Introduction: Early allograft disfunction (EAD) continues to be an important issue in liver transplantation, varying from 15 to 30%. This rate is particularly high in case of extended criteria donor (ECD) grafts due to significant ischemia-reperfusion injury leading to EAD. This injury is substantially reduced by thermoregulated oxygenated machine perfusion. The aim of the paper was to assess the use of hypothermic oxygenated machine perfusion (HOPE) in ECD liver grafts in a high-volume liver transplantation center using a specific protocol. Method: Grafts with >30% macrosteatosis and with multiple ECD (at least 2 criteria) were perfused using dual HOPE (hepatic artery and portal vein perfusion), while HOPE (portal vein perfusion only) was used for the remaining ECD grafts. The main criteria to establish graft improvement were the improvement of arterial and portal perfusion flows, with lactate under 3 mmol/L throughout the procedure. Results: Between February 2016 and February 2022, 26 ECD liver grafts were harvested from DBD (donation after brain death) donors and benefitted from HOPE. Dual HOPE was used in 8 grafts (30.7%). Criteria for graft improvement were met in all grafts except 5 (19.2%), where lactate was over 3 mmol/L, with a median of 3.6 (range 3.5-6.1). The median follow-up was 5 months (range 2-44). No EAD was encountered. Conclusion: By using a combined protocol of HOPE and dual HOPE, ECD liver grafts may be safely used by avoiding early graft dysfunction.

Budd-Chiari syndrome (BCS) represents a rare medical entity which has an estimated incidence of 0.1 to 10 people per million every year. It is defined by the obstruction of the flow in the inferior vena cava or the hepatic veins. Various classifications have been proposed. So, it can be acute or chronic and primary or secondary. The chronic form is more frequent and is characterized by signs of portal hypertension. Liver transplantation is the ultimate therapeutic management of Budd-Chiari syndrome. Primary BCS is mostly a result of hematological disorders and hypercoagulable conditions. Secondary BCS appears due to invasion or extrinsic pressure of the veins from various reasons, including hepatocellular carcinoma (HCC), liver abscesses and cysts. We presented a rare case of a young lady with Budd Chiari syndrome and IVC thrombosis who were transplanted with hepatic left lobe from her sister.

Post liver transplantation (LT) fibrosis has a negative impact on graft function. Cytokine production in the host immune response after LT may contribute to the variable CYP3A-dependent immunosuppressive drug disposition, with subsequent impact on liver fibrogenesis, together with host-related factors. We aimed to investigate whether the cytochrome P4503A5*3 (CYP3A5*3) or TBX21 genotypes impact post-LT liver fibrogenesis. Furthermore, the impact of immunosuppressants on cellular apoptosis has been evaluated using human hepatocytes harvested from cirrhotic explanted livers. We have enrolled 98 LT recipients that were followed for occurrence of liver fibrosis for at least 12 months. There was a statistically significant higher trough level of TAC in patients with homozygous CC-TBX21 genotype (7.83 ± 2.84 ng/ml) vs. 5.66 ± 2.16 ng/ml in patients without this genotype (p = 0.009). The following variables were identified as risk factors for fibrosis ≥2: donor age (p = 0.02), neutrophil to lymphocyte ratio (p = 0.04) and TBX21 genotype CC (p = 0.009). In the cell culture model cytometry analysis has indicated the lowest apoptotic cells percentage in human cirrhotic hepatocytes cultures treated with mycophenolate mofetil (MMF) (5%) and TAC + MMF (2%) whereas the highest apoptosis percentage was registered for the TAC alone (11%). The gene expression results are concordant to cytometry study results, indicating the lowest apoptotic effect for MMF and MMF + TAC immunosuppressive regimens. The allele 1993C of the SNP rs4794067 may predispose to the development of late significant fibrosis of the liver graft. MMF-based regimens have a favourable anti-apoptotic profile in vitro, supporting its use in case of LT recipients at high risk for liver graft fibrosis.

