Biochemistry and transcriptome analysis reveal condensed tannins alleviate liver injury induced by regulating cholesterol metabolism pathway

Free cholesterol has been considered to be a critical risk factor of nonalcoholic fatty liver disease(NAFLD).It remains unknown whether dietary intake of condensed tannins(CTs)have distinguishable effects to alleviate liver damage caused by a high cholesterol diet.Male C57BL/6 mice were fed a high cholesterol diet for 6 weeks,and given CTs treatment at a dosage of 200 mg/(kg·day)at the same time.The results indicated that compared with mice fed a normal diet,a high cholesterol diet group resulted in significant weight loss,dysregulation of lipid metabolism in blood and liver,and oxidative stress in the liver,but CTs treatment dramatically reversed these negative effects.Hematoxylin and eosin(H&E)staining and frozen section observation manifested that CTs treatment could effectively reduce the deposition of liver cholesterol and tissue necrosis caused by high cholesterol intake.CTs alleviated liver injury mainly by regulating the expression of related genes in cholesterol metabolism pathway and AMPK phosphorylation.Our results confirmed that CTs have remarkable cholesterol lowering and anti-liver injury effects in vivo.

Trend of robot-assisted surgery system in gastrointestinal and liver surgery: A bibliometric analysis

BACKGROUND Robot-assisted gastrointestinal and liver surgery has been an important development direction in the field of surgery in recent years and it is also one of the fastest developing and most concerning fields in surgical operations.AIM To illustrate the major areas of research and forward-looking directions over the past twenty-six years.METHODS Using the Web of Science Core Collection database,a comprehensive review of scholarly articles pertaining to robot-assisted gastrointestinal and liver surgery was researched out between 2000 and 2023.We used Citespace(Version 6.2.4)and Bibliometrix package(Version 4.3.0)to visualize the analysis of all publications including country,institutional affiliations,authors,and keywords.RESULTS In total,346 articles were retrieved.Surgical Endoscopy had with the largest number of publications and was cited in this field.The United States was a core research country in this field.Yonsei University was the most productive institution.The current focus of this field is on rectal surgery,long-term prognosis,perioperative management,previous surgical experience,and the learning curve.CONCLUSION The scientific interest in robot-assisted gastrointestinal and liver surgery has experienced a significant rise since 1997.This study provides new perspectives and ideas for future research in this field.

Causal association between 731 immunocyte phenotypes and liver cirrhosis: A bidirectional two-sample mendelian randomization analysis

BACKGROUND Liver cirrhosis is a progressive hepatic disease whose immunological basis has attracted increasing attention.However,it remains unclear whether a concrete causal association exists between immunocyte phenotypes and liver cirrhosis.AIM To explore the concrete causal relationships between immunocyte phenotypes and liver cirrhosis through a mendelian randomization(MR)study.METHODS Data on 731 immunocyte phenotypes were obtained from genome-wide assoc-iation studies.Liver cirrhosis data were derived from the Finn Gen dataset,which included 214403 individuals of European ancestry.We used inverse variable weighting as the primary analysis method to assess the causal relationship.Sensitivity analyses were conducted to evaluate heterogeneity and horizontal pleiotropy.RESULTS The MR analysis demonstrated that 11 immune cell phenotypes have a positive association with liver cirrhosis[P<0.05,odds ratio(OR)>1]and that 9 immu-nocyte phenotypes were negatively correlated with liver cirrhosis(P<0.05,OR<1).Liver cirrhosis was positively linked to 9 immune cell phenotypes(P<0.05,OR>1)and negatively linked to 10 immune cell phenotypes(P<0.05;OR<1).None of these associations showed heterogeneity or horizontally pleiotropy(P>0.05).CONCLUSION This bidirectional two-sample MR study demonstrated a concrete causal association between immunocyte phenotypes and liver cirrhosis.These findings offer new directions for the treatment of liver cirrhosis.

