Examining the Hepatic Immune System in Children With Liver Disease With Fine Needle Aspiration.

OBJECTIVES: Liver biopsy is the standard in diagnosing liver diseases. Yet, it provides little space to perform comprehensive immune profiling of the liver. Hence, we explored whether fine needle aspirates (FNAs) could be used to elucidate the hepatic immunity in children. METHODS: We enrolled 74 children undergoing diagnostic (n = 17) or protocol biopsy (n = 57) following liver transplantation (LT). Matched blood and FNAs were obtained. Additionally, explant liver tissue was collected from children (n = 14) undergoing LT. Immune cells were isolated from peripheral blood, FNAs and explanted livers. Immune-phenotypical profiling was done by flow cytometry. RESULTS: Biopsied patients (58% female) were at a median age of 46 months (interquartile range [IQR]: 12-118) and LT patients (71% female) were 48 months (IQR: 21-134, P = 0.78) old. CD69+, a hallmark of tissue-resident immune cells was expressed in 1.3% of CD3+ T cells from blood being higher in FNA (20%) and tissue (49%, P < 0.001). CD4+ T-cell frequencies in tissue (13%) and FNAs (20%) were lower compared to blood (35%, P < 0.001) whereas CD8+ T cells in tissue (33.5%) and FNA (32%) were higher than in blood (25%, P < 0.01). Mucosal associated invariant T cells were enriched in liver tissue (8.8%) and in the FNA (4.4%) compared to blood (1.7%, P < 0.001). Whereas the percentage of total Tregs (CD4+CD25+FOXP3+CD127low/-) decreased, the proportion of activated Tregs (CD4+CD45RA-FOXP3high) increased in FNA and explant. Breg (CD19+CD20+CD24highCD38high) frequencies were similar in all groups. CONCLUSION: FNA is a practical method to sample the liver immune system collecting even small cell subsets such as regulatory T/B cells.

Evaluation of pulmonary arterial stiffness and comparison with right ventricular functions in patients with cirrhosis preparing for liver transplantation.

OBJECTIVE: Pulmonary complications are common in patients with liver cirrhosis. Devolopment of pulmonary hypertension (PH) is associated with a poor prognosis in these patients. Pulmonary arterial stiffness (PAS) is considered an early sign of pulmonary vascular remodeling. The aim of this study is to investigate PAS and compare it with right ventricular (RV) functions in patients with cirrhosis who are scheduled for liver transplantation. METHODS: The study included 52 cirrhosis patients (mean age 51.01 ± 12.18 years, male gender 76.9%) who were prepared for liver transplantation and 59 age and sex matched (mean age 51.28 ± 13.63 years, male gender 62.7%) healthy individuals. Patients with left ventricular ejection fraction (LVEF) less than 55%, ischemic heart disease, more than mild valvular heart disease, chronic pulmonary disease, congenital heart disease, rheumatic disease, moderate to high echocardiographic PH probability, rhythm or conduction disorders on electrocardiography were excluded from the study. In addition to conventional echocardiographic parameters, PAS value, pulmonary vascular resistance (PVR) and RV ejection efficiency was calculated by the related formulas with transthoracic echocardiography (TTE). RESULTS: Demographic characteristics and cardiovascular risk factors of the groups were similar. PAS, PVR, and sPAP values were found to be significantly higher in the patient group (20.52 ± 6.52 and 13.73 ± 2.05; 1.43 ± 0.15 and 1.27 ± 0.14; 27.69 ± 3.91 and 23.37 ± 3.81 p < 0.001, respectively). RV FAC and RV Ee were significantly lower and RV MPI was significantly higher in the patient group (45.31 ± 3.85 and 49.66 ± 3.62, p < 0.001; 1.69 ± 0.35 and 1.85 ± 0.23, p = 0.005; 0.39 ± 0.07 and 0.33 ± 0.09, p = 0.001, respectively). PAS was significantly correlated with RV FAC and MPI (r = -0.423, p < 0.001; r = 0.301, p = 0.001, respectively). CONCLUSIONS: Increased PAS in cirrhosis patients may be associated with early pulmonary vascular involvement. Evaluation of RV functions is important to determine the prognosis in these patients. FAC, MPI, and RV Ee measurements instead of TAPSE or RV S' may be more useful in demonstrating subclinical dysfunction. The correlation of PAS with RV FAC and MPI may indicate that RV subclinical dysfunction is associated with early pulmonary vascular remodeling in patients with liver cirrhosis.

