Extracorporeal liver surgery(ELS), also known as liver autotransplantation, is a hybrid(cross-fertilized) surgery incorporating the technical knowledge from extreme liver and transplant liver surgeries, and recently b...Extracorporeal liver surgery(ELS), also known as liver autotransplantation, is a hybrid(cross-fertilized) surgery incorporating the technical knowledge from extreme liver and transplant liver surgeries, and recently became more embraced and popularized among leading centers. ELS could be summarized into three major categories, namely, ex-situ liver resection and autotransplantation(ELRA), ante-situm liver resection and autotransplantation(ALRA) and auxiliary partial liver autotransplantation(APLA). The successful development of ELS during the past 37 years is definitely inseparable from continuous effort s done by Chinese surgeons and researchers. Especially, the precision liver surgery paradigm has allowed to transform ELS into a modularized, more simplified, and standardized surgery, to upgrade surgical skills, to improve peri-operative outcome and long-term survival, to increase the capability of surgeons to select more complex diseases and to expand the level of medical service to the population. This review highlights the Chinese contributions to the field of ELS, focusing thereby on features of different surgical types, technical innovations, disease selection and surgical indication, patient prognosis and future perspectives.展开更多
Transplantation of the left lateral section(LLS)of the liver is now an established practice for treating advanced diffuse and unresectable focal liver diseases in children,with variants of the LLS primarily used in in...Transplantation of the left lateral section(LLS)of the liver is now an established practice for treating advanced diffuse and unresectable focal liver diseases in children,with variants of the LLS primarily used in infants.However,the surgical challenge of matching the size of an adult donor's graft to the volume of a child's abdomen remains significant.This review explores historical developments,various approaches to measuring the required functional liver mass,and techniques to prevent complications associated with large-for-size grafts in infants.展开更多
To the Editor:Theoretically,autologous liver transplantation is posited as a treatment for patients experiencing traumatic liver rupture.How-ever,the procedural complexity and its infrequent application by the medical...To the Editor:Theoretically,autologous liver transplantation is posited as a treatment for patients experiencing traumatic liver rupture.How-ever,the procedural complexity and its infrequent application by the medical community have resulted in a lack of documented suc-cesses.This report presented the efficacious intervention in a pa-tient presenting with polytraumatic injuries involving the thoracic and abdominal regions,namely right-sided hemothorax,contusion and hematoma of the right lung,splenic rupture,lateral damage to the common bile duct,disruption of the left portal vein branch and left hepatic duct,incisions in the hepatic segments IV,V,VI,VII,and VIII,laceration of the right adrenal gland,rupture of the right hepatic venous trunk and retro-hepatic inferior vena cava(RHIVC),and pancreatic hematoma.展开更多
Liver transplantation represents a complex surgical procedure and serves as a curative treatment for patients presenting an acute or chronic end-stage liver disease, or carefully selected liver malignancy. A significa...Liver transplantation represents a complex surgical procedure and serves as a curative treatment for patients presenting an acute or chronic end-stage liver disease, or carefully selected liver malignancy. A significant gap still exists between the number of available donor organs and potential recipients. The use of an otherwise-wasted resected liver lobe from patients with benign liver tumors is a new, albeit small, option to alleviate the allograft shortage. This review provides evidence that resected liver lobes may be used successfully in liver transplantation.展开更多
The prognosis of drug-induced acute liver failure(ALF)is poor,with a survival rate of 27.1%without liver transplantation.Liver transplantation significantly improved survival rates to 66.2%.[1]The shortage of availabl...The prognosis of drug-induced acute liver failure(ALF)is poor,with a survival rate of 27.1%without liver transplantation.Liver transplantation significantly improved survival rates to 66.2%.[1]The shortage of available grafts can be addressed by living donor liver transplantation(LDLT),an effective and safe method that expands the donor pool,enhances timely transplantation,and improves patient survival.展开更多
Over the past six decades,liver transplantation(LT)has evolved from an experimental procedure into a standardized and life-saving intervention,reshaping the landscape of organ transplantation.Driven by pioneering brea...Over the past six decades,liver transplantation(LT)has evolved from an experimental procedure into a standardized and life-saving intervention,reshaping the landscape of organ transplantation.Driven by pioneering breakthroughs,technological advancements,and a deepened understanding of immunology,LT has seen remarkable progress.Some of the most notable breakthroughs in the field include advances in immunosuppression,a revised model for end-stage liver disease,and artificial intelligence(AI)-integrated imaging modalities serving diagnostic and therapeutic roles in LT,paired with ever-evolving technological advances.Additionally,the refinement of transplantation procedures,resulting in the introduction of alternative transplantation methods,such as living donor LT,split LT,and the use of marginal grafts,has addressed the challenge of organ shortage.Moreover,precision medicine,guiding personalized immunosuppressive strategies,has significantly improved patient and graft survival rates while addressing emergent issues,such as short-term complications and early allograft dysfunction,leading to a more refined strategy and enhanced postoperative recovery.Looking ahead,ongoing research explores regenerative medicine,diagnostic tools,and AI to optimize organ allocation and posttransplantation car.In summary,the past six decades have marked a transformative journey in LT with a commitment to advancing science,medicine,and patient-centered care,offering hope and extending life to individuals worldwide.展开更多
