Expanding the liver donor pool worldwide with hepatitis C infected livers, is it the time?

Liver transplantation(LT)provides a life-saving option for cirrhotic patients with complications and hepatocellular carcinoma.Despite the increasing number of liver transplants performed each year,the number of LT candidates on the waitlist remains unchanged due to an imbalance between donor organ supply and the demand which increases the waitlist time and mortality.Living donor liver transplant had a great role in increasing the donor pool and shortened waitlist time for LT candidates.Nevertheless,further strategies can be implemented to increase the pool of potential donors in deceased donor LT,such as reducing the rate of organ discards.Utilizing hepatitis C virus(HCV)seropositive liver grafts is one of the expanded donor organ criteria.A yearly increase of hundreds of transplants is anticipated as a result of maximizing the utilization of HCV-positive organs for HCV-negative recipients.Direct-acting antiviral therapy's efficacy has revolutionized the treatment of HCV infection and the use of HCV-seropositive donors in transplantation.The American Society of Transplantation advises against performing transplants from HCV-infected liver donors(D+)into HCV-negative recipient(R-)unless under Institutional Review Board-approved study rules and with full informed consent of the knowledge gaps associated with such transplants.Proper selection of patients to be transplanted with HCV-infected grafts and confirming their access to direct-acting antivirals if needed is im-portant.National and international consensuses are needed to regulate this process to ensure the maximum benefit and the least adverse events.

Extended criteria brain-dead organ donors:Prevalence and impact on the utilisation of livers for transplantation in Brazil

BACKGROUND Despite its association with higher postoperative morbidity and mortality,the use of extended criteria donor(ECD)livers for transplantation has increased globally due to the high demand for the procedure.AIM To investigate the prevalence of ECD in donation after brain death(DBD)and its impact on organ acceptance for transplantation.METHODS Retrospective analysis of DBD organ offers for liver transplantation between 2017 and 2020 in a high-volume transplant centre.The incidence of the Eurotransplant risk factors to define an ECD(ET-ECD)among DBD donors and the likelihood of organ acceptance over the years were analysed.The relationship between organ refusal for transplantation,the occurrence,and the number of ET-ECD was assessed by simple and multiple logistic regression adjustment.RESULTS A total of 1619 organ donors were evaluated.Of these,78.31%(n=1268)had at least one ET-ECD criterion.There was an increase in the acceptance of ECD DBD organs for transplantation(1 criterion:from 23.40%to 31.60%;2 criteria:from 13.10%to 27.70%;3 criteria:From 6.30%to 13.60%).For each addition of one ETECD variable,the estimated chance of organ refusal was 64.4%higher(OR 1.644,95%CI 1.469-1.839,P<0.001).Except for the donor serum sodium>165 mmol/L(P=0.310),all ET-ECD criteria increased the estimated chance of organ refusal for transplantation.CONCLUSION A high prevalence of ECD DBD was observed.Despite the increase in their utilisation,the presence and the number of extended donor criteria were associated with an increased likelihood of their refusal for transplantation.

Recent advances in computerized imaging and its vital roles in liverdisease diagnosis, preoperative planning, and interventional liversurgery: A review

The earliest and most accurate detection of the pathological manifestations of hepatic diseases ensures effective treatments and thus positive prognostic outcomes.In clinical settings,screening and determining the extent of a pathology are prominent factors in preparing remedial agents and administering approp-riate therapeutic procedures.Moreover,in a patient undergoing liver resection,a realistic preoperative simulation of the subject-specific anatomy and physiology also plays a vital part in conducting initial assessments,making surgical decisions during the procedure,and anticipating postoperative results.Conventionally,various medical imaging modalities,e.g.,computed tomography,magnetic resonance imaging,and positron emission tomography,have been employed to assist in these tasks.In fact,several standardized procedures,such as lesion detection and liver segmentation,are also incorporated into prominent commercial software packages.Thus far,most integrated software as a medical device typically involves tedious interactions from the physician,such as manual delineation and empirical adjustments,as per a given patient.With the rapid progress in digital health approaches,especially medical image analysis,a wide range of computer algorithms have been proposed to facilitate those procedures.They include pattern recognition of a liver,its periphery,and lesion,as well as pre-and postoperative simulations.Prior to clinical adoption,however,software must conform to regulatory requirements set by the governing agency,for instance,valid clinical association and analytical and clinical validation.Therefore,this paper provides a detailed account and discussion of the state-of-the-art methods for liver image analyses,visualization,and simulation in the literature.Emphasis is placed upon their concepts,algorithmic classifications,merits,limitations,clinical considerations,and future research trends.