Background: The aim of this study was to investigate the impact of postoperative complications on the long-term outcomes of patients who had undergone simultaneous resection (SR) of colorectal cancer and synchronous liver metastases (SCLMs). Methods: We conducted a single-institution survival cohort study in patients with SR, collecting clinical, pathological, and postoperative complication data. The impact of these variables on overall survival (OS) and disease-free survival (DFS) was compared by log rank test. Multivariate Cox regression analysis identified independent prognostic factors. Results: Out of 243 patients, 122 (50.2%) developed postoperative complications: 54 (22.2%) major complications (Clavien–Dindo grade III–V), 86 (35.3%) septic complications, 59 (24.2%) hepatic complications. Median comprehensive complication index (CCI) was 8.70. Twelve (4.9%) patients died postoperatively. The 3- and 5-year OS and DFS rates were 60.7%, 39.5% and 28%, 21.5%, respectively. Neither overall postoperative complications nor major and septic complications or CCI had a significant impact on OS or DFS. Multivariate analysis identified the N2 stage as an independent prognostic of poor OS, while N2 stage and four or more SCLMs were independent predictors for poor DFS. Conclusion: N2 stage and four or more SCLMs impacted OS and/or DFS, while CCI, presence, type, or grade of postoperative complications had no significant impact on long-term outcomes.

Background and Objectives: Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is the leading cause of cancer-related mortality. It arises and progresses against fibrotic or cirrhotic backgrounds mainly due to infection with hepatitis viruses B (HBV) or C (HCV) or non-viral causes that lead to chronic inflammation and genomic changes. A better understanding of molecular and immune mechanisms in HCC subtypes is needed. Materials and Methods: To identify transcriptional changes in primary HCC tumors with or without hepatitis viral etiology, we analyzed the transcriptomes of 24 patients by next-generation sequencing. Results: We identified common and unique differentially expressed genes for each etiological tumor group and analyzed the expression of SLC, ATP binding cassette, cytochrome 450, cancer testis, and heat shock protein genes. Metascape functional enrichment analysis showed mainly upregulated cell-cycle pathways in HBV and HCV and upregulated cell response to stress in non-viral infection. GeneWalk analysis identified regulator, hub, and moonlighting genes and highlighted CCNB1, ACTN2, BRCA1, IGF1, CDK1, AURKA, AURKB, and TOP2A in the HCV group and HSF1, HSPA1A, HSP90AA1, HSPB1, HSPA5, PTK2, and AURKB in the group without viral infection as hub genes. Immune infiltrate analysis showed that T cell, cytotoxic, and natural killer cell markers were significantly more highly expressed in HCV than in non-viral tumors. Genes associated with monocyte activation had the highest expression levels in HBV, while high expression of genes involved in primary adaptive immune response and complement receptor activity characterized tumors without viral infection. Conclusions: Our comprehensive study underlines the high degree of complexity of immune profiles in the analyzed groups, which adds to the heterogeneous HCC genomic landscape. The biomarkers identified in each HCC group might serve as therapeutic targets.

We present a case of a 63-year-old male with HCC developed on viral cirrhosis (HVB-HVD) Child C, MELD 15 who was performed a cadaveric orthotopic liver transplantation (marginal graft previous perfused and oxygenated using the Liver Assist Device).After one month, in the context of a febrile episode, the patient was discovered a biliary stenosis associated with biliary fistulae for which he was placed a biliary stent (ERCP).The afterwards abdominal CT revealed absence of the visualization of the graft common hepatic artery and its intrahepatic branches.An arteriography in an emergency manner was performed, with administration of Actylise, and then continued with Ilomedin and Heparin administration, but with no improved imaging appearance.The patient underwent a liver retransplantation -the arterial anastomose was performed between the donor superior mesenteric artery (due to the anatomical variant: accessory right hepatic artery from superior mesenteric artery) and the recipient infrarenal aorta (using iliac cadaveric arterial graft).18 months after the retransplantation, the CT scan revealed homogeneous hepatic graft and permeable vascular axis.