Liver transplantation(LT)has made significant progress in the treatment of end stage liver disease(ESLD).However,many patients still die from disease progression while awaiting transplantation.As the number of patient...Liver transplantation(LT)has made significant progress in the treatment of end stage liver disease(ESLD).However,many patients still die from disease progression while awaiting transplantation.As the number of patients on LT waiting lists is increasing,and the organ shortage crisis is obvious,various efforts have been made to increase the pool of available liver grafts[1].In addition to living donor liver transplantation(LDLT),improving the utilization rate of extended criteria donor(ECD)livers is an important way.However,under traditional cold storage,ECD livers are usually associated with a higher risk of ischemic biliary disease,early allograft dysfunction(EAD)or even primary nonfunction(PNF).The frequently described definition in the literature for ECD grafts generally includes elderly,steatotic,long cold ischemia time(CIT),grafts obtained from donation after circulatory death(DCD),split liver grafts,donors with increased risk of infectious disease transmission and prolonged donor intensive care unit stay[2].展开更多
Cirrhosis represents the end stage of chronic liver disease,significantly reducing life expectancy as it progresses from a compensated to a decompensated state,leading to serious complications.Recent improvements in m...Cirrhosis represents the end stage of chronic liver disease,significantly reducing life expectancy as it progresses from a compensated to a decompensated state,leading to serious complications.Recent improvements in medical treatment have created a shift in cirrhosis management.Various causes,including hepatitis viruses,alcohol consumption,and fatty liver disease,contribute to cirrhosis and are closely linked to liver cancer.The disease develops through hepatocyte necrosis and regeneration,resulting in fibrosis and sinusoidal capillarization,leading to portal hypertension and complications such as ascites,hepatic encephalopathy,and organ dysfunction.Cirrhosis also holds an increased risk of hepatocellular carcinoma.Diagnosing cirrhosis involves assessing fibrosis scores through blood tests and measuring liver stiffness through elastography.Liver transplantation is the definitive treatment for endstage liver disease and acute liver failure.展开更多
Endocrine disorders frequently lead to metabolic disturbances that significantly affect liver function.Understanding the complex interplay between hormonal imbalances and liver dysfunction is essential for advancing t...Endocrine disorders frequently lead to metabolic disturbances that significantly affect liver function.Understanding the complex interplay between hormonal imbalances and liver dysfunction is essential for advancing targeted therapeutic strategies.This comprehensive review explores the pathophysiological mechanisms linking major endocrine disorders to liver disease,with a focus on the roles of the thyroid,parathyroid,pancreas,adrenal glands,and sex hormones.Thyroid dysfunction is associated with alterations in liver enzyme levels and metabolic regulation,often resulting in hepatic steatosis or cholestasis.Hyperparathyroidism and consequent hypercalcemia have been linked to hepatic calcifications.Insulin resistance,both hepatic and peripheral,contributes to excessive lipid accumulation in the liver,exacerbating steatotic changes.Adrenal gland disorders,particularly in the setting of chronic liver disease,impair cortisol metabolism and may worsen hepatic injury.Additionally,sex hormones such as estrogen and testosterone modulate the progression of liver fibrosis and influence the development of metabolic syndrome.The intricate relationship between endocrine and hepatic systems underscores the need for a multidisciplinary approach in the management of liver disease.Addressing underlying hormonal disturbances may enhance patient outcomes and prevent further hepatic deterioration.Future research should prioritize integrative therapeutic strategies that concurrently target endocrine and liver dysfunction.展开更多
Metabolic dysfunction-associated steatotic liver disease,previously known as nonalcoholic fatty liver disease(NAFLD),is becoming increasingly common and is associated with significant morbidity and mortality related t...Metabolic dysfunction-associated steatotic liver disease,previously known as nonalcoholic fatty liver disease(NAFLD),is becoming increasingly common and is associated with significant morbidity and mortality related to both liver and non-liver issues.In its early stages,NAFLD is characterized by immune cell dysregulation,which suggests that immune-targeted therapies could be a viable treatment option for nonalcoholic steatohepatitis.A recent study by Zhu et al.investigated the role of autoantibodies in metabolic dysfunction-associated stea-totic liver disease at various histological stages.While the research provided valuable insights,several methodological concerns are noted,which include the study’s retrospective design,a limited panel of autoantibodies,and a lack of a prospective study design that adequately controls for confounding factors such as age,comorbidities and lifestyle.Furthermore,the interpretation of positive antinuclear antibodies as evidence of autoimmune involvement in NAFLD is questioned due to the possibility of nonspecific immune responses.Recommend-ations to improve the study’s design include conducting prospective studies,implementing more detailed antibody profiling,and adjusting for demographic and clinical factors.Future studies should address these issues to improve the clinical relevance and credibility of findings related to autoimmunity in NAFLD.展开更多
Mucinous cystic neoplasms of the liver(MCN-L)are rare cystic lesions characterized by mucin-producing epithelium and ovarian-like stroma.Although they constitute fewer than 5%of hepatic cystic lesions,MCN-L poses sign...Mucinous cystic neoplasms of the liver(MCN-L)are rare cystic lesions characterized by mucin-producing epithelium and ovarian-like stroma.Although they constitute fewer than 5%of hepatic cystic lesions,MCN-L poses significant diagnostic challenges due to overlapping features with other cystic lesions and their potential for malignant transformation.Early recognition and definitive surgical intervention are therefore critical to ensure optimal patient outcomes.A literature review was conducted to summarize epidemiology,clinical presentation,diagnostic modalities,and management strategies for MCN-L.Additionally,from 2019 to 2025,9 patients with MCN-L were identified at our center.Clinical data and outcomes were retrospectively analyzed.MCN-L predominantly affects middle-aged women and presents as large,multiloculated cystic lesions without biliary communication.The revised 2010 World Health Organization classification emphasizes the presence of ovarian-like stroma for definitive diagnosis.Contrast-enhanced computed tomography or magnetic resonance imaging are often suggestive but not pathognomonic,reinforcing the need for histopathological confirmation.MCN-L remains a diagnostic and therapeutic challenge due to its resemblance to other cystic liver lesions.Complete surgical resection is the treatment of choice to prevent recurrence and malignant transformation,reinforcing the importance of early intervention.Further research is needed to improve diagnostic accuracy and refine management strategies.