Are the criteria always right? Assessment of hepatocellular carcinoma cases in living donor liver transplantation at a high-volume center

Background/aim: With the increased experience in living donor liver transplantation (LDLT), it has been adopted for the treatment of hepatocellular carcinoma (HCC), with emerging discussions of criteria beyond tumor size and number. In contrast to deceased donor liver transplantation (DDLT), recipient selection for LDLT is not limited by organ allocation systems. We discuss herein the assessment, criteria, and experience with liver transplantation (LT) in HCC cases at a high-volume LDLT center. Material and methods: Between August 2006 and December 2017, 191 adult LT HCC recipients with at least one-year follow-up were retrospectively analyzed. Results: In 191 patients, one-, three- and five-year survival rates were 87.2%, 81.6%, and 76.2%, respectively, including early postoperative mortality. In 174 patients with long-term follow-up, one-, three- and five-year disease-free survival rates were 91.6%, 87.7%, and 84.4%, respectively. When multivariate analysis was utilized, tumor differentiation was the only factor which statistically affected survival (p = 0.025). Conclusion: LDLT allows us to push the limits forward and the question "Are the criteria always right?" is always on the table. We can conclude that, with the advantage of LDLT, every HCC patient deserves a case-by-case basis discussion for LT under scientific literature support. In borderline cases, tumor biopsy might help determine the decision for LT.

A comparison of rates and severity of chronic kidney disease in deceased-donor and living-donor liver transplant recipients: times matter

Background/aim: The progression of chronic kidney disease (CKD) in recipients of living-donor liver transplant (LDLT) compared to deceased-donor liver transplant (DDLT) has not been studied in the literature. We hypothesize that CKD stage progression in LDLT recipients is reduced compared to that of their DDLT counterparts. Materials and methods: A retrospective study was undertaken including 999 adult, single-organ, primary liver transplant recipients (218 LDLT and 781 DDLT) at 2 centers between January 2003 and December 2012, in which CKD progression and regression were evaluated within the first 3 years after transplantation. Results: Waiting time from evaluation to transplantation was significantly lower in LDLT patients compared to recipients of DDLT. CKD stage progression from preoperative transplant evaluation to transplantation was significantly greater in DDLT. Deceased-donor liver transplant recipients continued to have higher rates of clinically significant renal disease progression (from stage I­II to stage III­V) across multiple time points over the first 3 years posttransplant. Furthermore, a greater degree of CKD regression was observed in recipients of LDLT. Conclusion: It can be concluded that LDLT provides excellent graft and patient survival, significantly reducing the overall incidence of clinically significant CKD stage progression when compared to DDLT. Moreover, there is a significantly higher incidence of CKD stage regression in LDLT compared to DDLT. These observations were maintained in both high and low model for end-stage liver disease(MELD)populations. This observation likely reflects earlier access to transplantation in LDLT as one of the contributing factors to preventing CKD progression.

Results of pediatric living donor compared to deceased donor liver transplantation in the PELD/MELD era: Experience from two centers on two different continents.

The LDLT option in the pediatric population allows recipients to be transplanted early. A total of 202 consecutive pediatric liver transplants from two different institutions--108 (LDLT) and 94 (DDLT)--were retrospectively compared. Overall, one- and three-yr patient and graft survival were similar between DDLT and LDLT. ACR was greater in recipients of DDLT at one and three yr (50.8% and 61.0%) compared to LDLT (30.8% and 32.2%) (p = 0.002). When the data were stratified according to PELD/MELD score, LDLT with a low score had better one- and three-yr graft survival (96.2% and 96.2%) compared to DDLT (88.2% and 85.2%) (p = 0.02), with comparable patient survival (p = 0.75). Patient and graft survival were similar between DDLT and LDLT in the high PELD/MELD group. Lower incidence of ACR in both low and high PELD/MELD groups was (29.6% and 34.3%) for LDLT compared to DDLT (50.3% and 53.3%, p = 0.002 and p = 0.028, respectively). Regardless of PELD/MELD score, status, age group, and recipient weight, LDLT provides excellent patient and graft survival with a lower incidence of rejection compared to DDLT.

A very original case of a mini accessory liver lobe with its own gallbladder.