Introduction: We present our 6-year experience with liver surgery and ablative techniques. Method: An observational retrospective analysis from a prospectively maintained database was performed in our department. All the patients with liver resection, liver resection combined with intraoperative ablative techniques and percutaneous ablative techniques were included from January 1st 2014 to December 31st 2020. Results: There were 249 patients analyzed: 273 patients with liver resection, 12 patients with liver resection combined with intraoperative MWA, 9 patients with open surgery MWA, 12 patients with percutaneous MWA, 1 patient with TACE and MWA, 1 patient with TACE and PEI, 10 patients with TACE, and 2 patients with PEI. Conclusion: Liver disease should be managed in specialized centers which can offer a wide range of therapeutic options. With the improvement of the surgical technique and perioperative care, including optimized postoperative complication management, and carried out by well-trained surgeons, liver surgery can be performed with low mortality and acceptable morbidity.

Background:The liver transplantation program of Fundeni Clinical Institute reached a milestone (1000 operations performed by the same team in 20 years).It is a program for both adults and children, including cadaveric and living donor liver transplantations.We analyze the indications and results to emphasize the advantages of a combined program.Methods: Between April 2000 and March 2020, 957 patients received 1,000 LTs at a single institution (Fundeni Clinical Institute, Bucharest, Romania).The demographics of donors and recipients, indications for liver transplantations, surgical procedures and results were analyzed.Results: Deceased donor liver transplantation (DDLT): 831 DDLTs in 790 patients (83.1%): whole LT in 769 patients (80.4%), split LT in 17 patients (2%), reduced-size LT in 2 patients (0.5%), auxiliary LT in 1 patient (0.1%) and domino LT in 1 patient (0.1%).Living donor liver transplantation (LDLT): 169 LDLTs in 167 patients (17.2%) using right hemiliver in 121 patients (12.6%), left lateral section in 28 patients (2.9%), left hemiliver in 9 patients (0.9%), left hemiliver with segment 1 in 6 patients (0.6%), and dual graft LDLT in 3 patients (0.3%).Overall major morbidity rate was 42.2% (422 patients), while perioperative mortality was 8.3% (79 patients).Retransplantation rate was 4.5% (43 patients).The estimated 1-, 3-, 5and 10-year overall survival rates for LT patients were 82.3%, 77.8%, 76.3% and 71.2%, respectively.Conclusions: A combined cadaveric and living donor LT program including all surgical variant LT procedures offers the possibility to increase the volume with the well-known consequences on the postoperative results.The living donor program has a positive influence on the waiting list mortality; using both cadaveric and living donors enhance the possibilities in the case of an urgent retransplantation.

Background: The purposes of the study were to determine the variations in hepatic arterial supply, to delineate the optimal methods of arterial anastomoses and reconstructions in liver transplantation and to analyse the incidence of arterial complications. Methods: The surgical anatomy of the extrahepatic arterial vascularization was investigated retrospectively in 209 donors and patients who underwent liver transplantation at Fundeni Clinical Institute (Bucharest, Romania) from January 1, 2015 to December 31, 2017. The vascular anatomy of the hepatic grafts was classified according to Michels’ description and other rare variations. Results: Anatomical variants of the classical pattern were detected in 26.3% of the livers (n = 55). The most common variant was a replaced right hepatic artery arising from the superior mesenteric artery (n = 17; 8.13%), followed by a common hepatic artery from superior mesenteric artery (n = 6; 2.87%). Arterial reconstructions were reported in 97 cases (45.5%). In recipients, used sites were intermediate: common hepatic artery (CHA) in 73.8% (n = 158), distal: proper hepatic artery (PHA) or common hepatic artery/gastro-duodenal artery bifurcation (CHA/GDA bifurcation) in 16.4% (n = 35) and proximal: coeliac trunk-splenic artery-aorta (CT–SA–A) in 9.3% (n = 20) of patients. Most common reconstructions were short graft artery (CT) on the recipient CHA (n = 33, 34.02%) and long graft artery: complex reconstruction between CT and superior mesenteric artery (SMA) - accessory right hepatic artery (RHA) from SMA on CHA (n = 12, 12.37%) and right hepatic graft artery on PHA or CHA/GDA bifurcation (n = 16, 16.49%). Conclusion: The information about the different hepatic arterial patterns, as well as establishing specific methods for arterial anastomoses and reconstructions is important in the determination of better outcomes.