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most widespread chronic liver disease signified by serious life-threatening conditions.The prevalence of MASLD increases along the growing prevalen...Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most widespread chronic liver disease signified by serious life-threatening conditions.The prevalence of MASLD increases along the growing prevalence in obesity and metabolic syndrome.To minimize costs and complications,non-invasive diagnostic tools,including transient elastography(TE),were introduced for assessment of MASLD.TE measures liver stiffness(LS),a clinical marker for the diagnosis of liver fibrosis and cirrhosis.LS measurements are based on ultrasound wave imaging and quantification.Vibration-controlled TE,including FibroScan®,is commonly used TE methods which can accurately identify the degree of liver fibrosis and cirrhosis progression.TE was reported to predict the progression towards hepatocellular carcinoma,portal hypertension,and varices.However,the accuracy of LS diagnostics alone in patients with MASLD remains controversial.TE measurements have several limitations,including inadequate precision due to focal liver lesions,cholestasis,inflammation,and other pathological and anatomical factors which can lead to the stiffness variability.Overestimations of TE readings were reported in obese patients with body mass index(BMI)over 30 kg/m2,and older patients with ascites,diabetes,or hypertension.Not all MASLD patients have high BMI.The prevalence of obesity among MASLD patients varies worldwide,indicating the urgent need for comprehensive diagnostic tools.In patients with MASLD,improved diagnostic accuracy has been demonstrated by combining LS measurements with other blood test-based scores and simple clinical parameters(agile scores based on age,sex,platelet count,aminotransferases,and diabetes).This study reviews the limitations of TE-based diagnostics and discusses the combined scoring algorithm.In conclusion,the sequence of LS measurements along assessment of other important clinical markers is an effective,low-cost,reliable tool to identify and monitor fibrosis progression in MASLD.展开更多
BACKGROUND In metabolic dysfunction-associated steatotic liver disease(MASLD)the identi-fication of patients at high risk of evolution to metabolic dysfunction-associated steatohepatitis(MASH)is challenging.AIM To inv...BACKGROUND In metabolic dysfunction-associated steatotic liver disease(MASLD)the identi-fication of patients at high risk of evolution to metabolic dysfunction-associated steatohepatitis(MASH)is challenging.AIM To investigate the performance of different ultrasound(US)-based techniques for the non-invasive assessment of liver fibrosis,steatosis,and inflammation in these patients.METHODS We collected data from consecutive patients who underwent liver biopsy for suspected MASLD between January 2019 and December 2021.Two-dimensional shear-wave elastography,sound speed plane-wave US,attenuation plane-wave US,viscosity plane-wave US(Vi.PLUS)using Aixplorer MACH 30 system,and transient elastography and controlled attenuation parameter from FibroScan were measured before biopsy.RESULTS A total of 120 participants were enrolled.Both transient elastography and two-dimensional shear-wave elasto-graphy showed good performance for the diagnosis of advanced fibrosis[area under the receiver operating charac-teristic curve(AUROC)=0.93 and 0.90,respectively].The diagnostic performance of Vi.PLUS for the presence of both ballooning grade≥1 and lobular inflammation≥1 was good with an AUROC of 0.72.A score based on Vi.PLUS,aspartate aminotransferase,and sound speed plane-wave US[viscosity-aspartate aminotransferase-speed of sound MASH ultrasound score(VAS-MASH-US score)]had a good accuracy for the diagnosis of MASH(AUROC=0.75).VAS-MASH-US score>0.6 showed a good sensitivity for MASH diagnosis(79.0%).According to decision curve analysis,the application of the VAS-MASH-US score would lead to a more accurate selection of patients who are candidates to undergo liver biopsy and would reduce the need for invasive procedures for patients at low risk of MASH.CONCLUSION Multiparametric US allows the non-invasive assessment of steatosis,inflammation,and fibrosis in patients with MASLD.Liver viscosity improved the capability of non-invasively identifying patients with MASH.展开更多
Background:Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. While liver transplantation (LT) provides the best long-term survival, it is constrained by organ scarcity and strict criteria....Background:Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. While liver transplantation (LT) provides the best long-term survival, it is constrained by organ scarcity and strict criteria. Liver resection (LR) is often the initial treatment for patients with solitary tumors and preserved liver function. The high recurrence rates associated with LR has prompted the exploration of sequential living donor liver transplantation (seq LDLT) after LR as a strategy for HCC patients with high-risk of recurrence.Methods:We analyzed data from 27 adult patients who underwent seq LDLT after LR for HCC at Kaohsiung Chang Gung Memorial Hospital (KCGMH) between June 1994 and December 2023. Patients were selected based on high-risk histopathological features post-LR or as part of downstaging strategy. Outcomes measured included overall survival (OS) and disease-free survival (DFS).Results:Among 765 HCC patients who underwent LDLT, 204 received LR before LDLT, and 27 underwent seqL DLT. Five patients (19%) underwent living donor liver transplantation (LDLT) following LR as a downstaging strategy while the rest received seqL DLT as a preemptive strategy. The median age was 53.5 years with 85%males. Chronic hepatitis B was the predominant underlying disease (74%). The 1-, 3-, and 5-year OS and DFS rates were 100%, 96.0%, 96.0%and 100%, 96.2%, 96.2%, respectively, with two patients experiencing HCC recurrence. One patient died from HCC recurrence. High-risk histopathological features included microvascular invasion (52%), satellite nodules (15%), multiple tumors (26%), tumors> 5 cm(19%), and a total tumor diameter> 10 cm (7%).Conclusions:Seq LDLT offers a promising, tailored approach for managing HCC with adverse histopathologic features. Combining seq LDLT, downstaging strategies, and multidisciplinary treatments can achieve satisfactory OS and DFS in carefully selected patients, highlighting the need for refined criteria to identify the best candidates.展开更多
