BACKGROUND Cancer-associated fibroblasts(CAFs),crucial components of the tumor microenvironment in primary and metastatic tumors,can impact the activity of cancer cells and contribute to their progression.Given their ...BACKGROUND Cancer-associated fibroblasts(CAFs),crucial components of the tumor microenvironment in primary and metastatic tumors,can impact the activity of cancer cells and contribute to their progression.Given their extensive interactions with cancer cells and other stromal cells,we aimed to evaluate the prognostic value of CAFs in patients with liver cancer(LC).AIM To investigate the association between CAF expression and clinicopathological characteristics as well as overall survival(OS)in patients with LC,including hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(iCCA).METHODS We performed a meta-analysis of cohort studies with available data on the effects of CAF expression on both clinicopathological characteristics and OS via hazard ratios(HRs)and risk ratios with 95%confidence intervals(CIs).Studies were subgrouped on the basis of CAF markers and cancer type,and the subgroup effects of CAF expression on both HCC and iCCA were analyzed through meta-regression.The Newcastle-Ottawa Scale was used to evaluate the included studies to guarantee their quality and minimize the possibility of bias.RESULTS Nine trials were selected and included a total of 1518 patients.According to our primary meta-analysis,the expression of CAFs in LC patients was significantly associated with a decrease in OS(LC:HR:1.62;95%CI:1.34-1.97;P<0.001;HCC:HR:1.67;95%CI:1.34-2.07;P<0.001;iCCA:HR:1.47;95%CI:0.97-2.23;P=0.07);nevertheless,it was not significantly associated with almost all clinicopathologic characteristics,including tumor size,venous infiltration,alpha-fetoprotein level,and differentiation grade.According to the subgroup analysis of smooth muscle actin(SMA)markers in both HCC patients and iCCA patients,high CAF expression in HCC(HR:2.29;95%CI:1.01-5.22;P=0.048)and iCCA(HR:2.04;95%CI:1.09-3.81;P=0.025)patients was a significant indicator of poor OS.Moreover,the clinicopathological characteristics were also verified by the SMA marker,which had a nearly significant effect on the venous infiltration of iCCA(risk ratio:2.70;95%CI:0.97-7.49;P=0.057).CONCLUSION High CAF expression,evaluated by both mixed markers and SMAs,is significantly associated with poor OS in patients with LC,including both HCC patients and iCCA patients.However,further research is necessary since how CAF expression and clinicopathologic features are related is yet unknown.展开更多
BACKGROUND Acute liver failure(ALF)is a loss of liver function due to a severe hepatic insult.Studies utilizing the azoxymethane(AOM)mouse model of ALF,which also generates hepatic encephalopathy,have primarily focuse...BACKGROUND Acute liver failure(ALF)is a loss of liver function due to a severe hepatic insult.Studies utilizing the azoxymethane(AOM)mouse model of ALF,which also generates hepatic encephalopathy,have primarily focused on development of neurological deficits.However,the molecular processes that generate liver damage have not been fully characterized.Therefore,a more comprehensive characterization of the hepatic consequences of AOM toxicity is needed to better understand this disease model.AIM To identify molecular pathology contributing to hepatic injury during the progression of AOM-induced ALF.METHODS C57BL/6 mice were injected with AOM to produce ALF and hepatic encephalopathy.Tissue was collected at defined stages of neurological decline up to coma.Liver injury,CYP2E1 expression,oxidative stress,inflammation,apoptosis,necroptosis,and hepatocellular senescence were assessed.RESULTS Increased hepatic necrosis and exacerbated liver injury were observed after AOM injection as mice progressed towards coma.CYP2E1 expression decreased in AOM-treated mice as liver injury progressed.Malondialdehyde,myeloperoxidase and other measures of oxidative stress were significantly increased during AOM-induced ALF.Hepatic CCL2 and tumor necrosis factorαexpression increased as AOM-induced liver injury progressed.Mixed lineage kinase domain-like protein phosphorylation was increased early during the progression of AOM-induced liver injury.Measures of apoptosis and cellular senescence all increased as the time course of AOM progressed.CONCLUSION These data support that necrosis,oxidative stress,inflammation,apoptosis,and senescence were elevated in AOMtreated mice,with inflammation being the earliest significant change.展开更多
BACKGROUND Repeated application of the Pringle maneuver is a key obstacle to safe minimally invasive repeat liver resection(MISRLR).However,limited technical guidance is available.AIM To study the utility of newly dev...BACKGROUND Repeated application of the Pringle maneuver is a key obstacle to safe minimally invasive repeat liver resection(MISRLR).However,limited technical guidance is available.AIM To study the utility of newly developed Pringle taping method guided by liver surface in MISRLR.METHODS We retrospectively reviewed 72 cases of MISRLR performed by a single surgeon at two centers from August 2015 to July 2024.Beginning in October 2019,a liver surface-guided encirclement of hepatoduodenal ligament(LSEH)was used for repeat Pringle taping.Perioperative outcomes including Pringle taping success,operative time,blood loss,conversion rate,morbidity,and mortality were assessed.RESULTS Laparoscopic and robotic approaches were used in 63 patients and 9 patients,respectively.The median operative time,blood loss,and hospital stay were 331.5 minutes,70 mL,and 8 days,respectively.Open conversion occurred in two cases(2.8%)due to severe adhesions and right renal vein injury.Clavien-Dindo grade≥III complications occurred in 5.6%of cases with no mortality.Anti-adhesion barriers were used in 54 patients(75.0%).LSEH was attempted in 57 cases,improving Pringle taping success from 33.0%to 91.4%(P<0.001).LSEH succeeded in all patients with prior open liver resection(n=11).Among 6 patients in whom LSEH failed,3 patients(50.0%)had undergone a third liver resection,and 1 patient had a history of distal gastrectomy with choledochoduodenostomy.CONCLUSION The newly developed LSEH technique for Pringle taping in MISRLR was feasible,enhancing safety and reproducibility even in patients with a history of open liver resection.展开更多
Liver metastases are a leading contributor to cancer-related illness and death,occurring far more frequently than primary liver tumors.Their management remains highly challenging due to the complexity of disease behav...Liver metastases are a leading contributor to cancer-related illness and death,occurring far more frequently than primary liver tumors.Their management remains highly challenging due to the complexity of disease behavior and the need for an individualized,multidisciplinary approach.Effective care increasingly relies on integrating sophisticated diagnostic techniques,advanced systemic and locoregional therapies,and molecularly tailored treatment strategies.This review provides an in-depth analysis of the current clinicopathological perspectives on liver metastases.It explores their epidemiology,mechanisms of spread,histological growth patterns,diagnostic imaging advancements,molecular characteristics,and therapeutic interventions.Additionally,it examines the broader implications for patient quality of life(QoL),healthcare costs,and the particular difficulties associated with managing liver metastases in pediatric patients and individuals with rare malignancies.The article outlines the diverse histopathological features and tumor–liver interface growth patterns,emphasizing their prognostic and therapeutic significance.It evaluates contemporary imaging modalities–including magnetic resonance imaging and computed tomography(CT)with hepatocyte-specific agents,positron emission tomography/CT,and contrast-enhanced ultrasound–and highlights the emerging importance of liquid biopsy and molecular profiling in shaping treatment decisions.The review discusses available treatment options such as chemotherapy,targeted agents,immunotherapies,surgical resection,liver transplantation,and various locoregional therapies.Furthermore,it addresses evolving fields like prognostic scoring systems,radiomics,artificial intelligence(AI)applications,and patient–derived organoid and xenograft models.A summary of current clinical trials and translational research initiatives reflects the fast-paced evolution of this field.The management of liver metastases is rapidly advancing,driven by precision oncology principles and collaborative,multidisciplinary care.The integration of molecular diagnostics,novel therapeutic approaches,and cutting–edge technologies–including AI and organoid-based personalized drug testing-is poised to enhance treatment selection,improve clinical outcomes,and support better QoL.These innovations hold the potential to transform the outlook for patients with liver metastases,moving toward more durable disease control in appropriately selected cases.展开更多