Influence of donor age on liver transplantation outcomes: A multivariate analysis and comparative study

BACKGROUND The growing disparity between the rising demand for liver transplantation(LT)and the limited availability of donor organs has prompted a greater reliance on older liver grafts.Traditionally,utilizing livers from elderly donors has been associated with outcomes inferior to those achieved with grafts from younger donors.By accounting for additional risk factors,we hypothesize that the utili-zation of older liver grafts has a relatively minor impact on both patient survival and graft viability.AIM To evaluate the impact of donor age on LT outcomes using multivariate analysis and comparing young and elderly donor groups.METHODS In the period from April 2013 to December 2018,656 adult liver transplants were performed at the University Hospital Merkur.Several multivariate Cox propor-tional hazards models were developed to independently assess the significance of donor age.Donor age was treated as a continuous variable.The approach involved univariate and multivariate analysis,including variable selection and assessment of interactions and transformations.Additionally,to exemplify the similarity of using young and old donor liver grafts,the group of 87 recipients of elderly donor liver grafts(≥75 years)was compared to a group of 124 recipients of young liver grafts(≤45 years)from the dataset.Survival rates of the two groups were estimated using the Kaplan-Meier method and the log-rank test was used to test the differences between groups.RESULTS Using multivariate Cox analysis,we found no statistical significance in the role of donor age within the constructed models.Even when retained during the entire model development,the donor age's impact on survival remained insignificant and transformations and interactions yielded no substantial effects on survival.Consistent insigni-ficance and low coefficient values suggest that donor age does not impact patient survival in our dataset.Notably,there was no statistical evidence that the five developed models did not adhere to the proportional hazards assumption.When comparing donor age groups,transplantation using elderly grafts showed similar early graft function,similar graft(P=0.92),and patient survival rates(P=0.86),and no significant difference in the incidence of postoperative complications.CONCLUSION Our center's experience indicates that donor age does not play a significant role in patient survival,with elderly livers performing comparably to younger grafts when accounting for other risk factors.

A Bioinformatics Analysis of FAM3A to Identify its Potential Role as a Biomarker in Liver Hepatocellular Cancer

Liver hepatocellular cancer(LIHC)is positioned as the third cancer with the highest mortalities worldwide,and high mortalities are associated with late diagnosis and recurrence.This study advances bioinformatics analysis of FAM3A expression in LIHC to evaluate its potential as a prognostic,diagnostic and therapeutic biomarker.Bioinformatics tools such as UALCAN,GEPIA2,KM plotter,TIMER2 and cBioPortal are employed to conduct analysis.Initially,the expression analysis revealed up-regulation of FAM3A in LIHC based on various variables.Further,the study observed that FAM3A methylation regulates expression as variation in methylation level of FAM3A was assessed in LIHC.Moreover,this over-expression of FAM3A results in poor overall survival(OS)in LIHC patients.All of these proposed that FAM3A has a role in the progression and development of LIHC.While examined association of FAM3A expression and infiltration level of CD8+T cells in LIHC patients using TIMER2 revealed that FAM3A has a positive correlation with purity in LIHC that highlights the molecular landscape.Analysis of genetic alteration revealed minute role of FAM3A in LIHC still provides valuable insight.Overall,our findings reveal that FAM3A has potential as diagnostic,therapeutic and prognostic biomarkers in LIHC.

Global trends and hotspots of treatment for nonalcoholic fatty liver disease:A bibliometric and visualization analysis(2010-2023)

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is chronic,with its progression leading to liver fibrosis and end-stage cirrhosis.Although NAFLD is increasingly common,no treatment guideline has been established.Many mechanistic studies and drug trials have been conducted for new drug development to treat NAFLD.An up-to-date overview on the knowledge structure of NAFLD through bibliometrics,focusing on research hotspots,is necessary to reveal the rational and timely directions of development in this field.AIM To research the latest literature and determine the current trends in treatment for NAFLD.METHODS Publications related to treatment for NAFLD were searched on the Web of Science Core Collection database,from 2010 to 2023.VOSviewers,CiteSpace,and R package“bibliometrix”were used to conduct this bibliometric analysis.The key information was extracted,and the results of the cluster analysis were based on network data for generating and investigating maps for country,institution,journal,and author.Historiography analysis,bursts and cluster analysis,cooccurrence analysis,and trend topic revealed the knowledge structure and research hotspots in this field.GraphPad Prism 9.5.1.733 and Microsoft Office Excel 2019 were used for data analysis and visualization.RESULTS In total,10829 articles from 120 countries(led by China and the United States)and 8785 institutions were included.The number of publications related to treatment for NAFLD increased annually.While China produced the most publications,the United States was the most cited country,and the United Kingdom collaborated the most from an international standpoint.The University of California-San Diego,Shanghai Jiao Tong University,and Shanghai University of Traditional Chinese Medicine produced the most publications of all the research institutions.The International Journal of Molecular Sciences was the most frequent journal out of the 1523 total journals,and Hepatology was the most cited and co-cited journal.Sanyal AJ was the most cited author,the most co-cited author was Younossi ZM,and the most influential author was Loomba R.The most studied topics included the epidemiology and mechanism of NAFLD,the development of accurate diagnosis,the precise management of patients with NAFLD,and the associated metabolic comorbidities.The major cluster topics were“emerging drug,”“glucagon-like peptide-1 receptor agonist,”“metabolic dysfunction-associated fatty liver disease,”“gut microbiota,”and“glucose metabolism.”CONCLUSION The bibliometric study identified recent research frontiers and hot directions,which can provide a valuable reference for scholars researching treatments for NAFLD.