BACKGROUND Clinically significant portal hypertension(CSPH)is a crucial prognostic deter-minant for liver-related events(LREs)in patients with compensated viral cir-rhosis.Liver stiffness measurement(LSM)-related mark...BACKGROUND Clinically significant portal hypertension(CSPH)is a crucial prognostic deter-minant for liver-related events(LREs)in patients with compensated viral cir-rhosis.Liver stiffness measurement(LSM)-related markers may help to predict the risk of LREs.AIM To evaluate the value of LSM and its composite biomarkers[LSM-platelet ratio(LPR),LSM-albumin ratio(LAR)]in predicting LREs.METHODS This study retrospectively enrolled compensated viral cirrhosis patients with CSPH.The Cox regression model was employed to examine the prediction of LSM,LPR,and LAR for LREs.The model performance was assessed through receiver operating characteristic,decision curve,and time-dependent area under the curve analysis.The Kaplan-Meier curve was used to evaluate the cumulative incidence of LREs,and further stratified analysis of different LREs was per-formed.RESULTS A total of 598 patients were included,and 319 patients(53.3%)developed LREs during follow-up.Multivariate proportional hazards modeling demonstrated that LSM,LPR,and LAR were independent predictors of LREs.LPR had better performance in predicting LREs than LAR and LSM(area under the curve=0.780,0.727,0.683,respectively,all P<0.05).The cumulative incidence of LREs in the high-risk group were significantly higher than that in the low-risk group(P<0.001).Among the different LREs,LPR was superior to LSM and LAR in predicting liver decompensation,while the difference in predicting hepatocellular carcinoma and liver-related death was relatively small.CONCLUSION LPR is superior to LSM and LAR in predicting LREs in compensated viral cirrhosis patients with CSPH,especially in predicting liver decompensation.展开更多
BACKGROUND Colorectal polyps are commonly observed in patients with chronic liver disease(CLD)and pose a significant clinical concern because of their potential for malignancy.AIM To explore the clinical characteristi...BACKGROUND Colorectal polyps are commonly observed in patients with chronic liver disease(CLD)and pose a significant clinical concern because of their potential for malignancy.AIM To explore the clinical characteristics of colorectal polyps in patients with CLD,a nomogram was established to predict the presence of adenomatous polyps(AP).METHODS Patients with CLD who underwent colonoscopy at Tianjin Second People’s Hospital from January 2020 to May 2023 were evaluated.Clinical data including laboratory results,colonoscopy findings,and pathology reports were collected.Key variables for the nomogram were identified through least absolute shrinkage and selection operator regression,followed by multivariate logistic regression.The performance of the model was evaluated using the area under the receiver area under curve,as well as calibration curves and decision curve analysis.RESULTS The study enrolled 870 participants who underwent colonoscopy,and the detection rate of AP in patients with CLD was 28.6%.Compared to individuals without polyps,six risk factors were identified as predictors for AP occurrence:Age,male sex,body mass index,alcohol consumption,overlapping metabolic dysfunction-associated steatotic liver disease,and serum ferritin levels.The novel nomogram(AP model)demonstrated an area under curve of 0.801(95%confidence interval:0.756-0.845)and 0.785(95%confidence interval:0.712-0.858)in the training and validation groups.Calibration curves indicated good agreement among predicted and actual probabilities(training:χ^(2)=11.860,P=0.157;validation:χ^(2)=7.055,P=0.530).The decision curve analysis underscored the clinical utility of the nomogram for predicting the risk of AP.CONCLUSION The AP model showed reasonable accuracy and provided a clinical foundation for predicting the occurrence of AP in patients with CLD,which has a certain predictive value.展开更多
BACKGROUND This case report describes a protocol developed by Danaun Medical Clinic for the introduction of a pioneering intervention comprising intravenous human placen-tal extract(HPE)therapy to improve the liver fu...BACKGROUND This case report describes a protocol developed by Danaun Medical Clinic for the introduction of a pioneering intervention comprising intravenous human placen-tal extract(HPE)therapy to improve the liver function of patients with chronic liver disease(CLD).CASE SUMMARY This study involved data from patients whose chief complaint was reduced quality of life attributable to CLD.The new treatment approach resulted in improvements in the liver function and fatty liver of 30 patients with CLD.Im-provements were observed using abdominal ultrasonography.Unlike traditional methods,this protocol provided more sustainable and meaningful results.Treat-ment with 10 mL of HPE administered intravenously once or twice per week significantly improved liver function.The observed improvements in fatty liver and liver function suggest the utility of this approach for the management of patients with CLD.CONCLUSION This case series highlights the potential of innovative treatments for patients with CLD that could improve the quality of life of the patients.展开更多
Liver cancer remains a leading cause of mortality worldwide,and precise diagnostic tools are essential for effective treatment planning.Liver Tumors(LTs)vary significantly in size,shape,and location,and can present wi...Liver cancer remains a leading cause of mortality worldwide,and precise diagnostic tools are essential for effective treatment planning.Liver Tumors(LTs)vary significantly in size,shape,and location,and can present with tissues of similar intensities,making automatically segmenting and classifying LTs from abdominal tomography images crucial and challenging.This review examines recent advancements in Liver Segmentation(LS)and Tumor Segmentation(TS)algorithms,highlighting their strengths and limitations regarding precision,automation,and resilience.Performance metrics are utilized to assess key detection algorithms and analytical methods,emphasizing their effectiveness and relevance in clinical contexts.The review also addresses ongoing challenges in liver tumor segmentation and identification,such as managing high variability in patient data and ensuring robustness across different imaging conditions.It suggests directions for future research,with insights into technological advancements that can enhance surgical planning and diagnostic accuracy by comparing popular methods.This paper contributes to a comprehensive understanding of current liver tumor detection techniques,provides a roadmap for future innovations,and improves diagnostic and therapeutic outcomes for liver cancer by integrating recent progress with remaining challenges.展开更多
Liver transplantation is hindered by organ shortage. The potential way to relieve this issue is to expand the donor pool via extending the donor criteria and make full use of all available grafts. The concept of “no-...Liver transplantation is hindered by organ shortage. The potential way to relieve this issue is to expand the donor pool via extending the donor criteria and make full use of all available grafts. The concept of “no-donor” liver transplantation allows grafts to be recovered from other liver recipients. This review summarizes the current clinical practice of “no-donor” liver transplantation, focusing on the experiences of Chinese transplant teams. Domino liver transplantation was introduced by Furtado in 1995 and implemented later in 2013 in China, and novel donor indications including some essential-to-treat inherited metabolic liver-based diseases have emerged. The concept of cross-auxiliary domino liver transplantation brings a further expansion of the domino liver graft pool, and the first pair of liver transplantation performed “rigorously without donation” was accomplished in our center in 2018. Our experience with this original transplantation procedure is hereby reviewed. In order to further promote and make successful “no-donor” liver transplantation, close co-operation between researchers, surgeons, physicians, organ procurement organizations, as well as ethical committees is required.展开更多
