The impact of subdermal adipose derived stem cell injections and early excision on systemic oxidative stress and wound healing in rats with severe scald burns.

AIM: This study aims to develop an experimental treatment model effective against oxidative stress in the acute period of severe burns and to analyze the mechanisms of healing large wound defects. METHODS: Five rats, including 2 females and 3 males, were used as donors to obtain adipose-derived stem cells (ADSC) from the inguinal fat pad. The stem cells were labeled with green fluorescent protein. The study included four groups of 17 rats, each with grade 3 scalding burns on 30 % of their body surface, and a control group of 10 rats with an equal number of males and females. After early excision, 106 ADSC-derived stem cells were administered subdermally to the burned wound and autografted to the stem cell group (n = 17). The early excision group (n = 17) received early excision and autograft, with 2 ml of normal saline injected subdermally into the burn wound edge. The PLM group (n = 17) was treated with a polylactic membrane (PLM) dressing after the burn. No treatment was given to the burn group (n = 17). Ten rats from all groups were sacrificed on the 4th day post-burn for oxidative stress evaluation. The control group (n = 10) was sacrificed on day 4. Blood and tissue samples were collected post-sacrifice. Oxidative stress and inflammation in the blood, as well as cell damage in the skin, liver, kidneys, and lungs, were investigated histopathologically and biochemically on the 4th day post-burn. On the 70th day after burn, wound healing was examined macroscopically and histopathologically. RESULTS: On the 4th day, oxidative stress results showed that the levels of Total Oxidative Capacity (TOC) in the blood were lowest in the stem cell (7.4 [6-8.8]), control (6.7 [5.9-7.6]), and early excision (7.5 [6.6-8.5]) groups, with no significant difference between them. The burn group (14.7 [12.5-16.9]) had the highest TOC levels. The PLM group (9.7 [8.6-10.7]) had lower TOC levels than the burn group but higher levels than the other groups. Histopathological examination on the 4th day revealed low liver caspase-3 immunoreactivity in the stem cell and early excision groups among the burn groups. Caspase-3 immunoreactivity levels were as follows: stem cell group (20 [10-30]), early excision group (25 [15-50]), PLM group (70 [50-100]), control group (0), and burn group (80 [60-120]). Other oxidative stress and end-organ damage outcomes were consistent with these results. All rats in the stem cell group had burn wounds that healed completely by the 70th day. Examination of the skin and its appendages from the stem cell group with an immunofluorescence microscope demonstrated green coloration, indicating incorporation of stem cells. CONCLUSION: Stem cells may have the potential to form new skin and its appendages, providing better healing for large skin defects. Early excision treatment, by removing local necrotic tissues after extensive and deep burns, can prevent end-organ damage due to systemic oxidative stress and inflammation. We also believe that when these two treatments are used together, they can achieve the best results.

Peripheral blood platelet counts identify prognostically diverse clinical phenotypes in hepatocellular carcinoma.

Background: The factors responsible for hepatocellular carcinoma (HCC) growth are not precisely known. Aims: To study the clinical parameters associated with increases in maximum tumor diameter (MTD). Methods: A new cohort of 944 prospectively accrued HCC patients was analyzed for large size associations. Results: Patients were ordered into MTD terciles. Blood platelets, GGT and AST levels significantly increased and total bilirubin decreased with increase in MTD. Similar results were found only for platelets, in patients with low alpha-fetoprotein (AFP) levels, for whom biomarkers are scanty. Survival significantly decreased for patients with high platelet or GGT levels, even when AFP levels were low.Comparison of patients with low and high platelet levels showed that in the ≤6cm MTD group, patients with higher platelet numbers had lower total bilirubin and AST, and higher albumin, hemoglobin and percent patients with portal vein thrombosis (PVT) than those with lower platelets. Univariable logistic analysis on HCCs >6cm versus ≤6cm revealed significantly higher odds ratios for elevated blood platelet, AFP, GGT and ALKP levels. Cox regression analysis on death showed that in ≤6cm MTD patients, significant hazard ratios were for platelets, GGT, AFP, ALKP and PVT; but not for >6cm MTD patients, suggesting different mechanisms. Given the association of higher platelets with larger tumors and good liver function, their precursors are suggested to be small tumors with higher platelets and endogenous tumor factors. However, patients with low platelets and larger HCCs might have a different HCC lineage, likely associated with liver inflammation factors. Conclusions: Blood platelet levels are a potential marker for HCC phenotype and prognosis, including in patients with low AFP. They may also be a therapeutic target.

