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

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

Diagnostic and therapeutic role of endoscopic ultrasound in liver diseases:A systematic review and meta-analysis

BACKGROUND In hepatology,the clinical use of endoscopic ultrasound(EUS)has experienced a notable increase in recent times.These applications range from the diagnosis to the treatment of various liver diseases.Therefore,this systematic review summarizes the evidence for the diagnostic and therapeutic roles of EUS in liver diseases.AIM To examine and summarize the current available evidence of the possible roles of the EUS in making a suitable diagnosis in liver diseases as well as the therapeutic accuracy and efficacy.METHODS PubMed,Medline,Cochrane Library,Web of Science,and Google Scholar databases were extensively searched until October 2023.The methodological quality of the eligible articles was assessed using the Newcastle-Ottawa scale or Cochrane Risk of Bias tool.In addition,statistical analyses were performed using the Comprehensive Meta-Analysis software.RESULTS Overall,45 articles on EUS were included(28 on diagnostic role and 17 on therapeutic role).Pooled analysis demonstrated that EUS diagnostic tests had an accuracy of 92.4%for focal liver lesions(FLL)and 96.6%for parenchymal liver diseases.EUS-guided liver biopsies with either fine needle aspiration or fine needle biopsy had low complication rates when sampling FLL and parenchymal liver diseases(3.1%and 8.7%,respectively).Analysis of data from four studies showed that EUS-guided liver abscess had high clinical(90.7%)and technical success(90.7%)without significant complications.Similarly,EUS-guided interventions for the treatment of gastric varices(GV)have high technical success(98%)and GV obliteration rate(84%)with few complications(15%)and rebleeding events(17%).CONCLUSION EUS in liver diseases is a promising technique with the potential to be considered a first-line therapeutic and diagnostic option in selected cases.

Role of albumin-bilirubin score in non-malignant liver disease

The albumin-bilirubin(ALBI)score,which was proposed to assess the prognosis of patients with hepatocellular carcinoma,has gradually been extended to other liver diseases in recent years,including primary biliary cholangitis,liver cirrhosis,hepatitis,liver transplantation,and liver injury.The ALBI score is often compared with classical scores such as the Child-Pugh and model for end-stage liver disease scores or other noninvasive prediction models.It is widely employed because of its immunity to subjective evaluation indicators and ease of obtaining detection indicators.An increasing number of studies have confirmed that it is highly accurate for assessing the prognosis of patients with chronic liver disease;additionally,it has demonstrated good predictive performance for outcomes beyond survival in patients with liver diseases,such as decompensation events.This article presents a review of the application of ALBI scores in various non-malignant liver diseases.

Liver transplantation as an alternative for the treatment of intrahepatic cholangiocarcinoma: Past, present, and future directions

Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.Unfortunately,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor size.Liver transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable tumors.Initially,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes.Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA.Another selection criterion is the tumor response to neoadjuvant therapy.Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant therapy.Another index that helps predict the treatment outcome is the biomarker.Improved survival outcomes have also opened the door for living donor LT for iCCA.Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection.The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.

Liver transplantation as an alternative for the treatment of perihilar cholangiocarcinoma: A critical review

Background:Perihilar cholangiocarcinoma(phCCC)is a dismal malignancy.There is no consensus regard-ing the best treatment for patients with unresectable phCCC.The present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical practice.Data sources:The search was conducted in PubMed,Embase,Cochrane,and LILACS.The related references were searched manually.Inclusion criteria were:reports in English or Portuguese literature that a)patients with confirmed diagnosis of phCCC;b)patients treated with a curative intent;c)patients with the outcomes of liver resection and liver transplantation.Case reports,reviews,letters,editorials,conference abstracts and papers with full-text unavailability were excluded from the analysis.Results:Most of the current literature is based on observational retrospective studies with low grades of evidence.Liver resection has better long-term outcomes than systemic chemotherapy or palliation ther-apy and liver transplantation is a good alternative for selected patients with unresectable phCCC.All candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahep-atic diseases.As a general rule,patients presenting with a tumor having a longitudinal size>3 cm or extending below the cystic duct,lymph node disease,confirmed extrahepatic dissemination;intraoper-atively diagnosed metastatic disease;a history of other malignancies within the last five years,and did not complete chemoradiation regimen and were medically unfit should not be considered for transplan-tation.Some of these criteria should be individually assessed.Liver transplantation or resection should only be considered in highly experienced hepatobiliary centers,and any decision-making must be based on a multidisciplinary evaluation.Conclusions:phCCC is a complex condition with high morbidity.Surgical therapies,including hepatec-tomy and liver transplantation,are the best option for better long-term disease-free survival.