Laparoscopic liver resection for hepatocellular carcinoma complicated with significant portal hypertension:A propensity score-matched survival analysis

Background: Significant portal hypertension(SPH) is a relative contraindication for patients with resectable hepatocellular carcinoma(HCC). However, increasing evidence indicates that liver resection is feasible for HCC patients with SPH. Methods: HCC patients with cirrhosis who underwent laparoscopic liver resection(LLR) in two centers from January 2013 to April 2018 were included. Surgical and survival outcomes were analyzed to explore potential prognostic factors. Propensity score matching(PSM) analysis was performed to minimize bias. Results: A total of 165 patients were divided into two groups based on the presence(SPH, n = 76) or absence(non-SPH, n = 89) of SPH. Patients in the SPH group had longer operative time, more blood loss, and more advanced TNM stage than patients in the non-SPH group( P < 0.05). However, there were no significant differences in the postoperative 90-day mortality rate( n = 0), overall postoperative complications(47.4% vs. 41.6%, P = 0.455), Clavien-Dindo classification( P = 0.347), conversion to open surgery(9.2% vs. 6.7%, P = 0.557), or length of hospitalization(16 vs. 15 days, P = 0.203) between the SPH and non-SPH groups before PSM. Similar results were obtained after PSM. The 1-, 3-, and 5-year overall survival(OS) and recurrence-free survival rates in the SPH group were not significantly different from those in the non-SPH group both before and after PSM(log-rank P > 0.05). After PSM, alpha-fetoprotein(AFP) ≥ 400 μg/L [hazard ratio(HR) = 4.71, 95% confidence interval(CI): 2.69-8.25], ascites(HR = 2.18, 95% CI: 1.30-3.66), American Society of Anesthesiologists(ASA) classification(Ⅲ vs. Ⅱ)(HR = 2.13, 95% CI: 1.11-4.07) and tumor diameter > 5 cm(HR = 3.91, 95% CI: 2.02-7.56) independently predicted worse OS. Conclusions: LLR for patients with HCC complicated with SPH appears feasible at the price of increasing operative time and blood loss. AFP, ascites, ASA classification and tumor diameter may predict the prognosis of HCC complicated with SPH after LLR.

Prognostic Factors of Liver Transplantation for Hepatocellular Carcinoma: A Surveillance, Epidemiology, and End Results (SEER) Database Analysis

Objective We aimed to identify new,more accurate risk factors of liver transplantation for liver cancer through using the Surveillance,Epidemiology,and End Results(SEER)database.Methods Using the SEER database,we identified patients that had undergone surgical resection for non-metastatic hepatocellular carcinoma(HCC)and subsequent liver transplantation between 2010 and 2017.Overall survival(OS)was estimated using Kaplan-Meier plotter.Cox proportional hazards regression modelling was used to identify factors independently associated with recurrent disease[presented as adjusted hazard ratios(HR)with 95%CIs].Results Totally,1530 eligible patients were included in the analysis.There were significant differences in ethnicity(P=0.04),cancer stage(P<0.001),vascular invasion(P<0.001)and gall bladder involvement(P<0.001)between the groups that survived,died due to cancer,or died due to other causes.In the Cox regression model,there were no significant differences in OS at 5 years with different operative strategies(autotransplantation versus allotransplantation),nor at survival at 1 year with neoadjuvant radiotherapy.However,neoadjuvant radiotherapy did appear to improve survival at both 3 years(HR:0.540,95%CI:0.326–0.896,P=0.017)and 5 years(HR:0.338,95%CI:0.153–0.747,P=0.007)from diagnosis.Conclusion This study demonstrated differences in patient characteristics between prognostic groups after liver resection and transplantation for HCC.These criteria can be used to inform patient selection and consent in this setting.Preoperative radiotherapy may improve long-term survival post-transplantation.