An Elbow Patch Reconstruction Technique for Narrowed Remnant Portal Veins during Right Lobe Living Donor Hepatectomy: A Rescue Surgery.

Background: Treatment of established portal vein narrowing after living donor hepatectomy is challenging. We aimed to present a new approach termed the "elbow patch reconstruction technique" to correct the narrowed remnant portal vein just or late after right lobe living donor hepatectomy. Methods: Demographic and clinical data of 12 living liver donors with narrowed remnant portal veins and treated with the "elbow patch reconstruction technique" were prospectively collected and retrospectively evaluated. Anatomic variation of the portal vein was defined in accordance with the Nakamura classification; six of the living liver donors had type A, three had type B, and the remaining three had type C. In eight of the living liver donors with a narrowed remnant portal vein, diagnosis was detected by intraoperative Doppler ultrasonography and visual inspection by experienced transplant surgeons in the living donor hepatectomy procedure. In the remaining four living liver donors, diagnosis was performed postoperatively when elevation of liver enzymes was noticed during the routine liver function test and Doppler US. The diagnosis was confirmed by multidetector computed tomography. Results: Data from nine males and three females aged 18 to 54 years were analyzed. All of the living liver donors were followed up for a median of 1710 days (min-max: 1178-4447 days; IQR: 1516 days), and none of the living liver donors had any structural or functional complications in the portal vein. Conclusions: Narrowing remnant portal veins are rare, but they are a life-threatening complication in living liver donors, and this condition requires urgent management. Image guided interventions and narrowed segment resection with end-to-end anastomosis using a vascular graft carried a potential risk for thrombosis and restenosis. To avoid these complications, we shared a technique named "elbow patch reconstruction technique". This technique can be very effective in relieving the narrowing of the remnant portal vein after right lobe living donor hepatectomy.

Enhanced role of multipair donor swaps in response to size incompatibility: The first two 5-way and the first 6-way liver paired exchanges.

A significant portion of liver transplantations in many countries is conducted via living-donor liver transplantation (LDLT). However, numerous potential donors are unable to donate to their intended recipients due to factors such as blood type incompatibility or size incompatibility. Despite this, an incompatible donor for one recipient may still be a viable donor for another patient. In recent decades, several transplant centers have introduced liver paired exchange (LPE) programs, facilitating donor exchanges between patients and their incompatible donors, thereby enabling compatible transplants. Initially, LPE programs in Asia primarily involved ABO-i pairs, resulting in 2-way exchanges mainly between blood type A and B recipients and donors. This practice has led to a modest 1% to 2% increase in LDLTs at some centers. Incorporating size incompatibility alongside blood type incompatibility further enhances the efficacy and significance of multiple-pair LPEs. Launched in July 2022, a single-center LPE program established at Inonu University Liver Transplant Institute in Malatya, Türkiye, has conducted thirteen 2-way, nine 3-way, four 4-way, two 5-way, and one 6-way LPEs until February 2024. In 2023 alone, this program facilitated 64 LDLTs, constituting 27.7% of the total 231 LDLTs performed. This paper presents the world's first two 5-way LPEs and the first 6-way LPE.

The Effect of Pringle Maneuver Applied during Living Donor Hepatectomy on the Ischemia-Reperfusion Injury Observed in the Donors and Recipients.