Detection and characterization of Hepatitis E virus from commercial rabbit livers in Hebei, China

Rabbit hepatitis E virus(HEV)has been reported for years and is thought to have the potential for zoonotic transmission from rabbits to humans.As reported,HEV genotype 3(gt3)is the most prevalent form of HEV in rabbits.To determine the prevalence of HEV in commercial rabbit livers,176 liver samples were collected from an abattoir in Hebei Province,China.Three(1.7%)samples tested positive for RNA of HEV-0RF2(open reading frames-2).Sequence analysis showed that the three isolates shared high identities with each other(94.08-98.85%).Further analysis showed that all the rabbit strains clustered together in the branch of HEV gt3.Further study by immunohistochemistry(IHC)assays showed that 131(74.4%)liver samples were positive for HEV ORF2 protein.Pathological changes including cell degeneration,inflammatory cell infiltration and bile duct epithelial cell hyperplasia were observed under microscopy.These findings indicated the presence of HEV in commercial livers of rabbits.Additional studies should be conducted to investigate the infectivity of rabbit HEV(rHEV)and the potential risks of zoonotic transmission of rHEV from rabbits to human beings.

THE ACTIVITY OF 0~6-METHYLGUANINE DNA METHYL-TRANSFERASE IN LIVERS OF DUCKS FROM QIDONG AND QINGPU

O6-methylguanine DNA methyltransferase (O6-AT) is an enzyme for the repair of the promutagenic structure, O6-aIkylguanine, from alkylated DNA, therefore low activity of O6-AT is involved in the predisposition of tissues to some nitrosamines and the development of cancer. The levels of O6-AT in livers of ducks from Qidong (Qd), a high incidence area of liver cancer, and from Qingpu(Qp), a relatively low incidence area were determined in this study. The results showed that the activity of O6-AT was higher in Qp than in Qd. It suggested that some nitrosamine in Qd might be one of factors responsible for the higher incidence of ducks liver cancer, because these ducks were more sensitive to nitrosa-mine.

Heme oxygenase-1 protects donor livers from ischemia/reperfusion injury:The role of Kupffer cells

AIM:To examine whether heme oxygenase (HO)-1 overexpression would exert direct or indirect effects on Kupffer cells activation, which lead to aggravation of reperfusion injury.METHODS: Donors were pretreated with cobalt protoporphyrin (CoPP) or zinc protoporphyrin (ZnPP), HO-1 inducer and antagonist, respectively. Livers were stored at 4℃ for 24 h before transplantation. Kupffer cells were isolated and cultured for 6 h after liver reperfusion.RESULTS: Postoperatively, serum transaminases were significantly lower and associated with less liver injury when donors were pretreated with CoPP, as compared with the ZnPP group. Production of the cytokines tumor necrosis factor-α and interleukin-6 generated by Kupffer cells decreased in the CoPP group. The CD14 expression levels (RT-PCR/Western blots) of Kupffer cells from CoPP-pretreated liver grafts reduced.CONCLUSION: The study suggests that the potential utility of HO-1 overexpression in preventing ischemia/reperfusion injury results from inhibition of Kupffer cells activation.