Global scientific production of robotic liver resection from 2003 to 2022:A bibliometric analysis

Objective:With the widespread application of robotic liver surgery,the body of literature related to robotic liver resection is growing.However,there is a lack of understanding of the publication activities surrounding robotic liver resection research.This bibliometric study aimed to detect the global publication distributions of robotic liver resection research over the past 20 years.Methods:Articles on robotic liver resection published from January 1,2003 to August 31,2022 were extracted from the Web of Science Core Collection database.The publication language was restricted to English.Literature distribution analyses were performed at the country/region,institution,author,and journal levels.In addition,each author's productivity was assessed with Lotka's law.Academic influence was assessed by local citation score and global citation score.The keywords evolution was also analyzed.R software and HistCite were applied for the analyses.Results:A total of 685 articles were identified,with 4107 local citations and 9458 global citations.These articles were published in 156 journals and written by 2449 authors from 785 institutions in 49 countries/regions.The cumulative publication number of the last 5 years accounted for 66.3%(454/685)of the total publication number.The USA played a leading role in the publication output(212,30.9%),followed by Italy(120,17.5%)and China(104,15.2%).The three countries also had the most citations.Yonsei University from South Korea had the highest publication number(30,4.4%).The Asian Journal of Surgery published the most articles(51,7.4%),and Surgical Endoscopy and Other Interventional Techniques had the most local citations(575)and global citations(1115).Sucandy published 44 articles,ranking first in productivity.Choi had many more citations than other scholars,with 465 local citations and 1253 global citations.Lotka's law reflected that the majority of the authors(1783,72.8%)wrote one document.The top 5 most prominent keywords were“surgery”,“hepatocellular-carcinoma”,“outcomes”,“hepatectomy”,and“experience”.Conclusion:The number of publications on robotic liver resection research has been rapidly increasing over the last 20 years.The most prolific countries/regions and institutions also had strong academic influence.The articles,institutions and authors with high citations mainly came from USA,China,South Korea,Italy,and Singapore.The research hotspots shifted from survival to complications,mortality,and augmented reality.

Correction:Propensity-matched analysis of patients with intrahepatic cholangiocarcinoma or mixed hepatocellularcholangiocarcinoma and hepatocellular carcinoma undergoing a liver transplant

Rereading the article“Propensity-matched analysis of patients with intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma and hepatocellular carcinoma undergoing a liver transplant”(DOI:10.5306/wjco.v13.i8.688),published on August 24,we observe,with concern,that figures 3 and 4 are wrong.The authors have attached the correct figures for correction.

Value of Texture Analysis on Gadoxetic Acid-enhanced MR for Detecting Liver Fibrosis in a Rat Model