Background and Objectives: The aim of this study is to evaluate the clinical and laboratory changes of ischemia and reperfusion injury in the remnant livers of donors with and without Pringle maneuver. Furthermore, we evaluated the recipients who have been transplanted with liver grafts from these donors. Methods and Materials: A total of 108 patients (54 living liver donors and 54 liver recipients) who underwent donor hepatectomy and recipients who living donor liver transplantation, were included in this randomized double-blind study between February 2021 and June 2021. The donors were divided into two groups: Pringle maneuver applied (n = 27) and Pringle maneuver not applied (n = 27). Similarly, recipients with implanted liver obtained from these donors were divided into two groups as the Pringle maneuver was performed (n = 27) and not performed (n = 27). Blood samples from donors and recipients were obtained on pre-operative, post-operative 0 h day (day of surgery), post-operative 1st day, post-operative 2nd day, post-operative 3rd day, post-operative 4th day, post-operative 5th day, and liver tissue was taken from the graft during the back table procedures. Liver function tests and complete blood count, coagulation tests, IL-1, IL-2, IL-6, TNF-α, and ß-galactosidase measurements, and histopathological findings were examined. Results: There was no statistically significant difference in the parameters of biochemical analyses for ischemia-reperfusion injury at all periods in the donors with and without the Pringle maneuver. Similarly, there was no statistically significant difference between in the recipients in who received liver grafts harvested with and without the Pringle maneuver. There was no statistically significant difference between the two recipient groups in terms of perioperative bleeding and early bile duct complications (p = 0.685). In the histopathological examinations, hepatocyte damage was significantly higher in the Pringle maneuver group (p = 0.001). Conclusions: Although the histological scoring of hepatocyte damage was found to be higher in the Pringle maneuver group, the Pringle maneuver did not augment ischemia-reperfusion injury in donors and recipients that was evaluated by clinical and laboratory analyses.

Microvascular Invasion in Hepatocellular Carcinoma: Some Puzzling Facets.

BACKGROUND/AIMS: Hepatocellular carcinoma is the main type of primary liver cancer. Macroscopic vascular invasion is usually identified during imaging, whereas microvascular invasion is usually determined by histopathological evaluation. We aim to identify the association between microvascular invasion and other markers of tumor aggressiveness and to identify the role of microvascular invasion in the prognosis of patients who were treated by liver transplantation for hepatocellular carcinoma. MATERIALS AND METHODS: This is a single-center retrospective analysis of prospectively collected data. Patients who received liver transplantation for hepatocellular carcinoma were included in the study. Data were collected regarding sociodemographic variables, criteria of selection for liver transplantation, pretransplant alpha-fetoprotein, presence or absence of microvascular invasion, presence or absence of recurrence, overall survival, and disease-free survival. Data were analyzed using Statistical Package for the Social Sciences. RESULTS: Sociodemographic laboratory values and radiologic tumor characteristics were found to be similar in patients with or without microvascular invasion. Our study revealed that microvascular invasion is associated with increased recurrence, decreased diseasedfree survival, and decreased overall survival, only for patients with hepatocellular carcinoma beyond Milan criteria at the time of liver transplantation. CONCLUSION: For patients beyond Milan criteria, but not within Milan criteria, microvascular invasion plays a significant role in predicting recurrence and shorter survival after liver transplantation.

Transplant and non-transplant HCC patients at a single institution.