Inborn errors of metabolism(IEM)are rare disorders,most are liver-based with liver transplantation(LT)emerging as an effective cure in the pediatric population.LT has been shown to offer a cure or deter disease progre...Inborn errors of metabolism(IEM)are rare disorders,most are liver-based with liver transplantation(LT)emerging as an effective cure in the pediatric population.LT has been shown to offer a cure or deter disease progression and provide symptomatic improvement in patients with IEM.Each metabolic disorder is unique,with the missing enzyme or transporter protein causing substrate deficiency or toxic byproduct production.Knowledge about the distribution of deficient enzymes,the percentage of enzymes replaced by LT,and the extent of extrahepatic involvement helps anticipate and manage complications in the perioperative period.Most patients have multisystem involvement and can be on complex dietary regimens.Metabolic decompensation can be triggered due to the stress response to surgery,fasting and other unanticipated complications perioperatively.Thus,a multidisciplinary team’s input including those from metabolic specialists is essential to develop disease and patient-specific strategies for the perioperative management of these patients during LT.In this review,we outline the classification of IEM,indications for LT along with potential benefits,basic metabolic defects and their implications,details of extrahepatic involvement and perioperative management strategies for LT in children with some of the commonly presenting IEM,to assist anesthesiologists handling this cohort of patients.展开更多
BACKGROUND While varices and variceal bleeds are well-known and feared complications of advanced cirrhosis and portal hypertension,omental variceal bleed are a rare sequala even in patients with known esophageal or ga...BACKGROUND While varices and variceal bleeds are well-known and feared complications of advanced cirrhosis and portal hypertension,omental variceal bleed are a rare sequala even in patients with known esophageal or gastric varices.While rare,omental varices pose a risk for hemoperitoneum if ruptured,which is a lifethreatening complication with high mortality rates despite surgical intervention.CASE SUMMARY This report reviews the case of a patient 36-year-old female with alcohol related cirrhosis decompensated by ascites,but no history of varices admitted for hemorrhagic shock from spontaneous rupture of omental varices requiring emergency surgery.She underwent the first documented successful orthotopic liver transplantation the same admission.CONCLUSION This case report and literature review stresses the importance of early consideration and identification of intraabdominal variceal sources in cirrhotic patients with refractory shock.展开更多
Liver transplantation is a life-saving procedure for patients with end-stage liver diseases and acute liver failure.With advances in surgical techniques and immunosuppressive regimens,patient survival rates have signi...Liver transplantation is a life-saving procedure for patients with end-stage liver diseases and acute liver failure.With advances in surgical techniques and immunosuppressive regimens,patient survival rates have significantly improved.While the systemic complications of post-transplantation are well recognized,ophthalmic manifestations remain underreported.Ophthalmic complications can significantly impair visual function and increase morbidity in these patients.Prolonged immunosuppression makes the patients susceptible to the opportunistic pathogens such as Cytomegalovirus,Candida,Aspergillus,etc.Other common findings include dry eye disease,cataracts and retinal vascular complications which further contribute to the long-term morbidity in these patients.Early ophthalmic evaluation and prompt management are essential to prevent irreversible vision loss and improve post-transplant outcomes.High index of suspicion and multidisciplinary approach is essential to facilitate early diagnosis and treatment.This review highlights the range of ophthalmic complications observed in liver transplant recipients and underscores the need for future research focused on understanding the underlying pathophysiological mechanisms and refining the prophylactic protocols to improve outcomes in this unique patient population.展开更多
BACKGROUND The liver represents a common site of distant metastasis in patients with esophageal cancer(EC).Conventional chemotherapy(CMT)presents limited efficacy for EC,and EC patients with liver metastases typically...BACKGROUND The liver represents a common site of distant metastasis in patients with esophageal cancer(EC).Conventional chemotherapy(CMT)presents limited efficacy for EC,and EC patients with liver metastases typically experience a poor prognosis,highlighting an urgent need to explore novel treatment approaches.This study evaluated the overall efficacy and safety of CMT vs CMT combined with immune checkpoint inhibitors(ICIs)in the treatment of EC patients with liver metastases.Furthermore,prognostic factors influencing outcomes in this patient population were identified.AIM To evaluate the efficacy and safety of first-line chemoimmunotherapy for EC patients with liver metastases and to analyze prognostic factors.METHODS This retrospective study included 126 EC patients with liver metastases at Zhejiang Cancer Hospital between 2014 and 2024.Patients receiving CMT were compared with those receiving CMT+ICI.Analyzed variables included clinicopathological features,treatment history,characteristics of metastasis,systemic and local treatments,overall survival(OS),and treatment-related adverse events(TRAEs).Prognostic factors were evaluated using univariate and multivariate Cox proportional-hazards regression models.Finally,efficacy outcomes and TRAE profiles were compared between the two groups.RESULTS A significant difference in median OS was identified between the two groups(10.8 months in the CMT group vs 20.8 months in the CMT+ICI group,P=0.004).The CMT+ICI group also demonstrated a significantly longer median progression-free survival of 11.7 months(P<0.001).Patients receiving combination therapy exhibited significantly improved systemic objective response rate and disease control rate.Multivariate analysis identified key factors significantly influencing OS in EC patients with liver metastases:Karnofsky Performance Status score≥70,receipt of local therapy for liver metastases,and the number of cycles of CMT and immunotherapy received.Furthermore,the incidence of TRAEs did not significantly differ between the CMT+ICI and CMT groups.CONCLUSION For EC patients with liver metastases,the combination of CMT and ICIs demonstrates significantly superior efficacy compared with CMT alone,while maintaining manageable TRAEs.展开更多
Liver transplantation(LT)remains the optimal life-saving intervention for patients with end-stage liver disease.Despite the recent advances in LT several barriers,including organ allocation,donor-recipient matching,an...Liver transplantation(LT)remains the optimal life-saving intervention for patients with end-stage liver disease.Despite the recent advances in LT several barriers,including organ allocation,donor-recipient matching,and patient education,persist.With the growing progress of artificial intelligence,particularly large language models(LLMs)like ChatGPT,new applications have emerged in the field of LT.Current studies demonstrating usage of ChatGPT in LT include various areas of application,from clinical settings to research and education.ChatGPT usage can benefit both healthcare professionals,by decreasing the time spent on non-clinical work,but also LT recipients by providing accurate information.Future potential applications include the expanding usage of ChatGPT and other LLMs in the field of LT pathology and radiology as well as the automated creation of discharge summaries or other related paperwork.Additionally,the next models of ChatGPT might have the potential to provide more accurate patient education material with increased readability.Although ChatGPT usage presents promising applications,there are certain ethical and practical limitations.Key concerns include patient data privacy,information accuracy,misinformation possibility and lack of legal framework.Healthcare providers and policymakers should collaborate for the establishment of a controlled framework for the safe use of ChatGPT.The aim of this minireview is to summarize current literature on ChatGPT in LT,highlighting both opportunities and limitations,while also providing future possible applications.展开更多
