Interaction between cadherins, vimentin, and V-set and immunoglobulin domain containing 1 in gastric-type hepatocellular carcinoma.

In hepatocellular carcinomas (HCCs), the role of the cell surface protein V-set and immunoglobulin domain containing 1 (VSIG1), which is known as a specific marker of the gastric mucosa and testis, has not yet been determined. We examined VSIG1 immunohistochemical (IHC) expression in 105 consecutive samples provided by HCC patients, along with the IHC expression of three of the biomarkers known to be involved in the epithelial-mesenchymal transition (EMT): vimentin (VIM), and E- and N-cadherin (encoded by CDH1 and CDH2 genes). IHC subcellular localization of thyroid transcription factor 1 (TTF1), in which nuclear-to-cytoplasmic translocation is known to cause a lineage shift from lung to gastric-type adenocarcinoma, was also checked. The obtained data were validated using the miRNET program. In the examined HCC samples, VSIG1 expression was observed in the cytoplasm of normal hepatocytes and downregulated in 47 of the 105 HCCs (44.76%). In 29 cases (27.62%), VSIG1 was co-expressed with cytoplasmic TTF1. VSIG1 expression was positively correlated with both E-cadherin and N-cadherin and negatively correlated with VIM (p < 0.0001). The VSIG1+/E-cadherin+/N-cadherin-/VIM phenotype was seen in 13 cases (12.4%) and was characteristic of well-differentiated (G1/2) carcinomas diagnosed in pT1/2 stages. Like pulmonary carcinomas, simultaneous cytoplasmic positivity of HCC cells for VSIG1 and TTF1 may be a potential indicator of a lineage shift from conventional to gastric-type HCC. The E-cadherin/VSIG1 complex can help suppress tumor growth by limiting HCC dedifferentiation. The miRNET-based interaction between VSIG1/VIM/CDH1/CDH2 genes might be interconnected by miR-200b-3p, a central regulator of EMT which also targets VIM and VSIG1.

Clinical significance of personalized tacrolimus dosing by adjusting to donor CYP3A-status in liver transplant recipients.

Donor's CYP3A-status (CYP3A5 genotype and CYP3A4 expression) can provide prognostic information regarding tacrolimus-metabolizing capacity of the liver graft and initial tacrolimus dosing for therapeutic blood concentrations in liver transplants. The present work prospectively investigated whether CYP3A-status guided tacrolimus therapy has any potential clinical benefit for recipients in the early postoperative period. METHODS: The contribution of preliminary assaying of donor CYP3A-status to the optimization of initial tacrolimus therapy and to the reduction of adverse events (acute rejection, infection, nephrotoxicity) was investigated in 112 liver transplant recipients (CYPtest group) comparing to 101 control patients on tacrolimus concentration guided therapy. RESULTS: The time for achieving therapeutic tacrolimus concentration was significantly reduced, confirming potential benefit of initial tacrolimus therapy adjusted to donor's CYP3A-status over classical clinical practice of tacrolimus concentration guided treatment (4 vs 8 days, P < 0.0001). Acute rejection episodes (3.6 vs 23.8%, P < 0.0001) and tacrolimus induced nephrotoxicity (8 vs 27%, P = 0.0004) were less frequent in CYPtest group than in control patients, whereas occurrence of infectious disease was not influenced by tacrolimus dosing strategy (3.6 vs 5.9% in CYPtest and control groups, P > 0.05). Acute rejection was often accompanied with tacrolimus blood concentrations lower than 10 ng mL-1 (20/24 of control and 2/4 of CYPtest patients), while nephrotoxicity was associated with high tacrolimus concentrations (>20 ng mL-1 ) in the first week after transplantation (13/27 of control and 2/9 of CYPtest patients). CONCLUSION: CYP3A-status guided therapy significantly improved the risk of misdosing induced early adverse effects (acute rejection, nephrotoxicity).

Outcomes of first versus third kidney transplantations: propensity score matching and paired subgroup analysis-a single-centre experience.

