Assessing hepatic steatosis by magnetic resonance in potential living liver donors.

PURPOSE: To determine the accuracy of magnetic resonance imaging-proton density fat fraction (MRI-PDFF) measurements for detecting liver fat content in potential living liver donors and to compare these results using liver biopsy findings. METHODS: A total of 139 living liver donors (men/women: 83/56) who underwent MRI between January 2017 and September 2021 were included in this analysis retrospectively. The PDFFs were measured using both MR spectroscopy (MRS) and chemical shift-based MRI (CS-MRI) for each donor in a blinded manner. RESULTS: Significant positive correlations were found between liver biopsy and MRS-PDFF and CS-MRI PDFF in terms of hepatic steatosis detection [r = 0.701, 95% confidence interval (CI): 0.604-0.798, r = 0.654, 95% CI: 0.544-0.765, P < 0.001, respectively). A weak level correlation was observed between liver biopsy, MRI methods, and vibration-controlled transient elastography attenuation parameters in 42 available donors. Based on receiver operating characteristic (ROC) analysis, MRS-PDFF and CS-MRI PDFF significantly distinguished >5% of histopathologically detected hepatic steatosis with an area under the ROC curve (AUC) of 0.837 ± 0.036 (P < 0.001, 95% CI: 0.766-0.907) and 0.810 ± 0.036 (P < 0.001, 95% CI: 0.739-0.881), respectively. The negative predictive values (NPVs) of MRS-PDFF and CS-MRI PDFF were 88.3% and 81.3%, respectively. In terms of distinguishing between clinically significant hepatic steatosis (≥10% on histopathology), the AUC of MRS-PDFF and CS-MRI were 0.871 ± 0.034 (P < 0.001 95% CI: 0.804-0.937) and 0.855 ± 0.036 (P < 0.001, 95% CI: 0.784-0.925), respectively. The NPVs of MRS-PDFF and CS-MRI were 99% and 92%, respectively. CONCLUSION: The methods of MRS-PDFF and CS-MRI PDFF provide a non-invasive and accurate approach for assessing hepatic steatosis in potential living liver donor candidates. These MRI PDFF techniques present a promising clinical advantage in the preoperative evaluation of living liver donors by eliminating the requirement for invasive procedures like liver biopsy.

Indications to LDLT: a changing pathway?

Liver transplantation (LT) revolutionized the outlook for cirrhotic patients, offering a potential cure with over 80% life expectancy after 5 years. Cirrhosis, with or without hepatocellular carcinoma (HCC), is the primary LT indication. Living donor LT (LDLT) initially explored as an alternative, declined due to poorer outcomes. Studies on LDLT improved outcomes through precise recipient selection, emphasizing the importance of careful donor/recipient matching. Emerging concepts like left lobe preference and minimally invasive donor approaches enhance LDLT outcomes. The RAPID technique shows promise in both cirrhotic and non-cirrhotic livers. LDLT gains significance in transplant oncology, particularly for liver tumors like colorectal liver metastases (CLM), offering better survival than alternatives. Optimal timing integrates chemotherapy with the transplant. As LT indications evolve, LDLT finds a growing role in oncology, surpassing deceased donor transplants in certain scenarios. The decreasing prevalence of virus-related uncompensated cirrhosis highlights the expanding space for LDLT in liver transplantation.

Biliary complications after adult-to-adult living-donor liver transplantation: An international multicenter study of 3633 cases.