PURPOSE: Anatomic variation of the hepatobiliary system is often related to the biliary tract and vascular supply of the liver. We present here one of the smallest accessory hepatobiliary system. METHODS: The case of a 30-year-old male who was a living liver donor is presented. RESULTS: During the dissection of the portal hilum, 1.5 cm of accessory liver (AL) tissue was noted below the left lobe of the liver. This AL tissue had a gallbladder of 1.5 cm and which had a cystic duct opening to the bile duct of the accessory liver. The AL bile duct opened to the left bile duct of the liver. The arterial and portal supply of the AL came from the left artery and left portal vein of the liver. The accessory gallbladder also had a cystic artery coming from the arterial branch of the AL. It was noted that the hepatic vein of the AL opened directly to left lobe tissue. CONCLUSIONS: The hepatobiliary system has many anatomic variations, but this case is rare and original in the literature in that it may be a cause of confusion and even a false diagnosis.

Living donor liver transplantation in an adult patient with situs inversus totalis.

Situs inversus totalis (SIT) is a rare congenital anomaly, and liver transplantation (LT) in an adult SIT patient is extremely rare. Liver transplantation in a SIT patient is also technically challenging due to reversed anatomical structures. Here we present the case of an 18-year-old female with SIT in whom left lobe living donor LT was performed. The patient suffered from cirrhosis due to autoimmune hepatitis. The recipient and donor are doing well without complications 20 months after LT. Situs inversus totalis should not be considered a contraindication for LT. If possible, use of a living donor left lobe graft for LT is more feasible than a living donor right lobe graft. It is also technically easier than using deceased donor full-size liver graft in SIT patients who require liver transplantation.

Leiomyosarcoma of the retrohepatic vena cava: Report of a case treated with resection and reconstruction with polytetrafluoroethylene vascular graft.

Leiomyosarcoma of the vena cava is a rare malignant tumor. A 61-year-old woman was admitted with right upper quadrant abdominal pain. Computed tomography revealed a retrohepatic vena cava tumor originating 2 cm below the confluence of the hepaic veins and ending 2 cm above the renal veins. The tumor was resected with 1 cm clear surgical margins, without requiring liver resection. Polytetrafluoroethylene vascular graft was used for reconstruction of the vena cava. Now 32 months postoperatively, there has been no recurrence or metastasis. Radical resection with negative surgical margins is the best curative therapy for leiomyosarcoma. Polytetrafluoroethylene vascular graft can be used in extensive tumors located at the vena cava.

Donor bile duct evaluation with magnetic resonance cholangiography in living-donor liver transplantation: a novel anatomical classification for predicting surgical techniques.

PURPOSE: To propose a novel, inclusive classification that facilitates the selection of the appropriate donor and surgical technique in living-donor liver transplantation (LDLT). METHODS: The magnetic resonance cholangiography examinations of 201 healthy liver donors were retrospectively evaluated. The study group was classified according to the proposed classification. The findings were compared with the surgical technique used in 93 patients who underwent transplantation. The Couinaud, Huang, Karakas, Choi, and Ohkubo classifications were also applied to all cases. RESULTS: There were 118 right-lobe donors (58.7%) and 83 left-lateral-segment donors (41.3%). Fifty-six (28.8%) of the cases were classified as type 1, 136 (67.7%) as type 2, and 7 (3.5%) as type 3 in the proposed classification; all cases could be classified. The number of individuals able to become liver donors was 93. A total of 36 cases were type 1, 56 were type 2, and 1 was type 3. Of the type 1 donors, 83% required single anastomosis during transplantation, whereas six patients classified as type 1 required two anastomoses, all of which were caused by technical challenges during resection. Moreover, 51.8% of the cases classified as type 2 required additional anastomosis during transplantation. The type 3 patient required three anastomoses. The type 1 and type 2 donors required a different number of anastomoses (P < 0.001). CONCLUSION: The proposed classification in this study includes all anatomical variations. This inclusive classification accurately predicts the surgical technique for LDLT.

Hepatic Artery Intimal Dissection During Living Donor Liver Transplantation: A New Modified Approach.

Ensuring optimal arterial flow in solid organ transplantation is very important. Insufficient flow causes important problems such as bile duct problems, intrahepatic abscess formation, and organ loss. Arterial intimal dissection is an important factor that negatively affects organ blood flow. In this study, hepatic artery dissections that we detected in patients who underwent living donor liver transplantation in our clinic were defined, and the microvascular intima-adventitial fixation technique, which can be considered a new approach, was described.

Literature Review and 2 Cases of Isolated Chylothorax After Pediatric Living-Donor Liver Transplant.