BACKGROUND The Streptococcus salivarius(S.salivarius)group,which produces the enzyme urease has been identified as a potential contributor to ammonia production in the gut.Researchers have reported that patients with ...BACKGROUND The Streptococcus salivarius(S.salivarius)group,which produces the enzyme urease has been identified as a potential contributor to ammonia production in the gut.Researchers have reported that patients with minimal HE had an increased abundance of the S.salivarius group,which is a specific change in the gut microbiota that distinguishes them from healthy individuals.The correlation between the aggregation of specific bacterial species and fibrosis progression in chronic liver disease(CLD)is yet to be fully elucidated.AIM To quantify S.salivarius using digital PCR(dPCR)as a liver fibrosis marker of CLD.METHODS This study retrospectively analysed 52 patients with CLD.To quantify S.salivarius in patients with CLD using dPCR,we evaluated the specificity and sensitivity of S.salivarius bacterial load using dPCR for a type strain.Next,we evaluated the clinical usefulness of dPCR for S.salivarius load quantification for detecting liver fibrosis in patients with CLD.The liver fibrosis stage was categorized into mild and advanced fibrosis based on pathological findings.RESULTS The dPCR assay revealed that S.salivarius was highly positive for the tnpA gene.The lower limit of quantification for dPCR using the tnpA gene with a 1μL template comprising 1.28×102 CFU/mL was 4.3 copies.After considering the detection range in dPCR,we adjusted the extracted DNA concentration to 5.0×10-4 ng/μL from 200 mg stool samples.The median bacterial loads of S.salivarius in stool sample from patients with mild and advanced fibrosis were 1.9 and 7.4 copies/μL,respectively.The quantification of S.salivarius load was observed more frequently in patients with advanced fibrosis than in those with mild fibrosis(P=0.032).CONCLUSION Quantifying of S.salivarius load using digital PCR is a useful biomarker for liver fibrosis in patients with CLD.展开更多
基金supported by grants from the Beijing Hospitals Authority Youth Program (12022B4010)BTCH Young Talent En-lightenment Program (2024QMRC24)CAMS Innovation Fund for Medical Sciences (2019-I2M-5–056)。
文摘Extracorporeal liver surgery(ELS), also known as liver autotransplantation, is a hybrid(cross-fertilized) surgery incorporating the technical knowledge from extreme liver and transplant liver surgeries, and recently became more embraced and popularized among leading centers. ELS could be summarized into three major categories, namely, ex-situ liver resection and autotransplantation(ELRA), ante-situm liver resection and autotransplantation(ALRA) and auxiliary partial liver autotransplantation(APLA). The successful development of ELS during the past 37 years is definitely inseparable from continuous effort s done by Chinese surgeons and researchers. Especially, the precision liver surgery paradigm has allowed to transform ELS into a modularized, more simplified, and standardized surgery, to upgrade surgical skills, to improve peri-operative outcome and long-term survival, to increase the capability of surgeons to select more complex diseases and to expand the level of medical service to the population. This review highlights the Chinese contributions to the field of ELS, focusing thereby on features of different surgical types, technical innovations, disease selection and surgical indication, patient prognosis and future perspectives.
文摘Transplantation of the left lateral section(LLS)of the liver is now an established practice for treating advanced diffuse and unresectable focal liver diseases in children,with variants of the LLS primarily used in infants.However,the surgical challenge of matching the size of an adult donor's graft to the volume of a child's abdomen remains significant.This review explores historical developments,various approaches to measuring the required functional liver mass,and techniques to prevent complications associated with large-for-size grafts in infants.
基金supported by a grant from the Climbing Project for Medical Talent of Zhongnan Hospital,Wuhan University(PDJH202215).
文摘To the Editor:Theoretically,autologous liver transplantation is posited as a treatment for patients experiencing traumatic liver rupture.How-ever,the procedural complexity and its infrequent application by the medical community have resulted in a lack of documented suc-cesses.This report presented the efficacious intervention in a pa-tient presenting with polytraumatic injuries involving the thoracic and abdominal regions,namely right-sided hemothorax,contusion and hematoma of the right lung,splenic rupture,lateral damage to the common bile duct,disruption of the left portal vein branch and left hepatic duct,incisions in the hepatic segments IV,V,VI,VII,and VIII,laceration of the right adrenal gland,rupture of the right hepatic venous trunk and retro-hepatic inferior vena cava(RHIVC),and pancreatic hematoma.
基金supported by grants from the National Natural Science Foundation of China (82150 0 04)the National Municipal Key Clinical Specialtythe Clinical Research Project for Major Diseases in Municipal Hospitals (SHDC2020CR1022B)。
文摘Liver transplantation represents a complex surgical procedure and serves as a curative treatment for patients presenting an acute or chronic end-stage liver disease, or carefully selected liver malignancy. A significant gap still exists between the number of available donor organs and potential recipients. The use of an otherwise-wasted resected liver lobe from patients with benign liver tumors is a new, albeit small, option to alleviate the allograft shortage. This review provides evidence that resected liver lobes may be used successfully in liver transplantation.
基金approved by the Ethics Committee of the Second Affiliated Hospital,Zhejiang University School of Medicine(2024-0690).
文摘The prognosis of drug-induced acute liver failure(ALF)is poor,with a survival rate of 27.1%without liver transplantation.Liver transplantation significantly improved survival rates to 66.2%.[1]The shortage of available grafts can be addressed by living donor liver transplantation(LDLT),an effective and safe method that expands the donor pool,enhances timely transplantation,and improves patient survival.