BACKGROUND: In the Eurotransplant, 12.6% of kidney transplantations are a repeat procedure. Third transplants are significantly more complex than first and second ones. We compared the results of first (PRT) versus third (TRT) transplantations. METHODS: Between 2011 and 2016, we performed 779 deceased donor adult kidney transplantations, 14.2% out of them were second, 2.6% (20) third, and 0.3% fourth. We compared the pre-, intra-, and postoperative data, kidney function, and survival rate. RESULTS: Recipients of TRT were younger (53.4 vs. 47.3 p = 0.02). HCV infection rate (20%, p = 0.00) is ten times higher. The operation time is longer (132 vs. 152 min, p = 0.02), and delayed graft function is much more frequent (22.4% vs. 60%, p = 0.00). Induction therapy was given to every TRT (7.9% vs.100%), but as a result, the rejection rate was the same (~ 15%). Hospital stay is a week longer. Patient's survival at 1, 3, and 5 years for PRT is 96.4%, 93.9%, and 91.2% and for TRT is 90%, 85%, and 78.4%, respectively (p = 0.023). TRT's odds ratio of fatal outcome is 4.35 (1.5-12.5). Graft survival at 1, 3, and 5 years for PRT is 93.1%, 91.4%, and 90.3% and for TRT is 75%, 75%, and 75%, respectively (p = 0.020). TRT's odds ratio of graft loss is 3.14 (1.1-8.9). Of PRT 85.76%, out of PRT 85.76%, while out of TRT 60% live with a functioning graft, p=0.00149. CONCLUSION: In a third transplant, both graft and patient survival are significantly inferior to primer ones. Careful selection is required to minimize the patient risk and graft loss.

[Benign liver tumours - current diagnostics and therapeutic modalities]. / A jóindulatú májdaganatok korszerû diagnosztikája és kezelési elvei.

The most common benign liver tumours are haemangiomas, focal nodular hyperplasia and hepatocellular adenoma. We perform a review of the literature and show the current diagnostic and therapeutic modalities based on the EASL Clinical Practice Guideline. With the widespread use of ultrasound, the detection of liver lesions is increased. They are usually found in women of childbearing age with atypical abdominal pain or incidentally. Contrast-enhanced US, CT or MRI are usually necessary for differential diagnosis. In atypical appearance or in malignancy suspect cases biopsy could be performed. For symptomatic patients conservative therapy can be sufficient. In haemorrhagic cases transarterial embolisation can be useful, also for tumour size decreasing before surgery. In patients with persisting symptoms, with vessel or soft tissue compression effect or in malignancy suspect cases definitive surgical treatment is advised. In men with hepatocellular adenoma primary resection is appropriate because of the higher risk for malignant transformation. As alternative treatment options radiofrequency ablation, irradiation, chemotherapy, monoclonal antibody therapy or liver transplantation are published.

Quantitative morphometric and immunohistochemical analysis and their correlates in cirrhosis--A study on explant livers.

BACKGROUND: Reproducible structural analysis was made on cirrhotic human liver samples in order to reveal potential connections between morphological and laboratory parameters. MATERIAL AND METHODS: Large histological samples were taken from segment VII of 56 cirrhotic livers removed in connection with liver transplantation. Picro Sirius red and immunohistochemically (smooth muscle actin [SMA], cytokeratin 7 [CK7], Ki-67) stained sections were digitalized and morphometric evaluation was performed. RESULTS: The Picro Sirius-stained fibrotic area correlated with the average thickness of the three broadest septa, extent of SMA positivity, alkaline phosphatase (ALP) values and it was lower in the viral hepatitis related cirrhoses than in samples with non-viral etiology. The extent of SMA staining increased with the CK7-positive ductular reaction. The proliferative activity of the hepatocytes correlated positively with the Ki-67 labeling of the ductular cells and inversely with the septum thickness. These data support the potential functional connection among different structural components, for example, myofibroblasts, ductular reaction and fibrogenesis but challenges the widely proposed role of ductular cells in regeneration. CONCLUSION: Unbiased morphological characterization of cirrhotic livers can provide valuable, clinically relevant information. Similar evaluation of routine core biopsies may increase the significance of this 'Gold Standard' examination.

