Cirrhotic Liver of Liver Transplant Recipients Accumulate Silver and Co-Accumulate Copper.

Silver-based materials are widely used in clinical medicine. Furthermore, the usage of silver containing materials and devices is widely recommended and clinically approved. The impact on human health of the increasing use of silver nanoparticles in medical devices remains understudied, even though Ag-containing dressings are known to release silver into the bloodstream. In this study, we detected a widespread and sometimes significant silver accumulation both in healthy and sick liver biopsies, levels being statistically higher in patients with various hepatic pathologies. 28 healthy and 44 cirrhotic liver samples were investigated. The median amount of 0.049 ppm Ag in livers was measured in cirrhotic livers while the median was 0.0016 ppm for healthy livers (a more than 30-fold difference). The mean tissue concentrations of essential metals, Fe and Zn in cirrhotic livers did not differ substantially from healthy livers, while Cu was positively correlated with Ag. The serum levels of gamma-glutamyl transpeptidase (GGTP) was also positively correlated with Ag in cirrhotic livers. The increased Ag accumulation in cirrhotic livers could be a side effect of wide application of silver in clinical settings. As recent studies indicated a significant toxicity of silver nanoparticles for human cells, the above observation could be of high importance for the public health.

Hepatic abscess: a rare complication after liver transplant.

BACKGROUND: This study was conducted to evaluate the predisposing factors, microbiology, treatment, and outcomes associated with hepatic abscess, a rare but serious complication which may accur after an orthotopic liver transplant (OLT). METHODS: This was a retrospective study based on a prospectively maintained database of 1100 patients who underwent OLT at the Medical University of Warsaw. An abscess was defined on imaging as solitary or multiple localized parenchymal collections in patients with clinical signs of infection, with or without positive cultures from blood or abscess aspirate. RESULTS: Fifteen patients (1.4%) developed hepatic abscess, including 12 (80%) with multiple abscesses. Predisposing factors included biliary pathology (eight patients), hepaticojejunostomy (six patients), and hepatic artery stenosis or thrombosis (five patients). Ten patients were treated using multiple percutaneous and endoscopic interventional procedures in addition to antimicrobial treatment whereas five were treated solely with antibiotics. Five patients (33.3%) died due to multi-organ failure secondary to abscess treatment, including one unsuccessful case of re-OLT. Thirteen patients (87%) had bacterial growth and five (33.3%) had fungal growth in their blood or abscess aspirates. CONCLUSIONS: Hepatic abscess after liver transplantation may be treated successfully with percutaneous and endoscopic intervention, along with antibiotics according to the results of microbial cultures of blood and/or abscess aspirates.

Combination of morphologic criteria and α-fetoprotein in selection of patients with hepatocellular carcinoma for liver transplantation minimizes the problem of posttransplant tumor recurrence.

BACKGROUND: Serum α-fetoprotein concentration (AFP) might be a useful addition to morphologic criteria for selecting patients with hepatocellular carcinoma (HCC) for liver transplantation (LT). The aim of this study was to evaluate the role of AFP in selecting HCC patients at minimal risk of posttransplant tumor recurrence in the setting of existing criteria. METHODS: This retrospective cohort study was based on 121 HCC patients after LT performed at a single institution. AFP was evaluated as a predictor of posttransplant tumor recurrence with respect to fulfillment of the Milan, University of California, San Francisco (UCSF), and Up-to-7 criteria. RESULTS: There was a nearly linear association between AFP and the risk of HCC recurrence (p < 0.001 for linear effect; p = 0.434 for nonlinear effect). AFP predicted HCC recurrence in patients (1) beyond the Milan criteria (p < 0.001; optimal cutoff 200 ng/ml); (2) within the UCSF criteria (p = 0.001; optimal cutoff 100 ng/ml) and beyond them (p = 0.015; optimal cutoff 200 ng/ml); and (3) within the Up-to-7 criteria (p = 0.001; optimal cutoff 100 ng/ml) and beyond them (p = 0.023; optimal cutoff 100 ng/ml) but not in patients within the Milan criteria (p = 0.834). Patients within either UCSF and Up-to-7 criteria with AFP level <100 ng/ml exhibited superior (100 %) 5-year recurrence-free survival-significantly higher than those within UCSF (p = 0.005) or Up-to-7 (p = 0.001) criteria with AFP levels higher than the estimated cutoffs or beyond with AFP levels less than the estimated cutoffs. CONCLUSIONS: Combining the UCSF and Up-to-7 criteria with an AFP level <100 ng/ml is associated with minimal risk of tumor recurrence. Hence, this combination might be useful for selecting HCC patients for LT.