Glycyrrhizinate reduces portal hypertension in isolated perfused rat livers with chronic hepatitis

AIM:To investigate the effects of diammonium glycyrrhizinate(Gly)on portal hypertension(PHT)in isolated portal perfused rat liver(IPPRL)with carbon tetrachloride(CCl4)-induced chronic hepatitis.METHODS:PHT model was replicated with CCl4 in rats for 84 d.Model was identified by measuring the ascetic amounts,hepatic function,portal pressure in vivo,splenic index,and pathological alterations.Inducible nitric oxide synthase(iNOS)in liver was assessed by immunohistochemistry.IPPRLs were performed at d0,d28,d56,and d84.After phenylephrine-induced constriction,Gly was geometrically used to reduce PHT.Gly action was expressed as median effective concentration(EC50)and area under the curve(AUC).Underlying mechanism was exploited by linear correlation between AUC values of Gly and existed iNOS in portal triads.RESULTS:PHT model was confirmed with ascites,splenomegaly,serum biomarkers of hepatic injury,and elevated portal pressure.Pathological findings had shown normal hepatic structure at d0,degenerations at d28,fibrosis at d56,cirrhosis at d84in PHT rats.Pseudo lobule ratios decreased and collagen ratios increased progressively along with PHT development.Gly does dose-dependently reduce PHT in IPPRLs with CCl4-induced chronic hepatitis.Gly potencies were increased gradually along with PHT development,characterized with its EC50at 2.80×10-10,3.03×10-11,3.77×10-11and 4.65×10-11mol/L at d0,d28,d56and d84,respectively.Existed iNOS was located at hepatocyte at d0,stellate cells at d28,stellate cells and macrophages at d56,and macrophages in portal triads at d84.Macrophages infiltrated more into portal triads and expressed more iNOS along with PHT development.AUC values of Gly were positively correlated with existed iNOS levels in portal triads.CONCLUSION:Gly reduces indirectly PHT in IPPRL with CCl4-induced chronic hepatitis.The underlying mechanisms may relate to rescue NO bioavailability from macrophage-derived peroxynitrite in portal triads.

Progress in bioreactors of bioartificial livers

BACKGROUND: Bioartificial liver support systems are becoming an effective therapy for hepatic failure. Bioreactors, as key devices in these systems, can provide a favorable growth and metabolic environment, mass exchange, and immunological isolation as a platform. Currently, stagnancy in bioreactor research is the main factor restricting the development of bioartificial liver support systems. DATA SOURCES: A PubMed database search of English-language literature was performed to identify relevant articles using the keywords 'bioreactor', 'bioartificial liver', 'hepatocyte', and 'liver failure'. More than 40 articles related to the bioreactors of bioartificial livers were reviewed. RESULTS: Some progress has been made in the improvement of structures, functions, and modified macromolecular materials related to bioreactors in recent years. The current data on the improvement of bioreactor configurations for bioartificial livers or on the potential of the use of certain scaffold materials in bioreactors, combined with the clinical efficacy and safety evaluation of cultured hepatocytes in vitro, indicate that the AMC (Academic Medical Center) BAL bioreactor and MELS (modular extracorporeal liver support) BAL bioreactor system can partly replace the synthetic and metabolic functions of the liver in phase I clinical studies. In addition, it has been indicated that the microfluidic PDMS (polydimethylsiloxane) bioreactor, or SlideBioreactor, and the microfabricated grooved bioreactor are appropriate for hepatocyte culture, which is also promising for bioartificial livers. Similarly, modified scaffolds can promote the adhesion, growth, and function of hepatocytes, and provide reliable materials for bioreactors. CONCLUSIONS: Bioreactors, as key devices in bioartificial livers, play an important role in the therapy for liver failure both now and in the future. Bioreactor configurations are indispensable for the development of bioartificial livers used for liver failure, just as the modified scaffold materials available for bioreactors are favorable to the construction of effective bioartificial livers.

The effects of ischemia-reperfusion injury and hepatic artery ischemia on CD14 expression in canine auto-transplantation livers

