BACKGROUND： Functional imaging such as CT perfusion can detect morphological and hemodynamic changes in he- patocellular carcinoma （HCC）. Pre-carcinoma and early HCC nodules are difficult to differentiate by observ...BACKGROUND： Functional imaging such as CT perfusion can detect morphological and hemodynamic changes in he- patocellular carcinoma （HCC）. Pre-carcinoma and early HCC nodules are difficult to differentiate by observing only their hemodynamics changes. The present study aimed to investi- gate hemodynamic parameters and evaluate their differential diagnostic cut-off between pre-carcinoma and early HCC nodules using CT perfusion and receiver operating characteristic （ROC） curves. METHODS： Male Wistar rats were randomly divided into control （n=20） and experimental （n=70） groups. Diethylnitrosamine （DEN） was used to induce pre-carcinoma and early HCC nodules in the experimental group. Perfusion scanning was carried out on all survival rats discontinuously from 8 to 16 weeks. Hepatic portal perfusion （HPP）, hepatic arterial fraction （HAF）, hepatic arterial perfusion （HAP）, hepatic blood volume （HBV）, hepatic blood flow （HBF）, mean transit time （MTT） and permeability of capillary vessel surface （PS） data were provided by mathematical deconvolution model. The perfusion parameters were compared among the three groups of rats （control, pre-carcinoma and early HCC groups） using the Kruskal-Wallis test and analyzed with ROC curves. Histological examination of the liver tissues with hematoxylin and eosin staining was performed after CT scan.RESULTS： For HPP, HAF, HBV, HBF and MTT, there were significant differences among the three groups （P〈0.05）. HAF had the highest areas under the ROC curves： 0.80 （control vs pre-carcinoma groups） and 0.95 （control vs early HCC groups） with corresponding optimal cut-offs of 0.37 and 0.42, respectively. The areas under the ROC curves for HPP was 0.79 （control vs pre-carcinoma groups） and 0.92 （control vs early HCC groups） with corresponding optimal cut-offs of 136.60 mL/min/100 mg and 108.47 mL/min/100 mg, respectively. CONCLUSIONS： CT perfusion combined with ROC curve analysis is a new diagnosis model for distinguishing between pre-carcinoma and early HCC nodules. HAF and HPP are the ideal reference indices.展开更多
The Josephinum Medical History Museum in Vienna houses an extensive collection of anatomical wax models,including a detailed model of the human liver(Figure 1).This unique collection was originally acquired for the Mi...The Josephinum Medical History Museum in Vienna houses an extensive collection of anatomical wax models,including a detailed model of the human liver(Figure 1).This unique collection was originally acquired for the Military Medical-Surgical Academy,established in Vienna in 1785 by Emperor Joseph II,who was also,at that time,the Archduke of Austria(1).展开更多
The potential of induced pluripotent stem cells(iPSCs)for modeling and treating metabolic associated fatty liver disease(MAFLD)and metabolic associated steatohepatitis(MASH)is emerging.MAFLD is a growing global health...The potential of induced pluripotent stem cells(iPSCs)for modeling and treating metabolic associated fatty liver disease(MAFLD)and metabolic associated steatohepatitis(MASH)is emerging.MAFLD is a growing global health concern,currently with limited treatment options.While primary mesenchymal stem cells hold promise,iPSCs offer a versatile alternative due to their ability to differentiate into various cell types,including iPSC-derived mesenchymal stem cells.However,challenges remain,including optimizing differentiation protocols,ensuring cell safety,and addressing potential tumorigenicity risks.In addition,iPSCs offer the possibility to generate complex cellular models,including three-dimensional organoid models,which are closer representations of the human disease than animal models.Those models would also be valuable for drug discovery and personalized medicine approaches.Overall,iPSCs and their derivatives offer new perspectives for advancing MAFLD/MASH research and developing novel therapeutic strategies.Further research is needed to overcome current limitations and translate this potential into effective clinical applications.展开更多
Constructing an in vitro vascularized liver tissue model that closely simulates the human liver is crucial for promoting cell proliferation,mimicking physiological heterogeneous structures,and recreating the cellular ...Constructing an in vitro vascularized liver tissue model that closely simulates the human liver is crucial for promoting cell proliferation,mimicking physiological heterogeneous structures,and recreating the cellular microenvironment.However,the layer-by-layer printing method is significantly constrained by the rheological properties of the bioink,making it challenging to form complex three-dimensional vascular structures in low-viscosity soft materials.To overcome this limitation,we developed a cross-linkable biphasic embedding medium by mixing low-viscosity biomaterials with gelatin microgel.This medium possesses yield stress and self-healing properties,facilitating efficient and continuous three-dimensional shaping of sacrificial ink within it.By adjusting the printing speed,we controlled the filament diameter,achieving a range from 250μm to 1000μm,and ensuring precise control over ink deposition locations and filament shapes.Using the in situ endothelialization method,we constructed complex vascular structures and ensured close adhesion between hepatocytes and endothelial cells.In vitro experiments demonstrated that the vascularized liver tissue model exhibited enhanced protein synthesis and metabolic function compared to mixed liver tissue.We also investigated the impact of varying vascular densities on liver tissue function.Transcriptome sequencing revealed that liver tissues with higher vascular density exhibited upregulated gene expression in metabolic and angiogenesis-related pathways.In summary,this method is adaptable to various materials,allowing the rheological properties of the supporting bath and the tissue's porosity to be modified using microgels,thus enabling precise regulation of the liver tissue microenvironment.Additionally,it facilitates the rapid construction of three-dimensional vascular structures within liver tissue.The resulting vascularized liver tissue model exhibits enhanced biological functionality,opening new opportunities for biomedical applications.展开更多
BACKGROUND Liver transplantation aims to increase the survival of patients with end-stage liver diseases and improve their quality of life.The number of organs available for transplantation is lower than the demand.To...BACKGROUND Liver transplantation aims to increase the survival of patients with end-stage liver diseases and improve their quality of life.The number of organs available for transplantation is lower than the demand.To provide fair organ distribution,predictive mortality scores have been developed.AIM To compare the Acute Physiology and Chronic Health Evaluation IV(APACHE IV),balance of risk(BAR),and model for end-stage liver disease(MELD)scores as predictors of mortality.METHODS Retrospective cohort study,which included 283 adult patients in the postoperative period of deceased donor liver transplantation from 2014 to 2018.RESULTS The transplant recipients were mainly male,with a mean age of 58.1 years.Donors were mostly male,with a mean age of 41.6 years.The median cold ischemia time was 3.1 hours,and the median intensive care unit stay was 5 days.For APACHE IV,a mean of 59.6 was found,BAR 10.7,and MELD 24.2.The 28-day mortality rate was 9.5%,and at 90 days,it was 3.5%.The 28-day mortality prediction for APACHE IV was very good[area under the curve(AUC):0.85,P<0.001,95%CI:0.76-0.94],P<0.001,BAR(AUC:0.70,P<0.001,95%CI:0.58–0.81),and MELD(AUC:0.66,P<0.006,95%CI:0.55-0.78),P<0.008.At 90 days,the data for APACHE IV were very good(AUC:0.80,P<0.001,95%CI:0.71–0.90)and moderate for BAR and MELD,respectively,(AUC:0.66,P<0.004,95%CI:0.55–0.77),(AUC:0.62,P<0.026,95%CI:0.51–0.72).All showed good discrimination between deaths and survivors.As for the best value for liver transplantation,it was significant only for APACHE IV(P<0.001).CONCLUSION The APACHE IV assessment score was more accurate than BAR and MELD in predicting mortality in deceased donor liver transplant recipients.展开更多