Early post-operative prediction of morbidity and mortality after a major liver resection for colorectal metastases.

BACKGROUND: An early prediction of poor outcomes is essential in the management of patients after a liver resection. The aim of this study was to evaluate the role of selected biochemical parameters on post-operative day 1 (POD 1) in the prediction of morbidity and mortality after a liver resection for colorectal metastases. METHOD: This retrospective study was based on 236 major liver resections for colorectal metastases performed between 2006 and 2011. Results of biochemical tests of blood samples obtained on POD 1 were assessed as predictors of primary outcome measures (hepatic and overall morbidity, 90-day mortality) using multiple regression and receiver-operating characteristics (ROC). RESULTS: Hepatic morbidity, overall morbidity and 90-day mortality rates were 18.6%, 28.0% and 4.7%, respectively. On the basis of multiple regression analysis and comparisons of the prediction models, serum bilirubin was selected for the prediction of hepatic (>2.05 mg/dl, sensitivity 69.2%, specificity 71.2%) and overall (>2.05 mg/dl, sensitivity 61.1% and specificity 71.2%) morbidity, and aspartate aminotransferase (AST) was selected for the prediction of 90-day mortality (>798 U/l, sensitivity 62.5% and specificity 90.4%). DISCUSSION: Biochemical analyses of blood on POD1 enables stratification of patients into low- and high-risk groups for negative outcomes, with serum bilirubin associated with overall and hepatic morbidity and AST associated with mortality.

Results of liver transplantation in the Department of General, Transplant and Liver Surgery at the Medical University of Warsaw in patients with chronic hepatitis B and C viruses infection.

INTRODUCTION: Cirrhosis related to hepatitis C virus (HCV) and hepatitis B virus (HBV) infection is the most frequent indication for liver transplantation worldwide. Progress in prophylaxis of posttransplant HBV recurrence has led to major improvements in long-term outcomes of patients after liver transplantation. Conversely, impaired posttransplant survival of patients with HCV infection was reported in several studies, mainly due to recurrence of viral infection. The purpose of this study was to compare long-term results of liver transplantation between patients with HBV monoinfection, HCV monoinfection and HBV/HCV coinfection. MATERIAL AND METHODS: A total of 1090 liver transplantations were performed in the Department of General, Transplant and Liver Surgery in cooperation with the Department of Immunology, Internal Medicine, and Transplantology at the Transplantation Institute Medical University of Warsaw between December 1994 and May 2012. After exclusion of patients with cirrhosis of non-viral etiology, patients with malignant tumors, and patients with acute liver failure, the final study cohort comprised 209 patients with HBV (HBV+/HCV- subgroup; n = 56) or HCV (HBV-/HCV+ subgroup; n = 119) monoinfection or HBV/HCV coinfection (HBV+/HCV+; n = 34). These subgroups of patients were compared in terms of long-term results of transplantations, defined by 5-year patient and 5-year graft survival estimates. RESULTS: Overall and graft survival rates after 5-years for the whole study cohort were 74.5% and 72.6%, respectively. Five-year overall survival was 70.4% for patients within the HBV+/HCV- subgroup, 77.8% for patients within the HBV-/HCV+ subgroup, and 68.5% for patients within the HBV+/HCV+ subgroup. The corresponding rates of graft survival were 67.0%, 76.3%, and 68.5% for patients within the HBV+/HCV-, HBV-/ HCV+, and HBV+/HCV+ subgroups, respectively. Observed differences were non-significant, both in terms of overall (p = 0.472) and graft (p = 0.461) survival rates. CONCLUSIONS: Both overall and graft survival rates after liver transplantations performed in the Department of General, Transplant and Liver Surgery in cooperation with the Department of Immunology, Internal Medicine, and Transplantology at the Transplantation Institute Medical University of Warsaw in patients with HBV and HCV infection are comparable to those reported by other European and American centers. In contrast to other studies, obtained results do not confirm the negative impact of HCV infection on long-term outcomes of patients.

