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 transplantant (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.

Alternative forms of portal vein revascularization in liver transplant recipients with complex portal vein thrombosis.

BACKGROUND & AIMS: Complex portal vein thrombosis (PVT) is a challenge in liver transplantation (LT). Extra-anatomical approaches to portal revascularization, including renoportal (RPA), left gastric vein (LGA), pericholedochal vein (PCA), and cavoportal (CPA) anastomoses, have been described in case reports and series. The RP4LT Collaborative was created to record cases of alternative portal revascularization performed for complex PVT. METHODS: An international, observational web registry was launched in 2020. Cases of complex PVT undergoing first LT performed with RPA, LGA, PCA, or CPA were recorded and updated through 12/2021. RESULTS: A total of 140 cases were available for analysis: 74 RPA, 18 LGA, 20 PCA, and 28 CPA. Transplants were primarily performed with whole livers (98%) in recipients with median (IQR) age 58 (49-63) years, model for end-stage liver disease score 17 (14-24), and cold ischemia 431 (360-505) minutes. Post-operatively, 49% of recipients developed acute kidney injury, 16% diuretic-responsive ascites, 9% refractory ascites (29% with CPA, p <0.001), and 10% variceal hemorrhage (25% with CPA, p = 0.002). After a median follow-up of 22 (4-67) months, patient and graft 1-/3-/5-year survival rates were 71/67/61% and 69/63/57%, respectively. On multivariate Cox proportional hazards analysis, the only factor significantly and independently associated with all-cause graft loss was non-physiological portal vein reconstruction in which all graft portal inflow arose from recipient systemic circulation (hazard ratio 6.639, 95% CI 2.159-20.422, p = 0.001). CONCLUSIONS: Alternative forms of portal vein anastomosis achieving physiological portal inflow (i.e., at least some recipient splanchnic blood flow reaching transplant graft) offer acceptable post-transplant results in LT candidates with complex PVT. On the contrary, non-physiological portal vein anastomoses fail to resolve portal hypertension and should not be performed. IMPACT AND IMPLICATIONS: Complex portal vein thrombosis (PVT) is a challenge in liver transplantation. Results of this international, multicenter analysis may be used to guide clinical decisions in transplant candidates with complex PVT. Extra-anatomical portal vein anastomoses that allow for at least some recipient splanchnic blood flow to the transplant allograft offer acceptable results. On the other hand, anastomoses that deliver only systemic blood flow to the allograft fail to resolve portal hypertension and should not be performed.

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.

Recommendations for Hepatitis B Immunoglobulin and Antiviral Prophylaxis Against Hepatitis B Recurrence After Liver Transplantation.

The combination of hepatitis B immunoglobulin and potent nucleos(t)ide analogs after liver transplantation is considered as the standard of care for prophylaxis against hepatitis B virus recurrence. However, the recommended doses, route of administration, and duration of HBIG administration remain unclear. Moreover, hepatitis B immunoglobulin-free prophylaxis with potent nucleos(t)ide analogs has shown promising disease outcomes in preventing hepatitis B virus recurrence. The current recommendations, produced by the Turkish Association for the Study of the Liver, Acute Liver Failure and Liver Transplantation Special Interest Group, suggest a reduced need for hepatitis B immunoglobulin administration with effective long-term suppression of hepatitis B virus replication using potent nucleos(t) ide analogs after liver transplantation.

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.

Delta MELD as a predictor of early outcome in adult-to-adult living donor liver transplantation.

BACKGROUND/AIMS: An increased post-operative mortality risk has been reported among patients who undergo living donor liver transplantation (LDLT) with higher model for end-stage liver disease (MELD) scores. In this study, we investigated the effect of MELD score reduction on post-operative outcomes in patients with a high MELD (≥20) score by pre-transplant management. MATERIALS AND METHODS: We retrospectively analyzed 386 LDLT cases, and patients were divided into low-MELD (<20, n=293) vs. high-MELD (≥20, n=93) groups according to their MELD score at the time of index hospitalization. Patients in the high-MELD group were managed specifically according to a treatment algorithm in an effort to decrease the MELD score. Patients in the high-MELD group were further divided into 2 subgroups: (1) responders (n=34) to pre-transplant treatment with subsequent reduction of the MELD score by a minimum of 1 point vs. (2) non-responders (n=59), whose MELD score remained unchanged or further increased on the day of LDLT. Responders vs. non-responders were compared according to etiology, demographics, and survival.