In this editorial,we comment on the article by Teerasarntipan et al published in a recent issue of the World Journal of Gastroenterology.Dengue infection is a major mosquito-borne disease with global significance.Deng...In this editorial,we comment on the article by Teerasarntipan et al published in a recent issue of the World Journal of Gastroenterology.Dengue infection is a major mosquito-borne disease with global significance.Dengue-induced severe hepatitis(DISH)is a rare complication though severe,as it can lead to acute liver failure(ALF)with an incidence rate between 0.7%and 2.0%and mortality rates from 47.0%to 58.8%.In this context,the identification of patients at risk of ALF could improve prognosis in DISH patients.Teerasarntipan et al retrospectively enrolled 2532 dengue patients,counting 193 DISH and 20 ALF.The authors explored the prognostic role of liver-specific scores,as the model for end-stage liver disease(MELD)score,albumin-bilirubin(ALBI)score,easy(EZ)-ALBI score,and platelet-ALBI(PALBI)score.Univariate analysis identified international normalized ratio(INR),total bilirubin,albumin,and creatinine as independent laboratory factors associated with ALF,while age,gender,and liver comorbidities were not linked to in-hospital mortality.The presence of dengue shock syndrome significantly increased mortality,with an odds ratio(OR)of 28.05(95%CI:7.21-109.18,P<0.001).High INR and low albumin were laboratory markers associated with death from DISH,with ORs of 5.83(95%CI:2.59-13.12,P<0.001)and 0.15(95%CI:0.05-0.44,P<0.001),respectively.Multivariate analysis confirmed that INR remained the only significant predictor of both ALF and death,with adjusted ORs of 19.54(95%CI:3.37-113.38,P<0.001)and 3.86(95%CI:1.13-13.18,P=0.031),respectively.Among prognostic models,the MELD score performed best in predicting ALF,with a very high accuracy[area under the receiver operating characteristic curve(AUROC)of 0.929,87.5%sensitivity,89.3%specificity at a cutoff of 16],followed by the EZ-ALBI,ALBI,and PALBI scores,with AUROCs of 0.865,0.832,and 0.797,respectively.As MELD remains the best scoring system for predicting poor outcomes in DISH-related ALF,EZ-ALBI is a valid adjunct tool that could improve medical care in these patients.展开更多
To analyze time intervals of inflammation and regeneration in a cholestatic rat liver model.METHODSIn 36 Lewis rats, divided into six groups of 6 animals (postoperative observation periods: 1, 2, 3, 4, 6, 8 wk), the m...To analyze time intervals of inflammation and regeneration in a cholestatic rat liver model.METHODSIn 36 Lewis rats, divided into six groups of 6 animals (postoperative observation periods: 1, 2, 3, 4, 6, 8 wk), the main bile duct was ligated with two ligatures and observed for the periods mentioned above. For laboratory evaluation, cholestasis parameters (bilirubin, γ-GT), liver cell parameters (ASAT, ALAT) and liver synthesis parameters (quick, albumin) were determined. For histological analysis, HE, EvG, ASDCL and HMGB-1 stainings were performed. Furthermore, we used the mRNA of IL-33, GADD45a and p-21 for analyzing cellular stress and regeneration in cholestatic rats.RESULTSIn chemical laboratory and histological evaluation, a distinction between acute and chronic cholestatic liver injury with identification of inflammation and regeneration could be demonstrated by an increase in cholestasis (bilirubin: 1-wk group, 156.83 ± 34.12 μmol/L, P = 0.004) and liver cell parameters (ASAT: 2-wk group, 2.1 ± 2.19 μmol/L.s, P = 0.03; ALAT: 2-wk group, 1.03 ± 0.38 μmol/L.s, P = 0.03) after bile duct ligation (BDL). Histological evaluation showed an increase of bile ducts per portal field (3-wk group, 48 ± 6.13, P = 0.004) during the first four weeks after bile duct ligation. In addition to inflammation, which is an expression of acute cholestasis, there was an increase of necrotic areas in the histological sections (2-wk group, 1.38% ± 2.28% per slide, P = 0.002). Furthermore, the inflammation could be verified by ASDCL (4-wk group, 22 ± 5.93 positive cells per portal field, P = 0.041) and HMGB-1 [2-wk group, 13 ± 8.18 positive cells per field of view (FoV), P = 0.065] staining. Therefore, in summary of the laboratory evaluation and histological studies, acute cholestasis could be found during the first four weeks after bile duct ligation. Subsequently, the described parameters declined so that chronic cholestasis could be assumed. For quantification of secondary biliary cirrhosis, eosin staining was performed, which did not reveal any signs of liver remodeling, thus precluding the development of a chronic cholestasis model. Additionally, to establish the chronic cholestasis model, we evaluated liver regeneration capacity through measurements of IL-33, p-21 and GADD45a mRNA.CONCLUSIONWe created a chronic cholestasis model. The point of inflammatory and regenerative balance was reached after four weeks. This finding should be used for experimental approaches dealing with chronic cholestatic liver damage.展开更多
In pre-clinical phase of new drug development,it is particularly important to establish an in vitro model to mimic the metabolism situation of human body.The aim of the in vitro model is to reduce the usage of experim...In pre-clinical phase of new drug development,it is particularly important to establish an in vitro model to mimic the metabolism situation of human body.The aim of the in vitro model is to reduce the usage of experimental animals and to make a more accurate prediction of the drug metabolism in vivo.Microfluidic chip is an emerging technology to establish predictive models.By integrating subcellular fractions,hepatocytes or liver tissue in the microfluidic chips,more predictive in vitro metabolism models can be established for drug development.The microfluidic platform offers dynamic and controlled fluids,as well as sophisticated liver tissue assembly to remodel the physiological and pathological microenvironment of liver in the human body.This review updates the microfluidic-based liver drug metabolism models since 2011,and summarizes the development of different models based on different chip vectors(subcellular components,primary hepatocytes,and tissue sections).It serves as a guide for newcomers to this dynamic field.展开更多
Background and Aims: To better understand nonalcoholic steatohepatitis (NASH) disease progression and to evaluate drug targets and compound activity, we undertook the devel-opment of an in vitro 3D model to mimic live...Background and Aims: To better understand nonalcoholic steatohepatitis (NASH) disease progression and to evaluate drug targets and compound activity, we undertook the devel-opment of an in vitro 3D model to mimic liver architecture and the NASH environment. Methods:We have developed an in vitro preclinical 3D NASH model by coculturing primary hu-man hepatocytes, human stellate cells, liver endothelial cells and Kupffer cells embedded in a hydrogel of rat collagen on a 96-well plate. A NASH-like environment was induced by ad-dition of medium containing free fatty acids and tumor ne-crosis factor-α. This model was then characterized by biochemical, imaging and transcriptomics analyses. Results:We succeeded in defining suitable culture conditions to main-tain the 3D coculture for up to 10 days in vitro, with the lowest level of steatosis and reproducible low level of inflammation and fibrosis. NASH disease was induced with a custom me-dium mimicking NASH features. The cell model exhibited the key NASH disease phenotypes of hepatocyte injury, steatosis, inflammation, and fibrosis. Hepatocyte injury was highlighted by a decrease of CYP3A4 expression and activity, without loss of viability up to day 10. Moreover, the model was able to stimulate a stable inflammatory and early fibrotic environ-ment, with expression and secretion of several cytokines. A global gene expression analysis confirmed the NASH induc-tion. Conclusions:This is a new in vitro model of NASH dis-ease consisting of four human primary cell-types that exhibits most features of the disease. The 10-day cell viability and cost effectiveness of the model make it suitable for medium throughput drug screening and provide attractive avenues to better understand disease physiology and to identify and characterize new drug targets.展开更多
AIM To investigate whether the short-term prognosis of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF) could be improved by using a modified model for end-stage liver disease(MELD) including serum ...AIM To investigate whether the short-term prognosis of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF) could be improved by using a modified model for end-stage liver disease(MELD) including serum lactate.METHODS This clinical study was conducted at the First Affiliated Hospital, Fujian Medicine University, China. From 2009 to 2015, 236 patients diagnosed with HBV-related ACLF at our center were recruited for this 3-month followup study. Demographic data and serum lactate levels were collected from the patients. The MELD scores with or without serum lactate levels from survival and nonsurvival groups were recorded and compared.RESULTS Two hundred and thirty-six patients with HBV-ACLF were divided into two groups: survival group(S) andnon-survival group(NS). Compared with the NS group, the patients in survival the S group had a significantly lower level of serum lactate(3.11 ± 1.98 vs 4.67 ± 2.43, t = 5.43, P < 0.001) and MELD score(23.33 ± 5.42 vs 30.37 ± 6.58, t = 9.01, P = 0.023). Furthermore, serum lactate level was positively correlated with MELD score(r = 0.315, P < 0.001). Therefore, a modified MELD including serum lactate was developed by logistic regression analysis(0.314 × lactate + 0.172 × MELD-5.923). In predicting 3-month mortality using the MELD-LAC model, the patients from the S group had significantly lower baseline scores(-0.930 ± 1.34) when compared with those from the NS group(0.771 ± 1.32, t = 9.735, P < 0.001). The area under the receiver operating characteristic curve(AUROC) was 0.859 calculated by using the MELD-LAC model, which was significantly higher than that calculated by using the lactate level(0.790) or MELD alone(0.818). When the cutoff value was set at-0.4741, the sensitivity, specificity, positive predictive value and negative predictive value for predicting short-term mortality were 91.5%, 80.10%, 94.34% and 74.62%, respectively. When the MELD-LAC scores at baseline level were set at-0.5561 and 0.6879, the corresponding mortality rates within three months were 75% and 90%, respectively.CONCLUSION The short-term prognosis of HBV-related ACLF was improved by using a modified MELD including serum lactate from the present 6-year clinical study.展开更多