Personalizing initial calcineurin inhibitor dosing by adjusting to donor CYP3A-status in liver transplant patients.

AIMS: Inter-individual variability in dose requirements of calcineurin inhibitors (CNI) has been linked to genetic polymorphisms of CYP3A enzymes. CYP3A5*3, CYP3A4*1B and CYP3A4*22 alleles of liver grafts may explain about one third of the inter-individual differences in pharmacokinetics of ciclosporin and tacrolimus in recipients. However, non-genetic factors, influencing CYP3A expression, can contribute to the variability of CYP3A function due to phenoconversion. The present study evaluated the association between CYP3A4 expression combined with CYP3A5 genotype of donor livers and recipients' CNI therapy after transplantation. METHODS: The contribution of donors' CYP3A5 genotype and CYP3A4 expression to the blood concentrations and dose requirements of CNIs was evaluated in 131 liver transplant recipients. RESULTS: The recipients with grafts from normal CYP3A4 expresser donors carrying CYP3A5*3/*3 required CNI maintenance doses more or less similar to the bodyweight-controlled starting doses (9.1 mg kg(-1) of ciclosporin and 0.1 mg kg(-1) of tacrolimus). The patients transplanted with grafts from low CYP3A4 expressers required substantial reduction (by about 50%, 4.2 mg kg(-1) of ciclosporin, 0.047 mg kg(-1) of tacrolimus, P < 0.001), while the recipients with grafts from high expressers or with grafts carrying at least one copy of the functional CYP3A5*1 allele required an increase (by about 50% [12.8-13.8 mg kg(-1)] for ciclosporin and 100% [0.21 mg kg(-1) ] for tacrolimus, P < 0.001) of the initial CNI dose for achieving target blood concentrations. CONCLUSIONS: Donor livers' CYP3A-status, taking both CYP3A5 allelic variations and CYP3A4 expression into account, can better identify the risk of CNI over- or underexposure, and may contribute to the avoidance of misdosing-induced graft injury in the early post-operative period.

Extrahepatic arteries of the human liver - anatomical variants and surgical relevancies.

The purpose of our study was to investigate the anatomical variations of the extrahepatic arterial structures of the liver with particular attention to rare variations and their potential impact on liver surgery. A total of 50 human abdominal organ complexes were used to prepare corrosion casts. A multicomponent resin mixture was injected into the abdominal aorta. The portal vein was injected with a different colored resin in 16 cases. Digestion of soft tissues was achieved using cc. KOH solution at 60-65 °C. Extrahepatic arterial variations were classified according to Michels. All specimens underwent 3D volumetric CT reconstruction. Normal anatomy was seen in 42% of cases, and variants were seen in the other 58%. No Michels type VI or X variations were present; however, in 18% of cases the extrahepatic arterial anatomy did not fit into Michels' classification. We report four new extrahepatic arterial variations. In contrast to the available data, normal anatomy was found much less frequently, whereas the prevalence of unclassified arterial variations was higher. We detected four previously unknown variations. Our data may contribute to the reduction of complications during surgical and radiological interventions in the upper abdomen.

Optimal line of hepatotomy for left lateral living donor liver transplantation according to the anatomical variations of left hepatic duct system.

Multiple duct anastomoses during LLS transplantation increase the incidence of biliary complications. The optimal plane of hepatotomy that results in the least number of bile ducts at the surface was investigated according to LHD variations. Ducts of 30 human livers were injected with resin and LHD branching on 3D-CT reconstructions were analyzed. Ducts on the virtual hepatotomy surface were estimated in three splitting lines. Variations with subtypes were described. Ia (66.7%): ducts from segments (S.) II-III form a common trunk and S.IV duct joins it. Ib (10%): common trunk formed by ducts from S.II-S.III while S.IV duct joins the common hepatic duct. IIa (16.67%): S.IV duct drains into S.III duct. IIc (3.33%): S.IV duct drains into both S.II and S.III ducts. III (3.33%): trifurcation of S.II, S.III and S.IV ducts. When the virtual hepatotomy line was on the FL, there was a single duct for the anastomosis in 30% of cases but two, three, or four ducts in 53.3%, 10%, and 3.3%, respectively. Division 1 cm to the right of the FL resulted in one duct (70%), but S.IV duct injury may occur. LLS hepatotomy should not necessarily be performed along the FL. Variations must be taken into consideration to minimize the number of biliary anastomoses during liver implantation.

