was also significantly higher in Era 3 (79.6% in Era 1 and 86.1% in Era 2 vs. 92.1% in Era 3, P=0.002). Routine AS drainage via segment 5 and/or 8 veins using synthetic grafts is a technique to fit all RL grafts in LDLT. Addition of SAL effectively prevents early graft dysfunction and significantly improves the outcome.

Major complications of adult right lobe living liver donors.

BACKGROUND: The right lobe of the liver is generally preferred for living donor liver transplantation in adult patients with end-stage liver disease. It is important to know the preoperative factors relating to the major postoperative complications. We therefore evaluated the possible risk factors for predicting postoperative complications in right lobe liver donors. METHODS: Data from 378 donors who had undergone right lobe hepatectomy at our center were evaluated retrospectively. The factors we evaluated included donor age, gender, body mass index (BMI), remnant liver volume, operation time, history of previous abdominal surgery, inclusion of the middle hepatic vein and variations in the portal and bile systems. RESULTS: Of the 378 donors, 219 were male and 159 female. None of the donors died, but 124 (32.8%) donors experienced complications including major complications (Clavien scores III and IV) in 27 (7.1%). Univariate analysis showed that complications were significantly associated with male gender and higher BMI (P<0.05), but not with donor age, remnant liver volume, operation time, graft with middle hepatic vein, variations in the portal and bile systems and previous abdominal surgery (P<0.05). Multivariate logistic regression analysis showed that major complications were significantly associated with male gender (P=0.005) and higher BMI (P=0.029). Moreover, the Chi-square test showed that there were significant relationships between major complications and male gender (P=0.010, X2=6.614, df=1) and BMI >25 kg/m2 (P=0.031, X2=8.562, df=1). Of the 96 male donors with BMI >25 kg/m2, 14 (14.6%) with major complications had significantly smaller mean remnant liver volume than those (82, 85.4%) without major complications (32.50%+/-4.45% vs 34.63%+/-3.11%, P=0.029). CONCLUSION: Male donors with BMI >25 kg/m2 and a remnant liver volume ≤32.50% had a significantly increased risk for major complications.

Living donor right lobe liver transplantation as a treatment for hepatic alveolar echinococcosis: report of three cases.

Echinococcus alveolaris is a parasite from tenia family which causes tumor-like lesions in the livers of infected people. If it is not diagnosed in the early stage of the disease, it frequently causes multiple cysts in the liver. The clinical importance of the disease is rapid progression, infiltration into different tissues like a malignant tumor and capacity of creating metastatic masses. The disease could be treated either by surgical resection or liver transplantation. The resection of the cystic disease is the preferred treatment method. In cases where resection is not possible, liver transplantation is the choice of treatment. Here we present three cases which were admitted to the hospital with unresectable hepatic alveolar echinococcosis and treated by liver transplantation successfully. Patients for whom surgical resection is not possible, we recommend liver transplantation as the treatment method.

Living Donor Liver Transplantation Outcomes for Hepatocellular Carcinoma Beyond Milan or UCSF Criteria.

Liver transplantation (LT) is the most effective treatment for hepatocellular carcinoma (HCC) that arises from cirrhosis. The Milan and the University of California, San Francisco (UCSF) selection criteria have resulted in major improvements in patient survival. We assessed our outcomes for patients with HCC that were beyond the Milan and UCSF criteria after living donor liver transplantation. We reviewed the data for 109 patients with cirrhosis and HCC who underwent living donor right lobe liver transplantation (living donor liver transplantation; LDLT) during the period from July 2004 to July 2012. Sixteen (14.7 %) patients had HCC recurrences during a mean follow-up of 35.4 ± 26.2 months (range 4-100 months). The mean time to recurrence was 11 ± 9.4 months (range 4-26 months). Survival rates were not significantly different between patients with HCC that met and were beyond the Milan and UCSF criteria (p = 0.761 and p = 0.861, respectively). The Milan and UCSF criteria were not independent risk factors for HCC recurrence or patient survival. Only poorly differentiated tumors were associated with a lower survival rate (OR = 8.656, 95 % confidence interval (CI) 2.01-37.16; p = 0.004). Survival rates for patients with HCC that were beyond conventional selection criteria should encourage reconsidering the acceptable thresholds of these criteria so that more HCC patients may undergo LT without affecting outcomes.