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.

The COVID-19 pandemic: Clinical practice advice for gastroenterologists, hepatologists, and liver transplant specialists.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a novel acute infectious disease that has rapidly reached staggering pandemic proportions. This review addresses gastroenterologists, hepatologists, liver transplant (LT) specialists, and health-care professionals working in the field of liver diseases and liver transplantation. It has been written based on a limited number of publications, recommendations of national and international liver and organ transplantation societies, and experiences of patients with COVID-19 around the world. The purpose of this review is to provide information addressing questions and concerns about COVID-19, to reveal the effects of the novel disease on patients with chronic liver disease and LT recipients, and to share information about ways in which this pandemic will affect clinical practices. We, the Turkish Association for the Study of the Liver (TASL), would like to remind you that this text is actually not a practical guide. It is imperative to act according to the standards set by health-care institutions and the Ministry of Health, Republic of Turkey.

Adult living donor liver transplantation from donors with Gilbert's syndrome: Is it safe?

BACKGROUNDS: We evaluate whether it is safe to accept donors with Gilbert's syndrome (GS) for a living donor liver transplantation (LDLT) or not. This study is the first controlled study to be conducted. METHODS: Between January 2004 and May 2014, 600 LDLTs which used right lobe liver grafts were performed in our center. Forty-five of the 600 donors had a GS diagnosis. For a control group, 99 donors without GS who had completed 1 year or more of follow-up were selected retrospectively and consecutively. The clinical results of the donors and recipients were then analyzed. RESULTS: A total of 45 donors with GS and 99 donors without GS were included. There were no significant differences in patient demographics, actual graft weight, remnant ratio, portal and ductal variations, pre-peri-post-operative liver enzymes. The donors with GS had significantly higher bilirubin levels compared with the control group at first reading, at maximal peak, and post-operative 1-7 days, 1st and 6th months (P < .001 for all readings). Post-operative complication ratio was 40% in GS, 34.3% in non-GS group. In GS and non-GS group, hospitalization period was 10.2 and 9.2 days, respectively. The 1-year donor survival rate was 100% for both groups and 1-year recipient survival was similar who have donors with GS and non-GS (93.3%; 92.9%, P = .93). CONCLUSIONS: The use of right lobe grafts from donors with GS appears to be safe for donor health.

Comorbidity Index as a Selection Tool for Living Donor Liver Transplantation in Elderly Patients.

BACKGROUND: Previously published data have shown that age alone is not a contraindication for living donor liver transplantation (LDLT). However, careful evaluation is needed to identify the patients who are unlikely to benefit from LDLT. We hypothesized that the Charlson Comorbidity Index (CCI) could be used as one of the criteria for risk stratification in elderly patients undergoing LDLT. PATIENTS AND METHODS: There were 951 patients who underwent LDLT between October 2004 and February 2018. All recipients who were older than 60 years of age at the time of transplantation were identified. The comorbidity score was retrospectively assessed for each elderly patient according to the Charlson Comorbidity Index. Univariate and multivariate Cox regression analyses were performed to identify independent predictive factors for survival in elderly patients after LDLT. RESULTS: There were 96 patients (10.1%) in the age of > 60 years. All patients received the right lobe of their donor. Out of these patients, 18 (18.7%) died in the median time of 4 months. The remaining 78 patients (81.2%) are alive, with a median survival of 33 months. The CCI of these patients was significantly lower compared to the other 18 patients (2 versus 4). None of the patients with a CCI above 4 survived longer than 12 months. The results of the multivariate Cox regression analyses have shown that pulmonary disease, renal disease, and CCI are independent negative predictive factors for survival. CONCLUSION: The results of our study show clearly that the CCI has a significant influence on survival after LDLT in elderly patients and can be used as one of the selection criteria for LDLT in elderly patients.

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.