Objective： To study the effect of ischemia-reperfusion injury（IRI） and hepatic artery ischemia（HAI） on CD14 expression in canine auto-transplantation livers. Methods：Liver orthotopic auto-transplantation models were applied with 30 healthy male Xi＇ an canines which were randomly divided into a control group, simultaneous reperfusion（SR） group and HAI group, CD14 protein expression, Malonaldehyde （MDA） Contents in hepatic tissues and ALT values in serum were detected, and the pathological changes of hepatic tissues was investigated under the light microscopy. Results：The level of CD14 protein expression in SR and HAI group tended to be time-dependent and both higher than controls with statistical significance（P 〈 0.01）; The peak values of these two groups both occurred at 4 h, but the level in HAI group （11.94 ± 0.43） was evidently higher than that in SR group（3.04 ± 0.34）. MDA contents in liver tissue, ALT values in serum and pathological changes showed the same changing tendency as CD 14 expression. Conclusion：（1） Up-regulation of CD14 expression may be the receptor-mechanism of Kupffer cells（KCs） activation in liver transplantation. （2） HAI can upregulate CD14 expression after portal vein reperfusion, improve the activity of KCs further more, increase OFRs production and cooperate with portal reperfusion, and finally aggravate the grafts injury.

Steatotic livers are susceptible to normothermic ischemiareperfusion injury from mitochondrial Complex-Ⅰ?dysfunction

AIM: To assess the effects of ischemic preconditioning(IPC, 10-min ischemia/10-min reperfusion) on steatotic liver mitochondrial function after normothermic ischemia-reperfusion injury(IRI).METHODS: Sixty male Sprague-Dawley rats were fed8-wk with either control chow or high-fat/high-sucrose diet inducing > 60% mixed steatosis. Three groups(n = 10/group) for each dietary state were tested:(1) the IRI group underwent 60 min partial hepatic ischemia and 4 h reperfusion;(2) the IPC group underwent IPC prior to same standard IRI; and(3) sham underwent t h e s a m e s u r g e r y w i t h o u t I R I o r I P C. H e p a t i c mitochondrial function was analyzed by oxygraphs. Mitochondrial Complex-Ⅰ, Complex-Ⅱ enzyme activity, serum alanine aminotransferase(ALT), and histological injury were measured.RESULTS: Steatotic-IRI livers had a greater increase in ALT(2476 ± 166 vs 1457 ± 103 IU/L, P < 0.01) and histological injury following IRI compared to the lean liver group. Steatotic-IRI demonstrated lower Complex-Ⅰ?activity at baseline [78.4 ± 2.5 vs 116.4 ± 6.0 nmol/(min.mg protein), P < 0.001] and following IRI [28.0 ± 6.2 vs 104.3 ± 12.6 nmol/(min.mg protein), P < 0.001]. Steatotic-IRI also demonstrated impaired Complex-Ⅰ?function post-IRI compared to the lean liver IRI group. Complex-Ⅱ activity was unaffected by hepatic steatosis or IRI. Lean liver mitochondrial function was unchanged following IRI. IPC normalized ALT and histological injury in steatotic livers but had no effect on overall steatotic liver mitochondrial function or individual mitochondrial complex enzyme activities. CONCLUSION: Warm IRI impairs steatotic liver Complex-Ⅰ?activity and function. The protective effects of IPC in steatotic livers may not be mediated through mitochondria.

Strategies to rescue steatotic livers before transplantation in clinical and experimental studies

The shortage of donor livers has led to an increased use of organs from expanded criteria donors. Included are livers with steatosis, a metabolic abnormality that increases the likelihood of graft complications posttransplantation. After a brief introduction on the etiology, pathophysiology, categories and experimental models of hepatic steatosis, we herein review the methods to rescue steatotic donor livers before transplantation applied in clinical and experimental studies. The methods span the spectrum of encouraging donor weight loss, employing drug therapy, heat shock preconditioning, ischemia preconditioning and selective anesthesia on donors, and the treatment on isolated grafts during preservation. These methods work at different stages of transplantation process, although share similar molecular mechanisms including lipid metabolism stimulation through enzymes or nuclear receptor e.g. , peroxisomal proliferator-activated receptor, or anti-inflammation through suppressing cytokines e.g. , tumor necrosis factor-α, or antioxidant therapies to alleviate oxidative stress. This similarity of molecular mechanisms implies possible future attempts to reinforce each approach by repeating the same treatment approach at several stages of procurement and preservation, as well as utilizing these alternative approaches in tandem.

