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.

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.

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.

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.

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.

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.

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.

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.

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.

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 liver transplantation for obese patients: challenges and outcomes.

Living donor liver transplantation (LDLT) is an accepted option for end-stage liver disease, particularly in countries in which there are organ shortages. However, little is known about LDLT for obese patients. We sought to determine the effects of obesity on pretransplant living donor selection for obese recipients and their outcomes. On the basis of body mass index (BMI) values, 148 patients were classified as normal weight (N), 148 were classified as overweight (OW), and 74 were classified as obese (O). O recipients had significantly greater BMI values (32.1 ± 1.6 versus 23.2 ± 1.9 kg/m(2), P < 0.001) and received larger actual grafts (918.9 ± 173 versus 839.4 ± 162 g, P = 0.002) than recipients with normal BMI values. Donors who donated to O recipients had a greater mean BMI (26.3 ± 3.8 kg/m(2)) than those who donated to N recipients (24.4 ± 3.2 kg/m(2), P = 0.001). Although O recipients were more likely to face some challenges in finding a suitable living donor, there were no differences in graft survival [hazard ratio (HR) = 0.955, 95% confidence interval (CI) = 0.474-1.924, P = 0.90] or recipient survival (HR = 0.90, 95% CI = 0.56-1.5, P = 0.67) between the 3 groups according to an adjusted Cox proportional hazards model. There were no significant differences in posttransplant complication rates between the 3 recipient groups or in the morbidity rates for the donors who donated to O recipients versus the donors who donated to OW and N recipients (P = 0.26). Therefore, we recommend that obese patients undergo pretransplant evaluations. If they are adequately evaluated and selected, they should be considered for LDLT.

Anatomical variations of donor portal vein in right lobe living donor liver transplantation: the safe use of variant portal veins.

In right lobe (RL) living donor liver transplantation (LDLT), portal vein (PV) variations are of immense clinical significance. In this study, we describe in detail our PV reconstruction techniques in RL grafts with variant PV anatomy and evaluate the impact of accompanying biliary variations on the recipient outcomes. In a total of 386 RL LDLTs performed between July 2004 and July 2012, the clinical data on 52 (13%) transplants using RL grafts with variant PV anatomy were retrospectively analyzed. Portal vein anatomy was classified as type 2 in 20 patients, type 3 in 24 patients, and type 4 in eight patients. The PV reconstruction techniques utilized included back-wall plasty (n = 21), back-wall plasty with saphenous vein graft interposition (n = 6), saphenous vein graft interposition (n = 5), cryopreserved iliac vein Y-graft interposition (n = 6), and quiltplasty (n = 3). There was no donor mortality. In a median follow-up of 29 months, none of the recipients had vascular complications. Anomalous PV anatomy was associated with a high (54%) incidence of biliary variations; however, these variations did not result in increased biliary complication rate. Overall, the 1- and 3-year patient survival rates of recipients were 91% and 81%, respectively. Vascular and biliary variations in RL grafts render LDLT technically more challenging. By employing appropriate reconstruction techniques, it is possible to successfully use RL grafts with PV variations without endangering recipient and donor safety.

Glasgow coma scale and APACHE-II scores affect the liver transplantation outcomes in patients with acute liver failure.

BACKGROUND: The timing and selection of patients for liver transplantation in acute liver failure are great challenges. This study aimed to investigate the effect of Glasgow coma scale (GCS) and APACHE-II scores on liver transplantation outcomes in patients with acute liver failure. METHOD: A total of 25 patients with acute liver failure were retrospectively analyzed according to age, etiology, time to transplantation, coma scores, complications and mortality. RESULTS: Eighteen patients received transplants from live donors and 7 had cadaveric whole liver transplants. The mean duration of follow-up after liver transplantation was 39.86+/-40.23 months. Seven patients died within the perioperative period and the 1-, 3-, 5-year survival rates of the patients were 72%, 72% and 60%, respectively. The parameters evaluated for the perioperative deaths versus alive were as follows: the mean age of the patients was 33.71 vs 28 years, MELD score was 40 vs 32.66, GCS was 5.57 vs 10.16, APACHE-II score was 23 vs 18.11, serum sodium level was 138.57 vs 138.44 mmol/L, mean waiting time before the operation was 12 vs 5.16 days. Low GCS, high APACHE-II score and longer waiting time before the operation (P<0.01) were found as statistically significant factors for perioperative mortality. CONCLUSION: Lower GCS and higher APACHE-II scores are related to poor outcomes in patients with acute liver failure after liver transplantation.

Successful treatment of severe hepatorenal syndrome with living donor liver transplantation.

Hepatorenal syndrome is defined as renal failure caused by acute or chronic liver failure without any laboratory or histological reasons. The exact etiology of this syndrome is unknown. However, vasodilatation in the splanchnic area as a result of cirrhosis and portal hypertension, reflex systemic and splanchnic vasoconstriction are the basic pathophysiological reasons of this syndrome. The decrease of renal perfusion, decrease in glomerular filtration rate, sodium retention and deterioration of excretion of free water are the major renal problems and these remain progressive according to the stage of liver disease. The treatment of this syndrome is correction of the underlying problem. Here, we report a patient who was having hemodialysis due to renal failure as a consequence of liver cirrhosis for three months and returned back to his normal life without a need for dialysis after liver transplantation.

Recipient splenic artery utilization for arterial re-anastomosis in living donor liver transplantation: single-center experience.

Thrombosis of recipient hepatic artery is a life threatening complication for liver transplantation. The etiology of hepatic arterial thrombosis is multi-factorial and can be caused by intimal dissection, poor surgical technique and coagulopathies. The patency of hepatic arterial flow is very important for both graft survival and patient survival. Intraoperative diagnosis of inadequate hepatic arterial flow found with Doppler ultrasonography is essential in order to achieve good results after liver transplantation. Urgent re-anastomosis is necessary when the arterial blood flow is insufficient. We performed 317 living donor liver transplantations from July 2004 to July 2011. We used recipient splenic artery for hepatic artery reconstruction in six patients. These six patients were included in this study. Using the recipient splenic artery is a simple, safe and practical alternative for hepatic artery re-anastomosis in living donor liver transplantations.

A new technique for the reconstruction of complex portal vein anomalies in right lobe living liver donors.

Living donor liver right lobe transplantation using donors with variation of the right sectorial portal vein is considered a challenging procedure in terms of the donor's safety and the complexity of reconstruction in the recipient. We describe an innovative technique to reconstruct double portal vein orifices via a deceased donor iliac vein graft. The postoperative course of the recipient was uneventful. Doppler ultrasound on the fourth postoperative month revealed equivalent flow in both portal vein branches. Reconstruction of double right portal vein branches using a cryopreserved iliac vein is a valuable technique for utilizing right lobe grafts with challenging portal vein anatomy.