Objective To explore the ability of texture analysis of gadoxetic acid-enhanced magnetic resonance imaging(MRI) T1 mapping images, as well as T1-weighted(T1 W), T2-weighted(T2 W) and apparent diffusion coefficient(ADC) maps for distinguishing between varying degrees of hepatic fibrosis in an experimental rat model.Methods Liver fibrosis in rats was induced by carbon tetrachloride intraperitoneal injection for 4–12 weeks(n = 30). In the control group(n = 10) normal saline was applied. The MRI protocol contained T2 W, diffusion weighted imaging, pre-and post-contrast image series of T1 W and T1 mapping images. METAVIR score was used to grade liver fibrosis as normal(F0), mild fibrosis(F1–2), and advanced fibrosis(F3–4). Texture parameters including mean gray-level intensity(Mean), standard deviation(SD), Entropy, mean of positive pixels(MPP), Skewness, and Kurtosis were obtained. Nonparametric Mann-Whitney U test was used to compare the average value of each texture parameter in each sequence for assessing the difference between F0 and F≥1 as well as F0–2 and F3–4. Receiver operating characteristic(ROC) curves were obtained to assess the diagnosing accuracy of the parameters for differentiating no liver fibrosis from liver fibrosis and rats with liver fibrosis grading F0–2 from those with grading F3–4. The area under ROC curve(AUC) was calculated to evaluate the diagnostic efficiency of texture parameters.Results Finally, 20 rats completed MR T1 mapping image scan. The pathologic staging of these 20 rats was no fibrosis(F0, n = 6), mild fibrosis(F1–2, n = 5) and advanced fibrosis(F3–4, n = 9). On pre-contrast T1 mapping image, Entropy was seen to be statistically significant higher in the F≥1 group than that in the F0 group at each spatial scaling factor(SSF) setting(P = 0.015, 0.015, 0.015, 0.013, 0.015 and 0.018 respectively to SSF = 0, 2, 3, 4,5, 6), and Mean of the F≥1 rats was statistically significant higher than that of the F0 rats at SSF 4, 5, 6(P = 0.004, 0.006, and 0.013, respectively). Entropy and Mean showed a moderate diagnostic performance in most SSF settings of T1 mapping pre-contrast images for differentiation of normal liver from liver fibrosis.Conclusion Certain texture features of gadoxetic acid-enhanced MR images, especially the Entropy of noncontrast T1 mapping image, was found to be a useful biomarker for the diagnosis of liver fibrosis.

Multi-factor analysis of initial poor graft function after orthotopic liver transplantation

BACKGROUND: In the early period of orthotopic liver transplantation (OLT), initial poor graft function (IPGF) is one of the complications which leads to primary graft non-function (PGNF) in serious cases. This study set out to establish the clinical risk factors resulting in IPGF after OLT. METHODS: Eighty cases of OLT were analyzed. The IPGF group consisted of patients with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) above 1500 IU/L within 72 hours after OLT, while those in the non-IPGF group had values below 1500 IU/L. Recipient-associated factors before OLT analyzed were age, sex, primary liver disease and Child-Pugh classification; factors analyzed within the peri-operative period were non-heart beating time (NHBT), cold ischemia time (CIT), rewarming ischemic time (RWIT), liver biopsy at the end of cold ischemia; and factors analyzed within 72 hours after OLT were ALT and/or AST values. A logistic regression model was applied to filter the possible factors resulting in IPGF. RESULTS: Donor NHBT, CIT and RWIT were significantly longer in the IPGF group than in the non-IPGF group; in the logistic regression model, NHBT was the risk factor leading to IPGF (P < 0.05), while CIT and RWIT were possible risk factors. In one case in the IPGF group, PGNF appeared with moderate hepatic steatosis. CONCLUSIONS: Longer NHBT is an important risk factor leading to IPGF, while serious steatosis in the donor liver, CIT and RWIT are potential risk factors.

Preoperative risk factor analysis in orthotopic liver transplantation with pretransplant artificial liver support therapy

AIM： To assess the value of pre-transplant artificial liver support in reducing the pre-operative risk factors relating to early mortality after orthotopic liver transplantation （OLT）. METHODS： Fifty adult patients with various stages and various etiologies undergoing OLT procedures were treated with molecular adsorbent recycling system （MARS） as preoperative liver support therapy. The study included two parts, the first one is to evaluate the medical effectiveness of single MARS treatment with some clinical and laboratory parameters, which were supposed to be the therapeutical pre-transplant risk factors, the second part is to study the patients undergoing OLT using the regression analysis on preoperative risk factors relating to early mortality （30 d） after OLT. RESULTS： In the 50 patients, the statistically significant improvement in the biochemical parameters was observed （pre-treatment and post-treatment）. Eight patients avoided the scheduled Ltx due to significant relief of clinical condition or recovery of failing liver function, 8 patients died, 34 patients were successfully bridged to Ltx, the immediate outcome of this 34 patients within 30d observation was： 28 kept alive and 6 patients died. CONCLUSION： Pre-operative SOFA, level of creatinine, INR, TNF-α, IL-10 are the main preoperative risk factors that cause early death after operation, MARS treatment before transplantion can relieve these factors significantly.