BACKGROUND: The indocyanine green (ICG) clearance test (clearance rate (K) and retention rate at 15 minutes (R(15))) is a sensitive indicator to evaluate liver function. The model for end-stage liver disease (MELD) sc...BACKGROUND: The indocyanine green (ICG) clearance test (clearance rate (K) and retention rate at 15 minutes (R(15))) is a sensitive indicator to evaluate liver function. The model for end-stage liver disease (MELD) score has emerged as a useful tool for estimating the mortality of patients awaiting liver transplantation and has recently been validated on patients with liver diseases of various etiologies and severity. In this study, we investigated the correlation between the ICG clearance test and MELD score of patients with liver cirrhosis. METHODS: From June 2007 to March 2008, 52 patients with liver cirrhosis admitted to our center were classified into Child-Pugh class A (8 patients), B (14) and C (30). The ICG clearance test (K value and R(15)) was performed by ICG pulse spectrophotometry (DDG-3300K), and the MELD scores of patients were calculated. RESULTS: As the Child-Pugh classification of liver function gradually deteriorated, the K value decreased, while R(15) and MELD score increased. There were significant statistical differences in K value, R(15) and MELD score in patients with different Child-Pugh classifications. Significant correlations were found between the parameters of the ICG clearance test (K value and R(15)) and MELD score. A negative correlation was observed between K value and MELD score (r=-0.892, P < 0.05), while a positive correlation was observed between R(15) and MELD score (r=0.804, P < 0.05). CONCLUSIONS: The ICG clearance test and MELD score are good parameters for evaluating liver function. Moreover, K value and R(15) have significant correlations with MELD score, especially the K value, which may be a convenient and appropriate indicator to evaluate liver function of patients with liver cirrhosis.展开更多
AIM To establish an inducible liver injury mouse model and transplant human hepatocytes to obtain liverhumanized mice.METHODS We crossed three mouse strains,including albumin(Alb)-cre transgenic mice,inducible diphthe...AIM To establish an inducible liver injury mouse model and transplant human hepatocytes to obtain liverhumanized mice.METHODS We crossed three mouse strains,including albumin(Alb)-cre transgenic mice,inducible diphtheria toxin receptor(DTR) transgenic mice and severe combined immune deficient(SCID)-beige mice,to create Alb-cre/DTR/SCID-beige(ADSB) mice,which coincidentally harbor Alb-cre and DTR transgenes and are immunodeficient. As the Cre expression is driven by the liver-specific promoter Alb(encoding ALB),the DTR stop signal flanked by two lox P sites can be deleted in the ADSB mice,resulting in DTR expression in the liver. ADSB mice aged 8-10 wk were injected intraperitoneally(i.p.) with diphtheria toxin(DT) and liver damage was assessed by serum alanine aminotransferase(ALT) level. Two days later,mouse livers were sampled for histological analysis,and human hepatocytes were transplanted into the livers on the same day. A human ALB enzyme-linked immunosorbent assay was performed 7,14,21 and 28 d after transplantation. Human CD68 immunohistochemistry was performed 30 and 90 d after transplantation.RESULTS We crossed Alb-cre with DTR and SCID-beige mice to obtain ADSB mice. These mice were found to have liver damage 4 d after i.p. injection of 2.5 ng/g bodyweight DT. Bodyweight began to decrease on day 2,increased on day 7,and was lowest on day 4(range,10.5%-13.4%). Serum ALT activity began to increase on day 2 and reached a peak value of 289.7 ± 16.2 IU/m L on day 4,then returned to background values on day 7. After transplantation of human liver cells,peripheral blood human ALB level was 1580 ± 454.8 ng/m L(range,750.2-3064.9 ng/m L) after 28 d and Kupffer cells were present in the liver at 30 d in ADSB mice.CONCLUSION Human hepatocytes were successfully repopulated in the livers of ADSB mice. The inducible mouse model of humanized liver in ADSB mice may have functional applications,such as hepatocyte transplantation,hepatic regeneration and drug metabolism.展开更多
BACKGROUND: Acute liver failure (ALF) remains a dramatic and unpredictable disease with high morbidity and mortality. Early and accurate prognostic assessment of patients with ALF is critically important for optimum c...BACKGROUND: Acute liver failure (ALF) remains a dramatic and unpredictable disease with high morbidity and mortality. Early and accurate prognostic assessment of patients with ALF is critically important for optimum clinical pathway. DATA SOURCES: Five English-language medical databases, MEDLINE, Science Direct, OVID, Springer Link and Wiley Interscience were searched for articles on 'acute liver failure', 'prognosis', and related topics. RESULTS: Multi-variable prognostic models including the King's College Hospital criteria and the model for end-stage liver disease score have been widely used in determination of the prognosis of ALF, but the results are far from satisfactory. Other prognostic indicators including serum Gc-globulin, arterial blood lactate, serum phosphate, arterial blood ammonia, and serum alpha-fetoprotein are promising but await further assessement. CONCLUSIONS: A reliable prognostic model to be developed in the future should not only have predictive value for poor outcome but also help to predict the survival of patients without a liver transplantation. Further studies are necessary to assess the prognostic accuracy of any new models. (Hepatobiliary Pancreat Dis Int 2010; 9: 122-128)展开更多
Background: Positron emission tomography(PET) is a noninvasive method to characterize different metabolic activities of tumors, providing information for staging, prognosis, and therapeutic response of patients with c...Background: Positron emission tomography(PET) is a noninvasive method to characterize different metabolic activities of tumors, providing information for staging, prognosis, and therapeutic response of patients with cancer. The aim of this study was to evaluate the feasibility of18F-fludeoxyglucose(18F-FDG) and 3’-deoxy-3’-18F-fluorothymidine(18F-FLT) PET in predicting tumor biological characteristics of colorectal cancer liver metastasis.Methods: The uptake rate of18F-FDG and18F-FLT in SW480 and SW620 cells was measured via an in vitro cell uptake assay. The region of interest was drawn over the tumor and liver to calculate the maximum standardized uptake value ratio(tumor/liver) from PET images in liver metastasis model. The correlation between tracer uptake in liver metastases and VEGF, Ki67 and CD44 expression was evaluated by linear regression.Results: Compared to SW620 tumor-bearing mice, SW480 tumor-bearing mice presented a higher rate of liver metastases. The uptake rate of18F-FDG in SW480 and SW620 cells was 6.07% ± 1.19% and2.82% ± 0.15%, respectively(t = 4.69, P = 0.04); that of18F-FLT was 24.81% ± 0.45% and 15.57% ± 0.66%, respectively(t = 19.99, P < 0.001). Micro-PET scan showed that all parameters of FLT were significantly higher in SW480 tumors than those in SW620 tumors. A moderate relationship was detected between metastases in the liver and18F-FLT uptake in primary tumors(r = 0.73, P = 0.0019).18F-FLT uptake was also positively correlated with the expression of CD44 in liver metastases(r = 0.81, P = 0.0049).Conclusions: The uptake of18F-FLT in metastatic tumor reflects different biological behaviors of colon cancer cells.18F-FLT can be used to evaluate the metastatic potential of colorectal cancer in nude mice.展开更多