In living-donor liver transplantation, biliary complications including bile leaks and biliary anastomotic strictures remain significant challenges, with incidences varying across different centers. This multicentric retrospective study (2016-2020) included 3633 adult patients from 18 centers and aimed to identify risk factors for these biliary complications and their impact on patient survival. Incidences of bile leaks and biliary strictures were 11.4% and 20.6%, respectively. Key risk factors for bile leaks included multiple bile duct anastomoses (odds ratio, [OR] 1.8), Roux-en-Y hepaticojejunostomy (OR, 1.4), and a history of major abdominal surgery (OR, 1.4). For biliary anastomotic strictures, risk factors were ABO incompatibility (OR, 1.4), blood loss >1 L (OR, 1.4), and previous abdominal surgery (OR, 1.7). Patients experiencing biliary complications had extended hospital stays, increased incidence of major complications, and higher comprehensive complication index scores. The impact on graft survival became evident after accounting for immortal time bias using time-dependent covariate survival analysis. Bile leaks and biliary anastomotic strictures were associated with adjusted hazard ratios of 1.7 and 1.8 for graft survival, respectively. The study underscores the importance of minimizing these risks through careful donor selection and preoperative planning, as biliary complications significantly affect graft survival, despite the availability of effective treatments.

Management of Established Small-for-size Syndrome in Post Living Donor Liver Transplantation: Medical, Radiological, and Surgical Interventions: Guidelines From the ILTS-iLDLT-LTSI Consensus Conference.

Small-for-size syndrome (SFSS) following living donor liver transplantation is a complication that can lead to devastating outcomes such as prolonged poor graft function and possibly graft loss. Because of the concern about the syndrome, some transplants of mismatched grafts may not be performed. Portal hyperperfusion of a small graft and hyperdynamic splanchnic circulation are recognized as main pathogenic factors for the syndrome. Management of established SFSS is guided by the severity of the presentation with the initial focus on pharmacological therapy to modulate portal flow and provide supportive care to the patient with the goal of facilitating graft regeneration and recovery. When medical management fails or condition progresses with impending dysfunction or even liver failure, interventional radiology (IR) and/or surgical interventions to reduce portal overperfusion should be considered. Although most patients have good outcomes with medical, IR, and/or surgical management that allow graft regeneration, the risk of graft loss increases dramatically in the setting of bilirubin >10 mg/dL and INR>1.6 on postoperative day 7 or isolated bilirubin >20 mg/dL on postoperative day 14. Retransplantation should be considered based on the overall clinical situation and the above postoperative laboratory parameters. The following recommendations focus on medical and IR/surgical management of SFSS as well as considerations and timing of retransplantation when other therapies fail.

Early period intensive care follow-up after liver transplantation in children: a single center experience.

BACKGROUND: Liver transplantation (LT) is a well-established, life-saving treatment for children with irreversible acute and chronic liver failure (LF). We aimed to evaluate the factors associated with morbidity and mortality in the early period of LT in children by reviewing our pediatric intensive care unit (PICU) experience. METHODS: We reviewed children`s medical records followed in the PICU after LT between May 2015-August 2021, including demographic parameters, indications for LT, operative variables, respiratory and circulatory support requirements, LT-related complications and survival. RESULTS: During this period, 40 pediatric patients who underwent LT were evaluated. LT was performed in 35 (87.5%) cases of chronic liver disease and 5 (12.5%) cases of acute liver failure. Twenty-four patients had chronic liver failure due to cholestatic liver disease. The patients` Pediatric Risk of Mortality (PRISM) III score was 18.82±SD (2-58) at PICU admission. 1-year survival was 87.5%, and overall survival was 85%. Younger age, low body weight, preoperative pediatric end-stage liver disease (PELD), and model for end-stage liver disease (MELD) values of 20 and higher were important risk factors for unfavorable outcomes after living donor liver transplantation (LDLT). These risk factors are both associated with technically more challenging vascular and bile duct reconstruction and higher complication rates, and increased mortality during the early period after LT. CONCLUSIONS: The early period of optimum PICU management in pediatric LT recipients is crucial for successful outcomes, which is also related to the patients` characteristics, disease severity scores, and surgical procedures.

Novel Benchmark for Adult-to-Adult Living-donor Liver Transplantation: Integrating Eastern and Western Experiences.