[Bacterial infection after orthotopic liver transplantation]. / Bakteriális infekciók májátültetés után.

INTRODUCTION: The authors reviewed the prevalence of postoperative infections, the results of bacterium cultures, and the incidence of multidrug resistance in their liver transplanted patients during a period between 2003 and 2012. AIM: The aim of this study was to analyse risk factors and colonisations of bacterial infections. METHOD: The files of 408 patients (281 bacterium cultures) were reviewed. RESULTS: Of the 408 patients 70 had a postoperative infection (17%); 58 patients (14.2%) had positive and 12 patients (2.9%) negative bacterial culture results. Cholangitis was found in 7 cases (12.1%), abdominal infection in 17 cases (29.3%), and pulmonary infection in 28 cases (48.3%). Postoperative infection was more frequent in patients with initial poor graft function, acute renal insufficiency, biliary complication, and in those with intraabdominal bleeding. The 1-, 3- and 5-year cumulative survival of patients who had infection was 70%, 56% and 56%, respectively, whereas the cumulative survival data of patients without infection was 94%, 87% and 85%, respectively (p<0.001). Multidrug resistance was found in 56% of the positive cultures, however, the one-year survival was not different in patients who had multidrug resistance positive and negative bacterial infection (both 70.2%). CONCLUSIONS: Infection control must target the management of multidrug resistance microbes through encouraging prevention, hygienic, and isolation rules, improving the operative, transfusion, and antimicrobial policy in a teamwork setting.

Morphological evaluation of experimental autologous rectus fascia sheath vascular grafts used for arterial replacement in a dog model.

Although experimental autologous patch or tubular conduit vascular grafts made from the internal rectus fascia sheath (IRFS) have been reported in the literature, thorough morphological evaluation and verification of the histological arterialisation of such grafts are lacking. Four purpose-bred Beagle dogs were utilised to create eight arterial internal rectus fascia sheath (ARFS) grafts implanted between bisected ends of the external iliac arteries. Four out of the eight ARFS grafts were patent after three months. Haematoxylin-eosin and Azan staining verified that the grafts gained a vessel-like layered structure with the presence of large amounts of collagen fibres. Although the inner surface of the intact IRFS was originally covered with claudin-5-negative and pancytokeratin-positive mesothelial cells in control samples, the internal cells of the ARFS grafts became claudin-5 positive and pancytokeratin negative like in intact arteries. Spindle-shaped cells of the wall of ARFS grafts were α-smooth muscle actin (α-SMA) positive just like the smooth muscle cells of intact arteries, but α-SMA immunoreactivity was negative in the intact IRFS. According to these findings, the fibroblast cells of the ARFS graft have changed into myofibroblast cells. The study has proved that ARFS grafts may be used as an alternative in arterial replacement, since the graft becomes morphologically and functionally similar to the host vessel via arterialisation.

Neuroimmunomodulation in human autoimmune liver disease.