Background and Aim: Patients with hepatocellular carcinoma (HCC) are managed in various hospital departments, which complicates the assessment of the overall picture. In our large liver transplant institute, we evaluate all HCC patients in a weekly multi-disciplinary liver tumor board, and their data are prospectively collected in an institutional HCC database to evaluate HCC causes, tumor features, treatments, and survival. Materials and Methods: Baseline data for patients (n=1322) were prospectively recorded, including hepatitis status, routine clinical serum parameters, radiological assessment of maximum tumor diameter (MTD), tumor number, presence of macroscopic portal vein thrombosis (PVT), and serum alpha-fetoprotein (AFP) levels. Results: Cirrhosis was found in 81.1% of patients; 58.5% had hepatitis B virus (HBV), 14.9% hepatitis C virus (HCV), 8.9% cryptogenic cirrhosis, and less than 2% had alcoholism. MTD was <5 cm in 61.95% of patients, and 31.9% had PVT. The median overall survival was more than six-fold greater for the 444 liver transplant patients than for those without surgery. Transplanted patients had smaller tumors, whereas larger tumors (MTD >10 cm) were primarily in the no-surgery group. Parallel differences were found for AFP levels (highest in the no-surgery group). PVT was present in similar proportions (25.0% for transplant, 28.0% for no-surgery). The presence of cirrhosis was higher in the transplant group. MTD and levels of serum AFP, gamma-glutamyl transferase (GGT), and blood platelets were prognostic parameters for transplant. Furthermore, AFP and GGT levels were prognostic for transplanted PVT patients. Only albumin was prognostic in the no-surgery patients. Conclusion: Transplanted HCC patients have longer survival, smaller tumors, and more severe liver damage than no-surgery patients. Prognostic subsets were identified within the surgery and the PVT groups.

HBV viral load and tumor and non-tumor factors in patients with HBV-associated HCC.

Background and Aim: Several tumor and non-tumor factors affect the prognosis of hepatocellular carcinoma (HCC) patients. This study aimed to investigate the effects of hepatitis B virus (HBV) viral load on tumor and non-tumor factors in patients with HBV-associated HCC. Materials and Methods: Patients with hepatitis B and HCC who presented to the HCC council at the Faculty of Medicine, Marmara University Liver Transplantation Institute, were included in our study. Patients were divided into two groups according to the presence or absence of HBV-DNA, and it was determined whether there were differences between these two groups with respect to tumor and non-tumor parameters. Results: Comparison of serum alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), hepatitis B surface antigen (HBsAg), and C-reactive protein (CRP) levels between HBV-DNA negative and positive patients showed significant differences (respectively p<0.01, p<0.01, p<0.05, and p<0.05). A major finding was a very significant difference between the two patient groups in terms of portal vein invasion (PVI) and venous invasion (p<0.001 and p<0.01, respectively). However, there was no significant difference in metastasis or lymph node involvement between HBV-DNA negative and positive patients. Conclusion: Our findings suggest that HBV viral load plays an important role in PVI in HCC patients, and there is a significant relationship between HBV viral load and inflammation.

The Value of Electroencephalogram (EEG) Findings in the Evaluation and Treatment Management of Pediatric Acute Liver Failure.

Background Pediatric acute liver failure (PALF) is still life-threatening and requires urgent care. The presence of encephalopathy is a clinical diagnosis, but it is more difficult to diagnose in children than in adults, and an electroencephalogram (EEG) can be invaluable. The role of EEG in managing the treatment of patients with PALF, other than the identification of encephalopathy, is unknown. This study aimed to investigate patients' EEGs, which may guide in choosing the most appropriate treatment in encephalopathy children. A further aim was to investigate a new score method, based on the laboratory results, which might indicate the presence of encephalopathy in cases with PALF. Methods Medical data of 33 PALF patients followed in our clinic were reviewed retrospectively. This study included 33 patients, whose EEG recording was taken on the first day of supportive treatment due to liver failure in the pediatric intensive care unit (PICU). The EEG findings were categorized into three classes: normal, epileptic and non-epileptic paroxysmal, and background encephalopathic patterns including widespread slowing and voltage suppression. Result This retrospective study included 13 male and 20 female patients with a mean age at presentation of 4.82±4.81 months whose EEG was performed on the first day of supportive therapy for liver failure in the PICU. The EEG findings were categorized into three groups: normal, epileptic and non-epileptic paroxysms, and encephalopathic patterns including diffuse background slowing and voltage suppression. Comparing EEG findings and treatments, we found that the normal EEG group responded well to liver-supporting therapy and the rate of plasmapheresis treatment was significantly higher in the diffuse slowing group. Patients with diffuse slowing of the EEG were 9.6 times more likely to receive plasmapheresis. We found that above a cut-off of ≥7.5 for the TAI (total bilirubin, albumin, and international normalized ratio (INR)) score used in our study, the risk of developing encephalopathy increased 14.4-fold. Conclusions In PALF, EEG findings can provide findings that will help clinicians in determining treatment selection and prognosis, as well as detecting epileptic focus and encephalopathy. The TAI score can be used to assess the risk of encephalopathy in cases of PALF, when it is challenging to identify encephalopathy or when an EEG is not possible.