Apoptosis induced by a low-carbohydrate and high-protein diet in rat livers

AIM: To determine whether high-protein, high-fat, and low-carbohydrate diets can cause lesions in rat livers.METHODS: We randomly divided 20 female Wistar rats into a control diet group and an experimental diet group. Animals in the control group received an AIN-93 M diet, and animals in the experimental group received an Atkins-based diet(59.46% protein, 31.77% fat, and 8.77% carbohydrate). After 8 wk, the rats were anesthetized and exsanguinated for transaminases analysis, and their livers were removed for flow cytometry, immunohistochemistry, and light microscopy studies. We expressed the data as mean ± standard deviation(sd) assuming unpaired and parametric data; we analyzed differences using the student's t-test. statistical significance was set at P < 0.05.RESULTS: We found that plasma alanine aminotransferase and aspartate aminotransferase levels were significantly higher in the experimental group than in the control group. According to flow cytometry, the percentages of nonviable cells were 11.67% ± 1.12% for early apoptosis, 12.07% ± 1.11% for late apoptosis, and 7.11% ± 0.44% for non-apoptotic death in the experimental diet group and 3.73% ± 0.50% for early apoptosis, 5.67% ± 0.72% for late apoptosis, and 3.82% ± 0.28% for non-apoptotic death in the control diet group. The mean percentage of early apoptosis was higher in the experimental diet group than in the control diet group. Immunohistochemistry for autophagy was negative in both groups. sinusoidal dilation around the central vein and small hepatocytes was only observed in the experimental diet group, and fibrosis was not identified by hematoxylin-eosin or Trichrome Masson staining in either group.CONCLUSION: Eight weeks of an experimental diet resulted in cellular and histopathological lesions in rat livers. Apoptosis was our principal finding; elevated plasma transaminases demonstrate hepatic lesions.

Effects of Exposure to Lead and Cadmium on the Oxidative Damage of Livers in Laying Hens

[Objective] To detect the effects of exposure to lead and cadmium on the oxidative damage of livers in laying hens. [Methods] One hundred and twenty 40-week-old Hyline brown hens were randomly divided into four groups. 100 mg / L Pb and / or 50 mg / L Cd was added into the drinking water for eight weeks. [Results] Compared with control group,AST and ALT activities in Pb group enhanced; but there were no significant differences. AST and ALT activities in Cd group and( Pb + Cd) group significantly or extremely significantly increased( P 【 0. 05 or P 【 0. 01). SOD activity,GSH- Px activity and GSH content in( Pb + Cd) group,Cd group and Pb group were significantly or extremely significantly lower than those in control group( P 【0. 05 or P 【0. 01). Among them,( Pb + Cd) group showed the greatest reduction( P 【0. 01). MDA contents in the three groups were significantly higher than that of control group; and( Pb +Cd) group was significantly higher than Pb group and Cd group. Cu,Fe and Zn contents in three groups were higher than those in control group in different degrees( P 【0. 05 or P 【0. 01). Se contents in Cd group and( Pb + Cd) group were significantly lower than that in control group( P 【0. 01). Residue contents in livers in Pb group and Cd group were significantly greater than that in control group; while residue content in( Pb + Cd) group was significantly higher than those in Pb group and Cd group. Ultrastructure showed that there were symptoms of mitochondrial swelling and fractured cristae in liver cells of laying hens after the exposure to Cd and Pb. In( Pb + Cd) group,these symptoms were even greater. [Conclusion] Oxidative damage and disturbance of trace element metabolism were one of the mechanisms for hepatotocity in laying hens induced by Pb and Cd,and synergistic effect lied in the coadministration.