AIM： To investigate the prognostic value of the model for end-stage liver disease （MELD） and three new MELD-based models combination with serum sodium in decompensated cirrhosis patients-the MELD with the incorpora...AIM： To investigate the prognostic value of the model for end-stage liver disease （MELD） and three new MELD-based models combination with serum sodium in decompensated cirrhosis patients-the MELD with the incorporation of serum sodium （MELD-Na）, the integrated MELD （iMELD）, and the MELD to sodium （MESO） index. METHODS： A total of 166 patients with decompensated cirrhosis were enrolled into the study. MELD, MELD- Na, iMELD and MESO scores were calculated for each patient following the original formula on the first day of admission. All patients were followed up at least 1 year. The predictive prognosis related with the four models was determined by the area under the receiver operating characteristic curve （AUC） of the four parameters. Kaplan-Meier survival curves were made using the cut-offs identified by means of receiver operating characteristic （ROC）. RESULTS： Out of 166 patients, 38 patients with significantly higher MELD-Na （28.84 ± 2.43 vs 14.72 ± 0.60）, iMELD （49.04 ± 1.72 vs 35.52 ± 0.67）, MESO scores （1.59 ± 0.82 vs 0.99 ± 0.42） compared to the survivors died within 3 mo （P 〈 0.001）. Of 166 patients, 75 with markedly higher MELD-Na （23.01 ± 1.51 vs 13.78 ± 0.69）, iMELD （44.06 ± 1.19 vs 34.12 ± 0.69）, MESO scores （1.37 ± 0.70 vs 0.93 ± 0.40） than the survivors died within 1 year （P 〈 0.001）. At 3 mo of enrollment, the iMELD had the highest AUC （0.841）, and was followed by the MELD-Na （0.766）, MESO （0.723）, all larger than MELD （0.773）; At year, the iMELD still had the highest AUC （0.783）, the difference between the iMELD and MELD was statistically significant （P 〈 0.05）. Survival curves showed that the three new models were all clearly discriminated the patients who survived or died in short-term as well as intermediate-term （P 〈 0.001）. CONCLUSION： Three new models, changed with serum sodium （MELD-Na, iMELD, MESO） can exactly predict the prognosis of patients with decompensated cirrhosis for short and intermediate period, and may enhance the prognostic accuracy of MELD. The iMELD is better prognostic model for outcome prediction in patients with decompensated cirrhosis.展开更多
BACKGROUND: Controversy exists over whether living donor liver transplantation (LDLT) should be offered to patients with high Model for End-stage Liver Disease (MELD) scores. This study tried to determine whether a hi...BACKGROUND: Controversy exists over whether living donor liver transplantation (LDLT) should be offered to patients with high Model for End-stage Liver Disease (MELD) scores. This study tried to determine whether a high MELD score would result in inferior outcomes of right-lobe LDLT. METHODS: Among 411 consecutive patients who received right-lobe LDLT at our center, 143 were included in this study. The patients were divided into two groups according to their MELD scores: a high-score group (MELD score ≥25; n=75) and a low-score group (MELD score 【25; n=68). Their demographic data and perioperative conditions were compared. Univariable and multivariable analyses were performed to identify risk factors affecting patient survival. RESULTS: In the high-score group, more patients required preoperative intensive care unit admission (49.3% vs 2.9%; P【0.001), mechanical ventilation (21.3% vs 0%; P【0.001), or hemodialysis (13.3% vs 0%; P=0.005); the waiting time before LDLT was shorter (4 vs 66 days; P【0.001); more blood was transfused during operation (7 vs 2 units; P【0.001); patients stayed longer in the intensive care unit (6 vs 3 days; P【0.001) and hospital (21 vs 15 days; P=0.015) after transplantation;more patients developed early postoperative complications (69.3% vs 50.0%; P=0.018); and values of postoperative peak blood parameters were higher. However, the two groups had comparable hospital mortality. Graft survival and patient overall survival at one year (94.7% vs 95.6%; 95.9% vs 96.9%), three years (91.9% vs 92.6%; 93.2% vs 95.3%), and five years (90.2% vs 90.2%; 93.2% vs 95.3%) were also similar between the groups. CONCLUSIONS: Although the high-score group had signifi-cantly more early postoperative complications, the two groups had comparable hospital mortality and similar satisfactory rates of graft survival and patient overall survival. Therefore, a high MELD score should not be a contraindication to right-lobe LDLT if donor risk and recipient benefit are taken into full account.展开更多
AIM: To study the practical use of the model for endstage liver disease (MELD) on clinic and assess its validity by the concordance (C)-statistic in predicting the prognosis of the patient with severe viral hepatitis....AIM: To study the practical use of the model for endstage liver disease (MELD) on clinic and assess its validity by the concordance (C)-statistic in predicting the prognosis of the patient with severe viral hepatitis.METHODS: One hundred and twenty-one patients were divided into plasma exchange group and non-plasma exchange group, and were graded with MELD formula.The death rate was observed within 3 mo.RESULTS: Eighty-one patients died within 3 mo (35 cases in PE group, 46 cases in non-PE group). The mortality of patients in PE group whose MELD score between 20-30and 30-40 were 31.6% and 57.7%, respectively, but in non-PE cases they were 67.6%, 81.3% respectively.There was significant difference between PE group and non-PE group (P＜0.05). However, the mortality of patients whose MELD score higher than 40 were 93.3% in PE group and 100% in non-PE group and there was no significant difference between the two groups (P= 0.65＞0.05). The optimal cut-off values of MELD to predict the prognosis of patients were 30 in PE group whose sensitivity, specificity and C-statistic were 80.0%, 52.0% and 0.777, but in non-PE group they were 25, 82.6%, 86.7% and 0.869, respectively.CONCLUSION: The MELD score can act as a disease severity index for patients with severe viral hepatitis, and the mortality of the patient increases with the increase of the MELD score. The MELD can accurately predict the short-term prognosis of patients with severe viral hepatitis.展开更多
AIM To investigate the morphological changes in the process of heteroserum induced rat liver fibrosis and the mechanism of fibrogenesis of this model. METHODS A model of heteroserum induced rat liver fibrosis was...AIM To investigate the morphological changes in the process of heteroserum induced rat liver fibrosis and the mechanism of fibrogenesis of this model. METHODS A model of heteroserum induced rat liver fibrosis was established by intraperitoneal injection of porcine serum. In addition to the observation of the morphological changes of this model, the infiltration of eosinophils and mast cells were measured quantitatively and the deposition of IgG and complement C 3 was detected by immunofluorescence. RESULTS The rat liver fibrosis was induced successfully at the end of the 8th week after the injection of heteroserum. Besides the increase of hepatic stellate cells (HSC) during the process of liver fibrosis, proliferation and activation of primary mesenchyma cells (PMCs) were also found. In the early stage, the infiltration of eosinophils and mast cells was significantly increased and the deposition of IgG and complement C 3 was positive in the portal tracts and septa, while gradually reduced after the injection was stopped. CONCLUSIONS This model is suitable for the research on liver fibrogenesis; the pathogenesis of this model may be related with the allergen induced late phase reaction (LPR) caused by the injection of heteroserum, and the HSCs and the PMCs are important sources of ECM producing cells.展开更多
BACKGROUND:Decreased cardiac contractility has been observed in cirrhosis,suggesting a latent cardiomyopathy in these patients.This study was designed to evaluate left ventricular structure and function in patients wi...BACKGROUND:Decreased cardiac contractility has been observed in cirrhosis,suggesting a latent cardiomyopathy in these patients.This study was designed to evaluate left ventricular structure and function in patients with end-stage liver disease by the model for end-stage liver disease(MELD)scoring system.METHODS:We recruited 82 patients(72 male,10 female;mean age 50.3±8.9 years)with end-stage liver disease who underwent orthotopic liver transplantation between January 2002 and May 2008.Seventy-eight patients had cirrhosis and 4 had primary liver cancer.Patients were categorized into three groups on the basis of MELD score:≤9(27 patients,33%);10-19(40,49%);and≥20(15,18%).The relationship between MELD score and cardiac structure and function was determined.Preoperative assessments of blood biochemistry,blood coagulation,serum virology,echocardiography and electrocardiography were performed.RESULTS:MELD score was positively correlated with enlarged left atrial diameter,increased interventricular septum thickness(IVST),increased aortic flow,corrected QT interval(QTc)extension and cardiac output(P=0.033,0.002,0.000,0.000 and 0.009,respectively).International normalized ratio also had a correlation with the above parameters and enlarged left ventricular end-diastolic diameter(P=0.043,0.010,0.000,0.001,0.016 and 0.008,respectively).Serum creatinine was positively correlated with IVST(r=0.257,P=0.020),but negatively correlated with early maximal ventricular filling velocity/late diastolic or atrial velocity ratio(r=-0.300,P=0.006).A difference of QTc>440 ms among the three groups was statistically significant(χ2=9.791,P=0.007).CONCLUSIONS:Abnormalities in cardiac structure and function are common in patients with end-stage liver disease.MELD score is a practically useful approach for the assessment of cardiac function in such patients.展开更多