BACKGROUND Perimenopausal women are prone to anxiety and depression due to fluctuating hormone levels,which significantly impair their quality of life.The current treatments have certain limitations.In traditional Chi...BACKGROUND Perimenopausal women are prone to anxiety and depression due to fluctuating hormone levels,which significantly impair their quality of life.The current treatments have certain limitations.In traditional Chinese medicine,liver-soothing formulas are commonly prescribed for mood-related disorders,but their overall efficacy in perimenopausal anxiety and depression remains uncertain and requires verification through meta-analysis.AIM To provide evidence-based support for clinical decision-making and research,a meta-analysis was conducted to evaluate the effectiveness of liver-soothing formulas in treating perimenopausal anxiety and depression.METHODS Relevant studies published up to April 2025 were retrieved from ClinicalTrials.gov,PubMed,Web of Science,EMBASE,and the Cochrane Library.Eligible studies were screened according to predefined inclusion and exclusion criteria.Data were extracted and analyzed using the Stata 12.0 software.RESULTS After searching and screening,12 articles involving 1798 patients(922 in the treatment group and 876 in the control group)were included in the analysis.Meta-analysis showed that the standardized scores for anxiety[standardized mean difference(SMD)=-0.71,95%confidence interval(95%CI):-1.06 to-0.36]and depression(SMD=-0.67,95%CI:-1.06 to-0.27)of the treatment group were lower than those of the control group.Subgroup analysis results revealed that for anxiety,liver-soothing formulas used alone(SMD=-0.34,95%CI:-0.50 to-0.18)or in combination(SMD=-0.88,95%CI:-1.43 to-0.34)both significantly reduced scores compared with the control group.For depression,monotherapy of liversoothing formulas showed no significant statistical difference between the treatment and control groups(SMD=-0.47,95%CI:-1.11 to 0.17),whereas combination therapy produced significantly lower standardized scale scores in the treatment group than in the control group,with a statistically significant difference(SMD=-0.83,95%CI:-1.39 to-0.28).Regarding Greene scores,no statistically significant difference was observed with monotherapy(SMD=0.87,95%CI:-0.32 to 2.06),whereas combination therapy had significantly lower Greene scores(SMD=-0.24,95%CI:-0.44 to-0.04).No statistically significant difference was found between the groups in the occurrence of adverse reactions(odds ratio=0.90,95%CI:0.57-1.43).However,liver-soothing formulas did not affect estrogen levels in perimenopausal women.CONCLUSION Compared with placebo,conventional Western medicine,or other interventions,the monotherapy of liver-soothing formulas demonstrates superior efficacy in treating perimenopausal anxiety.When used as an adjuvant,they exert a synergistic effect in alleviating negative emotions and improving overall perimenopausal symptoms.展开更多
Artificial intelligence(AI)is revolutionizing medical imaging,particularly in chronic liver diseases assessment.AI technologies,including machine learning and deep learning,are increasingly integrated with multiparame...Artificial intelligence(AI)is revolutionizing medical imaging,particularly in chronic liver diseases assessment.AI technologies,including machine learning and deep learning,are increasingly integrated with multiparametric ultrasound(US)techniques to provide more accurate,objective,and non-invasive evaluations of liver fibrosis and steatosis.Analyzing large datasets from US images,AI enhances diagnostic precision,enabling better quantification of liver stiffness and fat content,which are essential for diagnosing and staging liver fibrosis and steatosis.Combining advanced US modalities,such as elastography and doppler imaging with AI,has demonstrated improved sensitivity in identifying different stages of liver disease and distinguishing various degrees of steatotic liver.These advancements also contribute to greater reproducibility and reduced operator dependency,addressing some of the limitations of traditional methods.The clinical implications of AI in liver disease are vast,ranging from early detection to predicting disease progression and evaluating treatment response.Despite these promising developments,challenges such as the need for large-scale datasets,algorithm transparency,and clinical validation remain.The aim of this review is to explore the current applications and future potential of AI in liver fibrosis and steatosis assessment using multiparametric US,highlighting the technological advances and clinical relevance of this emerging field.展开更多
BACKGROUND Robotic assistance is increasingly used for donor and recipient hepatectomy in liver transplantation,yet existing evidence is fragmented and variably indirect.AIM To evaluate clinical outcomes,surgical perf...BACKGROUND Robotic assistance is increasingly used for donor and recipient hepatectomy in liver transplantation,yet existing evidence is fragmented and variably indirect.AIM To evaluate clinical outcomes,surgical performance,and economic effects of robotic-assisted donor and recipient hepatectomy in the transplant pathway.METHODS Following Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 and a priori registration,systematic reviews were included with or without meta-analysis.Four databases were searched through July 2025.Methodological quality was appraised with a measurement tool to assess systematic reviews(AMSTAR 2),and certainty was graded with grading of recommendations assessment,development and evaluation(GRADE).Evidence overlap was calculated via a citation-matrix-based corrected covered area(CCA).Effect sizes were prespecified as risk ratios(RR)for dichotomous outcomes and mean differences for continuous outcomes.RESULTS Five reviews met the inclusion criteria,four with meta-analyses and one consensus review used only for context.Donor(direct)findings were more favorable for robotics in terms of estimated blood loss(≈-117 mL)and length of stay(≈-0.6 days),although with longer operative time(≈+105 minutes).Absolute risks for donor complications were not estimable from ratio-only data.Recipient(indirect)meta-analysis indicated robotics to be favorable in terms of conversion(RR≈0.41)and severe morbidity(RR≈0.81),with a trend toward lower overall morbidity(RR≈0.92)and no difference in 30-day mortality.Differences in length of stay and operative time were small and heterogeneous.Economic evidence(indirect,network meta-analysis)suggested higher procedural costs for robotic vs laparoscopic intervention,but lower hospitalization costs vs open intervention,with laparoscopy the least expensive overall.AMSTAR 2 ratings were moderate-to-high across the reviews,GRADE certainty was low for key donor continuous outcomes,and low-to-moderate for recipient and economic outcomes.Overlap was slight(graded-corpus CCA=0.0%;including a contextual non-transplant review increased CCA to≈1.25%).CONCLUSION Robotic donor hepatectomy confers perioperative advantages at the cost of longer operative time.Recipient and economic findings are indirect and considered hypothesis-generating.Transplant-specific,prospective comparisons using a minimum standardized dataset and uniform outcome definitions are needed to resolve remaining uncertainties and to clarify the cost-utility correlation.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is an increasingly prevalent condition associated with hepatic complications and cardiovascular and renal events.Given its significant clinical impact,the...Metabolic dysfunction-associated steatotic liver disease(MASLD)is an increasingly prevalent condition associated with hepatic complications and cardiovascular and renal events.Given its significant clinical impact,the development of new strategies for early diagnosis and treatment is essential to improve patient outcomes.Over the past decade,the integration of artificial intelligence(AI)into gastroenterology has led to transformative advancements in medical practice.AI represents a major step towards personalized medicine,offering the potential to enhance diagnostic accuracy,refine prognostic assessments,and optimize treatment strategies.Its applications are rapidly expanding.This article explores the emerging role of AI in the management of MASLD,emphasizing its ability to improve clinical prediction,enhance the diagnostic performance of imaging modalities,and support histopathological confirmation.Additionally,it examines the development of AI-guided personalized treatments,where lifestyle modifications and close monitoring play a pivotal role in achieving therapeutic success.展开更多
Background:ZhiZi-BoPi Decoction(ZZBPD),a traditional prescription for liver and gallbladder protection,has garnered significant clinical interest due to its hepatoprotective properties.Despite its proven efficacy in m...Background:ZhiZi-BoPi Decoction(ZZBPD),a traditional prescription for liver and gallbladder protection,has garnered significant clinical interest due to its hepatoprotective properties.Despite its proven efficacy in mitigating intrahepatic cholestasis,the precise mechanisms underlying its therapeutic effects remain inadequately understood.This study aims to comprehensively investigate the pharmacological mechanisms underlying the therapeutic effects of ZZBPD in cholestatic liver injury(CLI).Methods:Firstly,we evaluated the hepatoprotective effects of ZZBPD on mice with CLI induced byα-naphthylisothiocyanate(ANIT),by measuring biochemical markers,inflammatory factors,and bile acid levels.Subsequently,we employed network pharmacology and single-cell RNA sequencing(scRNA-seq)to identify key targets and potential signaling pathways for the prevention and treatment of CLI.Finally,we further validated the mechanism of action of ZZBPD on these key targets through molecular docking,western blotting,and immunofluorescence techniques.Results:ZZBPD notably improved serum liver function,reduced hepatic inflammation,and restored bile acid balance.Through network pharmacology and scRNA-seq analysis,48 core targets were identified,including TNF,IL-6,and NFKB1,all of which are linked to the IL-17 and NF-κB signaling pathways,as shown by KEGG enrichment analysis.Molecular docking further confirmed stable interactions between ZZBPD’s key active components and molecules such as IL-6,IL-17,and NF-κB.Additionally,western blotting and immunofluorescence validated the downregulation of IL-17 and NF-κB protein expression in liver tissue.Conclusion:ZZBPD effectively treats CLI by activating pathways related to the bile acid receptor FXR,while also modulating the IL-17/NF-κB signaling pathway.This dual action enhances bile secretion and alleviates liver inflammation.These findings offer important insights into the pharmacological mechanisms of ZZBPD and underscore its potential as a promising therapeutic for CLI.展开更多