Bidirectional interaction between immune and nervous systems is considered an important biological process in health and disease. However, little is known about the mechanisms involved in their interaction in the human liver. This study examines the distribution of intrahepatic NPY, SP immunoreactive (IR) nerve fibers and their antomical relationship with immunocells containing tumor necrosis factor-α (TNF-α) and nuclear factor κB (NF-κB) in patients with autoimmune hepatitis. Liver specimens were obtained from control liver and autoimmune hepatitis patients. The immunoreactivity was determined by immunohisto- and immunocytochemistry and confocal laser microscopy. In hepatitis, the number of NPY-IR and SP-IR nerve fibers increased significantly. These IR nerve fibers were in very close contact with the lymphocytes. In healthy controls, no NPY-IR, SP-IR or NF-κB IR lymphocytes and only a few TNF-α positive cells, were observed. In hepatitis, some of the lymphocytes showed immunoreactivity for SP and NPY in the portal area. Fluorescent double-labeled immunostaining revealed that in these cells NPY did not colocalize with TNF-α or NF-κB. However, some of the SP fluorescence-positive immune cells exhibited immunostaining for p65 of NF-κB, where their labeling was detected in the nuclei. Under the electronmicroscope, these cells could be identified (lymphocytes, plasmacells and mast cells). The gap between the IR nerve fibers and immunocells was 1 µm or even less. Overexpression of SP in lymphocytes may amplify local inflammation, while NPY may contribute to liver homeostasis in hepatitis. Neural immunomodulation (SP antagonists and NPY) might be a novel therapeutic concept in the management of liver inflammation.

[Progress of the liver transplantation programme in Hungary]. / A hazai májátültetési program fejlodése.

The history of organ transplantation in Hungary dates back to 50 years, and the first succesful liver transplantation was performed in the United States in that time as well. The number of patients with end stage liver disease increased worldwide, and over 7000 patients die in each year due to liver disease in Hungary. The most effective treatment of end-stage liver disease is liver transplantation. The indications of liver transplantation represent a wide spectrum including viral, alcoholic or other parenchymal liver cirrhosis, but cholestatic liver disease and acute fulminant cases are also present in the daily routine. In pediatric patients biliary atresia and different forms of metabolic liver disorders represent the main indication for liver transplantation. The results of liver transplantation in Hungary are optimal with over 80% long-term survival. For better survival individual drug therapy and monitoring are introduced in liver transplant candidates.

[Kidney function and liver transplantation]. / Veseérintettség májátültetés során.

INTRODUCTION: In liver cirrhosis renal function decreases as well. Hepatorenal syndrome is the most frequent cause of the decrease, but primary kidney failure, diabetes mellitus and some diseases underlying endstage liver failure (such as hepatitis C virus infection) can also play an important role. In liver transplantation several further factors (total cross-clamping of vena cava inferior, polytransfusion, immunosuppression) impair the renal function, too. AIM: The aim of this study was to analyse the changes in kidney function during the first postoperative year after liver transplantation. METHOD: Retrospective data analysis was performed after primary liver transplantations (n = 319). RESULTS: impaired preoperative renal function increased the devepolment of postoperative complications and the first year cumulative patient survival was significantly worse (91,7% vs 69,9%; p<0,001) in this group. If renal function of the patients increased above 60 ml/min/1,73 m2 after the first year, patient survival was better. Independently of the preoperative kidney function, 76% of the patients had impaired kidney function at the first postoperative year. In this group, de novo diabetes mellitus was more frequently diagnosed (22,5% vs 9,5%; p = 0,023). CONCLUSIONS: Selection of personalized immunosuppressive medication has a positive effect on renal function.

[Hepatitis C virus recurrence after liver transplantation in Hungary. Trends over the past 10 years]. / Hepatitis C-vírus-fertozés kiújulása májátültetés után. Mi változott az elmúlt 10 évben?