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.

Alpha-fetoprotein and albumin inversely relate to each other and to tumor parameters in patients with hepatocellular carcinoma.

Background and Aim: Alpha-fetoprotein (AFP), an oncofetal protein and biomarker in hepatocellular carcinoma (HCC), has unclear roles and actions.To evaluate the relationships between AFP, liver function tests, and HCC aggressiveness. Materials and Methods: A retrospective analysis of an HCC patient database was conducted to examine the relationships between baseline serum AFP values, liver function tests, and tumor characteristics. Results: Statistically significant positive trends were observed between AFP levels and both AST and bilirubin, along with negative trends between AFP and albumin. Significant correlations were also found between AFP and MTD, multifocality, and PVT. Increases in MTD, multifocality, and PVT were noted even at low AFP levels, indicating both AFP-independent and AFP-dependent processes. However, these parameter changes were minimal compared to the substantial changes in AFP levels. Relationships between AFP-related liver and tumor characteristics were found to be similar but inverse to those for albumin, with normal albumin levels associated with more favorable tumor characteristics. Additionally, serum levels of albumin and AFP were inversely related. Conclusion: AFP and albumin levels significantly, but inversely, correlate with tumor parameters, suggesting that albumin may suppress HCC functions and could serve as a potential prognostic marker.

Changing trends in the etiology of liver transplantation in Turkiye: A multicenter study.

Background and Aim: This study aimed to identify the indications for liver transplantation (LT) based on underlying etiology and to characterize the patients who underwent LT. Materials and Methods: We conducted a multicenter cross-sectional observational study across 11 tertiary centers in Turkiye from 2010 to 2020. The study included 5,080 adult patients. Results: The mean age of patients was 50.3±15.2 years, with a predominance of female patients (70%). Chronic viral hepatitis (46%) was the leading etiological factor, with Hepatitis B virus infection at 35%, followed by cryptogenic cirrhosis (24%), Hepatitis C virus infection (8%), and alcohol-related liver disease (ALD) (6%). Post-2015, there was a significant increase in both the number of liver transplants and the proportion of living donor liver transplants (p<0.001). A comparative analysis of patient characteristics before and after 2015 showed a significant decline in viral hepatitis-related LT (p<0.001), whereas fatty liver disease-related LT significantly increased (p<0.001). Conclusion: Chronic viral hepatitis continues to be the primary indication for LT in Turkiye. However, the proportions of non-alcoholic fatty liver disease (NAFLD) and ALD-related LT have seen an upward trend over the years.

Development of a model to predict the risk of early graft failure after adult-to-adult living donor liver transplantation: An ELTR study.

Graft survival is a critical end point in adult-to-adult living donor liver transplantation (ALDLT), where graft procurement endangers the lives of healthy individuals. Therefore, ALDLT must be responsibly performed in the perspective of a positive harm-to-benefit ratio. This study aimed to develop a risk prediction model for early (3 months) graft failure (EGF) following ALDLT. Donor and recipient factors associated with EGF in ALDLT were studied using data from the European Liver Transplant Registry. An artificial neural network classification algorithm was trained on a set of 2073 ALDLTs, validated using cross-validation, tested on an independent random-split sample (n=518), and externally validated on United Network for Organ Sharing Standard Transplant Analysis and Research data. Model performance was assessed using the AUC, calibration plots, and decision curve analysis. Graft type, graft weight, level of hospitalization, and the severity of liver disease were associated with EGF. The model ( http://ldlt.shinyapps.io/eltr_app ) presented AUC values at cross-validation, in the independent test set, and at external validation of 0.69, 0.70, and 0.68, respectively. Model calibration was fair. The decision curve analysis indicated a positive net benefit of the model, with an estimated net reduction of 5-15 EGF per 100 ALDLTs. Estimated risks>40% and<5% had a specificity of 0.96 and sensitivity of 0.99 in predicting and excluding EGF, respectively. The model also stratified long-term graft survival ( p <0.001), which ranged from 87% in the low-risk group to 60% in the high-risk group. In conclusion, based on a panel of donor and recipient variables, an artificial neural network can contribute to decision-making in ALDLT by predicting EGF risk.