To establish practical,evidence-based strategies for noninvasive assessment and referral of patients with metabolic dysfunction-associated steatotic liver disease(MASLD)in Japan,we must address the urgent clinical nee...To establish practical,evidence-based strategies for noninvasive assessment and referral of patients with metabolic dysfunction-associated steatotic liver disease(MASLD)in Japan,we must address the urgent clinical need for accurate risk stratification and timely specialist intervention.A panel of 11 Japanese hepatology experts conducted a modified Delphi process to evaluate consensus recommendations regarding the use of noninvasive tests(NITs),including the fibrosis-4 index,enhanced liver fibrosis test,Mac-2-binding protein glycosylation isomer,type IV collagen 7S,cytokeratin-18 fragments,and imaging modalities such as ultrasound elastography and magnetic resonance elastography,for MASLD assessment and clinical referral.Practical algorithms were developed based on current Japanese data and panel consensus.The expert panel validated the utility of NITs as reliable tools for identifying patients with MASLD at risk for advanced fibrosis.Sequential use of NITs improved diagnostic accuracy and referral appropriateness while minimizing unnecessary specialist consultations.The proposed algorithms offer stepwise guidance for primary care physicians,supporting efficient,evidence-based decisionmaking.However,prospective longitudinal studies remain necessary for full prognostic validation of NITs in MASLD management.Noninvasive testing algorithms enable effective risk stratification and referral for MASLD in real-world Japanese practice with anticipated benefit for patient outcomes and healthcare systems.Broader adoption and further validation are warranted.展开更多
Liver fibrosis is a reversible wound-healing process aimed at maintaining organ integrity, and presents as the critical pre-stage of liver cirrhosis, which will eventually progress to hepatocellular carcinoma in the a...Liver fibrosis is a reversible wound-healing process aimed at maintaining organ integrity, and presents as the critical pre-stage of liver cirrhosis, which will eventually progress to hepatocellular carcinoma in the absence of liver transplantation. Fibrosis generally results from chronic hepatic injury caused by various factors, mainly viral infection, schistosomiasis, and alcoholism; however, the exact pathological mechanisms are still unknown. Although numerous drugs have been shown to have antifibrotic activity in vitro and in animal models, none of these drugs have been shown to be efficacious in the clinic. Importantly, hepatic stellate cells(HSCs) play a key role in the initiation, progression, and regression of liver fibrosis by secreting fibrogenic factors that encourage portal fibrocytes, fibroblasts, and bone marrow-derived myofibroblasts to produce collagen and thereby propagate fibrosis. These cells are subject to intricate cross-talk with adjacent cells, resulting in scarring and subsequent liver damage. Thus, an understanding of the molecular mechanisms of liver fibrosis and their relationships with HSCs is essential for the discovery of new therapeutic targets. This comprehensive review outlines the role of HSCs in liver fibrosis and details novel strategies to suppress HSC activity, thereby providing new insights into potential treatments for liver fibrosis.展开更多
Histological analysis of liver biopsies remains a standard against which other methods of assessment for the presence and amount of hepatic injury due to nonalcoholic fatty liver disease(NAFLD) are measured.Histologic...Histological analysis of liver biopsies remains a standard against which other methods of assessment for the presence and amount of hepatic injury due to nonalcoholic fatty liver disease(NAFLD) are measured.Histological evaluation remains the sole method of distinguishing steatosis from advanced forms of NAFLD,i.e.nonalcoholic steatohepatitis(NASH) and fibrosis.Included in the lesions of NAFLD are steatosis,lobular and portal inflammation,hepatocyte injury in the forms of ballooning and apoptosis,and fibrosis.However,patterns of these lesions are as distinguishing as the lesions themselves.Liver injury in adults and children due to NAFLD may have different histological patterns.In this review,the rationale for liver biopsy,as well as the histopathological lesions,the microscopically observable patterns of injury,and the differential diagnoses of NAFLD and NASH are discussed.展开更多
Nonalcoholic fatty liver disease(NAFLD), a hepatic manifestation of metabolic syndrome, is the most common chronic liver disease, and the prevalence is rapidly increasing worldwide. Nonalcoholic steatohepatitis(NASH),...Nonalcoholic fatty liver disease(NAFLD), a hepatic manifestation of metabolic syndrome, is the most common chronic liver disease, and the prevalence is rapidly increasing worldwide. Nonalcoholic steatohepatitis(NASH), the severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma(HCC). Although noninvasive clinical scores and image-based diagnosis for NAFLD have improved, histopathological evaluation of biopsy specimens remains the gold standard for diagnosing NAFLD/NASH. Steatosis, lobular inflammation, and hepatocellular ballooning are all necessary components for the diagnosis of NASH; fibrosis is also typically observed. Other histopathological abnormalities commonly observed in NASH include hepatocellular glycogenated nuclei, lipogranulomas, and acidophil bodies. The characteristics of pediatric NAFLD/NASH differ from adult NAFLD/NASH. Specifically, steatosis and portal inflammation are more severe in pediatric NAFLD, while intralobular inflammation and perisinusoidal fibrosis are milder. Although interobserver agreement for evaluating the extent of steatosis and fibrosis is high, agreement is low for intralobular and portal inflammation. A recently reported histological variant of HCC, steatohepatitic HCC(SH-HCC), showsfeatures that resemble non-neoplastic steatohepatitis,and is thought to be strongly associated with underlying NASH.In this report,we review the histopathological features of NAFLD/NASH.展开更多
Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in patients with diabetes mellitus and increasing evidence suggests that patients with type 2diabetes are at a particularly high risk for developing the prog...Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in patients with diabetes mellitus and increasing evidence suggests that patients with type 2diabetes are at a particularly high risk for developing the progressive forms of NAFLD,non-alcoholic steatohepatitis and associated advanced liver fibrosis.Moreover,diabetes is an independent risk factor for NAFLD progression,and for hepatocellular carcinoma development and liver-related mortality in prospective studies.Notwithstanding,patients with NAFLD have an elevated prevalence of prediabetes.Recent studies have shown that NAFLD presence predicts the development of type2 diabetes.Diabetes and NAFLD have mutual pathogenetic mechanisms and it is possible that genetic and environmental factors interact with metabolic derangements to accelerate NAFLD progression in diabetic patients.The diagnosis of the more advanced stages of NAFLD in diabetic patients shares the same challenges as in non-diabetic patients and it includes imaging and serological methods,although histopathological evaluation is still considered the gold standard diagnostic method.An effective established treatment is not yet available for patients with steatohepatitis and fibrosis and randomized clinical trials including only diabetic patients are lacking.We sought to outline the published data including epidemiology,pathogenesis,diagnosis and treatment of NAFLD in diabetic patients,in order to better understand the interplay between these two prevalent diseases and identify the gaps that still need to be fulfilled in the management of NAFLD in patients with diabetes mellitus.展开更多
基金Supported by the Sichuan Science and Technology Program,No.2024NSFSC1936.