BACKGROUND: With the establishment of genetically modified and gene knock-out models, the mouse has become an important animal model for liver transplantation. We examined hepatic rearterialization after liver transpl...BACKGROUND: With the establishment of genetically modified and gene knock-out models, the mouse has become an important animal model for liver transplantation. We examined hepatic rearterialization after liver transplantation in a mouse model. METHODS: Orthotopic liver transplantation was performed in 70 mice and sham-operation was performed in a control group of 40 mice. Based on the 'two-cuff' method, a continuous suture approach was applied to the suprahepatic inferior vena cava and a cuff approach to the portal vein and the infrahepatic inferior vena cava. A biliary stent was inserted into the bile duct. The hepatic artery was reconstructed with end-to-side anastomosis. The survival rate of recipients was monitored at 24 hours, one week, and one month after the operation. Liver function and morphology were evaluated one month postoperatively. RESULTS: Postoperative survival rates were 94.3% at 24 hours, 91.4% at one week, and 85.7% at one month. No significant difference was seen between the experimental and control groups in liver function. The hepatic tissue preserved normal structure. CONCLUSION: Owing to its high survival rate and stability, this surgical approach is ideal for establishing an orthotopic liver transplantation mouse model with hepatic artery reconstruction. (Hepatobiliary Pancreat Dis Jut 2010; 9: 264-268)展开更多
基金supported by grants from the National Natural Science Foundation of China(81301275,81471736 and 81671760)the National Science and Technology Pillar Program during the Twelfth Five-Year Plan Period(2015BAI01B09)Heilongjiang Province Foundation for Returness(LC2013C38)
文摘BACKGROUND： Functional imaging such as CT perfusion can detect morphological and hemodynamic changes in he- patocellular carcinoma （HCC）. Pre-carcinoma and early HCC nodules are difficult to differentiate by observing only their hemodynamics changes. The present study aimed to investi- gate hemodynamic parameters and evaluate their differential diagnostic cut-off between pre-carcinoma and early HCC nodules using CT perfusion and receiver operating characteristic （ROC） curves. METHODS： Male Wistar rats were randomly divided into control （n=20） and experimental （n=70） groups. Diethylnitrosamine （DEN） was used to induce pre-carcinoma and early HCC nodules in the experimental group. Perfusion scanning was carried out on all survival rats discontinuously from 8 to 16 weeks. Hepatic portal perfusion （HPP）, hepatic arterial fraction （HAF）, hepatic arterial perfusion （HAP）, hepatic blood volume （HBV）, hepatic blood flow （HBF）, mean transit time （MTT） and permeability of capillary vessel surface （PS） data were provided by mathematical deconvolution model. The perfusion parameters were compared among the three groups of rats （control, pre-carcinoma and early HCC groups） using the Kruskal-Wallis test and analyzed with ROC curves. Histological examination of the liver tissues with hematoxylin and eosin staining was performed after CT scan.RESULTS： For HPP, HAF, HBV, HBF and MTT, there were significant differences among the three groups （P〈0.05）. HAF had the highest areas under the ROC curves： 0.80 （control vs pre-carcinoma groups） and 0.95 （control vs early HCC groups） with corresponding optimal cut-offs of 0.37 and 0.42, respectively. The areas under the ROC curves for HPP was 0.79 （control vs pre-carcinoma groups） and 0.92 （control vs early HCC groups） with corresponding optimal cut-offs of 136.60 mL/min/100 mg and 108.47 mL/min/100 mg, respectively. CONCLUSIONS： CT perfusion combined with ROC curve analysis is a new diagnosis model for distinguishing between pre-carcinoma and early HCC nodules. HAF and HPP are the ideal reference indices.
文摘The Josephinum Medical History Museum in Vienna houses an extensive collection of anatomical wax models,including a detailed model of the human liver(Figure 1).This unique collection was originally acquired for the Military Medical-Surgical Academy,established in Vienna in 1785 by Emperor Joseph II,who was also,at that time,the Archduke of Austria(1).
基金American Heart Association Award,No.24IVPHA1288417and FCT Fellowships,No.2022.13253.BDANA.
文摘The potential of induced pluripotent stem cells(iPSCs)for modeling and treating metabolic associated fatty liver disease(MAFLD)and metabolic associated steatohepatitis(MASH)is emerging.MAFLD is a growing global health concern,currently with limited treatment options.While primary mesenchymal stem cells hold promise,iPSCs offer a versatile alternative due to their ability to differentiate into various cell types,including iPSC-derived mesenchymal stem cells.However,challenges remain,including optimizing differentiation protocols,ensuring cell safety,and addressing potential tumorigenicity risks.In addition,iPSCs offer the possibility to generate complex cellular models,including three-dimensional organoid models,which are closer representations of the human disease than animal models.Those models would also be valuable for drug discovery and personalized medicine approaches.Overall,iPSCs and their derivatives offer new perspectives for advancing MAFLD/MASH research and developing novel therapeutic strategies.Further research is needed to overcome current limitations and translate this potential into effective clinical applications.
基金the funding from the National Natural Science Foundation of China No.52275294the National Key Research and Development Program of China(No.2018YFA0703000)。
文摘Constructing an in vitro vascularized liver tissue model that closely simulates the human liver is crucial for promoting cell proliferation,mimicking physiological heterogeneous structures,and recreating the cellular microenvironment.However,the layer-by-layer printing method is significantly constrained by the rheological properties of the bioink,making it challenging to form complex three-dimensional vascular structures in low-viscosity soft materials.To overcome this limitation,we developed a cross-linkable biphasic embedding medium by mixing low-viscosity biomaterials with gelatin microgel.This medium possesses yield stress and self-healing properties,facilitating efficient and continuous three-dimensional shaping of sacrificial ink within it.By adjusting the printing speed,we controlled the filament diameter,achieving a range from 250μm to 1000μm,and ensuring precise control over ink deposition locations and filament shapes.Using the in situ endothelialization method,we constructed complex vascular structures and ensured close adhesion between hepatocytes and endothelial cells.In vitro experiments demonstrated that the vascularized liver tissue model exhibited enhanced protein synthesis and metabolic function compared to mixed liver tissue.We also investigated the impact of varying vascular densities on liver tissue function.Transcriptome sequencing revealed that liver tissues with higher vascular density exhibited upregulated gene expression in metabolic and angiogenesis-related pathways.In summary,this method is adaptable to various materials,allowing the rheological properties of the supporting bath and the tissue's porosity to be modified using microgels,thus enabling precise regulation of the liver tissue microenvironment.Additionally,it facilitates the rapid construction of three-dimensional vascular structures within liver tissue.The resulting vascularized liver tissue model exhibits enhanced biological functionality,opening new opportunities for biomedical applications.
文摘BACKGROUND Liver transplantation aims to increase the survival of patients with end-stage liver diseases and improve their quality of life.The number of organs available for transplantation is lower than the demand.To provide fair organ distribution,predictive mortality scores have been developed.AIM To compare the Acute Physiology and Chronic Health Evaluation IV(APACHE IV),balance of risk(BAR),and model for end-stage liver disease(MELD)scores as predictors of mortality.METHODS Retrospective cohort study,which included 283 adult patients in the postoperative period of deceased donor liver transplantation from 2014 to 2018.RESULTS The transplant recipients were mainly male,with a mean age of 58.1 years.Donors were mostly male,with a mean age of 41.6 years.The median cold ischemia time was 3.1 hours,and the median intensive care unit stay was 5 days.For APACHE IV,a mean of 59.6 was found,BAR 10.7,and MELD 24.2.The 28-day mortality rate was 9.5%,and at 90 days,it was 3.5%.The 28-day mortality prediction for APACHE IV was very good[area under the curve(AUC):0.85,P<0.001,95%CI:0.76-0.94],P<0.001,BAR(AUC:0.70,P<0.001,95%CI:0.58–0.81),and MELD(AUC:0.66,P<0.006,95%CI:0.55-0.78),P<0.008.At 90 days,the data for APACHE IV were very good(AUC:0.80,P<0.001,95%CI:0.71–0.90)and moderate for BAR and MELD,respectively,(AUC:0.66,P<0.004,95%CI:0.55–0.77),(AUC:0.62,P<0.026,95%CI:0.51–0.72).All showed good discrimination between deaths and survivors.As for the best value for liver transplantation,it was significant only for APACHE IV(P<0.001).CONCLUSION The APACHE IV assessment score was more accurate than BAR and MELD in predicting mortality in deceased donor liver transplant recipients.