OBJECTIVE: To define benchmark values for adult-to-adult living-donor liver transplantation (LDLT). BACKGROUND: LDLT utilizes living-donor hemiliver grafts to expand the donor pool and reduce waitlist mortality. Although references have been established for donor hepatectomy, no such information exists for recipients to enable conclusive quality and comparative assessments. METHODS: Patients undergoing LDLT were analyzed in 15 high-volume centers (≥10 cases/year) from 3 continents over 5 years (2016-2020), with a minimum follow-up of 1 year. Benchmark criteria included a Model for End-stage Liver Disease ≤20, no portal vein thrombosis, no previous major abdominal surgery, no renal replacement therapy, no acute liver failure, and no intensive care unit admission. Benchmark cutoffs were derived from the 75th percentile of all centers' medians. RESULTS: Of 3636 patients, 1864 (51%) qualified as benchmark cases. Benchmark cutoffs, including posttransplant dialysis (≤4%), primary nonfunction (≤0.9%), nonanastomotic strictures (≤0.2%), graft loss (≤7.7%), and redo-liver transplantation (LT) (≤3.6%), at 1-year were below the deceased donor LT benchmarks. Bile leak (≤12.4%), hepatic artery thrombosis (≤5.1%), and Comprehensive Complication Index (CCI ® ) (≤56) were above the deceased donor LT benchmarks, whereas mortality (≤9.1%) was comparable. The right hemiliver graft, compared with the left, was associated with a lower CCI ® score (34 vs 21, P < 0.001). Preservation of the middle hepatic vein with the right hemiliver graft had no impact neither on the recipient nor on the donor outcome. Asian centers outperformed other centers with CCI ® score (21 vs 47, P < 0.001), graft loss (3.0% vs 6.5%, P = 0.002), and redo-LT rates (1.0% vs 2.5%, P = 0.029). In contrast, non-benchmark low-volume centers displayed inferior outcomes, such as bile leak (15.2%), hepatic artery thrombosis (15.2%), or redo-LT (6.5%). CONCLUSIONS: Benchmark LDLT offers a valuable alternative to reduce waitlist mortality. Exchange of expertise, public awareness, and centralization policy are, however, mandatory to achieve benchmark outcomes worldwide.

Early Postoperative Serum Phosphate Drop Predicts Sufficient Hypertrophy After Liver Surgery.

OBJECTIVE: The aim of this study was to assess the impact of postoperative hypophosphatemia on liver regeneration after major liver surgery in the scenario of Associating Liver Partition with Portal vein ligation for Staged hepatectomy (ALPPS) and living liver donation (LLD). BACKGROUND: Hypophosphatemia has been described to reflect the metabolic demands of regenerating hepatocytes. Both ALPPS and LLD are characterized by an exceptionally strong liver regeneration and may be of particular interest in the context of posthepatectomy hypophosphatemia. METHODS: Serum phosphate changes within the first 7 postoperative days after ALPPS (n=61) and LLD (n=54) were prospectively assessed and correlated with standardized volumetry after 1 week. In a translational approach, postoperative phosphate changes were investigated in mice and in vitro . RESULTS: After ALPPS stage 1 and LLD, serum phosphate levels significantly dropped from a preoperative median of 1.08 mmol/L [interquartile range (IQR) 0.92-1.23] and 1.07 mmol/L (IQR 0.91-1.21) to a postoperative median nadir of 0.68 and 0.52 mmol/L, respectively. A pronounced phosphate drop correlated well with increased liver hypertrophy ( P <0.001). Patients with a low drop of phosphate showed a higher incidence of posthepatectomy liver failure after ALPPS (7% vs 31%, P =0.041). Like in humans, phosphate drop correlated significantly with degree of hypertrophy in murine ALPPS and hepatectomy models ( P <0.001). Blocking phosphate transporter (Slc20a1) inhibited cellular phosphate uptake and hepatocyte proliferation in vitro. CONCLUSION: Phosphate drop after hepatectomy is a direct surrogate marker for liver hypertrophy. Perioperative implementation of serum phosphate analysis has the potential to detect patients with insufficient regenerative capacity at an early stage.

Technical challenges in LDLT - Overcoming small for size syndrome and venous outflow reconstruction.