Liver transplantation as an alternative for the treatment of non-resectable liver colorectal cancer: Advancing the therapeutic algorithm

Colorectal cancer is a leading cause of cancerrelated mortality,with nearly half of the affected patients developing liver metastases.For three decades,liver resection(LR)has been the primary curative strategy,yet its applicability is limited to about 20%of cases.Liver transplantation(LT)for unresectable metastases was attempted unsuccessfully in the 1990s,with high rates of perioperative death and recurrence.There is now more interest in this strategy due to improvements in systemic therapies and surgical techniques.A significant study conducted by the Oslo group showed that patients receiving liver transplants had a 60%chance of survival after five years.Significantly better results have been achieved by using advanced imaging for risk stratification and further refining selection criteria,especially in the Norvegian SECA trials.This review carefully charts the development and history of LT as a treatment option for colorectal cancer liver metastases.The revolutionary path from the early days of exploratory surgery to the current situation of cautious optimism is traced,highlighting the critical clinical developments and improved patient selection standards that have made LT a potentially curative treatment for such challenging very well selected cases.

Metabolic disease and the liver: A review

Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common liver disease worldwide,with an estimated prevalence of 31%in Latin America.The presence of metabolic comorbidities coexisting with liver disease varies substantially among populations.It is acknowledged that obesity is boosting the type 2 diabetes mellitus“epidemic,”and both conditions are significant contributors to the increasing number of patients with MASLD.Nonalcoholic steatohepatitis represents a condition of chronic liver inflammation and is considered the most severe form of MASLD.MASLD diagnosis is based on the presence of steatosis,noninvasive scores and altered liver tests.Noninvasive scores of liver fibrosis,such as serum biomarkers,which should be used in primary care to rule out advanced fibrosis,are simple,inexpensive,and widely available.Currently,guidelines from international hepatology societies recommend using noninvasive strategies to simplify case finding and management of high-risk patients with MASLD in clinical practice.Unfortunately,there is no definite pharmacological treatment for the condition.Creating public health policies to treat patients with risk factors for MASLD prevention is essential.

Establishment and validation of an adherence prediction system for lifestyle interventions in non-alcoholic fatty liver disease

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is the most common liver disease worldwide,affecting about 1/4th of the global population and causing a huge global economic burden.To date,no drugs have been approved for the treatment of NAFLD,making the correction of unhealthy lifestyles the principle method of treatment.Identifying patients with poor adherence to lifestyle correction and attempting to improve their adherence are therefore very important.AIM To develop and validate a scale that can rapidly assess the adherence of patients with NAFLD to lifestyle interventions.METHODS The Exercise and Diet Adherence Scale(EDAS)was designed based on com-pilation using the Delphi method,and its reliability was subsequently evaluated.Demographic and laboratory indicators were measured,and patients completed the EDAS questionnaire at baseline and after 6 months.The efficacy of the EDAS was evaluated in the initial cohort.Subsequently,the efficacy of the EDAS was internally verified in a validation cohort.RESULTS The EDAS consisted of 33 items in six dimensions,with a total of 165 points.Total EDAS score correlated significantly with daily number of exercise and daily reduction in calorie intake(P<0.05 each),but not with overall weight loss.A total score of 116 was excellent in predicting adherence to daily reduction in calorie intake(>500 kacl/d),(sensitivity/specificity was 100.0%/75.8%),while patients score below 97 could nearly rule out the possibility of daily exercise(sensitivity/specificity was 89.5%/44.4%).Total EDAS scores≥116,97-115,and<97 points were indicative of good,average,and poor adherence,respectively,to diet and exercise recommendations.CONCLUSION The EDAS can reliably assess the adherence of patients with NAFLD to lifestyle interventions and have clinical application in this population.