文摘In this editorial,we comment on the article by Teerasarntipan et al published in a recent issue of the World Journal of Gastroenterology.Dengue infection is a major mosquito-borne disease with global significance.Dengue-induced severe hepatitis(DISH)is a rare complication though severe,as it can lead to acute liver failure(ALF)with an incidence rate between 0.7%and 2.0%and mortality rates from 47.0%to 58.8%.In this context,the identification of patients at risk of ALF could improve prognosis in DISH patients.Teerasarntipan et al retrospectively enrolled 2532 dengue patients,counting 193 DISH and 20 ALF.The authors explored the prognostic role of liver-specific scores,as the model for end-stage liver disease(MELD)score,albumin-bilirubin(ALBI)score,easy(EZ)-ALBI score,and platelet-ALBI(PALBI)score.Univariate analysis identified international normalized ratio(INR),total bilirubin,albumin,and creatinine as independent laboratory factors associated with ALF,while age,gender,and liver comorbidities were not linked to in-hospital mortality.The presence of dengue shock syndrome significantly increased mortality,with an odds ratio(OR)of 28.05(95%CI:7.21-109.18,P<0.001).High INR and low albumin were laboratory markers associated with death from DISH,with ORs of 5.83(95%CI:2.59-13.12,P<0.001)and 0.15(95%CI:0.05-0.44,P<0.001),respectively.Multivariate analysis confirmed that INR remained the only significant predictor of both ALF and death,with adjusted ORs of 19.54(95%CI:3.37-113.38,P<0.001)and 3.86(95%CI:1.13-13.18,P=0.031),respectively.Among prognostic models,the MELD score performed best in predicting ALF,with a very high accuracy[area under the receiver operating characteristic curve(AUROC)of 0.929,87.5%sensitivity,89.3%specificity at a cutoff of 16],followed by the EZ-ALBI,ALBI,and PALBI scores,with AUROCs of 0.865,0.832,and 0.797,respectively.As MELD remains the best scoring system for predicting poor outcomes in DISH-related ALF,EZ-ALBI is a valid adjunct tool that could improve medical care in these patients.
文摘To analyze time intervals of inflammation and regeneration in a cholestatic rat liver model.METHODSIn 36 Lewis rats, divided into six groups of 6 animals (postoperative observation periods: 1, 2, 3, 4, 6, 8 wk), the main bile duct was ligated with two ligatures and observed for the periods mentioned above. For laboratory evaluation, cholestasis parameters (bilirubin, γ-GT), liver cell parameters (ASAT, ALAT) and liver synthesis parameters (quick, albumin) were determined. For histological analysis, HE, EvG, ASDCL and HMGB-1 stainings were performed. Furthermore, we used the mRNA of IL-33, GADD45a and p-21 for analyzing cellular stress and regeneration in cholestatic rats.RESULTSIn chemical laboratory and histological evaluation, a distinction between acute and chronic cholestatic liver injury with identification of inflammation and regeneration could be demonstrated by an increase in cholestasis (bilirubin: 1-wk group, 156.83 ± 34.12 μmol/L, P = 0.004) and liver cell parameters (ASAT: 2-wk group, 2.1 ± 2.19 μmol/L.s, P = 0.03; ALAT: 2-wk group, 1.03 ± 0.38 μmol/L.s, P = 0.03) after bile duct ligation (BDL). Histological evaluation showed an increase of bile ducts per portal field (3-wk group, 48 ± 6.13, P = 0.004) during the first four weeks after bile duct ligation. In addition to inflammation, which is an expression of acute cholestasis, there was an increase of necrotic areas in the histological sections (2-wk group, 1.38% ± 2.28% per slide, P = 0.002). Furthermore, the inflammation could be verified by ASDCL (4-wk group, 22 ± 5.93 positive cells per portal field, P = 0.041) and HMGB-1 [2-wk group, 13 ± 8.18 positive cells per field of view (FoV), P = 0.065] staining. Therefore, in summary of the laboratory evaluation and histological studies, acute cholestasis could be found during the first four weeks after bile duct ligation. Subsequently, the described parameters declined so that chronic cholestasis could be assumed. For quantification of secondary biliary cirrhosis, eosin staining was performed, which did not reveal any signs of liver remodeling, thus precluding the development of a chronic cholestasis model. Additionally, to establish the chronic cholestasis model, we evaluated liver regeneration capacity through measurements of IL-33, p-21 and GADD45a mRNA.CONCLUSIONWe created a chronic cholestasis model. The point of inflammatory and regenerative balance was reached after four weeks. This finding should be used for experimental approaches dealing with chronic cholestatic liver damage.
基金National Natural Science Foundation of China(Grant No.81573684 and 81530097)Beijing Municipal Science and Technology Project(Grant No.Z181100002218028)National Key Technology R&D Program “New Drug Innovation” of China(Grant No.2018ZX09711001-008-003)
文摘In pre-clinical phase of new drug development,it is particularly important to establish an in vitro model to mimic the metabolism situation of human body.The aim of the in vitro model is to reduce the usage of experimental animals and to make a more accurate prediction of the drug metabolism in vivo.Microfluidic chip is an emerging technology to establish predictive models.By integrating subcellular fractions,hepatocytes or liver tissue in the microfluidic chips,more predictive in vitro metabolism models can be established for drug development.The microfluidic platform offers dynamic and controlled fluids,as well as sophisticated liver tissue assembly to remodel the physiological and pathological microenvironment of liver in the human body.This review updates the microfluidic-based liver drug metabolism models since 2011,and summarizes the development of different models based on different chip vectors(subcellular components,primary hepatocytes,and tissue sections).It serves as a guide for newcomers to this dynamic field.
基金This work was supported by grants from the Agence Nationale pour la Recherche(ANR-16-RHUS-0006-PreciNASH).
文摘Background and Aims: To better understand nonalcoholic steatohepatitis (NASH) disease progression and to evaluate drug targets and compound activity, we undertook the devel-opment of an in vitro 3D model to mimic liver architecture and the NASH environment. Methods:We have developed an in vitro preclinical 3D NASH model by coculturing primary hu-man hepatocytes, human stellate cells, liver endothelial cells and Kupffer cells embedded in a hydrogel of rat collagen on a 96-well plate. A NASH-like environment was induced by ad-dition of medium containing free fatty acids and tumor ne-crosis factor-α. This model was then characterized by biochemical, imaging and transcriptomics analyses. Results:We succeeded in defining suitable culture conditions to main-tain the 3D coculture for up to 10 days in vitro, with the lowest level of steatosis and reproducible low level of inflammation and fibrosis. NASH disease was induced with a custom me-dium mimicking NASH features. The cell model exhibited the key NASH disease phenotypes of hepatocyte injury, steatosis, inflammation, and fibrosis. Hepatocyte injury was highlighted by a decrease of CYP3A4 expression and activity, without loss of viability up to day 10. Moreover, the model was able to stimulate a stable inflammatory and early fibrotic environ-ment, with expression and secretion of several cytokines. A global gene expression analysis confirmed the NASH induc-tion. Conclusions:This is a new in vitro model of NASH dis-ease consisting of four human primary cell-types that exhibits most features of the disease. The 10-day cell viability and cost effectiveness of the model make it suitable for medium throughput drug screening and provide attractive avenues to better understand disease physiology and to identify and characterize new drug targets.
文摘AIM To investigate whether the short-term prognosis of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF) could be improved by using a modified model for end-stage liver disease(MELD) including serum lactate.METHODS This clinical study was conducted at the First Affiliated Hospital, Fujian Medicine University, China. From 2009 to 2015, 236 patients diagnosed with HBV-related ACLF at our center were recruited for this 3-month followup study. Demographic data and serum lactate levels were collected from the patients. The MELD scores with or without serum lactate levels from survival and nonsurvival groups were recorded and compared.RESULTS Two hundred and thirty-six patients with HBV-ACLF were divided into two groups: survival group(S) andnon-survival group(NS). Compared with the NS group, the patients in survival the S group had a significantly lower level of serum lactate(3.11 ± 1.98 vs 4.67 ± 2.43, t = 5.43, P < 0.001) and MELD score(23.33 ± 5.42 vs 30.37 ± 6.58, t = 9.01, P = 0.023). Furthermore, serum lactate level was positively correlated with MELD score(r = 0.315, P < 0.001). Therefore, a modified MELD including serum lactate was developed by logistic regression analysis(0.314 × lactate + 0.172 × MELD-5.923). In predicting 3-month mortality using the MELD-LAC model, the patients from the S group had significantly lower baseline scores(-0.930 ± 1.34) when compared with those from the NS group(0.771 ± 1.32, t = 9.735, P < 0.001). The area under the receiver operating characteristic curve(AUROC) was 0.859 calculated by using the MELD-LAC model, which was significantly higher than that calculated by using the lactate level(0.790) or MELD alone(0.818). When the cutoff value was set at-0.4741, the sensitivity, specificity, positive predictive value and negative predictive value for predicting short-term mortality were 91.5%, 80.10%, 94.34% and 74.62%, respectively. When the MELD-LAC scores at baseline level were set at-0.5561 and 0.6879, the corresponding mortality rates within three months were 75% and 90%, respectively.CONCLUSION The short-term prognosis of HBV-related ACLF was improved by using a modified MELD including serum lactate from the present 6-year clinical study.