Living Donor Liver Transplantation (LDLT) emerged as an alternative treatment option for patients with end-stage liver disease waiting for an organ from a deceased donor. In addition to allowing for a faster access to transplantation, LDLT provides improved recipient outcomes when compared to deceased donor LT. However, it represents a more complex and demanding procedure for the transplant surgeon. In addition to a comprehensive preoperative donor assessment and stringent technical considerations during the donor hepatectomy to ensure upmost donor safety, the recipient procedure also comes with intrinsic challenges during LDLT. A proper approach during both procedures will result in favorable donor and recipient's outcomes. Hence, it is critical for the transplant surgeon to know how to overcome such technical challenges and avoid deleterious complications. One of the most feared complications following LDLT is small-for-size syndrome (SFSS). Although, surgical advances and deeper understanding of the pathophysiology behind SFSS has allowed for a safer implementation of LDLT, there is currently no consensus on the best strategy to prevent or manage this complication. Therefore, we aim to review current practices in technically challenging situations during LDLT, with a particular focus on management of small grafts and venous outflow reconstructions, as they possess one of the biggest technical challenges faced during LDLT.

Revival of associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma: An international multicenter study with promising outcomes.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma has been considered to be contraindicated due to the initial poor results. Given the recent reports of improved outcomes, we aimed to collect the recent experiences of different centers performing associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma to analyze factors related to improved outcomes. METHODS: This proof-of-concept study collected contemporary cases of associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma and analyzed for morbidity, short and long-term survival, and factors associated with outcomes. RESULTS: In total, 39 patients from 8 centers underwent associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma from 2010 to 2020. The median preoperative future liver remnant volume was 323 mL (155-460 mL). The median future liver remnant increase was 58.7% (8.9% -264.5%) with a median interstage interval of 13 days (6-60 days). Post-stage 1 and post-stage 2 biliary leaks occurred in 2 (7.7%) and 4 (15%) patients. Six patients (23%) after stage 1 and 6 (23%) after stage 2 experienced grade 3 or higher complications. Two patients (7.7%) died within 90 days after stage 2. The 1-, 3-, and 5-year survival was 92%, 69%, and 55%, respectively. A subgroup analysis revealed poor survival for patients undergoing additional vascular resection and lymph node positivity. Lymph node-negative patients showed excellent survival demonstrated by 1-, 3-, and 5-year survival of 86%, 86%, and 86%. CONCLUSION: This study highlights that the critical attitude toward associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma needs to be revised. In selected patients with perihilar cholangiocarcinoma, associating liver partition and portal vein ligation for staged hepatectomy can achieve favorable survival that compares to the outcome of established surgical treatment strategies reported in benchmark studies for perihilar cholangiocarcinoma including 1-stage hepatectomy and liver transplantation.

Diagnostic Dilemma of Lactic Acidosis in an Infant After Liver Transplant: A Case Report.

Thiamine is the cofactor of many enzymes involved in energy metabolism. Patients under total parenteral nutrition are at risk for thiamine deficiency if there is renal thiamine loss or increased thiamine requirements to mitigate systemic diseases. Thiamine deficiency symptoms include seizures, neuropathy, ataxia, peripheral vasodilation, myocardial insufficiency, sudden collapse, and death. In this report, we present an infant liver transplant recipient with progressive lactic acidosis that responded well to thiamine replacement to mitigate a lack of thiamine in total parenteral nutrition.

Outcomes of Surgical Strategies for Living Donor Liver Transplantation in Patients With Portal Vein Thrombosis: A Cohort Study.