Clinical Implication of Plasma CD163 in Patients With Acute-on-Chronic Liver Failure.

BACKGROUND: It was postulated that CD163 plasma level should be incorporated into existing predictive systems to improve prognostic performance in patients with acute-on-chronic liver failure (ACLF). PATIENTS AND METHODS: Plasma CD163 was assessed in 24 consecutive patients with ACLF (17 male, 7 female; mean age 54.9 years; 50% with alcohol-related liver disease) and compered with the existing scoring tools to predict the availability of transplantation or survival without liver transplant (LT). RESULTS: There were no differences in plasma CD163 levels between graft recipients and deceased patients on the waiting list or transplant survivors vs nonsurvivors. CD163 did not correlate with CLIF-ACLF, CLIF Consortium organ failure score (CLIF-OF), and ACLF grades (all P < .05). However, sequential organ failure assessment (SOFA), CLIF Consortium acute-on-chronic liver failure score (CLIF-C) ACLF, and CLIF-C OF scores correlated significantly with mortality (P < .01) in contrast to Child-Pugh scale and Model for End-Stage Liver Disease score (all P > .05). Transplanted survivors and deceased individuals differed robustly with respect to the SOFA and CLIF-SOFA scores and the CLIF-C OF, CLIF-C Grade, and CLIF-C ACLF scales (all P < .05). CLIF-C performed well in ACLF prognostication with an area under receiver operating characteristic curve (AUROC) 0.893 (95% CI, 0.766-1), surpassing in that respect CD163 with AUROC of 0.664 (95% CI, 0417-0.911). CONCLUSIONS: Our preliminary results showed that the plasma CD163 level in patients with ACLF played only a minor role in predicting LT futility/benefit, with no impact on the narrow transplant window. Moreover, to optimize LT outcomes, newly developed CLIF-C scales showed superior predictive value.

Actuarial Patency Rates of Hepatico-Jejunal Anastomosis after Repair of Bile Duct Injury at a Reference Center.

Background: Bile duct injury complicates patients' lives, despite the subsequent repair. Repairing the injury must restore continuity of the bile tree and bring the patient into a state of cure referred to as "patency". Actuarial primary or actuarial secondary patency rates, depending on whether the patient underwent primary or secondary repair of injury, are proposed to be a proper metric in evaluating outcomes. This study was undertaken to assess outcomes of 669 patients with bile duct injuries Strasberg D and E type referred to the department from public surgical wards between 1990 and 2020. In 442 patients, no attempt was made to repair prior to a referral, and in 227 an attempt to repair was made which failed. Methods: Observations were summarized on December 31st, 2020. The retrospective analysis included: primary patency attained (Grade A result), secondary patency attained (Grade C result), patency loss, and actuarial patency rates of the bile tree at 2, 5, and 10 years. Results: Twenty-five (3.7%) patients died after repair surgery. Actuarial patency rates at 2, 5, and 10 years of follow-up were 93%, 88%, and 74% or 86%, 75%, and 55% in patients attaining Grade A and Grade C outcomes, respectively (p < 0.001). Conclusion: Bile duct injury stands out as a surgical challenge, requiring specialized management at a referral center. Improper proceeding after an injury is the factor leading to faster loss of anastomotic patency.