OBJECTIVES: Chylothorax without chylous ascites after liver transplant is rare. We present 2 cases of isolated chylothorax after liver transplant and a literature review. MATERIALS AND METHODS: We compiled a literature review of chylothorax cases after abdominal surgery and analyzed the cases related to liver transplant. The demographic information, follow-up results, and treatment details of our 2 cases of chylothorax after living-donor pediatric livertransplant were discussed. RESULTS: An 8-month-old child and a 15-month-old child with cholestatic liver disease and urea cycle defect, respectively, underwent living-donor left lateral segment liver transplant. Patients who presented with chylothorax after discharge were treated conservatively. CONCLUSIONS: Isolated chylothorax is rare complication after abdominal surgery, which is mostly possible to treat with conservative methods. Interventional procedures and a surgical approach should only be performed in resistant cases when conservative treatment has failed.

Anesthesia Management in Laparoscopic Donor Hepatectomy: The First Report from Turkey.

BACKGROUND: We aimed to report a single-center experience in laparoscopic donor left-side and right-side hepatectomy cases regarding preoperative evaluation, perioperative and anesthetic management protocols, and postoperative follow-up. METHODS: Laparoscopic donor left-side and right-side hepatectomy cases were included in the study because of their excessive transection area and bleeding potential. Medical records of living donors were reviewed in terms of age, sex, body mass index (BMI), presence of consanguinity with the recipient, perioperative and early postoperative biochemical parameters, hemodynamic changes during surgery, duration of surgery, the ratio of liver volume to total liver volume, perioperative complications, and length of hospital stay. RESULTS: Eighty-one laparoscopic living-donor hepatectomy procedures were performed in our unit between 2018 and 2022. Six laparoscopic donor right-side cases and two left-side cases were retrospectively reviewed. Donors' mean age and BMI were 29.6 ± 8.6 years and 23.1 ± 4.3, respectively. The average weights of the right and left lobe liver grafts were 727 g and 279 g, respectively, constituting 65.8% and 22.7% of the total liver volume, respectively. The mean operation time was 593 ± 94 minutes, and the mean volume of blood loss was 437 ± 294 mL. A major complication, namely portal vein stenosis, developed in 1 donor (1/8), and portal vein patency was achieved postoperatively. CONCLUSIONS: Anesthesia management and teamwork between surgeons and anesthesiologists are the most important building blocks for donor safety, which is of the utmost priority. Effective communication and cooperation in the operating room may prevent potential donor complications and improve postoperative recovery time.

Living Donor-Initiated Domino Split-Liver Transplantation in Pediatric Setup: A Case Report With Literature Review.

BACKGROUND: In patients undergoing liver transplantation for metabolic diseases, removing the patient's liver for transplantation to another recipient is called "domino liver transplantation." The extracted liver can be divided and transplanted into 2 recipients, which is called domino split-liver transplantation in the literature. However, in our study, the domino liver was obtained from a pediatric patient. METHODS: A patient with maple syrup urine disease (MSUD) underwent a living donor liver transplant, and the explanted liver was divided in situ into right and left lobes and transplanted to 2 separate patients. Demographic data, surgical techniques, postoperative period, and patient follow-ups were evaluated. RESULTS: The father's left lobe liver graft was transplanted into a 12-year-old boy with MSUD. The removed liver was divided in situ into right and left lobes. The left lobe was transplanted to a 14-year-old male patient, whereas the right lobe was transplanted to a 67-year-old male patient. The donor and the first recipient were discharged on postoperative days 5 and 22. The second pediatric patient who underwent domino split-left lobe transplantation was discharged on postoperative day 23. The adult patient who underwent domino split-right lobe transplantation died on postoperative day 12 owing to massive esophageal variceal bleeding. CONCLUSION: Patients who underwent liver transplantation due to MSUD are among the best donor choices for domino liver transplantation. If the extracted liver has a sufficient volume and anatomic features for a split, it can be used in "selected cases."

Using Pericholedochal Varix Inflow for Complete Portal Vein Thrombosis in Living Donor Liver Transplantation: A Case Report.

One of the crucial steps of liver transplantation is to provide the portal inflow. Portal vein thrombosis is the most challenging factor to achieve. Using a pericholedochal varix for portal inflow in a patient with complete portal vein thrombosis in living donor liver transplantation (LDLT) is a rare technique. We present our experience of a LDLT with PVT.

Liver Transplant and Improvements in Cholesterol Biosynthesis Defects: A Case Report of Smith-Lemli-Opitz Syndrome.