文摘BACKGROUND Cancer-associated fibroblasts(CAFs),crucial components of the tumor microenvironment in primary and metastatic tumors,can impact the activity of cancer cells and contribute to their progression.Given their extensive interactions with cancer cells and other stromal cells,we aimed to evaluate the prognostic value of CAFs in patients with liver cancer(LC).AIM To investigate the association between CAF expression and clinicopathological characteristics as well as overall survival(OS)in patients with LC,including hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(iCCA).METHODS We performed a meta-analysis of cohort studies with available data on the effects of CAF expression on both clinicopathological characteristics and OS via hazard ratios(HRs)and risk ratios with 95%confidence intervals(CIs).Studies were subgrouped on the basis of CAF markers and cancer type,and the subgroup effects of CAF expression on both HCC and iCCA were analyzed through meta-regression.The Newcastle-Ottawa Scale was used to evaluate the included studies to guarantee their quality and minimize the possibility of bias.RESULTS Nine trials were selected and included a total of 1518 patients.According to our primary meta-analysis,the expression of CAFs in LC patients was significantly associated with a decrease in OS(LC:HR:1.62;95%CI:1.34-1.97;P<0.001;HCC:HR:1.67;95%CI:1.34-2.07;P<0.001;iCCA:HR:1.47;95%CI:0.97-2.23;P=0.07);nevertheless,it was not significantly associated with almost all clinicopathologic characteristics,including tumor size,venous infiltration,alpha-fetoprotein level,and differentiation grade.According to the subgroup analysis of smooth muscle actin(SMA)markers in both HCC patients and iCCA patients,high CAF expression in HCC(HR:2.29;95%CI:1.01-5.22;P=0.048)and iCCA(HR:2.04;95%CI:1.09-3.81;P=0.025)patients was a significant indicator of poor OS.Moreover,the clinicopathological characteristics were also verified by the SMA marker,which had a nearly significant effect on the venous infiltration of iCCA(risk ratio:2.70;95%CI:0.97-7.49;P=0.057).CONCLUSION High CAF expression,evaluated by both mixed markers and SMAs,is significantly associated with poor OS in patients with LC,including both HCC patients and iCCA patients.However,further research is necessary since how CAF expression and clinicopathologic features are related is yet unknown.
基金Supported by The Department of Veterans Affairs Biomedical Laboratory Research&Development Service Award,No.BX003486(to McMillin M)National Institutes of Health Awards,No.R01DK112803 and No.R01DK135995(to DeMorrow S).
文摘BACKGROUND Acute liver failure(ALF)is a loss of liver function due to a severe hepatic insult.Studies utilizing the azoxymethane(AOM)mouse model of ALF,which also generates hepatic encephalopathy,have primarily focused on development of neurological deficits.However,the molecular processes that generate liver damage have not been fully characterized.Therefore,a more comprehensive characterization of the hepatic consequences of AOM toxicity is needed to better understand this disease model.AIM To identify molecular pathology contributing to hepatic injury during the progression of AOM-induced ALF.METHODS C57BL/6 mice were injected with AOM to produce ALF and hepatic encephalopathy.Tissue was collected at defined stages of neurological decline up to coma.Liver injury,CYP2E1 expression,oxidative stress,inflammation,apoptosis,necroptosis,and hepatocellular senescence were assessed.RESULTS Increased hepatic necrosis and exacerbated liver injury were observed after AOM injection as mice progressed towards coma.CYP2E1 expression decreased in AOM-treated mice as liver injury progressed.Malondialdehyde,myeloperoxidase and other measures of oxidative stress were significantly increased during AOM-induced ALF.Hepatic CCL2 and tumor necrosis factorαexpression increased as AOM-induced liver injury progressed.Mixed lineage kinase domain-like protein phosphorylation was increased early during the progression of AOM-induced liver injury.Measures of apoptosis and cellular senescence all increased as the time course of AOM progressed.CONCLUSION These data support that necrosis,oxidative stress,inflammation,apoptosis,and senescence were elevated in AOMtreated mice,with inflammation being the earliest significant change.
文摘BACKGROUND Repeated application of the Pringle maneuver is a key obstacle to safe minimally invasive repeat liver resection(MISRLR).However,limited technical guidance is available.AIM To study the utility of newly developed Pringle taping method guided by liver surface in MISRLR.METHODS We retrospectively reviewed 72 cases of MISRLR performed by a single surgeon at two centers from August 2015 to July 2024.Beginning in October 2019,a liver surface-guided encirclement of hepatoduodenal ligament(LSEH)was used for repeat Pringle taping.Perioperative outcomes including Pringle taping success,operative time,blood loss,conversion rate,morbidity,and mortality were assessed.RESULTS Laparoscopic and robotic approaches were used in 63 patients and 9 patients,respectively.The median operative time,blood loss,and hospital stay were 331.5 minutes,70 mL,and 8 days,respectively.Open conversion occurred in two cases(2.8%)due to severe adhesions and right renal vein injury.Clavien-Dindo grade≥III complications occurred in 5.6%of cases with no mortality.Anti-adhesion barriers were used in 54 patients(75.0%).LSEH was attempted in 57 cases,improving Pringle taping success from 33.0%to 91.4%(P<0.001).LSEH succeeded in all patients with prior open liver resection(n=11).Among 6 patients in whom LSEH failed,3 patients(50.0%)had undergone a third liver resection,and 1 patient had a history of distal gastrectomy with choledochoduodenostomy.CONCLUSION The newly developed LSEH technique for Pringle taping in MISRLR was feasible,enhancing safety and reproducibility even in patients with a history of open liver resection.
基金Supported by UMM Al-Qura University,Saudi Arabia,No.25UQU4350477GSSR05.