Liver transplantation as an alternative for the treatment of neuroendocrine liver metastasis: Appraisal of the current evidence

Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Studies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is limited.The goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of NELM.Data sources:A scoping literature search on LT and LR for NELM was performed with PubMed,including English articles up to March 2023.Results:International guidelines recommend LR for NELM in resectable,well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed therapies.Advanced liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free survival.In highly selected patients(based on the Milan criteria)with unresectable NELM,oncologic results of LT are promising.Prognostic factors include tumor biology(G1/G2)and burden,waiting time for LT,patient age and extrahepatic spread.Based on low-level evi-dence,LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to LR.The benefits of LT were lost in patients beyond the Milan NELM-criteria.Conclusions:With adherence to strict selection criteria especially tumor biology,LT for NELM is becoming a valuable option providing oncologic benefits compared to LR.Recent evidence suggests even stricter selection criteria with regard to tumor biology.

Muscle strength and non-alcoholic fatty liver disease/metabolicassociated fatty liver disease

This editorial comments on an article published in a recent issue of World Journal of Gastroenterology,entitled“Association of low muscle strength with metabolic dysfunction-associated fatty liver disease:A nationwide study”.We focused on the association between muscle strength and the incidence of non-alcoholic fatty liver disease(NAFLD)and metabolic-associated fatty liver disease(MAFLD),as well as the mechanisms underlying the correlation and related clinical applications.NAFLD,which is now redefined as MAFLD,is one of the most common chronic liver diseases globally with an increasing prevalence and is characterized by malnutrition,which may contribute to decreased muscle strength.Reduction of muscle strength reportedly has a pathogenesis similar to that of NAFLD/MAFLD,including insulin resistance,inflammation,sedentary behavior,as well as insufficient vitamin D.Multiple studies have focused on the relationship between sarcopenia or muscle strength and NAFLD.However,studies investigating the relationship between muscle strength and MAFLD are limited.Owing to the shortage of specific medications for NAFLD/MAFLD treatment,early detection is essential.Furthermore,the relationship between muscle strength and NAFLD/MAFLD suggests that improvements in muscle strength may have an impact on disease prevention and may provide novel insights into treatments including dietary therapy,as well as tailored physical activity.

Histopathological impact of SARS-CoV-2 on the liver:Cellular damage and long-term complications

Coronavirus disease 2019(COVID-19),caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome,multiple organ failure,and death.Despite extensive studies on the pathogenicity of SARS-CoV-2,its impact on the hepatobiliary system remains unclear.While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels,the exact source of this damage is not fully understood.Proposed mechanisms for injury include direct cytotoxicity,collateral damage from inflammation,drug-induced liver injury,and ischemia/hypoxia.However,evidence often relies on blood tests with liver enzyme abnormalities.In this comprehensive review,we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients,drawing from liver biopsies,complete autopsies,and in vitro liver analyses.We present evidence of the direct impact of SARS-CoV-2 on the liver,substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes,including mitochondrial swelling,endoplasmic reticulum dilatation,and hepatocyte apoptosis.Additional ly,we describe the diverse liver pathology observed during COVID-19 infection,encompassing necrosis,steatosis,cholestasis,and lobular inflammation.We also discuss the emergence of long-term complications,notably COVID-19-related secondary sclerosing cholangitis.Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.

Impact of microplastics and nanoplastics on liver health:Current understanding and future research directions

With continuous population and economic growth in the 21st century,plastic pollution is a major global issue.However,the health concern of microplastics/nanoplastics(MPs/NPs)decomposed from plastic wastes has drawn public attention only in the recent decade.This article summarizes recent works dedicated to understanding the impact of MPs/NPs on the liver-the largest digestive organ,which is one of the primary routes that MPs/NPs enter human bodies.The interrelated mechanisms including oxidative stress,hepatocyte energy re-distribution,cell death and autophagy,as well as immune responses and inflammation,were also featured.In addition,the disturbance of microbiome and gut-liver axis,and the association with clinical diseases such as metabolic dysfunction-associated fatty liver disease,steatohepatitis,liver fibrosis,and cirrhosis were briefly discussed.Finally,we discussed potential directions in regard to this trending topic,highlighted current challenges in research,and proposed possible solutions.

Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease

BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis.Peroxisome proliferator activated receptor(PPAR)α and δ play a key role in lipid metabolism and intestinal barrier homeostasis,which are major contributors to the pathological progression of ALD.Meanwhile,elafibranor(EFN),which is a dual PPARαand PPARδagonist,has reached a phase III clinical trial for the treatment of metabolic dysfunctionassociated steatotic liver disease and primary biliary cholangitis.However,the benefits of EFN for ALD treatment is unknown.AIM To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse model.METHODS ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol(EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly(1 mL/kg)for 8 weeks.EFN(3 and 10 mg/kg/day)was orally administered during the experimental period.Histological and molecular analyses were performed to assess the effect of EFN on steatohepatitis,fibrosis,and intestinal barrier integrity.The EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based assays.RESULTS The hepatic steatosis,apoptosis,and fibrosis in the ALD mice model were significantly attenuated by EFN treatment.EFN promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells,primarily through PPARαactivation.Moreover,EFN inhibited the Kupffer cell-mediated inflammatory response,with blunted hepatic exposure to lipopolysaccharide(LPS)and toll like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling.EFN improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory responses.The protective effect on intestinal barrier function in the EtOH-stimulated Caco-2 cells was predominantly mediated by PPARδ activation.CONCLUSION EFN reduced ALD-related fibrosis by inhibiting lipid accumulation and apoptosis,enhancing hepatocyte autophagic and antioxidant capacities,and suppressing LPS/TLR4/NF-κB-mediated inflammatory responses by restoring intestinal barrier function.

Protective mechanism of Coprinus comatus polysaccharide on acute alcoholic liver injury in mice,the metabolomics and gut microbiota investigation

Coprinus comatus polysaccharide(CCP)has significant hepatoprotective effect.To explore hepatoprotective mechanism of CCP,the study analyzed preventive effect of CCP on acute alcoholic liver injury in mice by histopathological examination and biochemical analysis.Simultaneously,hepatoprotective mechanism was also analyzed in conjunction with metabolomics and proliferation of gut microbiota.The results showed that CCP significantly decreased alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)levels in serum of alcoholic liver disease(ALD)mice.Histopathological examination showed that CCP can significantly improve liver damage.Metabolomics results showed that there were significant differences in the level of metabolites in liver tissue of control group,ALD group and CCP group,including taurine,xanthosine,fumaric acid and arachidonic acid,among others.Metabolites pathways analysis showed that hepatoprotective effect of CCP was related to energy metabolism,biosynthesis of unsaturated fatty acids,amino acids metabolism and lipid metabolism.Additionally,CCP inhibited an increase in the number of Clostridium perfringens,Enterobacteriaceae and Enterococcus,and a decrease in the number of Lactobacillus and Bifidobacterium in the gut of ALD mice.All these findings suggested that CCP treatment reversed the phenotype of ethanol-induced liver injury and the associated metabolites pathways.

Glucagon-like peptide 1 agonists are potentially useful drugs for treating metabolic dysfunction-associated steatotic liver disease

In this editorial,we comment on Yin et al’s recently published Letter to the editor.In particular,we focus on the potential use of glucagon-like peptide 1 receptor agonists(GLP-1RAs)alone,but even more so in combination therapy,as one of the most promising therapies in metabolic dysfunction-associated steatotic liver disease(MASLD),the new definition of an old condition,non-alcoholic fatty liver disease,which aims to better define the spectrum of steatotic pathology.It is well known that GLP-1RAs,having shown outstanding performance in fat loss,weight loss,and improvement of insulin resistance,could play a role in protecting the liver from progressive damage.Several clinical trials have shown that,among GLP-1RAs,semaglutide is a safe,well-studied therapeutic choice for MASLD patients;however,most studies demonstrate that,while semaglutide can reduce steatosis,including steatohepatitis histological signs(in terms of inflammatory cell infiltration and hepatocyte ballooning),it does not improve fibrosis.Combinations of therapies with different but complementary mechanisms of action are considered the best way to improve efficiency and slow disease progression due to the complex pathophysiology of the disease.In particular,GLP-1RAs associated with antifibrotic drug therapy,dual glucose-dependent insulinotropic polypeptide(GIP)/GLP-1RA or GLP-1 and glucagon RAs have promoted greater improvement in hepatic steatosis,liver biochemistry,and non-invasive fibrosis tests than monotherapy.Therefore,although to date there are no definitive indications from international drug agencies,there is the hope that soon the therapeutic lines in the most advanced phase of study will be able to provide a therapy for MASLD,one that will certainly include the use of GLP-1RAs as combination therapy.