文摘Over the past six decades,liver transplantation(LT)has evolved from an experimental procedure into a standardized and life-saving intervention,reshaping the landscape of organ transplantation.Driven by pioneering breakthroughs,technological advancements,and a deepened understanding of immunology,LT has seen remarkable progress.Some of the most notable breakthroughs in the field include advances in immunosuppression,a revised model for end-stage liver disease,and artificial intelligence(AI)-integrated imaging modalities serving diagnostic and therapeutic roles in LT,paired with ever-evolving technological advances.Additionally,the refinement of transplantation procedures,resulting in the introduction of alternative transplantation methods,such as living donor LT,split LT,and the use of marginal grafts,has addressed the challenge of organ shortage.Moreover,precision medicine,guiding personalized immunosuppressive strategies,has significantly improved patient and graft survival rates while addressing emergent issues,such as short-term complications and early allograft dysfunction,leading to a more refined strategy and enhanced postoperative recovery.Looking ahead,ongoing research explores regenerative medicine,diagnostic tools,and AI to optimize organ allocation and posttransplantation car.In summary,the past six decades have marked a transformative journey in LT with a commitment to advancing science,medicine,and patient-centered care,offering hope and extending life to individuals worldwide.
文摘Liver transplantation(LT)has made significant progress in the treatment of end stage liver disease(ESLD).However,many patients still die from disease progression while awaiting transplantation.As the number of patients on LT waiting lists is increasing,and the organ shortage crisis is obvious,various efforts have been made to increase the pool of available liver grafts[1].In addition to living donor liver transplantation(LDLT),improving the utilization rate of extended criteria donor(ECD)livers is an important way.However,under traditional cold storage,ECD livers are usually associated with a higher risk of ischemic biliary disease,early allograft dysfunction(EAD)or even primary nonfunction(PNF).The frequently described definition in the literature for ECD grafts generally includes elderly,steatotic,long cold ischemia time(CIT),grafts obtained from donation after circulatory death(DCD),split liver grafts,donors with increased risk of infectious disease transmission and prolonged donor intensive care unit stay[2].
文摘Cirrhosis represents the end stage of chronic liver disease,significantly reducing life expectancy as it progresses from a compensated to a decompensated state,leading to serious complications.Recent improvements in medical treatment have created a shift in cirrhosis management.Various causes,including hepatitis viruses,alcohol consumption,and fatty liver disease,contribute to cirrhosis and are closely linked to liver cancer.The disease develops through hepatocyte necrosis and regeneration,resulting in fibrosis and sinusoidal capillarization,leading to portal hypertension and complications such as ascites,hepatic encephalopathy,and organ dysfunction.Cirrhosis also holds an increased risk of hepatocellular carcinoma.Diagnosing cirrhosis involves assessing fibrosis scores through blood tests and measuring liver stiffness through elastography.Liver transplantation is the definitive treatment for endstage liver disease and acute liver failure.
文摘Endocrine disorders frequently lead to metabolic disturbances that significantly affect liver function.Understanding the complex interplay between hormonal imbalances and liver dysfunction is essential for advancing targeted therapeutic strategies.This comprehensive review explores the pathophysiological mechanisms linking major endocrine disorders to liver disease,with a focus on the roles of the thyroid,parathyroid,pancreas,adrenal glands,and sex hormones.Thyroid dysfunction is associated with alterations in liver enzyme levels and metabolic regulation,often resulting in hepatic steatosis or cholestasis.Hyperparathyroidism and consequent hypercalcemia have been linked to hepatic calcifications.Insulin resistance,both hepatic and peripheral,contributes to excessive lipid accumulation in the liver,exacerbating steatotic changes.Adrenal gland disorders,particularly in the setting of chronic liver disease,impair cortisol metabolism and may worsen hepatic injury.Additionally,sex hormones such as estrogen and testosterone modulate the progression of liver fibrosis and influence the development of metabolic syndrome.The intricate relationship between endocrine and hepatic systems underscores the need for a multidisciplinary approach in the management of liver disease.Addressing underlying hormonal disturbances may enhance patient outcomes and prevent further hepatic deterioration.Future research should prioritize integrative therapeutic strategies that concurrently target endocrine and liver dysfunction.
文摘Metabolic dysfunction-associated steatotic liver disease,previously known as nonalcoholic fatty liver disease(NAFLD),is becoming increasingly common and is associated with significant morbidity and mortality related to both liver and non-liver issues.In its early stages,NAFLD is characterized by immune cell dysregulation,which suggests that immune-targeted therapies could be a viable treatment option for nonalcoholic steatohepatitis.A recent study by Zhu et al.investigated the role of autoantibodies in metabolic dysfunction-associated stea-totic liver disease at various histological stages.While the research provided valuable insights,several methodological concerns are noted,which include the study’s retrospective design,a limited panel of autoantibodies,and a lack of a prospective study design that adequately controls for confounding factors such as age,comorbidities and lifestyle.Furthermore,the interpretation of positive antinuclear antibodies as evidence of autoimmune involvement in NAFLD is questioned due to the possibility of nonspecific immune responses.Recommend-ations to improve the study’s design include conducting prospective studies,implementing more detailed antibody profiling,and adjusting for demographic and clinical factors.Future studies should address these issues to improve the clinical relevance and credibility of findings related to autoimmunity in NAFLD.