Evaluation of Development of Nonalcoholic Fatty Pancreas Disease After Post-Endoscopic Retrograde Cholangiop ancreatography Pancreatitis in Liver Transplant Patients: Computerized Tomography Versus Ultrasound.

BACKGROUND/AIMS: Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most common serious adverse event in liver transplant patients The average incidence has been reported as 1.3%-15.1% in prospective series. In our study, we have prospectively evaluated the prevalence of nonalcoholic fatty pancreatic disease (NAFPD) after PEP via computerized tomography (CT) and determined the ratio of fatty pancreas by ultrasound imaging in liver transplant patients. MATERIALS AND METHODS: We have retrospectively analyzed 2922 patient files, and 146 patients were indicated for ERCP. PEP was observed in 32 patients. After presenting the significant association between the NAFPD and PEP, we prospectively reached 32 patients included in the study. Ten out of those patients have been performed ultrasound with regard to NAFPD. RESULTS: PEP was defined in 32 patients in whom CT was performed to investigate NAFPD. When the patients were contacted, it was observed that 12% were deceased, 71% were alive, but 15% of them were untraceable. Ultrasound has been performed on 10 of 32 patients to determine NAFPD. There was a significant reduction in post-PEP pancreas/spleen rate compared to pre-PEP pancreas/ spleen rate (P = .001). Both the pre-PEP and post-PEP pancreas-spleen difference dropped significantly (P = .002). CONCLUSION: Ultrasound imaging could be utilized as a scanning test and an alternative to evaluate and diagnose NAFPD, particularly in risky patients.

Discordance among aggressiveness characteristics of hepatocellular carcinoma: Portal vein thrombosis and multifocality, related to tumor size, but not to serum alpha-fetoprotein level.

Background and aims: Hepatocellular carcinoma (HCC) is characterized by several clinically important prognostic parameters, including portal vein thrombosis (PVT), tumor multifocality, and serum alpha-fetoprotein (AFP) levels, in addition to maximum tumor diameter (MTD). However, associations among these parameters have not been thoroughly examined. Thus, the study aimed to investigate the correlations among these HCC characteristics in a prospectively collected database. Methods: An 8080 HCC patient database derived from our weekly HCC council meeting was examined with respect to the correlations at baseline patient presentation between increases in MTD and changes in the percentage of patients with PVT, multifocality, or AFP levels. Results: The percentage of patients with PVT and with multifocality (tumor nodule numbers ≥3) significantly increased with enlarging MTD, regardless of the serum AFP level, showing the independence of PVT and multifocality on AFP. The percentage of patients with multifocality increased with enlarging MTD, in the presence or absence of PVT, showing the independence of multifocality from PVT. Therefore, discordance was found between different tumor parameters. Conclusions: A statistically significant association was found between PVT and MTD and between multifocality and MTD, all three of which are independent of AFP. PVT and multifocality appeared to be independent of each other. Although PVT and multifocality were independent of AFP, they were also augmented with high serum AFP levels. The results suggest the possibility of multiple pathways of tumor progression in the later stages of HCC development.

Liver Transplantation for Hepatocellular Carcinoma in Patients with Inherited Metabolic Liver Diseases: A Single-Center Analysis.