Hepatobiliary phases in magnetic resonance imaging using liverspecific contrast for focal lesions in clinical practice

BACKGROUND Challenging lesions,difficult to diagnose through non-invasive methods,constitute an important emotional burden for each patient regarding a still uncertain diagnosis(malignant x benign).In addition,from a therapeutic and prognostic point of view,delay in a definitive diagnosis can lead to worse outcomes.One of the main innovative trends currently is the use of molecular and functional methods to diagnosis.Numerous liver-specific contrast agents havebeen developed and studied in recent years to improve the performance of liver magnetic resonance imaging(MRI).More recently,one of the contrast agents introduced in clinical practice is gadoxetic acid(gadoxetate disodium).AIM To demonstrate the value of the hepatobiliary phases using gadoxetic acid in MRI for the characterization of focal liver lesions(FLL)in clinical practice.METHODS Overall,302 Lesions were studied in 136 patients who underwent MRI exams using gadoxetic acid for the assessment of FLL.Two radiologists independently reviewed the MRI exams using four stages,and categorized them on a 6-point scale,from 0(lesion not detected)to 5(definitely malignant).The stages were:stage 1-images without contrast,stage 2-addition of dynamic phases after contrast(analogous to usual extracellular contrasts),stage 3-addition of hepatobiliary phase after 10 min(HBP 10’),stage 4-hepatobiliary phase after 20 min(HBP 20’)in addition to stage 2.RESULTS The interobserver agreement was high(weighted Kappa coefficient:0.81-1)at all stages in the characterization of benign and malignant FLL.The diagnostic weighted accuracy(Az)was 0.80 in stage 1 and was increased to 0.90 in stage 2.Addition of the hepatobiliary phase increased Az to 0.98 in stage 3,which was also 0.98 in stage 4.CONCLUSION The hepatobiliary sequences improve diagnostic accuracy.With growing potential in the era of precision medicine,the improvement and dissemination of the method among medical specialties can bring benefits in the management of patients with FLL that are difficult to diagnose.

Bioengineered humanized livers as better three-dimensional drug testing model system

AIM To develop appropriate humanized three-dimensional ex-vivo model system for drug testing. METHODS Bioengineered humanized livers were developed in this study using human hepatic stem cells repopulation within the acellularized liver scaffolds which mimics with the natural organ anatomy and physiology. Six cytochrome P-450 probes were used to enable efficient identification of drug metabolism in bioengineered humanized livers. The drug metabolism study in bioengineered livers was evaluated to identify the absorption, distribution, metabolism, excretion and toxicity responses.RESULTS The bioengineered humanized livers showed cellular and molecular characteristics of human livers. The bioengineered liver showed three-dimensional natural architecture with intact vasculature and extra-cellular matrix. Human hepatic cells were engrafted similar to the human liver. Drug metabolism studies provided a suitable platform alternative to available ex-vivo and in vivo models for identifying cellular and molecular dynamics of pharmacological drugs.CONCLUSION The present study paves a way towards the development of suitable humanized preclinical model systems for pharmacological testing. This approach may reduce the cost and time duration of preclinical drug testing and further overcomes on the anatomical and physiological variations in xenogeneic systems.

Fatty Acid Profiles of Livers from Two Marine Fishes Inhabiting Sudanese Red Sea Coast

Fish livers a good source of long-chain polyunsaturated fatty acids and omega 3, are usually discarded as a waste when fish are processed for human consumption in Sudan. Highly fresh Triaenodon obesus and Hipposcarus harid fish were purchased from Port Sudan fish central market during December 2014. The fatty acid profiles of the livers of these commercially important fish were determined. The polyunsaturated and saturated fatty acids ratio in the livers oil of T. obesus and H. harid was 1:2.2 and 1:1.38, respectively. The Palmatic (16:0), Pentadecenoic (12:0) and Arachidic acids were the highest in both species. The poly chain unsaturated fatty acids Linolenic (18:3n - 3), Eicosapentaenoic (20:5n - 3) and Docosahexaenoic (22:6n - 3) were detected in the liver of both species. The highest values of above poly chain unsaturated fatty acids were detected in T. obesus.

Comparative Study on the Dielectric Properties Between Living and Non-living from Human and Animal Livers

The data of dielectric properties of human tissues mainly come from animal tissues or human corpse at present. Up to now, there has not been a report of dielectric properties of human living liver. Our objective is to study the dielectric properties of human living liver and compare the results with those of animal living liver as well as the human non-living liver. In vitro measurements of living and non-living livers from human and rabbits are shown in the 10 Hz to 100 MHz range. Analysis of the conductivity, permittivity and characteristic parameters from the data were made. The conductivity of three kinds of liver were markedly different at low frequency of 0.06 s/m (living rabbit liver), 0.13 s/m (living human liver) and 0.24 s/m (non-living human liver). The Cole parameters that best characterize the liver of human and rabbit are R0 , fc1 , R1 , and R∞ The Cole parameters that best characterize the living and nonliving liver of human are R0 , fc1 , ΔR1 , ΔR2 and R ∞ . In conclusion, we can't substitute the dielectric properties of animal or human corpse liver for the living human liver. The results suggest that the dielectric properties of living human tissues has great significance on studying.