Lymphangioma Cavernosum with a Rare Location.

Lympangioma cavernosum in the abdominal cavity is a rare benign tumour. In most cases, such tumours are diagnosed in the oral cavity and neck. The aim of this paper is to present our clinical observations and review of existing literature to draw attention to this disease. A 25-year-old woman was admitted to our department for a symptomatic tumour in the lesser curvature of the stomach. The patient was first operated on as a three-year-old child because the tumour extended from the back wall of the stomach to the gastro-colonic ligament. The medical records showed that it was a benign tumour; however, no diagnosis was specified. No symptoms were observed for 22 years. Currently, the patient is admitted for epigastric pain. Abdominal computed tomography revealed an extensive mass located between the left segments of the liver and the lesser curvature of the stomach. The patient was operated on, and the tumour was completely removed. The patient's postoperative course was uneventful. Histopathological examination of the lymphangioma cavernosum was performed. Two months after the operation, the patient did not report any complaints.

Intraductal papillary neoplasm of the bile duct - A comprehensive review.

BACKGROUND: Intraductal papillary neoplasm of the bile ducts is a rare tumor type. Management decisions are currently based upon a small case series. The authors have large own experience with IPNB. OBJECTIVE: The review aims at reporting on clinicopathological features of IPNB in order to provide guidance for management. METHODS: We searched PubMed, Medline, Microsoft Academic and Embase databases to identify studies of relevance. The analysis of own experience was also included. RESULTS: We analyzed 59 retrospective series and 25 cases from authors' clinical experience. The main sign was jaundice and cholangitis, 33% and 48%, respectively. CT's were performed in 63-76% and MR in 40-56%. Intraductal mass was found in 31-32% and duct dilatation in 27-30%. Endoscopic Retrograde Cholangio-Pancreatography (ERCP) was performed in 48-62%. IPNB with invasive carcinoma was found in 35.7-60% and IPNB with intraepithelial neoplasia in 36-60%. Histopathological confirmation before surgery was rare. The main treatment of IPNB is resection, in our material, both, hepatectomy and hepatectomy plus bile duct resections were performed in 40% of patients. The percentage of postoperative complications was 20%. The 5-year survival rate of all IPNB's patients was 53.6%; in patients with associated invasive carcinoma - 22.2% and without invasive carcinoma - 100% (p â€‹= â€‹0.001). CONCLUSIONS: Early surgery is advisable for radiologically suspected IPNB. The results of treatment depend on histopathology. They are worse at intraductal invasive carcinoma than at neoplasm with neoplasia.

PEComa-A Rare Liver Tumor.

PEComa (perivascular epithelioid cell tumor) is a rare liver tumor. Decisions regarding patient management are currently based on a few small case series. The aim of this study was to report the clinicopathological features of PEComa in order to provide guidance for management, complemented by our own experience. This retrospective observational study included all patients with PEComa who underwent surgical treatment in two departments between 2002 and 2020. A total of 20 patients were diagnosed with PEComa following histopathological examination. The age of the patients ranged from 21 to 73 years. The majority of patients were women (85%). In most patients, the tumors were incidental. In diagnostic studies, PEComas with high arterial vascularization have been described. Liver resection was the treatment of choice. There was only one postoperative complication. During histopathological evaluation, tumors were composed mostly of epithelioid cells, rarely with spindle cell components, thick-walled vessels, and adipocytes in different proportions. Melanocytic markers (HMB45, MelanA) and at least one smooth muscle marker were expressed in all tumors. Features suggestive of malignancy were found in three cases. In conclusion, PEComa is a rare liver tumor that is usually diagnosed incidentally. In radiological studies, tumors with high arterial vascularization are observed. Liver resection is the treatment of choice.

Multimodal management of neuroendocrine liver metastases.