INTRODUCTION: Management of hepatitis C virus recurrence is a challenge after liver transplantation. AIM: The aim of the authors was to analyse the outcome of liver transplantation performed in hepatitis C virus positive patients during the past ten years and to compare recent data with a previous report of the authors. METHOD: The authors retrospectively evaluated the data (donors, recipients, perioperative characteristics, patient and graft survival, serum titer of hepatitis C virus RNA, histology) of 409 patients who underwent liver transplantation between 2003 and 2012. RESULTS: 156 patients were transplanted due to hepatitis C virus associated liver cirrhosis (38%). Worse outcome was observed in these patients in comparison to hepatitis C virus negative recipients. The cumulative patient survival rates at 1, 5, and 10 year were 80%, 61%, 51% in the hepatitis C virus positive group and 92%, 85%, 79% in the hepatitis C virus negative group, respectively (p<0.001). The cumulative graft survival rates at 1, 5 and 10 year were 79%, 59% and 50% in hepatitis C virus positive and 89%, 80% and 70% in hepatitis C virus negative patients (p<0.001). Hepatitis C virus recurrence was observed in the majority of the patients (132 patients, 85%), mainly within the first year (83%). The authors observed recurrence within 6 months in 71 patients (56%), and within 3 months in 26 patients (20%). The mean hepatitis C virus recurrence free survival was 243 days. Higher rate of de novo diabetes was detected in case of early recurrence. The cumulative patient survival rates at 1, 3, 5, 10 years were 98%, 89.5%, 81% and 65% when hepatitis C virus recurrence exceeded 3 months and 64%, 53%, 30.5% and 30.5% in patients with early recurrence (p<0.001). CONCLUSIONS: Poor outcome of liver transplantation in hepatitis C virus positive patients is still a challenge. Hepatitis C virus recurrence is observed earlier after liver transplantation in comparison with a previous report of the authors. De novo diabetes occurs more frequently in case of early recurrence. Despite an immediate start of antiviral treatment, early recurrence has a significant negative impact on the outcome of transplantation.

Estimation of drug-metabolizing capacity by cytochrome P450 genotyping and expression.

Many undesired side effects or therapeutic failures of drugs are the result of differences or changes in drug metabolism, primarily depending on the levels and activities of cytochrome P450 (P450) enzymes. To assess whether P450 expression profiles can reflect hepatic drug metabolism, we compared P450 mRNA levels in the liver or peripheral leukocytes with the corresponding hepatic P450 activities. A preliminary P450 genotyping for the most frequent polymorphisms in white populations (CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, CYP2D6*3, CYP2D6*4, CYP2D6*6, and CYP3A5*3) was carried out before P450 phenotyping, excluding the donors with nonfunctional alleles of CYP2C9, CYP2C19, and CYP2D6 and those with a functional CYP3A5*1 allele from a correlation analysis. The hepatic mRNA levels of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 displayed a strong association with P450 activities in the liver, whereas the expression of CYP1A2, CYP2C9, CYP2C19, and CYP3A4 in leukocytes was proven to reflect the hepatic activities of these P450 species. The leukocytes were found to be inappropriate cells for the assessment of hepatic CYP2B6 and CYP2D6 activities. Combining the results of P450 genotyping and phenotyping analyses, patients' drug-metabolizing capacities can be estimated by the P450 expression in the liver and in leukocytes with some limitations. Patients' genetic and nongenetic variations in P450 status can guide the appropriate selection of drugs and the optimal dose, minimizing the risk of harmful side effects and ensuring a successful outcome of drug therapy.

[Hepatic encephalopathy and liver transplantation]. / Hepaticus encephalopathia és májátültetés.

About 6500-7000 people/year die in Hungary due to liver cirrhosis which is often complicated with hepatic encephalopathy (HE). While conventional interpretation is that hepatic encephalopathy is a consequence of high blood ammonia level, recent data indicate that the degree of encephalopathy is related to systemic inflammatory response during decompensation. In this review the authors overview and analyze the latest treatment modalities of hepatic encephalopathy based on most recent findings. They found that frequently used evidence based treatment which apply metronidazole, neomycine or disaccharides was only partially effective in clinical studies. Use of rifaximine only is supported by grade I evidence, however it is quite a costly drug. The authors could not identify a generally accepted guideline for the treatment of HE with a systematic literature review, although it has significant effect on survival after liver transplantation. Therefore, the authors urge to develop a consensus guideline for the treatment of HE.

What Makes Cirrhosis Irreversible?-Consideration on Structural Changes.