文摘Mucinous cystic neoplasms of the liver(MCN-L)are rare cystic lesions characterized by mucin-producing epithelium and ovarian-like stroma.Although they constitute fewer than 5%of hepatic cystic lesions,MCN-L poses significant diagnostic challenges due to overlapping features with other cystic lesions and their potential for malignant transformation.Early recognition and definitive surgical intervention are therefore critical to ensure optimal patient outcomes.A literature review was conducted to summarize epidemiology,clinical presentation,diagnostic modalities,and management strategies for MCN-L.Additionally,from 2019 to 2025,9 patients with MCN-L were identified at our center.Clinical data and outcomes were retrospectively analyzed.MCN-L predominantly affects middle-aged women and presents as large,multiloculated cystic lesions without biliary communication.The revised 2010 World Health Organization classification emphasizes the presence of ovarian-like stroma for definitive diagnosis.Contrast-enhanced computed tomography or magnetic resonance imaging are often suggestive but not pathognomonic,reinforcing the need for histopathological confirmation.MCN-L remains a diagnostic and therapeutic challenge due to its resemblance to other cystic liver lesions.Complete surgical resection is the treatment of choice to prevent recurrence and malignant transformation,reinforcing the importance of early intervention.Further research is needed to improve diagnostic accuracy and refine management strategies.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most widespread chronic liver disease signified by serious life-threatening conditions.The prevalence of MASLD increases along the growing prevalence in obesity and metabolic syndrome.To minimize costs and complications,non-invasive diagnostic tools,including transient elastography(TE),were introduced for assessment of MASLD.TE measures liver stiffness(LS),a clinical marker for the diagnosis of liver fibrosis and cirrhosis.LS measurements are based on ultrasound wave imaging and quantification.Vibration-controlled TE,including FibroScan®,is commonly used TE methods which can accurately identify the degree of liver fibrosis and cirrhosis progression.TE was reported to predict the progression towards hepatocellular carcinoma,portal hypertension,and varices.However,the accuracy of LS diagnostics alone in patients with MASLD remains controversial.TE measurements have several limitations,including inadequate precision due to focal liver lesions,cholestasis,inflammation,and other pathological and anatomical factors which can lead to the stiffness variability.Overestimations of TE readings were reported in obese patients with body mass index(BMI)over 30 kg/m2,and older patients with ascites,diabetes,or hypertension.Not all MASLD patients have high BMI.The prevalence of obesity among MASLD patients varies worldwide,indicating the urgent need for comprehensive diagnostic tools.In patients with MASLD,improved diagnostic accuracy has been demonstrated by combining LS measurements with other blood test-based scores and simple clinical parameters(agile scores based on age,sex,platelet count,aminotransferases,and diabetes).This study reviews the limitations of TE-based diagnostics and discusses the combined scoring algorithm.In conclusion,the sequence of LS measurements along assessment of other important clinical markers is an effective,low-cost,reliable tool to identify and monitor fibrosis progression in MASLD.
文摘BACKGROUND In metabolic dysfunction-associated steatotic liver disease(MASLD)the identi-fication of patients at high risk of evolution to metabolic dysfunction-associated steatohepatitis(MASH)is challenging.AIM To investigate the performance of different ultrasound(US)-based techniques for the non-invasive assessment of liver fibrosis,steatosis,and inflammation in these patients.METHODS We collected data from consecutive patients who underwent liver biopsy for suspected MASLD between January 2019 and December 2021.Two-dimensional shear-wave elastography,sound speed plane-wave US,attenuation plane-wave US,viscosity plane-wave US(Vi.PLUS)using Aixplorer MACH 30 system,and transient elastography and controlled attenuation parameter from FibroScan were measured before biopsy.RESULTS A total of 120 participants were enrolled.Both transient elastography and two-dimensional shear-wave elasto-graphy showed good performance for the diagnosis of advanced fibrosis[area under the receiver operating charac-teristic curve(AUROC)=0.93 and 0.90,respectively].The diagnostic performance of Vi.PLUS for the presence of both ballooning grade≥1 and lobular inflammation≥1 was good with an AUROC of 0.72.A score based on Vi.PLUS,aspartate aminotransferase,and sound speed plane-wave US[viscosity-aspartate aminotransferase-speed of sound MASH ultrasound score(VAS-MASH-US score)]had a good accuracy for the diagnosis of MASH(AUROC=0.75).VAS-MASH-US score>0.6 showed a good sensitivity for MASH diagnosis(79.0%).According to decision curve analysis,the application of the VAS-MASH-US score would lead to a more accurate selection of patients who are candidates to undergo liver biopsy and would reduce the need for invasive procedures for patients at low risk of MASH.CONCLUSION Multiparametric US allows the non-invasive assessment of steatosis,inflammation,and fibrosis in patients with MASLD.Liver viscosity improved the capability of non-invasively identifying patients with MASH.
文摘Background:Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. While liver transplantation (LT) provides the best long-term survival, it is constrained by organ scarcity and strict criteria. Liver resection (LR) is often the initial treatment for patients with solitary tumors and preserved liver function. The high recurrence rates associated with LR has prompted the exploration of sequential living donor liver transplantation (seq LDLT) after LR as a strategy for HCC patients with high-risk of recurrence.Methods:We analyzed data from 27 adult patients who underwent seq LDLT after LR for HCC at Kaohsiung Chang Gung Memorial Hospital (KCGMH) between June 1994 and December 2023. Patients were selected based on high-risk histopathological features post-LR or as part of downstaging strategy. Outcomes measured included overall survival (OS) and disease-free survival (DFS).Results:Among 765 HCC patients who underwent LDLT, 204 received LR before LDLT, and 27 underwent seqL DLT. Five patients (19%) underwent living donor liver transplantation (LDLT) following LR as a downstaging strategy while the rest received seqL DLT as a preemptive strategy. The median age was 53.5 years with 85%males. Chronic hepatitis B was the predominant underlying disease (74%). The 1-, 3-, and 5-year OS and DFS rates were 100%, 96.0%, 96.0%and 100%, 96.2%, 96.2%, respectively, with two patients experiencing HCC recurrence. One patient died from HCC recurrence. High-risk histopathological features included microvascular invasion (52%), satellite nodules (15%), multiple tumors (26%), tumors> 5 cm(19%), and a total tumor diameter> 10 cm (7%).Conclusions:Seq LDLT offers a promising, tailored approach for managing HCC with adverse histopathologic features. Combining seq LDLT, downstaging strategies, and multidisciplinary treatments can achieve satisfactory OS and DFS in carefully selected patients, highlighting the need for refined criteria to identify the best candidates.