BACKGROUND: The incidence of neuroendocrine tumours (NET) has increased over the past three decades. Hepatic metastases which occur in up to 75% of NET patients significantly worsen their prognosis. New imaging techniques with increasing sensitivity enabling tumour detection at an early stage have been developed. The treatment encompasses a panel of surgical and non-surgical modalities. METHODS: This article reviews the published literature related to management of hepatic neuroendocrine metastases. RESULTS: Abdominal computer tomography, magnetic resonance tomography and somatostatin receptor scintigraphy are widely accepted imaging modalities. Hepatic resection is the only potentially curative treatment. Liver transplantation is justified in highly selected patients. Liver-directed interventional techniques and locally ablative measures offer effective palliation. Promising novel therapeutic options offering targeted approaches are under evaluation. CONCLUSIONS: The treatment of neuroendocrine liver metastases still needs to be standardized. Management in centres of expertise should be strongly encouraged in order to enable a multidisciplinary approach and personalized treatment. Development of molecular prognostic factors to select treatment according to patient risk should be attempted.

Fulminant liver failure following a marathon: Five case reports and review of literature.

BACKGROUND: The growing popularity of marathon and half-marathon runs has led to an increased number of patients presenting with exertion-induced heat stroke. Mild hepatic involvement is often observed in these patients; however, fulminant liver failure may occur in approximately 5% of all cases. Liver transplantation is a potentially curative approach for exertion-induced liver failure, although there is a lack of consensus regarding the criteria and optimal timing of this intervention. CASE SUMMARY: This paper describes 5 patients (4 men and 1 woman) who were referred to the department where this study was performed with the diagnosis of exertion-induced acute liver failure. Three patients underwent liver transplantation, 1 recovered spontaneously, and 1 patient died on day 11 following the exertion. CONCLUSION: Exertion-induced heat stroke may present as fulminant liver failure. These patients may recover with conservative treatment, may require liver transplantation, or may die. No definitive criteria are available to determine patient suitability for a conservative vs surgical approach.

Long-Term Health-Related Quality of Life in Living Liver Donors.

BACKGROUND In living donor liver transplantation (LDLT), 2 patients undergo surgery, and the advantages and disadvantages for both patients should be considered. This study evaluated the long-term quality of life in living liver donors, and its impact on their activities of daily living focusing on mood and mental health. MATERIAL AND METHODS In total, 101 living liver donors (69 female and 32 male patients, median age of 36.8 years) were surveyed at a median time of 61.8 months after liver donation (range 7-169 months). The generic Short Form Health Survey (SF-36), the Patient Health Questionnaire 9 (PHQ-9), and the Questionnaire of Physical Activity (IPAQ) were used. The results of SF-36 were compared to a matched control group (n=72) using the Wilcoxon test; the SF-36, the PHQ-9, and the IPAQ scores were analyzed using Spearman's rank correlation. Linear regression model was used to check for dependencies between variables of interest. The IPAQ results were compared between the study group and the general Polish population. RESULTS There were no significant differences in the SF-36 domains between the study group and control group except body pain, which was higher in the living liver donor group (P<0.05). In 30.6% of patients, the PHQ-9 survey revealed mood disturbances. The PHQ-9 scores were higher in female-donors (P<0.05). Both summary scores of the SF-36 correlated to the PHQ-9 (P<0.001). In 89.1% of patients, physical activity was below the population norm and was lower in female donors than in male donors (P<0.01). CONCLUSIONS LDLT had no impact on donors' physical and mental health. Physical activity of living liver donors was lower than that of the general population. The SF-36 and the IPAQ measures seem to be reliable in the care of living liver donors. The PHQ-9 survey results and the inclination to depression of female living liver donors requires further study.

Goblet cell carcinomas of the appendix: rare but aggressive neoplasms with challenging management.