文摘Liver metastases are a leading contributor to cancer-related illness and death,occurring far more frequently than primary liver tumors.Their management remains highly challenging due to the complexity of disease behavior and the need for an individualized,multidisciplinary approach.Effective care increasingly relies on integrating sophisticated diagnostic techniques,advanced systemic and locoregional therapies,and molecularly tailored treatment strategies.This review provides an in-depth analysis of the current clinicopathological perspectives on liver metastases.It explores their epidemiology,mechanisms of spread,histological growth patterns,diagnostic imaging advancements,molecular characteristics,and therapeutic interventions.Additionally,it examines the broader implications for patient quality of life(QoL),healthcare costs,and the particular difficulties associated with managing liver metastases in pediatric patients and individuals with rare malignancies.The article outlines the diverse histopathological features and tumor–liver interface growth patterns,emphasizing their prognostic and therapeutic significance.It evaluates contemporary imaging modalities–including magnetic resonance imaging and computed tomography(CT)with hepatocyte-specific agents,positron emission tomography/CT,and contrast-enhanced ultrasound–and highlights the emerging importance of liquid biopsy and molecular profiling in shaping treatment decisions.The review discusses available treatment options such as chemotherapy,targeted agents,immunotherapies,surgical resection,liver transplantation,and various locoregional therapies.Furthermore,it addresses evolving fields like prognostic scoring systems,radiomics,artificial intelligence(AI)applications,and patient–derived organoid and xenograft models.A summary of current clinical trials and translational research initiatives reflects the fast-paced evolution of this field.The management of liver metastases is rapidly advancing,driven by precision oncology principles and collaborative,multidisciplinary care.The integration of molecular diagnostics,novel therapeutic approaches,and cutting–edge technologies–including AI and organoid-based personalized drug testing-is poised to enhance treatment selection,improve clinical outcomes,and support better QoL.These innovations hold the potential to transform the outlook for patients with liver metastases,moving toward more durable disease control in appropriately selected cases.
文摘Inborn errors of metabolism(IEM)are rare disorders,most are liver-based with liver transplantation(LT)emerging as an effective cure in the pediatric population.LT has been shown to offer a cure or deter disease progression and provide symptomatic improvement in patients with IEM.Each metabolic disorder is unique,with the missing enzyme or transporter protein causing substrate deficiency or toxic byproduct production.Knowledge about the distribution of deficient enzymes,the percentage of enzymes replaced by LT,and the extent of extrahepatic involvement helps anticipate and manage complications in the perioperative period.Most patients have multisystem involvement and can be on complex dietary regimens.Metabolic decompensation can be triggered due to the stress response to surgery,fasting and other unanticipated complications perioperatively.Thus,a multidisciplinary team’s input including those from metabolic specialists is essential to develop disease and patient-specific strategies for the perioperative management of these patients during LT.In this review,we outline the classification of IEM,indications for LT along with potential benefits,basic metabolic defects and their implications,details of extrahepatic involvement and perioperative management strategies for LT in children with some of the commonly presenting IEM,to assist anesthesiologists handling this cohort of patients.
文摘BACKGROUND While varices and variceal bleeds are well-known and feared complications of advanced cirrhosis and portal hypertension,omental variceal bleed are a rare sequala even in patients with known esophageal or gastric varices.While rare,omental varices pose a risk for hemoperitoneum if ruptured,which is a lifethreatening complication with high mortality rates despite surgical intervention.CASE SUMMARY This report reviews the case of a patient 36-year-old female with alcohol related cirrhosis decompensated by ascites,but no history of varices admitted for hemorrhagic shock from spontaneous rupture of omental varices requiring emergency surgery.She underwent the first documented successful orthotopic liver transplantation the same admission.CONCLUSION This case report and literature review stresses the importance of early consideration and identification of intraabdominal variceal sources in cirrhotic patients with refractory shock.
文摘Liver transplantation is a life-saving procedure for patients with end-stage liver diseases and acute liver failure.With advances in surgical techniques and immunosuppressive regimens,patient survival rates have significantly improved.While the systemic complications of post-transplantation are well recognized,ophthalmic manifestations remain underreported.Ophthalmic complications can significantly impair visual function and increase morbidity in these patients.Prolonged immunosuppression makes the patients susceptible to the opportunistic pathogens such as Cytomegalovirus,Candida,Aspergillus,etc.Other common findings include dry eye disease,cataracts and retinal vascular complications which further contribute to the long-term morbidity in these patients.Early ophthalmic evaluation and prompt management are essential to prevent irreversible vision loss and improve post-transplant outcomes.High index of suspicion and multidisciplinary approach is essential to facilitate early diagnosis and treatment.This review highlights the range of ophthalmic complications observed in liver transplant recipients and underscores the need for future research focused on understanding the underlying pathophysiological mechanisms and refining the prophylactic protocols to improve outcomes in this unique patient population.
基金Supported by National Natural Science Foundation of China,No.82303672Zhejiang Provincial Health Commission and Zhejiang Provincial Administration of Traditional Chinese Medicine through the Targeted Project for Medical and Health Research,No.2025ZL017and China Primary Health Care Foundation,No.ZLMY20240311001ZJ.
文摘BACKGROUND The liver represents a common site of distant metastasis in patients with esophageal cancer(EC).Conventional chemotherapy(CMT)presents limited efficacy for EC,and EC patients with liver metastases typically experience a poor prognosis,highlighting an urgent need to explore novel treatment approaches.This study evaluated the overall efficacy and safety of CMT vs CMT combined with immune checkpoint inhibitors(ICIs)in the treatment of EC patients with liver metastases.Furthermore,prognostic factors influencing outcomes in this patient population were identified.AIM To evaluate the efficacy and safety of first-line chemoimmunotherapy for EC patients with liver metastases and to analyze prognostic factors.METHODS This retrospective study included 126 EC patients with liver metastases at Zhejiang Cancer Hospital between 2014 and 2024.Patients receiving CMT were compared with those receiving CMT+ICI.Analyzed variables included clinicopathological features,treatment history,characteristics of metastasis,systemic and local treatments,overall survival(OS),and treatment-related adverse events(TRAEs).Prognostic factors were evaluated using univariate and multivariate Cox proportional-hazards regression models.Finally,efficacy outcomes and TRAE profiles were compared between the two groups.RESULTS A significant difference in median OS was identified between the two groups(10.8 months in the CMT group vs 20.8 months in the CMT+ICI group,P=0.004).The CMT+ICI group also demonstrated a significantly longer median progression-free survival of 11.7 months(P<0.001).Patients receiving combination therapy exhibited significantly improved systemic objective response rate and disease control rate.Multivariate analysis identified key factors significantly influencing OS in EC patients with liver metastases:Karnofsky Performance Status score≥70,receipt of local therapy for liver metastases,and the number of cycles of CMT and immunotherapy received.Furthermore,the incidence of TRAEs did not significantly differ between the CMT+ICI and CMT groups.CONCLUSION For EC patients with liver metastases,the combination of CMT and ICIs demonstrates significantly superior efficacy compared with CMT alone,while maintaining manageable TRAEs.
文摘Liver transplantation(LT)remains the optimal life-saving intervention for patients with end-stage liver disease.Despite the recent advances in LT several barriers,including organ allocation,donor-recipient matching,and patient education,persist.With the growing progress of artificial intelligence,particularly large language models(LLMs)like ChatGPT,new applications have emerged in the field of LT.Current studies demonstrating usage of ChatGPT in LT include various areas of application,from clinical settings to research and education.ChatGPT usage can benefit both healthcare professionals,by decreasing the time spent on non-clinical work,but also LT recipients by providing accurate information.Future potential applications include the expanding usage of ChatGPT and other LLMs in the field of LT pathology and radiology as well as the automated creation of discharge summaries or other related paperwork.Additionally,the next models of ChatGPT might have the potential to provide more accurate patient education material with increased readability.Although ChatGPT usage presents promising applications,there are certain ethical and practical limitations.Key concerns include patient data privacy,information accuracy,misinformation possibility and lack of legal framework.Healthcare providers and policymakers should collaborate for the establishment of a controlled framework for the safe use of ChatGPT.The aim of this minireview is to summarize current literature on ChatGPT in LT,highlighting both opportunities and limitations,while also providing future possible applications.