文摘BACKGROUND: The indocyanine green (ICG) clearance test (clearance rate (K) and retention rate at 15 minutes (R(15))) is a sensitive indicator to evaluate liver function. The model for end-stage liver disease (MELD) score has emerged as a useful tool for estimating the mortality of patients awaiting liver transplantation and has recently been validated on patients with liver diseases of various etiologies and severity. In this study, we investigated the correlation between the ICG clearance test and MELD score of patients with liver cirrhosis. METHODS: From June 2007 to March 2008, 52 patients with liver cirrhosis admitted to our center were classified into Child-Pugh class A (8 patients), B (14) and C (30). The ICG clearance test (K value and R(15)) was performed by ICG pulse spectrophotometry (DDG-3300K), and the MELD scores of patients were calculated. RESULTS: As the Child-Pugh classification of liver function gradually deteriorated, the K value decreased, while R(15) and MELD score increased. There were significant statistical differences in K value, R(15) and MELD score in patients with different Child-Pugh classifications. Significant correlations were found between the parameters of the ICG clearance test (K value and R(15)) and MELD score. A negative correlation was observed between K value and MELD score (r=-0.892, P < 0.05), while a positive correlation was observed between R(15) and MELD score (r=0.804, P < 0.05). CONCLUSIONS: The ICG clearance test and MELD score are good parameters for evaluating liver function. Moreover, K value and R(15) have significant correlations with MELD score, especially the K value, which may be a convenient and appropriate indicator to evaluate liver function of patients with liver cirrhosis.
基金Supported by Shanghai Science and Technology Development Foundation Project,No.12140900300Shanghai Municipal Commission of Health and Family Planning Project,No.20144Y0073+1 种基金Shanghai Public Health Clinical Center Project,No.2014M08National Science and Technology Major Project,No.2017ZX10304402-001-012
文摘AIM To establish an inducible liver injury mouse model and transplant human hepatocytes to obtain liverhumanized mice.METHODS We crossed three mouse strains,including albumin(Alb)-cre transgenic mice,inducible diphtheria toxin receptor(DTR) transgenic mice and severe combined immune deficient(SCID)-beige mice,to create Alb-cre/DTR/SCID-beige(ADSB) mice,which coincidentally harbor Alb-cre and DTR transgenes and are immunodeficient. As the Cre expression is driven by the liver-specific promoter Alb(encoding ALB),the DTR stop signal flanked by two lox P sites can be deleted in the ADSB mice,resulting in DTR expression in the liver. ADSB mice aged 8-10 wk were injected intraperitoneally(i.p.) with diphtheria toxin(DT) and liver damage was assessed by serum alanine aminotransferase(ALT) level. Two days later,mouse livers were sampled for histological analysis,and human hepatocytes were transplanted into the livers on the same day. A human ALB enzyme-linked immunosorbent assay was performed 7,14,21 and 28 d after transplantation. Human CD68 immunohistochemistry was performed 30 and 90 d after transplantation.RESULTS We crossed Alb-cre with DTR and SCID-beige mice to obtain ADSB mice. These mice were found to have liver damage 4 d after i.p. injection of 2.5 ng/g bodyweight DT. Bodyweight began to decrease on day 2,increased on day 7,and was lowest on day 4(range,10.5%-13.4%). Serum ALT activity began to increase on day 2 and reached a peak value of 289.7 ± 16.2 IU/m L on day 4,then returned to background values on day 7. After transplantation of human liver cells,peripheral blood human ALB level was 1580 ± 454.8 ng/m L(range,750.2-3064.9 ng/m L) after 28 d and Kupffer cells were present in the liver at 30 d in ADSB mice.CONCLUSION Human hepatocytes were successfully repopulated in the livers of ADSB mice. The inducible mouse model of humanized liver in ADSB mice may have functional applications,such as hepatocyte transplantation,hepatic regeneration and drug metabolism.
基金supported by grants from the NationalS&T Major Project for Infectious Disease Control of China(2008ZX10002-005)the National High Technology Research and Development Program of China(2006AA02A140)+1 种基金the National Natural Science Foundation of China(30630023)Zhejiang Health Science Foundation(2009A076)
文摘BACKGROUND: Acute liver failure (ALF) remains a dramatic and unpredictable disease with high morbidity and mortality. Early and accurate prognostic assessment of patients with ALF is critically important for optimum clinical pathway. DATA SOURCES: Five English-language medical databases, MEDLINE, Science Direct, OVID, Springer Link and Wiley Interscience were searched for articles on 'acute liver failure', 'prognosis', and related topics. RESULTS: Multi-variable prognostic models including the King's College Hospital criteria and the model for end-stage liver disease score have been widely used in determination of the prognosis of ALF, but the results are far from satisfactory. Other prognostic indicators including serum Gc-globulin, arterial blood lactate, serum phosphate, arterial blood ammonia, and serum alpha-fetoprotein are promising but await further assessement. CONCLUSIONS: A reliable prognostic model to be developed in the future should not only have predictive value for poor outcome but also help to predict the survival of patients without a liver transplantation. Further studies are necessary to assess the prognostic accuracy of any new models. (Hepatobiliary Pancreat Dis Int 2010; 9: 122-128)
基金supported by grants from the National Natural Science Foundation of China(81471736 and 81671760)the National Science and Technology Pillar Program during the Twelfth Five-Year Plan Period(2015BAI01B09)Project of Research Foundation of the Talent of Scientific and Technical Innovation of Harbin City(2016RAXYJ063)
文摘Background: Positron emission tomography(PET) is a noninvasive method to characterize different metabolic activities of tumors, providing information for staging, prognosis, and therapeutic response of patients with cancer. The aim of this study was to evaluate the feasibility of18F-fludeoxyglucose(18F-FDG) and 3’-deoxy-3’-18F-fluorothymidine(18F-FLT) PET in predicting tumor biological characteristics of colorectal cancer liver metastasis.Methods: The uptake rate of18F-FDG and18F-FLT in SW480 and SW620 cells was measured via an in vitro cell uptake assay. The region of interest was drawn over the tumor and liver to calculate the maximum standardized uptake value ratio(tumor/liver) from PET images in liver metastasis model. The correlation between tracer uptake in liver metastases and VEGF, Ki67 and CD44 expression was evaluated by linear regression.Results: Compared to SW620 tumor-bearing mice, SW480 tumor-bearing mice presented a higher rate of liver metastases. The uptake rate of18F-FDG in SW480 and SW620 cells was 6.07% ± 1.19% and2.82% ± 0.15%, respectively(t = 4.69, P = 0.04); that of18F-FLT was 24.81% ± 0.45% and 15.57% ± 0.66%, respectively(t = 19.99, P < 0.001). Micro-PET scan showed that all parameters of FLT were significantly higher in SW480 tumors than those in SW620 tumors. A moderate relationship was detected between metastases in the liver and18F-FLT uptake in primary tumors(r = 0.73, P = 0.0019).18F-FLT uptake was also positively correlated with the expression of CD44 in liver metastases(r = 0.81, P = 0.0049).Conclusions: The uptake of18F-FLT in metastatic tumor reflects different biological behaviors of colon cancer cells.18F-FLT can be used to evaluate the metastatic potential of colorectal cancer in nude mice.