Goblet cell carcinomas (GCC) are a rare, aggressive sub-type of appendiceal tumours with neuroendocrine features, and controversy exists with regards to therapeutic strategy. We undertook a retrospective review of GCC patients surgically treated at two tertiary referral centres. Clinical and histopathological data were extracted from a prospectively maintained database. Survival analyses utilised Kaplan-Meier methodology. Twenty-one patients were identified (9 females). Median age at diagnosis was 55 years (range 32-77). There were 3, 6 and 9 grade 1, 2 and 3 tumours, respectively. One, 10, 5 and 5 patients had stage I, II, III and IV disease at diagnosis, respectively. There were 8, 10 and 3 Tang class A, B and C tumours, respectively. Index operation was appendectomy (n = 12), right hemicolectomy (n = 6) or resections including appendix/right colon, omentum and the gynaecological system (n = 3). Eight patients underwent completion right hemicolectomy. Surgery for recurrence included small bowel resection (n = 2), debulking with peritonectomy and heated intraperitoneal chemotherapy, and hysterectomy and bilateral salpingo-oophorectomy (all n = 1). Median follow-up was 30 months (range 2.5-123). One-, 3- and 5-year OS was 79.4, 60 and 60%, respectively. Mean OS (1-, 3-, and 5-year OS) for Tang class A, B and C tumours were 73.1 months (85.7, 85.7, 51.4%), 83.7 months (all 66.7%) and 28.5 months (66.7, 66.7%, not reached), respectively. Chromogranin A/B and 68Ga-DOTATATE PET/CT were not useful in follow-up, but CEA, CA 19-9, CA 125 and 18F-FDG PET/CT identified tumour recurrence. GCC must be clearly discriminated from relatively indolent appendiceal neuroendocrine neoplasms. 18F-FDG PET/CT and CEA/CA19-9/CA 125 are useful in detecting recurrence of GCC.

Serum levels of HGF, IL-6, and TGF-α after benign liver tumor resection.

PURPOSE: Literature is void of data on the relationship between pre- and postoperative levels of hepatocyte growth factor (HGF), interleukin 6 (IL-6), and tumor growth factor α (TGF-α) after liver resection performed for particular benign liver tumors. The purpose of this study was to assess whether there is a different degree of liver regeneration through the kinetics of HGF, IL-6, and TGF-α in 2 particular types of benign liver lesions. MATERIAL/METHODS: The study included 9 patients diagnosed with hepatic hemangioma and 13 patients with focal nodular hyperplasia (FNH) who underwent liver resection. HGF, IL-6, and TGF-α were measured using enzyme-linked immunosorbent assay (ELISA) from blood serum drawn at 6 time points during an 8-day period. Statistical analysis was based on two-factor variance analysis with replicate measurements. RESULTS: The HGF, IL-6, and TGF-α levels in patients who underwent FNH resection were not significantly different from the levels observed in hemangioma resection patients. Significant increases in HGF, IL-6, and TGF-α concentrations were observed only during the first 24h after resection in both groups of patients. CONCLUSIONS: Obtained results suggest that the pre- and post-operative levels of HGF, IL-6, and TGF-α do not depend on the particular type of benign tumor. After resection of FNH and hemangioma tumors, the serum levels of HGF, IL-6, and TGF-α increased at similar rates during the first 24h, followed by significant declines back to pre-operative levels.

Evolution Of The Results Of 1500 Liver Transplantations Performed In The Department Of General, Transplant And Liver Surgery Medical University Of Warsaw.