Effects of Moringa oleifera aqueous extract on the growth performance,blood characteristics,and histological features of gills and livers in Nile tilapia

Moringa oleifera is well known as a highly nutritious plant and a water purifier in fish culture.Tilapia fish has many impressive qualities making them very suitable for aquaculture.Therefore,this study aimed to evaluate the effect of supplementation of Moringa oleifera aqueous extract(MOAE)at varying concentrations(0,100,200,and 400 mg/kg diet for 90 days)on growth performance,hematological,and some biochemical parameters of Nile tilapia.Additionally,histological changes and immunohistochemical expression of caspase 3 in gills and livers were evaluated.Significant enhancements(P<0.05)in the final weight,weight gain,specific growth rate,red blood cells,hemoglobin,packed cell volume,white blood cells,and total serum protein were observed in fish fed 200 mg MOAE/kg diet compared with other groups.However,a significant reduction(P<0.05)of liver and kidney function tests and non-significant changes in lipid profile were recorded.On the other hand,fish fed 400 mg MOAE/kg diet revealed disturbance in the corresponding parameters.Severe histological degenerative changes were detected in the gills and liver of fish fed 400 mg MOAE/kg diet.In comparison,fish fed 200 mg MOAE/kg diet showed the best histo-architectures of these organs compared with other groups.Concomitant immune expressions of caspase 3 were determined where gills and liver of fish fed 400 mg MOAE/kg diet revealed extensive number of positive caspase 3 cells indicating severe apoptotic features.Accordingly,a dietary MOAE at 200 mg/kg diet is recommended to improve the growth performance,hematological parameters,liver and kidney functions in Nile tilapia.Meanwhile,caution must be considered when using MOAE at a concentration over 200 mg/kg diet.

Qualifying the suitability of living donor livers for pediatric liver transplantation:are we doing the right thing?

Over the last decades,liver transplantation has become the standard care for many forms of end-stage liver disease,both in adults and in children.The prognosis after pediatric liver transplantation(pLT)has steadily increased up to a patient survival at 5 years of 85%and an estimated graft half life of 31 years(1,2).In the early days of pLT,the transplanted organ originated from deceased donors.Since 1990,adult-to-child living donor liver transplantation(LDLT)programs have developed,which rapidly gained popularity,particularly in Europe and Asia(2,3).A major stimulus for LDLT has been the limited availability of deceased donors.The indications for liver transplantation have expanded,particularly for adult patients,at a higher rate than the availability of donor organs.Moreover,the quality of donor organs has steadily declined,resulting in a decreased utilization of livers from deceased donors for transplantation(4).The limited availability of qualified deceased donor livers has further stimulated LDLT:in Europe,for example,the percentage of living donor organs used for pLT increased from 7%before 2000 to 40%since 2010(1).

Ex vivo liver resection and auto-transplantation as an alternative for the treatment of liver malignancies: Progress and challenges

Hepatectomy is still the major curative treatment for patients with liver malignancies.However,it is still a big challenge to remove the tumors in the central posterior area,especially if their location involves the retrohepatic inferior vena cava and hepatic veins.Ex vivo liver resection and auto-transplantation(ELRA),a hybrid technique of the traditional liver resection and transplantation,has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation.Due to its technical difficulty,ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver transplantation.The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases,especially in the advanced alveolar echinococcosis.Recently,the application of ELRA for liver malignances has gained more attention.However,standardization of clinical practice norms and international consensus are still lacking.The prognostic impact in these oncologic patients also needs further evaluation.In this review,we summarized the principles and recent progresses on ELRA.