Several studies have shown that liver fibrosis, and even cirrhosis can be reversed, disproving the old "dogma" that cirrhosis is irreversible. In addition to scaring, vascular alterations appear to be critically important in the progression of chronic liver diseases. To overcome the "tipping-point" of cirrhosis, we need to understand in depth what might make it irreversible in some cases. Morphologically, the initial, as well as the advanced stages of cirrhosis are characterized by specific structural changes. The hallmark of the initial stage is the division of the original liver parenchyma by centro-central or porto-portal septa. No significant vascular changes are observed in this stage. The advanced stage is characterized by several morphological alterations: (i) The main feature is the parenchymal extinction, with intact portal vein branches, hepatic artery branches, and biliary ductules; (ii) In the extinct areas we observed numerous loops in the ductular network, indicating the disruption of the hepato-biliary junctions; (iii) Although the ductular progenitor cells are able to generate hepatocytes via the budding process, the newly formed hepatocyte nodules cannot re-establish the original lobular architecture due to their disorganized growth. In conclusion, this regenerative process characteristic for the advanced stage, contributes to circulatory disorders, perpetuates parenchymal injury and may lead to the irreversibility of cirrhosis.

Graft Arterial Dissection and Thrombosis After Kidney Transplantation With Undiagnosed Fibromuscular Dysplasia From a Deceased Donor: Case Report and Review.

BACKGROUND: Fibromuscular dysplasia (FMD), a relatively frequent arterial deformity with an estimated prevalence of 2% to 6% has been sporadically reported during deceased donor kidney donations. Only 8 case reports are available in the previous literature. CASE PRESENTATION: In our work, implantation of 2 kidneys from the same deceased donor with macroscopically evident and later histologically confirmed FMD are presented, one of which ended up as acute arterial complication. Renal arteries were cut short to allow safe implantation, but arterial dissection and thrombosis led to graft loss in the early perioperative period in the latter case. CONCLUSIONS: Although resection of the arterial segments affected by FMD as a routine may allow implantation, macroscopically healthy-looking arteries might still be affected and thus carry elevated postoperative risk. The aim of our case report is to make proposal for an onsite diagnosis of FMD in case of clinical suspicion.

Optimizing Survival for Hepatocellular Carcinoma After Liver Transplantation: A Single-Center Report and Current Perspectives.

BACKGROUND: Hepatocellular carcinoma (HCC) is the leading primary liver tumor and a main indication for transplant. Transplant criteria are based on clinicopathologic features, meanwhile adequate downstaging and molecular mechanisms are getting more attention in evolving therapeutic algorithm of HCC. The aim of our study was to overview the results of the Hungarian Liver Transplant Program in the field of HCC and introduce new aspects of personalized treatment options. METHODS: We performed retrospective analysis of survival and tumor recurrence of HCC-associated liver transplant recipients between October 2013 and December 2020. Patients were categorized in Milan criteria (MC), beyond MC but within University of California, San Francisco (UCSF), and beyond UCSF criteria groups after pathologic examination of the explanted liver. Demographic data and preoperative locoregional treatments were assessed. RESULTS: A total of 529 primer liver transplants were performed, 88 because of HCC. A total of 87 patients had underlying cirrhosis because of hepatitis C (54%), alcohol-related liver disease (33.7%), hepatitis B (4.5%), or unknown etiology. A total of 55.6% of the patients had at least one locoregional treatment. A total of 67.4% of the patients were within MC, 5.6% were within UCSF criteria, and 27% were beyond UCSF criteria. The 1-, 3-, and 5-year survival rates were 80%, 79%, and 75%. The outcome was better in early-stage tumors, but the difference was not significant (P = .745) CONCLUSIONS: The favorable survival in our department legitimates the strict transplant criteria of HCC. Adequate locoregional therapy as downstaging can expand recipient pool. Molecular tumor profiling may lead to personalized treatment of HCC.

Evolution of liver transplant waiting list in Hungary between 1995 and 2019. / Májvárólista 1995-2019: a hazai adatok nemzetközi összehasonlítása.