Progress in hepatitis B virus-related acute-on-chronic liver failure treatment in China:A large,multicenter,retrospective cohort study using a propensity score matching analysis

Background:Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)has a high short-term mortality.However,the treatment progression for HBV-ACLF in China in the past decade has not been well characterized.The present study aimed to determine whether the HBV-ACLF treatment has significantly improved during the past decade.Methods:This study retrospectively compared short-term(28/56 days)survival rates of two different nationwide cohorts(cohort I:2008-2011 and cohort II:2012-2015).Eligible HBV-ACLF patients were enrolled retrospectively.Patients in the cohorts I and II were assigned either to the standard medical therapy(SMT)group(cohort I-SMT,cohort II-SMT)or artificial liver support system(ALSS)group(cohort IALSS,cohort II-ALSS).Propensity score matching analysis was conducted to eliminate baseline differences,and multivariate logistic regression analysis was used to explore the independent factors for 28-day survival.Results:Short-term(28/56 days)survival rates were significantly higher in the ALSS group than those in the SMT group(P<0.05)and were higher in the cohort II than those in the cohort I(P<0.001).After propensity score matching,short-term(28/56 days)survival rates were higher in the cohort II than those in the cohort I for both SMT(60.7%vs.53.0%,50.0%vs.39.8%,P<0.05)and ALSS(66.1%vs.56.5%,53.0%vs.44.4%,P<0.05)treatments.The 28-day survival rate was higher in patients treated with nucleos(t)ide analogs than in patients without such treatments(P=0.046).Multivariate logistic regression analysis revealed that ALSS(OR=0.962,95%CI:0.951-0.973,P=0.038),nucleos(t)ide analogs(OR=0.927,95%CI:0.871-0.983,P=0.046),old age(OR=1.028,95%CI:1.015-1.041,P<0.001),total bilirubin(OR=1.002,95%CI:1.001-1.003,P=0.004),INR(OR=1.569,95%CI:1.044-2.358,P<0.001),COSSH-ACLF grade(OR=2.683,95%CI:1.792-4.017,P<0.001),and albumin(OR=0.952,95%CI:0.924-0.982,P=0.002)were independent factors for 28-day mortality.Conclusions:The treatment for patients with HBV-ACLF has improved in the past decade.

L-carnitine supplementation in non-alcoholic fatty liver disease: A systematic review and meta-analysis

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)dominates the landscape of modern hepatology.Affecting 25%of the general population,there is critical unmet need to identify broadly available,safe and cost-effective treatments.Cumulative evidence in animal and human models suggests that intrahepatic and skeletal muscle fatty acid oxidation is impaired in NAFLD,such that lipid accretion is not matched by efficient utilisation.L-carnitine is a crucial mediator of fatty acid metabolism in vivo,promoting mitochondrial lipidβ-oxidation and enhancing tissue metabolic flexibility.These physiological properties have generated research interest in L-carnitine as a potentially effective adjunctive therapy in NAFLD.AIM To systematically review randomised trials reporting effects of dietary L-carnitine supplementation on liver biochemistry,liver fat and insulin sensitivity in NAFLD.METHODS Search strategies,eligibility criteria and analytic methods were specified a priori(PROSPERO reference:CRD42018107063).Ovid MEDLINE,Ovid EMBASE,PubMed,Web of Science and the Cochrane Library were searched from their inception until April 2019.Outcome measures included serum concentrations of alanine and aspartate aminotransferase(ALT and AST),liver fat and insulin sensitivity assessed by the homeostasis model of insulin resistance(HOMA-IR).A random effects meta-analysis was performed for,ALT,AST and HOMA-IR measures separately.Between-study heterogeneity was measured using I2 statistics.RESULTS Five eligible randomised trials were included in the qualitative and quantitative synthesis(n=338).All of the 5 included trials assessed the effect of L-carnitine on serum ALT,identified from Italy,South Korea and Iran.Weighted mean difference(WMD)for ALT between L-carnitine and control groups after intervention was-25.34 IU/L[95%CI:-41.74-(-8.94);P=0.002].WMD for AST between L-carnitine and control groups was-13.68 IU/L(95%CI:-28.26-0.89;P=0.066).In three studies(n=204),HOMA-IR was evaluated.WMD for HOMA-IR between L-carnitine and control groups was-0.74 units[95%CI:-1.02-(-0.46);P<0.001].Two studies using validated outcome measures reported a significant reduction in liver fat in L-carnitine vs control groups post-intervention(P<0.001).CONCLUSION Pooled results indicate that L-carnitine supplementation attenuates ALT,liver fat and insulin resistance in NAFLD cohorts,confirming a beneficial effect of Lcarnitine for a highly prevalent condition with a growing economic burden.