Heparin is an effective treatment for preventing liver failure after hepatectomy

BACKGROUND Posthepatectomy liver failure(PHLF)is one of the most important causes of death following liver resection.Heparin,an established anticoagulant,can protect liver function through a number of mechanisms,and thus,prevent liver failure.AIM To look at the safety and efficacy of heparin in preventing hepatic dysfunction after hepatectomy.METHODS The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III(MIMIC-III)v1.4 pinpointed patients who had undergone hepatectomy for liver cancer,subdividing them into two cohorts:Those who were injected with heparin and those who were not.The statistical evaluations used were unpaired ttests,Mann-Whitney U tests,chi-square tests,and Fisher’s exact tests to assess the effect of heparin administration on PHLF,duration of intensive care unit(ICU)stay,need for mechanical ventilation,use of continuous renal replacement therapy(CRRT),incidence of hypoxemia,development of acute kidney injury,and ICU mortality.Logistic regression was utilized to analyze the factors related to PHLF,with propensity score matching(PSM)aiming to balance the preoperative disparities between the two groups.RESULTS In this study,1388 patients who underwent liver cancer hepatectomy were analyzed.PSM yielded 213 matched pairs from the heparin-treated and control groups.Initial univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched samples.Further analysis in the matched cohorts confirmed a significant association,with heparin reducing the risk of PHLF(odds ratio:0.518;95%confidence interval:0.295-0.910;P=0.022).Additionally,heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations,diminished requirements for respiratory support and CRRT,and lower incidences of hypoxemia and ICU mortality.CONCLUSION Liver failure is an important hazard following hepatic surgery.During ICU care heparin administration has been proved to decrease the occurrence of hepatectomy induced liver failure.This indicates that heparin may provide a hopeful option for controlling PHLF.

Alanine aminotransferase predicts incident steatotic liver disease of metabolic etiology: Long life to the old biomarker!

Alanine aminotransferase(ALT)serum levels increase because of hepatocellular damage.Metabolic dysfunction-associated fatty liver disease(MAFLD),which identifies steatotic liver disease(SLD)associated with≥2 metabolic abnormalities,has prominent sexual differences.The Metabolic Syndrome defines a cluster comprising abdominal obesity,altered glucose metabolism,dyslipidemia,and hypertension.Male sex,body mass index,glucose,lipids,ferritin,hypertension,and age independently predict ALT levels among blood donors.Over the last few decades,the reference range of ALT levels has been animatedly debated owing to attempts to update sex-specific reference ranges.With this backset,Chen et al have recently published a study which has two main findings.First,>80%of indi-viduals with MAFLD had normal ALT levels.Second,there was a linear increa-sing trend in the association between cumulative excess high-normal ALT levels and the rate of incident MAFLD.This study has biologically credible findings.However,it inaccurately considered sex differences in the MAFLD arena.Therefore,future studies on SLD owing to metabolic dysfunction should adopt locally determined and prospectively validated reference ranges of ALT and carefully consider sex differences in liver enzymes and MAFLD pathobiology.

Preoperative albumin-bilirubin score and liver resection percentage determine postoperative liver regeneration after partial hepatectomy