UNLABELLED: Liver transplantation is a well-established treatment of patients with end-stage liver disease and selected liver tumors. Remarkable progress has been made over the last years concerning nearly all of its aspects. The aim of this study was to evaluate the evolution of long-term outcomes after liver transplantations performed in the Department of General, Transplant and Liver Surgery (Medical University of Warsaw). MATERIAL AND METHODS: Data of 1500 liver transplantations performed between 1989 and 2014 were retrospectively analyzed. Transplantations were divided into 3 groups: group 1 including first 500 operations, group 2 including subsequent 500, and group 3 comprising the most recent 500. Five year overall and graft survival were set as outcome measures. RESULTS: Increased number of transplantations performed at the site was associated with increased age of the recipients (p<0.001) and donors (p<0.001), increased rate of male recipients (p<0.001), and increased rate of piggyback operations (p<0.001), and decreased MELD (p<0.001), as well as decreased blood (p=0.006) and plasma (p<0.001) transfusions. Overall survival was 71.6% at 5 years in group 1, 74.5% at 5 years in group 2, and 85% at 2.9 years in group 3 (p=0.008). Improvement of overall survival was particularly observed for primary transplantations (p=0.004). Increased graft survival rates did not reach the level of significance (p=0.136). CONCLUSIONS: Long-term outcomes after liver transplantations performed in the Department of General, Transplant and Liver Surgery are comparable to those achieved in the largest transplant centers worldwide and are continuously improving despite increasing recipient age and wider utilization of organs procured from older donors.

Next generation sequencing reveals microRNA isoforms in liver cirrhosis and hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) represents the major histological subtype of liver cancer. Tumorigenic changes in hepatic cells potentially result from aberrant expression of microRNAs (miRNAs). Individual microRNA gene may give rise to miRNAs of different length, named isomiRNAs that proved to be functionally relevant. Since microRNA length heterogeneity in hepatic tissue has not been described before, we employed next-generation sequencing to comprehensively analyze microRNA transcriptome in HCC tumors (n=24) and unaffected tissue adjacent to tumors (n=24), including samples with (n=15) and without cirrhosis (n=9). We detected 374 microRNAs expressed in liver, including miR-122-5p that constituted over 39% of the hepatic miRnome. Among the liver expressed miRs, the levels of 64 significantly differed between tumor and control samples (FDR<0.05, fold change>2). Top deregulated miRNAs included miR-1269a (T/N=22.95), miR-3144-3p (T/N=5.24), miR-183-5p (T/N=4.63), miR-10b-5p (T/N=3.87), miR-490-3p (T/N=0.13), miR-199a-5p (T/N=0.17), miR-199a-3p/miR-199b-3p (T/N=0.19), miR-214-5p (T/N=0.20) and miR-214-3p (T/N=0.21). Almost all miRNA genes produced several mature molecules differing in length (isomiRNAs). The reference sequence was not the most prevalent in 38.6% and completely absent in 10.5% of isomiRNAs. Over 26.1% of miRNAs produced isoforms carrying≥2 alternative seed regions, of which 35.5% constituted novel, previously unknown seeds. This fact sheds new light on the percentage of the human genome regulated by microRNAs and their variants. Among the most deregulated miRNAs, miR-199a-3p/miR-199b-3p (T/N fold change=0.18, FDR=0.005) was expressed in 9 isoforms with 3 different seeds, concertedly leading to upregulation of TGF-beta signaling pathway (OR=1.99; p=0.004). In conclusion, the study reveals the comprehensive miRNome of hepatic tissue and provides new tools for investigation of microRNA-dependent pathways in cirrhotic liver and hepatocellular carcinoma. This article is part of a Directed Issue entitled: Rare Cancers.

Enzymatic activity of type 1 iodothyronine deiodinase in selected liver tumors.

INTRODUCTION: Type 1 iodothyronine deiodinase (D1) converts thyroxin (T4) into tri-iodothyronine (T3). Strong evidence indicates that thyroid hormone metabolism is disturbed in neoplasms such as thyroid and breast cancer. However, there is limited data concerning the function of the D1 enzyme in liver tumors. We aimed to estimate the enzymatic activity of D1 in two different common liver tumors. MATERIAL AND METHODS: We obtained 20 tumor samples from patients who had undergone a liver resection. Of the tissue samples, there were 13 benign lesions of focal nodular hyperplasia (FNH) and 7 malignant lesions of hepatocellular carcinomas (HCC). The D1 activity was assessed by measuring the amount of radioactive iodine released in reaction to D1-catalysed deiodination. Groups were compared by the Mann-Whitney non-parametrical test for independent trials, and the Kruskal Wallis test. RESULTS: The enzymatic activity of D1 was not significantly altered in the FNH group (median = 536 fmol/mg of protein/min; p = 0.972) and HCC group (367 fmol/mg; p = 0.128) when compared to matched normal liver parenchyma controls (546 fmol/mg and 556 fmol/mg, respectively). CONCLUSIONS: Liver parenchyma expresses high levels of D1. The results clearly revealed that D1 activity was not significantly different between benign and malignant tumors (FNH and HCC) compared to healthy liver parenchyma cells.