文摘BACKGROUND Perimenopausal women are prone to anxiety and depression due to fluctuating hormone levels,which significantly impair their quality of life.The current treatments have certain limitations.In traditional Chinese medicine,liver-soothing formulas are commonly prescribed for mood-related disorders,but their overall efficacy in perimenopausal anxiety and depression remains uncertain and requires verification through meta-analysis.AIM To provide evidence-based support for clinical decision-making and research,a meta-analysis was conducted to evaluate the effectiveness of liver-soothing formulas in treating perimenopausal anxiety and depression.METHODS Relevant studies published up to April 2025 were retrieved from ClinicalTrials.gov,PubMed,Web of Science,EMBASE,and the Cochrane Library.Eligible studies were screened according to predefined inclusion and exclusion criteria.Data were extracted and analyzed using the Stata 12.0 software.RESULTS After searching and screening,12 articles involving 1798 patients(922 in the treatment group and 876 in the control group)were included in the analysis.Meta-analysis showed that the standardized scores for anxiety[standardized mean difference(SMD)=-0.71,95%confidence interval(95%CI):-1.06 to-0.36]and depression(SMD=-0.67,95%CI:-1.06 to-0.27)of the treatment group were lower than those of the control group.Subgroup analysis results revealed that for anxiety,liver-soothing formulas used alone(SMD=-0.34,95%CI:-0.50 to-0.18)or in combination(SMD=-0.88,95%CI:-1.43 to-0.34)both significantly reduced scores compared with the control group.For depression,monotherapy of liversoothing formulas showed no significant statistical difference between the treatment and control groups(SMD=-0.47,95%CI:-1.11 to 0.17),whereas combination therapy produced significantly lower standardized scale scores in the treatment group than in the control group,with a statistically significant difference(SMD=-0.83,95%CI:-1.39 to-0.28).Regarding Greene scores,no statistically significant difference was observed with monotherapy(SMD=0.87,95%CI:-0.32 to 2.06),whereas combination therapy had significantly lower Greene scores(SMD=-0.24,95%CI:-0.44 to-0.04).No statistically significant difference was found between the groups in the occurrence of adverse reactions(odds ratio=0.90,95%CI:0.57-1.43).However,liver-soothing formulas did not affect estrogen levels in perimenopausal women.CONCLUSION Compared with placebo,conventional Western medicine,or other interventions,the monotherapy of liver-soothing formulas demonstrates superior efficacy in treating perimenopausal anxiety.When used as an adjuvant,they exert a synergistic effect in alleviating negative emotions and improving overall perimenopausal symptoms.
文摘Artificial intelligence(AI)is revolutionizing medical imaging,particularly in chronic liver diseases assessment.AI technologies,including machine learning and deep learning,are increasingly integrated with multiparametric ultrasound(US)techniques to provide more accurate,objective,and non-invasive evaluations of liver fibrosis and steatosis.Analyzing large datasets from US images,AI enhances diagnostic precision,enabling better quantification of liver stiffness and fat content,which are essential for diagnosing and staging liver fibrosis and steatosis.Combining advanced US modalities,such as elastography and doppler imaging with AI,has demonstrated improved sensitivity in identifying different stages of liver disease and distinguishing various degrees of steatotic liver.These advancements also contribute to greater reproducibility and reduced operator dependency,addressing some of the limitations of traditional methods.The clinical implications of AI in liver disease are vast,ranging from early detection to predicting disease progression and evaluating treatment response.Despite these promising developments,challenges such as the need for large-scale datasets,algorithm transparency,and clinical validation remain.The aim of this review is to explore the current applications and future potential of AI in liver fibrosis and steatosis assessment using multiparametric US,highlighting the technological advances and clinical relevance of this emerging field.
文摘BACKGROUND Robotic assistance is increasingly used for donor and recipient hepatectomy in liver transplantation,yet existing evidence is fragmented and variably indirect.AIM To evaluate clinical outcomes,surgical performance,and economic effects of robotic-assisted donor and recipient hepatectomy in the transplant pathway.METHODS Following Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 and a priori registration,systematic reviews were included with or without meta-analysis.Four databases were searched through July 2025.Methodological quality was appraised with a measurement tool to assess systematic reviews(AMSTAR 2),and certainty was graded with grading of recommendations assessment,development and evaluation(GRADE).Evidence overlap was calculated via a citation-matrix-based corrected covered area(CCA).Effect sizes were prespecified as risk ratios(RR)for dichotomous outcomes and mean differences for continuous outcomes.RESULTS Five reviews met the inclusion criteria,four with meta-analyses and one consensus review used only for context.Donor(direct)findings were more favorable for robotics in terms of estimated blood loss(≈-117 mL)and length of stay(≈-0.6 days),although with longer operative time(≈+105 minutes).Absolute risks for donor complications were not estimable from ratio-only data.Recipient(indirect)meta-analysis indicated robotics to be favorable in terms of conversion(RR≈0.41)and severe morbidity(RR≈0.81),with a trend toward lower overall morbidity(RR≈0.92)and no difference in 30-day mortality.Differences in length of stay and operative time were small and heterogeneous.Economic evidence(indirect,network meta-analysis)suggested higher procedural costs for robotic vs laparoscopic intervention,but lower hospitalization costs vs open intervention,with laparoscopy the least expensive overall.AMSTAR 2 ratings were moderate-to-high across the reviews,GRADE certainty was low for key donor continuous outcomes,and low-to-moderate for recipient and economic outcomes.Overlap was slight(graded-corpus CCA=0.0%;including a contextual non-transplant review increased CCA to≈1.25%).CONCLUSION Robotic donor hepatectomy confers perioperative advantages at the cost of longer operative time.Recipient and economic findings are indirect and considered hypothesis-generating.Transplant-specific,prospective comparisons using a minimum standardized dataset and uniform outcome definitions are needed to resolve remaining uncertainties and to clarify the cost-utility correlation.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is an increasingly prevalent condition associated with hepatic complications and cardiovascular and renal events.Given its significant clinical impact,the development of new strategies for early diagnosis and treatment is essential to improve patient outcomes.Over the past decade,the integration of artificial intelligence(AI)into gastroenterology has led to transformative advancements in medical practice.AI represents a major step towards personalized medicine,offering the potential to enhance diagnostic accuracy,refine prognostic assessments,and optimize treatment strategies.Its applications are rapidly expanding.This article explores the emerging role of AI in the management of MASLD,emphasizing its ability to improve clinical prediction,enhance the diagnostic performance of imaging modalities,and support histopathological confirmation.Additionally,it examines the development of AI-guided personalized treatments,where lifestyle modifications and close monitoring play a pivotal role in achieving therapeutic success.