BACKGROUND: Adequate portal flow to the liver graft is the requirement of a successful liver transplant (LT). Historically, portal vein thrombosis (PVT) was a contraindication for LT, especially for living donor LT (LDLT), demanding technically more difficult operations and advanced technique. In this study, the outcomes of patients with and without PVT after LDLT were compared. METHODS: Adult LDLTs performed by 2 centers (n = 335) between 2013 and 2020 were included into this large cohort study. PVT was classified based on Yerdel classification grade 1 to 4. RESULTS: Sixty-two patients with PVT constituted 19% of the study cohort of 335 recipients. While mean platelet count was found to be lower (P = .011) in the PVT group, patient age (P = .035), operation duration (P = .001), and amount of intraoperative blood transfusion (P = .010) were found to be higher. Incidence of PVT was higher in female patients than males (22.7% vs 16.1%, P = .037). There was no significant difference in survival between patients with and without PVT on 30-day (P = .285), 90-day (P = .565), 1-year (P = .777), and overall survival (P = .917). Early thrombosis did not show a better survival rate than Grades 2, 3, or 4 PVT. Thrombosis limited to portal vein was not found to bring a survival advantage compared with Grade 3 and 4 thromboses. Eversion thrombectomy was the most common procedure (66%) to overcome PVT intraoperatively. CONCLUSION: Although technically more challenging, PVT is not a contraindication of LDLT. Similar outcomes can be achieved in LDLT in patients with PVT after proper restoration of portal flow, which eliminates the default survival disadvantage of patients with PVT.

Comparison of Anatomic and Non-Anatomic Liver Resection for Hepatocellular Carcinoma: A Retrospective Cohort Study.

Background and Objectives: The survival benefit of anatomical liver resection for hepatocellular carcinoma has not been elucidated yet. In this study, we aimed to investigate the effects of anatomic and non-anatomic liver resection on surgical outcomes in patients with hepatocellular carcinoma. Materials and Methods: A retrospective analysis of patients undergoing anatomic or non-anatomic resections due to hepatocellular carcinoma between March 2006 and October 2019 was conducted. Demographics, preoperative laboratory assessments, treatment strategies, and postoperative outcomes were analyzed. Results: The total cohort consisted of 94 patients, with a mean age of 63.1 ± 8.9 years, and 74.5% were male. A total of 41 patients underwent anatomic liver resection, and 53 patients underwent non-anatomic resection. The overall survival rates were found to be similar (5-year overall survival was 49.3% for anatomic resection and 44.5% for non-anatomic resection). Estimated median overall survival times were 58.5 months and 57.3 months, respectively (p = 0.777). Recurrence-free 1-, 3-, and 5-year survival rates were found to be 73.6%, 39.1%, and 32.8% in the non-anatomic resection group and 48.8%, 22.7%, and 22.7% in the anatomic resection group, respectively. Grade three or higher complication rates were found to be similar among the groups. Conclusions: This study did not find a difference between two surgical methods, in terms of survival. A tailored selection of the resection method should be made, with the aim of complete removal of tumoral lesions and leaving a suitable functional liver reserve, according to the parenchymal quality and volume of the liver remnant.

Reducing Risk for Acute Kidney Injury After Living Donor Hepatectomy by Protocolized Fluid Restriction: Single-Center Experience.

BACKGROUND: Acute kidney injury (AKI) is a potential complication after restricted fluid therapy for major surgery. The aim of this study was to evaluate the incidence of AKI for living liver donor hepatectomy in which applied intraoperative protocolized fluid restriction was used targeting a low central venous pressure (CVP) level with high pulse pressure variation (PPV) and systolic pressure variation (SPV). MATERIAL AND METHODS: Living liver donors were admitted for this retrospective observational study. Low CVP <5 mm Hg with high PPV<20% and SPV<15% were the targets of the clinical protocol to reduce intraoperative blood loss via protocolized fluid management until the end of the hepatic parenchymal division. KDIGO criteria were used for AKI definition. The SPSS version 11.5 program was used for statistical analysis. RESULTS: The study included 130 patients, 79 (60.8%) men and 51 (39.2%) women, with from 18 to 58 years of age. Donors underwent right and left lobe hepatectomies (116 and 14, respectively). The baseline CVP, the lowest CVP of hepatectomy, and the highest CVP measured after hepatectomy were 7.45 ± 2.41, 4.28 ± 1.12, 7.67 ± 2.09 mm Hg, respectively. Only 4 patients with right lobe hepatectomy developed AKI stage I (3.1%) in the first 24 hours. The 4 patients were recovered at 48 hours postoperatively. CONCLUSION: This study demonstrated that a CVP target of <5 mm Hg and high PPV/SPV via a simple fluid management modality with protocolized-fluid restriction until the procurement may not cause AKI in living liver donors in a closed follow-up anesthesia approach.