Diagnostic value of two dimensional shear wave elastography combined with texture analysis in early liver fibrosis

BACKGROUND Staging diagnosis of liver fibrosis is a prerequisite for timely diagnosis and therapy in patients with chronic hepatitis B.In recent years,ultrasound elastography has become an important method for clinical noninvasive assessment of liver fibrosis stage,but its diagnostic value for early liver fibrosis still needs to be further improved.In this study,the texture analysis was carried out on the basis of two dimensional shear wave elastography(2D-SWE),and the feasibility of 2D-SWE plus texture analysis in the diagnosis of early liver fibrosis was discussed.AIM To assess the diagnostic value of 2D-SWE combined with textural analysis in liver fibrosis staging.METHODS This study recruited 46 patients with chronic hepatitis B.Patients underwent 2DSWE and texture analysis;Young's modulus values and textural patterns were obtained,respectively.Textural pattern was analyzed with regard to contrast,correlation,angular second moment(ASM),and homogeneity.Pathological results of biopsy specimens were the gold standard;comparison and assessment of the diagnosis efficiency were conducted for 2D-SWE,texture analysis and their combination.RESULTS 2D-SWE displayed diagnosis efficiency in early fibrosis,significant fibrosis,severe fibrosis,and early cirrhosis(AUC>0.7,P<0.05)with respective AUC values of 0.823(0.678-0.921),0.808(0.662-0.911),0.920(0.798-0.980),and 0.855(0.716-0.943).Contrast and homogeneity displayed independent diagnosis efficiency in liver fibrosis stage(AUC>0.7,P<0.05),whereas correlation and ASM showed limited values.AUC of contrast and homogeneity were respectively 0.906(0.779-0.973),0.835(0.693-0.930),0.807(0.660-0.910)and 0.925(0.805-0.983),0.789(0.639-0.897),0.736(0.582-0.858),0.705(0.549-0.883)and 0.798(0.650-0.904)in four liver fibrosis stages,which exhibited equivalence to 2D-SWE in diagnostic efficiency(P>0.05).Combined diagnosis(PRE)displayed diagnostic efficiency(AUC>0.7,P<0.01)for all fibrosis stages with respective AUC of 0.952(0.841-0.994),0.896(0.766-0.967),0.978(0.881-0.999),0.947(0.835-0.992).The combined diagnosis showed higher diagnosis efficiency over 2D-SWE in early liver fibrosis(P<0.05),whereas no significant differences were observed in other comparisons(P>0.05).CONCLUSION Texture analysis was capable of diagnosing liver fibrosis stage,combined diagnosis had obvious advantages in early liver fibrosis,liver fibrosis stage might be related to the hepatic tissue hardness distribution.

Contrast-enhanced ultrasonography in the evaluation of incidental focal liver lesions: A cost-effectiveness analysis

AIM To determine whether contrast-enhanced ultrasonography(CEUS) as the first-line method is more costeffective in evaluating incidentally discovered focal liver lesions(FLLs) than is computed tomography(CT) and magnetic resonance imaging(MRI). METHODS Between 2010 and 2015, our prospective study enrolled 459 patients with incidentally found FLLs. The biological nature of FLLs was assessed by CEUS in all patients. CT or MRI examinations were added in unclear cases. The sensitivity and specificity of CEUS were calculated. The total costs of CEUS examinations and of the added examinations performed in inconclusive cases were calculated. Afterwards, the theoretical expenses for evaluating incidentally discovered FLLs using CT or MRI as the first-line method were calculated. The resultswere compared. RESULTS The total cost of the diagnostic process using CEUS for all enrolled patients with FLLs was 75884 USD. When the expenses for additional CT and MRI examinations performed in inconclusive cases were added, the total cost was 90540 US dollar(USD). If all patients had been examined by CT or MR as the first-line method, the costs would have been 78897 USD or 384235 USD, respectively. The difference between the cost of CT and CEUS was 3013 USD(4%) and that between MRI and CEUS was 308352 USD(406.3%). We correctly described 97.06% of benign or malignant lesions, with 96.99% sensitivity and 97.09% specificity. Positive predictive value was 94.16% and negative predictive value was 98.52%. In cases with 4 and more lesions, malignancy is significantly more frequent and inconclusive findings significantly less frequent(P < 0.001).CONCLUSION While the costs of CEUS and CT in evaluating FLLs are comparable, CEUS examination is far more costeffective in comparison to MRI.