Background: The need to maximize the use of donor organs and the issue of ischemia-reperfusion injury led to the use of thermoregulated oxygenated machine perfusion that improves the function of liver graft prior to transplantation. Among these methods, the HOPE (hypothermic oxygenated perfusion) protocol shows significant benefits. The aim of the paper is to analyze the early experience in using such procedure in a high-volume liver transplantation center. Methods: Normal liver grafts with cold ischemia time â?¥6 hours, marginal grafts and discarded (beyond ECD criteria) grafts were perfused using HOPE. Our selection criteria for dual HOPE (hepatic artery and portal perfusion) were steatosis, at least 3 associated ECD criteria, and discarded grafts. The main criteria to establish graft improvement were the progressive increase of arterial and portal flows, with lactate under 3 mmol/L or, even if over this value, with a decreasing trend during perfusion. Results: Whole liver grafts harvested from 28 donors between February 2016 and June 2021 benefitted from HOPE: 9 otherwise discarded grafts were assessed and considered not fit for transplantation, while the other 19 were ECD or standard grafts that were subsequently transplanted. Dual HOPE was used in 8 out of the 19 procedures (42.1%). We obtained a significant increase of arterial and portal flow (p=0.005 and p=0.001, respectively). In recipients, significant improvement of AST, ALT, INR and lactate values were recorded (p 0.001, p 0.001, p 0.001, and p=0.05, respectively). The rate of major postoperative complications (Dindo-Clavien grade 3) after LT was 26.3%, while the rate of early graft dysfunction was 15.8%. No PRS or acute rejection was recorded. The postoperative mortality rate was 15.8%. After a median follow-up of 9.3 months (range 2-44), the late major complication rate was 15.8%, without mortality. Conclusion: Machine perfusion is nowadays part of current clinical practice. This way, marginal liver grafts (DCD, ECD-DBD) may be safely used for transplantation improving the outcome, thus effectively enhance the use of a persistent scarce pool of donors. For best results, we believe that both techniques of HOPE (mono and dual HOPE) should be used based on specific selection criteria.

Background: Surgery for severe liver trauma remains challenging even for HPB surgeons, mainly due the hemodynamical instability, involvement of major vascular and biliary elements, impaired background liver and frequent anatomical variants. In this setting, despite conservative policy, major liver resection is still required in selected cases. Also salvage liver transplantation may be needed. Our study aims to analyze the results after definitive surgery for hepatic injury (HI) in a tertiary HPB center. Methods: Sixty-six patients with HI were admitted and treated in our center between June 2000 and June 2021. The median age was 29 years (mean 35, range 10-76). The male/female ratio was 50/16. According to the American Association for the Surgery of Trauma (AAST) system, HIs were grade II in one patient (1.5%), grade III in 11 pts (16.7%), grade IV in 25 pts (37.9%), and grade V in 29 pts (43.9%); no patient had grade I or VI HI. Results: Fifty-two pts (78.8%) benefitted from surgery and 14 pts (21.2%) from non-operative treatment (NOT). Perihepatic packing was previously performed in 38 pts (73.1%). Surgery consisted in hepatic resections (HR) in 51 pts (77.3%) and liver transplantation in one patient (1.5%). The rate of major HR was 51.9% (27 HRs). The overall major morbidity and mortality rates were 33.3% (20 pts) and 13.6% (9 pts), respectively. For surgery, the major complication rate was 35.3% (18 pts), while for major and minor HR were 40.7% (11 pts) and 29.2% (7 pts), respectively; the mortality rate was 15.7% (8 pts). After NOT, the major morbidity and mortality rates were 14.3% (2 pts) and 7.1% (1 pt), respectively. Conclusions: Hepatic resections, especially major ones and/or involving vascular and biliary reconstructions, as well as non-operative treatment for severe hepatic injuries, are to be carried out in tertiary HPB centers, thus minimizing the morbidity and mortality rates, while having the liver transplantation as salvage option.