Uses of a dedicated 3D reconstruction software with augmented and mixed reality in planning and performing advanced liver surgery and living donor liver transplantation (with videos).

The development of digital intelligent diagnostic and treatment technology has opened countless new opportunities for liver surgery from the era of digital anatomy to a new era of digital diagnostics, virtual surgery simulation and using the created scenarios in real-time surgery using mixed reality. In this article, we described our experience on developing a dedicated 3 dimensional visualization and reconstruction software for surgeons to be used in advanced liver surgery and living donor liver transplantation. Furthermore, we shared the recent developments in the field by explaining the outreach of the software from virtual reality to augmented reality and mixed reality.

Living liver donor hilar anatomical variations and impact of variant anatomy on transplant outcomes.

Donor anatomy is an essential part of donor selection and operative planning in living donor liver transplantation. In this study, variations of hilar structures, and the effects of variant anatomy on donor and recipient outcomes were evaluated. Living donor liver transplantations in a single center between January 2013 and December 2020 were retrospectively reviewed. In total, 203 liver transplantations were analyzed. Type 1 arterial anatomy, type 1 portal vein anatomy and type 1 bile duct anatomy were observed in 144 (70.9%), 173 (85.2%), and 129 (63.5%) donors, respectively. Variant biliary anatomy was observed more frequent in donors with variant portal vein branching than in those with type 1 portal anatomy (60.0% vs 32.3%, P = .004). The overall survival rates calculated for each hilar structure were similar between recipients receiving grafts with type 1 anatomy and those receiving grafts with variant anatomy. When donors with variant anatomy and donors with type 1 anatomy were compared in terms of hilar structure, no significant difference was observed in the frequency of complications and the frequency of serious complications. Biliary variations are more common in individuals with variant portal vein anatomy. Donor anatomic variations are not risk factors for inferior results of recipient survival or donor morbidity.

Sex Disparities in Outcomes Following Major Liver Surgery: New Powers of Estrogen?

AIM: To explore potential sex differences in outcomes and regenerative parameters post major hepatectomies. BACKGROUND: Although controversial, sex differences in liver regeneration have been reported for animals. Whether sex disparity exists in human liver regeneration is unknown. METHODS: Data from consecutive hepatectomy patients (55 females, 67 males) and from the international ALPPS (Associating-Liver-Partition-and-Portal-vein-ligation-for-Staged-hepatectomy, a two stage hepatectomy) registry (449 females, 729 males) were analyzed. Endpoints were severe morbidity (≥3b Clavien-Dindo grades), Model for End-stage Liver Disease (MELD) scores, and ALPPS interstage intervals. For validation and mechanistic insight, female-male ALPSS mouse models were established. t , χ 2 , or Mann-Whitney tests were used for comparisons. Univariate/multivariate analyses were performed with sensitivity inclusion. RESULTS: Following major hepatectomy (Hx), males had more severe complications ( P =0.03) and higher liver dysfunction (MELD) P =0.0001) than females. Multivariate analysis established male sex as a predictor of complications after ALPPS stage 1 (odds ratio=1.78; 95% confidence interval: 1.126-2.89; P =0.01), and of enhanced liver dysfunction after stage 2 (odds ratio=1.93; 95% confidence interval: 1.01-3.69; P =0.045). Female patients displayed shorter interstage intervals (<2 weeks, 64% females versus 56% males, P =0.01), however, not in postmenopausal subgroups. In mice, females regenerated faster than males after ALPPS stage 1, an effect that was lost upon estrogen antagonism. CONCLUSIONS: Poorer outcomes after major surgery in males and shorter ALPPS interstage intervals in females not necessarily suggest a superior regenerative capacity of female liver. The loss of interstage advantages in postmenopausal women and the mouse experiments point to estrogen as the driver behind these sex disparities. Estrogen's benefits call for an assessment in postmenopausal women, and perhaps men, undergoing major liver surgery.