BACKGROUND/AIMS: Liver transplantation is an acceptable treatment for some selected hepatocellular carcinoma. We report our experience of 6 patients with liver transplantation for hepatocellular carcinoma with background inherited metabolic disease. MATERIALS AND METHODS: This is a single-center retrospective, descriptive study. Consecutive patients who underwent liver transplantation for hepatocellular carcinoma with background inherited metabolic disease were included in the study. The record of the patients was accessed, and the following data were extracted: sociodemographic variables, type of metabolic disease, date of liver transplantation, tumor characteristics, laboratory parameters, Model for End-Stage Liver Disease score, immediate- and long-term outcome after transplantation, disease-free survival, and overall survival. Data were analyzed using Statistical Package for the Social Sciences version 25.0. RESULTS: Six patients received liver transplantation for hepatocellular carcinoma with background inherited metabolic liver disease. The median age was 4.5 years. The median Model for End-Stage Liver Disease score was 29.30. The median maximum tumor diameter was 2.15 cm. Three patients had multiple tumor nodules. Half of the patients had microvascular invasion. Four of the patients had a moderately differentiated tumor. Progressive familial intrahepatic cholestasis type II is the commonest inherited metabolic disease seen in 3 patients. Median follow-up is 46.1 months. Half of the patients are currently more than 5 years post liver transplantation with no features of recurrence. The estimated survival rates at 1, 3, and 5 years are 100%, 83.3%, and 83.3%, respectively. CONCLUSION: Liver transplant for these categories of patients is associated with good disease-free and overall survival, even in the presence of some seemingly poor prognostic features.

Effect of COVID-19 Pandemic on Patients Who Have Undergone Liver Transplantation: Retrospective Cohort Study.

BACKGROUND: In liver transplant (LT) recipients, immunosuppressive therapy may potentially increase the risk of severe COVID-19 and may increase the mortality in patients. However, studies have shown conflicting results, with various studies reporting poor outcomes while the others show no difference between the LT recipients and healthy population. The aim of this study is to determine the impact of the COVID-19 pandemic on survival of LT recipients. METHODS: This is a retrospective cohort study analyzing the data from 387 LT recipients diagnosed with COVID-19. LT recipients were divided into two groups: survival (n = 359) and non-survival (n = 28) groups. A logistic regression model was used to determine the independent risk factors for mortality. Machine learning models were used to analyze the contribution of independent variables to the mortality in LT recipients. RESULTS: The COVID-19-related mortality rate in LT recipients was 7.2%. Multivariate analysis showed that everolimus use (p = 0.012; OR = 6.2), need for intubation (p = 0.001; OR = 38.4) and discontinuation of immunosuppressive therapy (p = 0.047; OR = 7.3) were independent risk factors for mortality. Furthermore, COVID-19 vaccination reduced the risk of mortality by 100 fold and was the single independent factor determining the survival of the LT recipients. CONCLUSION: The effect of COVID-19 infection on LT recipients is slightly different from the effect of the disease on the general population. The COVID-19-related mortality is lower than the general population and vaccination for COVID-19 significantly reduces the risk of mortality.

The first 4-way liver paired exchange from an interdisciplinary collaboration between health care professionals and design economists.

We report initial results of a liver paired exchange (LPE) program established at the Liver Transplant Institute at Inonu University through collaboration with design economists. Since June 2022, the program has been using a matching procedure that maximizes the number of living donor liver transplants (LDLTs) to the patients in the pool subject to the ethical framework and the logistical constraints of the program. In 1 4-way and 4 2-way exchanges, 12 LDLTs have been performed via LPE in 2022. The 4-way exchange, generated in the same match run with a 2-way exchange, is a first worldwide. This match run generated LDLTs for 6 patients, revealing the value of the capacity to carry out larger than 2-way exchanges. With only 2-way exchanges, only 4 of these patients would receive a LDLT. The number of LDLTs from LPE can be increased by developing the capacity to perform larger than 2-way exchanges in either high-volume centers or multicenter programs.

Parameters Predicting Microvascular Invasion and Poor Differentiation in Hepatocellular Carcinoma Patients with Normal Alpha-fetoprotein Level Before Liver Transplantation.