BACKGROUND The success of liver resection relies on the ability of the remnant liver to regenerate.Most of the knowledge regarding the pathophysiological basis of liver regeneration comes from rodent studies,and data on humans are scarce.Additionally,there is limited knowledge about the preoperative factors that influence postoperative regeneration.AIM To quantify postoperative remnant liver volume by the latest volumetric software and investigate perioperative factors that affect posthepatectomy liver regenera-tion.METHODS A total of 268 patients who received partial hepatectomy were enrolled.Patients were grouped into right hepatectomy/trisegmentectomy(RH/Tri),left hepa-tectomy(LH),segmentectomy(Seg),and subsegmentectomy/nonanatomical hepatectomy(Sub/Non)groups.The regeneration index(RI)and late rege-neration rate were defined as(postoperative liver volume)/[total functional liver volume(TFLV)]×100 and(RI at 6-months-RI at 3-months)/RI at 6-months,respectively.The lower 25th percentile of RI and the higher 25th percentile of late regeneration rate in each group were defined as“low regeneration”and“delayed regeneration”.“Restoration to the original size”was defined as regeneration of the liver volume by more than 90%of the TFLV at 12 months postsurgery.RESULTS The numbers of patients in the RH/Tri,LH,Seg,and Sub/Non groups were 41,53,99 and 75,respectively.The RI plateaued at 3 months in the LH,Seg,and Sub/Non groups,whereas the RI increased until 12 months in the RH/Tri group.According to our multivariate analysis,the preoperative albumin-bilirubin(ALBI)score was an independent factor for low regeneration at 3 months[odds ratio(OR)95%CI=2.80(1.17-6.69),P=0.02;per 1.0 up]and 12 months[OR=2.27(1.01-5.09),P=0.04;per 1.0 up].Multivariate analysis revealed that only liver resection percentage[OR=1.03(1.00-1.05),P=0.04]was associated with delayed regeneration.Furthermore,multivariate analysis demonstrated that the preoperative ALBI score[OR=2.63(1.00-1.05),P=0.02;per 1.0 up]and liver resection percentage[OR=1.02(1.00-1.05),P=0.04;per 1.0 up]were found to be independent risk factors associated with volume restoration failure.CONCLUSION Liver regeneration posthepatectomy was determined by the resection percentage and preoperative ALBI score.This knowledge helps surgeons decide the timing and type of rehepatectomy for recurrent cases.

Role of gut-liver axis and glucagon-like peptide-1 receptor agonists in the treatment of metabolic dysfunction-associated fatty liver disease

Metabolic dysfunction-associated fatty liver disease(MAFLD)is a hepatic manifestation of the metabolic syndrome.It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries.MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma.Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis.The mechanisms involved in maintaining gut-liver axis homeostasis are complex.One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gutliver axis functionality.An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis.Moreover,alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis.Glucagon-like peptide-1 receptor agonists(GLP-1 RAs)are a class of drugs developed for the treatment of type 2 diabetes mellitus.They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis.The mechanisms reported to be involved in this effect include an improved regulation of glycemia,reduced lipid synthesis,β-oxidation of free fatty acids,and induction of autophagy in hepatic cells.Recently,multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment.A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD.This review presents the current understanding of the role of the gutliver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.

Staging liver fibrosis with various diffusion-weighted magnetic resonance imaging models

BACKGROUND Diffusion-weighted imaging(DWI)has been developed to stage liver fibrosis.However,its diagnostic performance is inconsistent among studies.Therefore,it is worth studying the diagnostic value of various diffusion models for liver fibrosis in one cohort.AIM To evaluate the clinical potential of six diffusion-weighted models in liver fibrosis staging and compare their diagnostic performances.METHODS This prospective study enrolled 59 patients suspected of liver disease and scheduled for liver biopsy and 17 healthy participants.All participants underwent multi-b value DWI.The main DWI-derived parameters included Mono-apparent diffusion coefficient(ADC)from mono-exponential DWI,intravoxel incoherent motion model-derived true diffusion coefficient(IVIM-D),diffusion kurtosis imaging-derived apparent diffusivity(DKI-MD),stretched exponential model-derived distributed diffusion coefficient(SEM-DDC),fractional order calculus(FROC)model-derived diffusion coefficient(FROC-D)and FROC model-derived microstructural quantity(FROC-μ),and continuous-time random-walk(CTRW)model-derived anomalous diffusion coefficient(CTRW-D)and CTRW model-derived temporal diffusion heterogeneity index(CTRW-α).The correlations between DWI-derived parameters and fibrosis stages and the parameters’diagnostic efficacy in detecting significant fibrosis(SF)were assessed and compared.RESULTS CTRW-D(r=-0.356),CTRW-α(r=-0.297),DKI-MD(r=-0.297),FROC-D(r=-0.350),FROC-μ(r=-0.321),IVIM-D(r=-0.251),Mono-ADC(r=-0.362),and SEM-DDC(r=-0.263)were significantly correlated with fibrosis stages.The areas under the ROC curves(AUCs)of the combined index of the six models for distinguishing SF(0.697-0.747)were higher than each of the parameters alone(0.524-0.719).The DWI models’ability to detect SF was similar.The combined index of CTRW model parameters had the highest AUC(0.747).CONCLUSION The DWI models were similarly valuable in distinguishing SF in patients with liver disease.The combined index of CTRW parameters had the highest AUC.