基金supported by the National Science Foundation of China(No.82405004,82474253)the Natural Science Foundation postdoctoral project of Chongqing(CSTB2022NSCQ-BHX0709)+2 种基金Chongqing Wanzhou District doctoral“through train”scientific research project(wzstc-20220124)Natural Science Foundation of Chongqing,China(No.Cstc2021jcyj-msxmX0996)Chongqing Wanzhou District Science and Health Joint Medical Research Project(wzstc-kw2023032)。
文摘Background:ZhiZi-BoPi Decoction(ZZBPD),a traditional prescription for liver and gallbladder protection,has garnered significant clinical interest due to its hepatoprotective properties.Despite its proven efficacy in mitigating intrahepatic cholestasis,the precise mechanisms underlying its therapeutic effects remain inadequately understood.This study aims to comprehensively investigate the pharmacological mechanisms underlying the therapeutic effects of ZZBPD in cholestatic liver injury(CLI).Methods:Firstly,we evaluated the hepatoprotective effects of ZZBPD on mice with CLI induced byα-naphthylisothiocyanate(ANIT),by measuring biochemical markers,inflammatory factors,and bile acid levels.Subsequently,we employed network pharmacology and single-cell RNA sequencing(scRNA-seq)to identify key targets and potential signaling pathways for the prevention and treatment of CLI.Finally,we further validated the mechanism of action of ZZBPD on these key targets through molecular docking,western blotting,and immunofluorescence techniques.Results:ZZBPD notably improved serum liver function,reduced hepatic inflammation,and restored bile acid balance.Through network pharmacology and scRNA-seq analysis,48 core targets were identified,including TNF,IL-6,and NFKB1,all of which are linked to the IL-17 and NF-κB signaling pathways,as shown by KEGG enrichment analysis.Molecular docking further confirmed stable interactions between ZZBPD’s key active components and molecules such as IL-6,IL-17,and NF-κB.Additionally,western blotting and immunofluorescence validated the downregulation of IL-17 and NF-κB protein expression in liver tissue.Conclusion:ZZBPD effectively treats CLI by activating pathways related to the bile acid receptor FXR,while also modulating the IL-17/NF-κB signaling pathway.This dual action enhances bile secretion and alleviates liver inflammation.These findings offer important insights into the pharmacological mechanisms of ZZBPD and underscore its potential as a promising therapeutic for CLI.
基金Supported by Japan Society for the Promotion of Science KAKENHI,No.25K11274.
文摘To establish practical,evidence-based strategies for noninvasive assessment and referral of patients with metabolic dysfunction-associated steatotic liver disease(MASLD)in Japan,we must address the urgent clinical need for accurate risk stratification and timely specialist intervention.A panel of 11 Japanese hepatology experts conducted a modified Delphi process to evaluate consensus recommendations regarding the use of noninvasive tests(NITs),including the fibrosis-4 index,enhanced liver fibrosis test,Mac-2-binding protein glycosylation isomer,type IV collagen 7S,cytokeratin-18 fragments,and imaging modalities such as ultrasound elastography and magnetic resonance elastography,for MASLD assessment and clinical referral.Practical algorithms were developed based on current Japanese data and panel consensus.The expert panel validated the utility of NITs as reliable tools for identifying patients with MASLD at risk for advanced fibrosis.Sequential use of NITs improved diagnostic accuracy and referral appropriateness while minimizing unnecessary specialist consultations.The proposed algorithms offer stepwise guidance for primary care physicians,supporting efficient,evidence-based decisionmaking.However,prospective longitudinal studies remain necessary for full prognostic validation of NITs in MASLD management.Noninvasive testing algorithms enable effective risk stratification and referral for MASLD in real-world Japanese practice with anticipated benefit for patient outcomes and healthcare systems.Broader adoption and further validation are warranted.
基金Supported by the National Natural Science Foundation of China,No.81300251
文摘Liver fibrosis is a reversible wound-healing process aimed at maintaining organ integrity, and presents as the critical pre-stage of liver cirrhosis, which will eventually progress to hepatocellular carcinoma in the absence of liver transplantation. Fibrosis generally results from chronic hepatic injury caused by various factors, mainly viral infection, schistosomiasis, and alcoholism; however, the exact pathological mechanisms are still unknown. Although numerous drugs have been shown to have antifibrotic activity in vitro and in animal models, none of these drugs have been shown to be efficacious in the clinic. Importantly, hepatic stellate cells(HSCs) play a key role in the initiation, progression, and regression of liver fibrosis by secreting fibrogenic factors that encourage portal fibrocytes, fibroblasts, and bone marrow-derived myofibroblasts to produce collagen and thereby propagate fibrosis. These cells are subject to intricate cross-talk with adjacent cells, resulting in scarring and subsequent liver damage. Thus, an understanding of the molecular mechanisms of liver fibrosis and their relationships with HSCs is essential for the discovery of new therapeutic targets. This comprehensive review outlines the role of HSCs in liver fibrosis and details novel strategies to suppress HSC activity, thereby providing new insights into potential treatments for liver fibrosis.
文摘Histological analysis of liver biopsies remains a standard against which other methods of assessment for the presence and amount of hepatic injury due to nonalcoholic fatty liver disease(NAFLD) are measured.Histological evaluation remains the sole method of distinguishing steatosis from advanced forms of NAFLD,i.e.nonalcoholic steatohepatitis(NASH) and fibrosis.Included in the lesions of NAFLD are steatosis,lobular and portal inflammation,hepatocyte injury in the forms of ballooning and apoptosis,and fibrosis.However,patterns of these lesions are as distinguishing as the lesions themselves.Liver injury in adults and children due to NAFLD may have different histological patterns.In this review,the rationale for liver biopsy,as well as the histopathological lesions,the microscopically observable patterns of injury,and the differential diagnoses of NAFLD and NASH are discussed.
文摘Nonalcoholic fatty liver disease(NAFLD), a hepatic manifestation of metabolic syndrome, is the most common chronic liver disease, and the prevalence is rapidly increasing worldwide. Nonalcoholic steatohepatitis(NASH), the severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma(HCC). Although noninvasive clinical scores and image-based diagnosis for NAFLD have improved, histopathological evaluation of biopsy specimens remains the gold standard for diagnosing NAFLD/NASH. Steatosis, lobular inflammation, and hepatocellular ballooning are all necessary components for the diagnosis of NASH; fibrosis is also typically observed. Other histopathological abnormalities commonly observed in NASH include hepatocellular glycogenated nuclei, lipogranulomas, and acidophil bodies. The characteristics of pediatric NAFLD/NASH differ from adult NAFLD/NASH. Specifically, steatosis and portal inflammation are more severe in pediatric NAFLD, while intralobular inflammation and perisinusoidal fibrosis are milder. Although interobserver agreement for evaluating the extent of steatosis and fibrosis is high, agreement is low for intralobular and portal inflammation. A recently reported histological variant of HCC, steatohepatitic HCC(SH-HCC), showsfeatures that resemble non-neoplastic steatohepatitis,and is thought to be strongly associated with underlying NASH.In this report,we review the histopathological features of NAFLD/NASH.
基金Supported by Conselho Brasileiro de Desenvolvimento Científico e Tecnológico(CNPq-Brasil)and Fundao Carlos Chagas Filho de AmparoàPesquisa do Estado do Rio de Janeiro(FAPERJ-Brasil)
文摘Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in patients with diabetes mellitus and increasing evidence suggests that patients with type 2diabetes are at a particularly high risk for developing the progressive forms of NAFLD,non-alcoholic steatohepatitis and associated advanced liver fibrosis.Moreover,diabetes is an independent risk factor for NAFLD progression,and for hepatocellular carcinoma development and liver-related mortality in prospective studies.Notwithstanding,patients with NAFLD have an elevated prevalence of prediabetes.Recent studies have shown that NAFLD presence predicts the development of type2 diabetes.Diabetes and NAFLD have mutual pathogenetic mechanisms and it is possible that genetic and environmental factors interact with metabolic derangements to accelerate NAFLD progression in diabetic patients.The diagnosis of the more advanced stages of NAFLD in diabetic patients shares the same challenges as in non-diabetic patients and it includes imaging and serological methods,although histopathological evaluation is still considered the gold standard diagnostic method.An effective established treatment is not yet available for patients with steatohepatitis and fibrosis and randomized clinical trials including only diabetic patients are lacking.We sought to outline the published data including epidemiology,pathogenesis,diagnosis and treatment of NAFLD in diabetic patients,in order to better understand the interplay between these two prevalent diseases and identify the gaps that still need to be fulfilled in the management of NAFLD in patients with diabetes mellitus.