Background The liver is one of the most frequently injured organs in abdominal trauma. The advancements in diagnosis and interventional therapy shifted the management of liver trauma towards a non-operative management (NOM). Nevertheless, in severe liver injuries (LI), surgical treatment often involving liver resection (LR) and rarely liver transplantation (LT) remains the main option. The present paper analyses a single center experience in a referral HPB center on a series of patients with high-grade liver trauma. Methods Forty-five patients with severe LI, that benefitted from NOM (6 pts), LRs (38 pts), and LT (1 pt) performed in our center between June 2000 and June 2019, were included in a combined prospective and retrospective study. The median age of the patients was 29 years (median 33, range 10-76), and the male/female ratio of 33/12. Almost all cases had blunt trauma, except 2 with stab wound (4.4%). Results LIs classified according to the American Association for the Surgery of Trauma (AAST) system were 13.3% (grade III), 44.2% (grade IV), and 42.2% (grade V); none were grade I, II or VI. The rate of major LR was 56.4% (22 LRs). The median operative time was 200 minutes (mean 236; range 150-420). The median blood loss was 750 ml (mean 940; range 500-6500). Overall and major complication rates were 100% (45 pts) and 33.3% (15 pts), respectively. Overall mortality rate was 15.6% (7 pts). Conclusions Severe liver trauma, often involving complex liver resections, should be managed in a referral HPB center, thus obtaining the best results in terms of morbidity and mortality.

Acute on chronic liver failure (ACLF) is a dynamic syndrome, but frequently associated with a high 1 month mortality rate. This is the first study applying the new European Association for the Study of the Liver- chronic liver failure consortium criteria to explore mortality on the waiting list (WL) and early after liver transplantation (LT) in a cohort of Romanian cirrhotic patients that improved or recovered after an episode of ACLF. To assess frequency and waitlist mortality for different grades of ACLF. An observational study was conducted; 257 patients with liver cirrhosis included on the WL between 2015 and 2017 were analyzed. The cumulative incidence of waitlist mortality or removal was calculated for combination of competing events using multivariable competing risks regression. ACLF-1 occurred in 12.07%, ACLF-2 in 7.39% and ACLF-3 in 8.56% of patients. Median Model for End Stage Liver Diseases (MELD) score at the moment of ACLF was 29. The main event while on the WL was death, followed by ACLF; patients with ACLF-3 had a significantly greater subhazard ratio for mortality of 2.25 (1.55-3.26) compared to patients with ACLF-1 or 2. LT proved to be associated with a significantly lower risk of death on the WL at 6 months after inclusion. One and 12 months post-transplant survival of patients with or without ACLF was similar (P = .77). Occurrence of an ACLF episode while on the WL is associated with a significantly high mortality rate, as well as MELD score at inclusion on the WL, renal and liver failure, presence of hepatic encephalopathy. Overall patient short and long term survival after LT is similar to non-ACLF patients in good selected cases.

Hepatocellular carcinoma (HCC) is a significant health problem. Globally is the second most common cause of cancer-associated death and the fifth most frequent neoplasm. The main risk factors for the onset of HCC are well recognized, including the presence of cirrhosis, chronic hepatitis C and hepatitis B infections and heavy alcohol consumption. In an early stage disease, there are potentially curative therapies, such as surgical resection, transplantation and loco-regional procedures. However, at the time of diagnosis, a large number of patients present an advanced stage disease, according to the Barcelona Clinic Liver Cancer (BCLC) classification. Background. Sorafenib chemotherapy is the first-line therapy for patients with hepatocellular carcinoma (HCC) in an advanced stage. The aim of this study was to evaluate prognostic factors of survival in HCC patients treated with sorafenib, in real-life clinical practice. Methods. We perform an retrospective, non-randomized study and we analyzed 162 patients with HCC who were treated with sorafenib 800 mg/day in Oncology Department of Fundeni Clinical Institute between 2009 and 2016. Results. Mortality in our patients group was more than 80%, with survival rate about 22 months and a median survival rate 13 months. The patients with liver cirrhosis has a severe evolution compared with those who has hepatitis. We found a good survival rate for HCV infected patients compared with HVB or VHB +VHD etiology. BCLC and Child-Pugh classification have an important role in overall survival.