The impact of surgical technique on the results of liver transplantation in patients with hepatocellular carcinoma.

BACKGROUND: Although piggyback technique has gained widespread acceptance for liver transplantation in general, there is an exceptional lack of data on the choice of appropriate surgical technique for patients with hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the impact of surgical technique on outcomes after liver transplantation for HCC. MATERIAL AND METHODS: We conducted a retrospective cohort study on 90 HCC patients who underwent liver transplantation with the conventional (n=19) or piggyback (n=71) technique. Both techniques were compared with respect to intraoperative variables and long-term outcomes, determined by 3-year overall (OS) and recurrence-free (RFS) survival. The potential role of confounding factors was excluded in a series of Cox proportional regression models. RESULTS: The piggyback technique was associated with shorter procedure duration (p=0.0005), shorter anatomical anhepatic phase (p<0.0001), shorter duration of total (p=0.018) and warm ischemia (p<0.0001), and fewer blood transfusions (p=0.006). Three-year OS was 89.1% after piggyback and 49.9% after conventional transplantation (p=0.0008), with 3-year RFS of 89.4% and 56.0% (p=0.0006), respectively. Piggyback transplantations provided outcomes superior to conventional procedures both in patients within (p=0.019 for OS; p=0.003 for RFS) and beyond (p=0.023 for OS; p=0.031 for RFS) Milan criteria. Multivariate analysis of the risks of death and recurrence confirmed the benefits of piggyback technique. CONCLUSIONS: Given its superior long-term outcome, piggyback transplantation might be considered primarily for HCC patients.

Post-transplant outcomes of patients with and without hepatitis C virus infection according to donor age and gender matching.

BACKGROUND: The purpose of this study was to evaluate the impact of donor age and donor-recipient gender matching on liver transplantation outcomes, focusing on differences between patients with and without hepatitis C virus (HCV) infection. MATERIAL AND METHODS: This retrospective cohort study evaluated 622 liver transplantation recipients. HCV (n=164) and non-HCV (n=458) patients were subdivided by donor age (≤ 30, 31-50, and >50 years) and donor-recipient gender configurations. Five-year patient survival (PS) and graft survival (GS) were set as outcome measures. RESULTS: Five-year PS was 83.1% for HCV-positive and 81.6% for HCV-negative patients (p=0.614), with the corresponding GS rates of 81.2% and 79.3% (p=0.538), respectively. In HCV patients, transplantations from donors older than 50 years were associated with lower PS (p=0.035) and GS (p=0.006) than those from donors aged 31-50 years. This difference was not observed among non-HCV recipients (PS, p=0.994; GS, p=0.878). Regarding donor-recipient gender configurations, outcomes were similar in HCV (PS, p=0.751; GS, p=0.592) and non-HCV patients (PS, p=0.217; GS, p=0.249), except for a tendency toward lower PS for male-to-female transplantations than female-to-female transplantations in non-HCV patients (p=0.064). Outcomes of HCV patients were superior to those of non-HCV patients after transplantation from donors aged 31-50 years (PS, p=0.080; GS, p=0.026). CONCLUSIONS: Avoiding the transplantation of grafts from donors aged over 50 years to patients with HCV infection might improve the general outcomes of liver transplantation programs. There is no specific rationale for gender matching with respect to HCV status.