Analysis of CD8^+CD28^-T-suppressor cells in living donor liver transplant recipients

BACKGROUND:Human CD8 + CD28 - T-suppressor(Ts) cells have been considered to indicate a reduced need for immunosuppression in pediatric liver-intestine transplant recipients and recipients of deceased heart-kidney transplants.However,in adult-to-adult living donor liver transplantation(A-A LDLT)little information is available and the clinical significance is still unknown. METHODS:Flow cytometry was used to detect the population of CD8+CD28 -Ts cells present in peripheral blood in A-A LDLT recipients(n=31),patients with end- stage liver disease(n=24)and healthy controls(n=19). Meanwhile,we tested the graft function and trough levels of immunosuppression in recipients.The clinical and follow- up data of 31 transplant recipients were analyzed. RESULTS:Compared with diseased controls(P=0.007) and healthy individuals(P=0.000),a notable expansion of CD8 + CD28 - Ts cells was found in recipients of A-A LDLT.This was associated with graft function,levels of immunosuppression and rejection episodes. CONCLUSIONS:To monitor the CD8 + CD28 - Ts cells levels is important to evaluate the immune state of recipients. Meanwhile,it is also important to promote expansion of CD8+CD28 -Ts cells in recipients of A-A LDLT,not only to sustain good graft function and decrease the dosage of immunosuppressants,but also to reduce the occurrence of rejection.

Propensity score analysis demonstrated the prognostic advantage of anatomical liver resection in hepatocellular carcinoma

AIM: To compare the prognoses of hepatocellular carcinoma (HCC) patients that underwent anatomic liver resection (AR) or non-anatomic liver resection (NAR) using propensity score-matched populations.

Proteomic analysis of differentially expressed proteins involving in liver metastasis of human colorectal carcinoma

BACKGROUND: Early diagnosis of liver metastasis of colorectal carcinoma is very important for the appropriate treatment of such patients. However, there has been no effective approach available for clinical application. The present study aimed to investigate the differential expression of proteins in patients with liver metastasis of colorectal carcinomas using proteomic analysis and evaluate its potentiality in clinical diagnosis. METHODS: Fluorescence two-dimensional differential in-gel electrophoresis (2-D DIGE) was used to analyze and compare the protein expression between normal mucosa, the primary focus, and liver metastases. Proteomic analysis was made to identify the differentially expressed proteins. Immunohistological staining was used to confirm the expression of differentially expressed proteins in colorectal carcinomas and areas of liver metastasis. RESULTS: A 1.5-fold difference was found with 46 differentially expressed proteins. In 20 differentially expressed proteins, 3 were down-regulated and 17 up-regulated in liver metastases. Proteomic analysis showed that the S-adenosylmethionine transgelin variant was down-regulated in liver metastasis tissues. Zinc finger protein 64 homolog (Zfp64), guanine nucleotide exchange factor 4 (GEF4), human arginase, glutathione S-transferases (GSTs) A3, and tumor necrosis factor a (TNF-alpha)-induced protein 9 were up-regulated in liver metastasis tissues. Immunohistochemical staining confirmed that human arginase expression was higher in liver metastases than in the primary focus. CONCLUSIONS: There was a significant difference in protein expression between the primary focus of colorectal carcinoma and liver metastases. The differentially regulated proteins were closely related to liver metastasis of colorectal carcinoma. Elevated human arginase may be an important molecular marker for liver metastasis from colorectal carcinoma. (Hepatobiliary Pancreat Dis Jut 2010; 9: 149-153)