Smith-Lemli-Opitz syndrome is an autosomal recessive metabolic disease characterized by mental retardation and multiple congenital anomalies. The main pathology is the lack of the enzyme 3ß-hydroxysterol Δ7-reductase, which is the last enzymatic step in cholesterol synthesis, ending with a low cholesterol level. Cholesterol is vitally important in cell membranes and myelination of the nervous system. The cholesterol level affects many systems of the body, especially the nervous system. The cause of liver involvement in Smith-Lemli-Opitz syndrome is unclear, and many hypotheses have been suggested. Here, we present the early results of a patient with Smith-Lemli-Opitz syndrome who underwent living-donor liver transplant due to cirrhosis. As a result of liver transplant, normal cholesterol levels were shown, as well as improvements in the patient's neurodevelopment and behavior. Early liver transplant may be considered for patients with a defect of cholesterol biosynthesis, even in the absence of cirrhosis, and may be a future treatment option to prevent risks of neurologic deterioration.

Trans-Arterial Radioembolization with Yttrium-90 of Unresectable and Systemic Chemotherapy Resistant Hepatoblastoma in Three Toddlers.

The aim of this short communication was to report the results of transarterial radioembolization (TARE) with Yttrium-90 (Y90) loaded resin microspheres in three toddlers with unresectable and systemic chemotherapy-resistant HB hepatoblastoma (HB). Six TARE procedures were performed on the patients. The dose required for treatment was calculated using partition model. Administered doses of Y90 were 1.369, 0.851, and 1.147 GBq. Complete radiological response in two patients and partial response enabling liver resection in one patient were achieved. Neither life-threatening nor minor complications developed after the treatment. These results demonstrates that HB is a radiosensitive neoplasm, and TARE-Y90 can be used as the primary, neoadjuvant and palliative treatment method in patients with unresectable and systemic chemotherapy-resistant HBs. However, studies with higher number of patients and long-term results are required.

Liver transplantation as a treatment option for three siblings with homozygous familial hypercholesterolemia.

FH is a hereditary inherited disorder of cholesterol metabolism. Homozygous form of the disease associates severe form of atherosclerotic disease. Clinicians have been tried to inhibit the progression of the homozygous FH with medical and surgical treatment. We here present three siblings with homozygous FH who were successfully treated with liver transplantation.

Patient With Hemophilia A Undergoing Consecutive Coronary Bypass and Live Donor Liver Transplantation: A Case Report.

Liver transplantation surgery due to cirrhosis in patients with hemophilia is rare and there are limited cases in the literature. We present a case of a patient with hemophilia A who underwent 2 consecutive surgeries owing to coronary artery disease and cryptogenic cirrhosis with hepatocellular carcinoma. After these surgeries, no bleeding or other complications were seen, and the factor VIII levels have not changed since liver transplantation in the follow-up.

Cardiac Intervention Before Liver Transplantation.

BACKGROUND: Cardiovascular complication is one of the leading causes of mortality after liver transplantation (LT). Thus, a thorough cardiac evaluation is a must before proceeding to a liver transplant surgery. Percutaneous coronary intervention (PCI) with stent and to a lesser extent coronary artery bypass grafting (CABG) are both valuable treatment options for patients with coronary artery disease. METHODS: A retrospective, single-center study that included patients who underwent cardiac intervention and subsequent LT for end-stage liver disease. All patients who had PCI or CABG were included in the study. RESULTS: Twenty-nine adult patients out of 51 had a cardiac intervention before liver transplantation. Twenty-four patients had a diagnostic PCI, 3 patients had therapeutic PCI with stent, and 2 had failed PCI and proceeded to CABG before liver transplant. The mean age of the patients was 60.5 years. There were 24 men. All patients had cirrhosis. The 2 CABG cases were done during the same admission with a 13- and 18-day interval between the CABG and the transplantation. Both cases were live-related liver transplantation. No mortality was reported. CONCLUSION: In case of PCI failure, CABG may be a valuable and safe treatment option for cirrhotic patients as a preparation for liver transplantation. Live donor liver transplantation may be a good back-up for those patients in case they develop hepatic decompensation.

Non-occlusive hepatic artery hypoperfusion syndrome and imaging findings: a systematic review.

Non-occlusive hepatic artery hypoperfusion syndrome (NHAHS), in other words, splenic steal, is a rare disorder that can arise following liver transplantation. After liver transplantation, its frequency has been defined as between 0.6 and 10.1%. The diversion of flow from hepatic to splenic arteries results in low perfused hepatic artery which causes elevated liver enzymes, hyperbilirubinemia, and graft dysfunction. This may result from a high resistance in the hepatic arteries, enlarged splenic arteries, a limited hepatic arterial flow due to high portal flow, or a discordance of the graft size and hepatic arterial flow. There may be a need for some prophylactic and/or posttransplant treatment procedures. We aimed to describe pre and post-treatment imaging findings of NHAHS.