Összefoglaló. Bevezetés: A májtranszplantációs program részeként 1995 óta létezik folyamatosan vezetett várólista Magyarországon. Célkituzés: A legfontosabb várólista-paraméterek megállapítása és nemzetközi összehasonlítása. Módszer: A szerzok az 1995. január 1. és 2019. december 31. között elso májátültetés céljából várólistára helyezett betegek adatait elemezték. Eredmények: Összesen 1722 beteget helyeztek várólistára, 1608 felnottet, 114 gyermeket. A férfiak aránya 51,2%, az átlagéletkor 45,6 év. Az évente regisztrált új jelöltek száma 25 év során közel az ötszörösére emelkedett. A listára helyezés leggyakoribb indikációja a víruseredetu cirrhosis volt (n = 451). Ezt követte a cholestaticus (n = 314) és az alkoholos májbetegség (n = 264). Rosszindulatú daganat, 82%-ban hepatocellularis carcinoma miatt 215 beteget regisztráltak. Krónikus betegségekben az átlagos Model for End-Stage Liver Disease pontszám a regisztráláskor 13,5 volt. A 2018. december 31-ig listára helyezettek (n = 1618) 61%-a részesült májátültetésben, 24%-a várakozás közben meghalt, 7%-a a mutétre alkalmatlanná vált. A mutét elotti medián várakozási ido 248 nap volt a krónikus és 2 nap az akut betegek listáján. A transzplantált tumoros betegek (n = 132) szignifikánsan rövidebb ideig vártak mutétre (medián 115,5 nap), mint a többi krónikus beteg (n = 803, medián 282 nap). Az Eurotransplanthoz való csatlakozás utáni idoszakban (2013. július 1. és 2018. december 31. között) a transzplantációs arány növekedett (67%), a várólista-halálozás (meghaltak + mutétre alkalmatlanná váltak) 24%-ra csökkent. Megbeszélés: A várólista folyamatos bovülése hozzájárult a hazai májátültetési program fejlodéséhez. A hazai várólista diagnózis szerinti összetétele a mások által közöltekkel nagyrészt egyezik. A transzplantáltak aránya a nemzetközi átlagnak megfelelo. A várólista-halálozás és a mutét elotti várakozási ido a magyarországinál alacsonyabb donációs aktivitású vagy jelentosen nagyobb várólistával rendelkezo országokéhoz hasonló. Következtetés: Várólista-paramétereink javításához a transzplantációk számának további növelése szükséges. Orv Hetil. 2022; 163(8): 301-311. INTRODUCTION: The Hungarian liver transplant program including waiting list started in 1995. OBJECTIVE: Evaluation of the wait-list parameters and comparing them with those in the literature. METHOD: Data of patients listed for primary liver transplantation between 1995 and 2019 were analyzed. RESULTS: A total of 1722 recipient candidates were registered on the liver transplant waiting list: 1608 adults (51.2% men) with mean age of 45.6 year and 114 patients aged <18 year. Virus-induced cirrhosis was the leading indication of listing (n = 451) and cholestatic liver diseases (n = 314) and alcoholic cirrhosis (n = 264) thereafter. The mean Model for End-Stage Liver Disease score was 13.5 for those with chronic disease. 61% of 1618 patients listed before December 31, 2018 underwent liver transplantation and 31% were removed from the wait-list for death or clinical deterioration. After joining Eurotransplant (period of 01. 07. 2013-31. 12. 2018), the transplant rate was 67%, the waiting list removal due to death/too sick for operation decreased to 24%. The median waiting time till transplantation was 248 days for those on elective and 2 days on acute list. Patients grafted with malignancy (n = 132) waited significantly shorter time than those with chronic non-malignant liver disease (median 115.5 versus 282 days). DISCUSSION: The composition of our waiting list by primary liver disease was similar to that of countries with large burden of hepatitis C. Transplant rate was average, wait-list mortality and waiting time were in line with those observed in low-donation countries or in the case of large volume waiting list. CONCLUSION: Listing of increasing the number of patients contributed to evolution of our liver transplant program. To improve our parameters, increasing transplant activity is warranted. Orv Hetil. 2022; 163(8): 301-311.