文摘AIM： To investigate the prognostic value of the model for end-stage liver disease （MELD） and three new MELD-based models combination with serum sodium in decompensated cirrhosis patients-the MELD with the incorporation of serum sodium （MELD-Na）, the integrated MELD （iMELD）, and the MELD to sodium （MESO） index. METHODS： A total of 166 patients with decompensated cirrhosis were enrolled into the study. MELD, MELD- Na, iMELD and MESO scores were calculated for each patient following the original formula on the first day of admission. All patients were followed up at least 1 year. The predictive prognosis related with the four models was determined by the area under the receiver operating characteristic curve （AUC） of the four parameters. Kaplan-Meier survival curves were made using the cut-offs identified by means of receiver operating characteristic （ROC）. RESULTS： Out of 166 patients, 38 patients with significantly higher MELD-Na （28.84 ± 2.43 vs 14.72 ± 0.60）, iMELD （49.04 ± 1.72 vs 35.52 ± 0.67）, MESO scores （1.59 ± 0.82 vs 0.99 ± 0.42） compared to the survivors died within 3 mo （P 〈 0.001）. Of 166 patients, 75 with markedly higher MELD-Na （23.01 ± 1.51 vs 13.78 ± 0.69）, iMELD （44.06 ± 1.19 vs 34.12 ± 0.69）, MESO scores （1.37 ± 0.70 vs 0.93 ± 0.40） than the survivors died within 1 year （P 〈 0.001）. At 3 mo of enrollment, the iMELD had the highest AUC （0.841）, and was followed by the MELD-Na （0.766）, MESO （0.723）, all larger than MELD （0.773）; At year, the iMELD still had the highest AUC （0.783）, the difference between the iMELD and MELD was statistically significant （P 〈 0.05）. Survival curves showed that the three new models were all clearly discriminated the patients who survived or died in short-term as well as intermediate-term （P 〈 0.001）. CONCLUSION： Three new models, changed with serum sodium （MELD-Na, iMELD, MESO） can exactly predict the prognosis of patients with decompensated cirrhosis for short and intermediate period, and may enhance the prognostic accuracy of MELD. The iMELD is better prognostic model for outcome prediction in patients with decompensated cirrhosis.
文摘BACKGROUND: Controversy exists over whether living donor liver transplantation (LDLT) should be offered to patients with high Model for End-stage Liver Disease (MELD) scores. This study tried to determine whether a high MELD score would result in inferior outcomes of right-lobe LDLT. METHODS: Among 411 consecutive patients who received right-lobe LDLT at our center, 143 were included in this study. The patients were divided into two groups according to their MELD scores: a high-score group (MELD score ≥25; n=75) and a low-score group (MELD score 【25; n=68). Their demographic data and perioperative conditions were compared. Univariable and multivariable analyses were performed to identify risk factors affecting patient survival. RESULTS: In the high-score group, more patients required preoperative intensive care unit admission (49.3% vs 2.9%; P【0.001), mechanical ventilation (21.3% vs 0%; P【0.001), or hemodialysis (13.3% vs 0%; P=0.005); the waiting time before LDLT was shorter (4 vs 66 days; P【0.001); more blood was transfused during operation (7 vs 2 units; P【0.001); patients stayed longer in the intensive care unit (6 vs 3 days; P【0.001) and hospital (21 vs 15 days; P=0.015) after transplantation;more patients developed early postoperative complications (69.3% vs 50.0%; P=0.018); and values of postoperative peak blood parameters were higher. However, the two groups had comparable hospital mortality. Graft survival and patient overall survival at one year (94.7% vs 95.6%; 95.9% vs 96.9%), three years (91.9% vs 92.6%; 93.2% vs 95.3%), and five years (90.2% vs 90.2%; 93.2% vs 95.3%) were also similar between the groups. CONCLUSIONS: Although the high-score group had signifi-cantly more early postoperative complications, the two groups had comparable hospital mortality and similar satisfactory rates of graft survival and patient overall survival. Therefore, a high MELD score should not be a contraindication to right-lobe LDLT if donor risk and recipient benefit are taken into full account.
文摘AIM: To study the practical use of the model for endstage liver disease (MELD) on clinic and assess its validity by the concordance (C)-statistic in predicting the prognosis of the patient with severe viral hepatitis.METHODS: One hundred and twenty-one patients were divided into plasma exchange group and non-plasma exchange group, and were graded with MELD formula.The death rate was observed within 3 mo.RESULTS: Eighty-one patients died within 3 mo (35 cases in PE group, 46 cases in non-PE group). The mortality of patients in PE group whose MELD score between 20-30and 30-40 were 31.6% and 57.7%, respectively, but in non-PE cases they were 67.6%, 81.3% respectively.There was significant difference between PE group and non-PE group (P＜0.05). However, the mortality of patients whose MELD score higher than 40 were 93.3% in PE group and 100% in non-PE group and there was no significant difference between the two groups (P= 0.65＞0.05). The optimal cut-off values of MELD to predict the prognosis of patients were 30 in PE group whose sensitivity, specificity and C-statistic were 80.0%, 52.0% and 0.777, but in non-PE group they were 25, 82.6%, 86.7% and 0.869, respectively.CONCLUSION: The MELD score can act as a disease severity index for patients with severe viral hepatitis, and the mortality of the patient increases with the increase of the MELD score. The MELD can accurately predict the short-term prognosis of patients with severe viral hepatitis.
文摘AIM To investigate the morphological changes in the process of heteroserum induced rat liver fibrosis and the mechanism of fibrogenesis of this model. METHODS A model of heteroserum induced rat liver fibrosis was established by intraperitoneal injection of porcine serum. In addition to the observation of the morphological changes of this model, the infiltration of eosinophils and mast cells were measured quantitatively and the deposition of IgG and complement C 3 was detected by immunofluorescence. RESULTS The rat liver fibrosis was induced successfully at the end of the 8th week after the injection of heteroserum. Besides the increase of hepatic stellate cells (HSC) during the process of liver fibrosis, proliferation and activation of primary mesenchyma cells (PMCs) were also found. In the early stage, the infiltration of eosinophils and mast cells was significantly increased and the deposition of IgG and complement C 3 was positive in the portal tracts and septa, while gradually reduced after the injection was stopped. CONCLUSIONS This model is suitable for the research on liver fibrogenesis; the pathogenesis of this model may be related with the allergen induced late phase reaction (LPR) caused by the injection of heteroserum, and the HSCs and the PMCs are important sources of ECM producing cells.
基金supported by a grant from the Science and Technology Bureau of Liaoning Province,China(2007225011-1)
文摘BACKGROUND:Decreased cardiac contractility has been observed in cirrhosis,suggesting a latent cardiomyopathy in these patients.This study was designed to evaluate left ventricular structure and function in patients with end-stage liver disease by the model for end-stage liver disease(MELD)scoring system.METHODS:We recruited 82 patients(72 male,10 female;mean age 50.3±8.9 years)with end-stage liver disease who underwent orthotopic liver transplantation between January 2002 and May 2008.Seventy-eight patients had cirrhosis and 4 had primary liver cancer.Patients were categorized into three groups on the basis of MELD score:≤9(27 patients,33%);10-19(40,49%);and≥20(15,18%).The relationship between MELD score and cardiac structure and function was determined.Preoperative assessments of blood biochemistry,blood coagulation,serum virology,echocardiography and electrocardiography were performed.RESULTS:MELD score was positively correlated with enlarged left atrial diameter,increased interventricular septum thickness(IVST),increased aortic flow,corrected QT interval(QTc)extension and cardiac output(P=0.033,0.002,0.000,0.000 and 0.009,respectively).International normalized ratio also had a correlation with the above parameters and enlarged left ventricular end-diastolic diameter(P=0.043,0.010,0.000,0.001,0.016 and 0.008,respectively).Serum creatinine was positively correlated with IVST(r=0.257,P=0.020),but negatively correlated with early maximal ventricular filling velocity/late diastolic or atrial velocity ratio(r=-0.300,P=0.006).A difference of QTc>440 ms among the three groups was statistically significant(χ2=9.791,P=0.007).CONCLUSIONS:Abnormalities in cardiac structure and function are common in patients with end-stage liver disease.MELD score is a practically useful approach for the assessment of cardiac function in such patients.
基金supported by a grant from the National Natural Science Foundation of China(No.30772055)
文摘BACKGROUND: With the establishment of genetically modified and gene knock-out models, the mouse has become an important animal model for liver transplantation. We examined hepatic rearterialization after liver transplantation in a mouse model. METHODS: Orthotopic liver transplantation was performed in 70 mice and sham-operation was performed in a control group of 40 mice. Based on the 'two-cuff' method, a continuous suture approach was applied to the suprahepatic inferior vena cava and a cuff approach to the portal vein and the infrahepatic inferior vena cava. A biliary stent was inserted into the bile duct. The hepatic artery was reconstructed with end-to-side anastomosis. The survival rate of recipients was monitored at 24 hours, one week, and one month after the operation. Liver function and morphology were evaluated one month postoperatively. RESULTS: Postoperative survival rates were 94.3% at 24 hours, 91.4% at one week, and 85.7% at one month. No significant difference was seen between the experimental and control groups in liver function. The hepatic tissue preserved normal structure. CONCLUSION: Owing to its high survival rate and stability, this surgical approach is ideal for establishing an orthotopic liver transplantation mouse model with hepatic artery reconstruction. (Hepatobiliary Pancreat Dis Jut 2010; 9: 264-268)