BACKGROUND/AIMS: The aim of this study is to evaluate the parameters that might be associated with pathologically diagnosed microvascular invasion and poor differentiation, using complete blood count and routine clinical biochemistry test results, in hepatocellular carcinoma patients before liver transplantation. MATERIALS AND METHODS: The data of patients who underwent liver transplantation for hepatocellular carcinoma at our institute, between March 2006 and November 2021, was researched retrospectively. RESULTS: The incidence of microvascular invasion was 28.6%, poor differentiation rate was 9.3%, hepatocellular carcinoma recurrence rate after liver transplantation was 12.1%, and median time to recurrence was 13 months, in the patients with normal alpha-fetoprotein levels. After univariate and multivariate analysis, maximum tumor diameter >4.5 cm and the number of nodules (n > 5) were found to be independent risk factors for microvascular invasion, and number of nodules >4 and mean platelet volume ≤8.6 fL were found to be independent risk factors for poor differentiation. Serum alpha-fetoprotein levels were still within the normal range at the recurrence time, in 53% of the patients who had recurrence after liver transplantation, but surprisingly were elevated in 47% of the patients at time of hepatocellular carcinoma recurrence. CONCLUSIONS: In hepatocellular carcinoma patients with normal alpha-fetoprotein levels before liver transplantation, independent risk factors of the presence of microvascular invasion were maximum tumor diameter and number of nodules, and independent risk factors of poor differentiation were mean platelet volume and number of nodules. Furthermore, serum alpha-fetoprotein levels were still normal at time of recurrence in 53% of hepatocellular carcinoma patients whose alpha-fetoprotein levels were normal before liver transplantation but were elevated in 47% of the patients at recurrence time, despite having normal levels before liver transplantation.

Evaluation of Bone Mineral Metabolism After Liver Transplantation by Bone Mineral Densitometry and Biochemical Markers.

AIM: This study aimed to evaluate the course of bone and mineral metabolism after liver transplantation (LT) in patients with chronic liver disease. METHODS: One hundred four patients who had undergone LT and had a minimum of 6 months of follow-up after LT were included in this prospective cohort study. The following parameters were evaluated for each patient: preoperative and postoperative (postoperative day [POD]30, POD90, POD180) osteocalcin, bone-specific alkaline phosphatase (BALP), type 1 collagen, beta-C-terminal end telopeptide (ß-CTx), vitamin D, parathyroid hormone (PTH), ALP, calcium, phosphate, sedimentation, and bone mineral densitometer scores (L2, L4, L total, and F total). The parameters were compared in terms of sex, presence of liver tumor (hepatocellular carcinoma [HCC; n = 19] vs non-HCC [n = 85]), and presence of autoimmune liver disease (autoimmune liver disease [ALD; n = 8] vs non-ALD [n = 96]). RESULTS: The median age of the patients (n = 81 men and n = 23 women) was 52 years (95% CI, 50-56). There was a significant change in the defined time intervals in parameters such as osteocalcin (P < .001), BALP (P < .001), ß-CTx (P < .001), vitamin D (P < .001), PTH (P < .001), ALP (P = .001), calcium (P < .001), phosphate (P = .001), L2 (P = .038), L total (P = .026), and F total (P < .001) scores. There was a significant difference in POD90 ALP (P = .033), POD180 calcium (P = .011), POD180 phosphate (P = .011), preoperative sedimentation (P = .032), and POD180 F total (P = .013) scores between both sexes. There was a significant difference in POD180 osteocalcin (P = .023), POD180 ß-CTx (P = .017), and preOP calcium (P = .003) among the HCC and non-HCC groups. Furthermore, we found significant differences in preoperative ALP (P = .008), preoperative sedimentation (P = .019), POD90 (P = .037) and POD180 L2 (P = .005) scores, preoperative (P = .049) and POD180 L4 (P = .017), and POD180 L total (P = .010) and F total (P = .022) scores between the patients with and without ALD. CONCLUSION: This study shows that the bone and mineral metabolism of the LT recipients was negatively affected after LT. In addition, we showed that bone and mineral metabolism was more prominent in patients with HCC, and bone mineral density scores were higher in patients with ALD.