基金Supported by the High-Level Chinese Medicine Key Discipline Construction Project,No.zyyzdxk-2023005Capital’s Funds for Health Improvement and Research,No.2024-1-2173+2 种基金National Natural Science Foundation of China,No.82474419 and No.82474426Beijing Municipal Natural Science Foundation,No.7232272Beijing Traditional Chinese Medicine Technology Development Fund Project,No.BJZYZD-2023-12.
文摘BACKGROUND Clinically significant portal hypertension(CSPH)is a crucial prognostic deter-minant for liver-related events(LREs)in patients with compensated viral cir-rhosis.Liver stiffness measurement(LSM)-related markers may help to predict the risk of LREs.AIM To evaluate the value of LSM and its composite biomarkers[LSM-platelet ratio(LPR),LSM-albumin ratio(LAR)]in predicting LREs.METHODS This study retrospectively enrolled compensated viral cirrhosis patients with CSPH.The Cox regression model was employed to examine the prediction of LSM,LPR,and LAR for LREs.The model performance was assessed through receiver operating characteristic,decision curve,and time-dependent area under the curve analysis.The Kaplan-Meier curve was used to evaluate the cumulative incidence of LREs,and further stratified analysis of different LREs was per-formed.RESULTS A total of 598 patients were included,and 319 patients(53.3%)developed LREs during follow-up.Multivariate proportional hazards modeling demonstrated that LSM,LPR,and LAR were independent predictors of LREs.LPR had better performance in predicting LREs than LAR and LSM(area under the curve=0.780,0.727,0.683,respectively,all P<0.05).The cumulative incidence of LREs in the high-risk group were significantly higher than that in the low-risk group(P<0.001).Among the different LREs,LPR was superior to LSM and LAR in predicting liver decompensation,while the difference in predicting hepatocellular carcinoma and liver-related death was relatively small.CONCLUSION LPR is superior to LSM and LAR in predicting LREs in compensated viral cirrhosis patients with CSPH,especially in predicting liver decompensation.
基金Supported by the National Natural Science Foundation of China,No.62375202Natural Science Foundation of Tianjin,No.23JCYBJC00950+1 种基金Tianjin Health Science and Technology Project Key Discipline Special,No.TJWJ2022XK034Research Project in Key Areas of Traditional Chinese Medicine in 2024,No.2024022.
文摘BACKGROUND Colorectal polyps are commonly observed in patients with chronic liver disease(CLD)and pose a significant clinical concern because of their potential for malignancy.AIM To explore the clinical characteristics of colorectal polyps in patients with CLD,a nomogram was established to predict the presence of adenomatous polyps(AP).METHODS Patients with CLD who underwent colonoscopy at Tianjin Second People’s Hospital from January 2020 to May 2023 were evaluated.Clinical data including laboratory results,colonoscopy findings,and pathology reports were collected.Key variables for the nomogram were identified through least absolute shrinkage and selection operator regression,followed by multivariate logistic regression.The performance of the model was evaluated using the area under the receiver area under curve,as well as calibration curves and decision curve analysis.RESULTS The study enrolled 870 participants who underwent colonoscopy,and the detection rate of AP in patients with CLD was 28.6%.Compared to individuals without polyps,six risk factors were identified as predictors for AP occurrence:Age,male sex,body mass index,alcohol consumption,overlapping metabolic dysfunction-associated steatotic liver disease,and serum ferritin levels.The novel nomogram(AP model)demonstrated an area under curve of 0.801(95%confidence interval:0.756-0.845)and 0.785(95%confidence interval:0.712-0.858)in the training and validation groups.Calibration curves indicated good agreement among predicted and actual probabilities(training:χ^(2)=11.860,P=0.157;validation:χ^(2)=7.055,P=0.530).The decision curve analysis underscored the clinical utility of the nomogram for predicting the risk of AP.CONCLUSION The AP model showed reasonable accuracy and provided a clinical foundation for predicting the occurrence of AP in patients with CLD,which has a certain predictive value.
文摘BACKGROUND This case report describes a protocol developed by Danaun Medical Clinic for the introduction of a pioneering intervention comprising intravenous human placen-tal extract(HPE)therapy to improve the liver function of patients with chronic liver disease(CLD).CASE SUMMARY This study involved data from patients whose chief complaint was reduced quality of life attributable to CLD.The new treatment approach resulted in improvements in the liver function and fatty liver of 30 patients with CLD.Im-provements were observed using abdominal ultrasonography.Unlike traditional methods,this protocol provided more sustainable and meaningful results.Treat-ment with 10 mL of HPE administered intravenously once or twice per week significantly improved liver function.The observed improvements in fatty liver and liver function suggest the utility of this approach for the management of patients with CLD.CONCLUSION This case series highlights the potential of innovative treatments for patients with CLD that could improve the quality of life of the patients.
基金the“Intelligent Recognition Industry Service Center”as part of the Featured Areas Research Center Program under the Higher Education Sprout Project by the Ministry of Education(MOE)in Taiwan,and the National Science and Technology Council,Taiwan,under grants 113-2221-E-224-041 and 113-2622-E-224-002.Additionally,partial support was provided by Isuzu Optics Corporation.
文摘Liver cancer remains a leading cause of mortality worldwide,and precise diagnostic tools are essential for effective treatment planning.Liver Tumors(LTs)vary significantly in size,shape,and location,and can present with tissues of similar intensities,making automatically segmenting and classifying LTs from abdominal tomography images crucial and challenging.This review examines recent advancements in Liver Segmentation(LS)and Tumor Segmentation(TS)algorithms,highlighting their strengths and limitations regarding precision,automation,and resilience.Performance metrics are utilized to assess key detection algorithms and analytical methods,emphasizing their effectiveness and relevance in clinical contexts.The review also addresses ongoing challenges in liver tumor segmentation and identification,such as managing high variability in patient data and ensuring robustness across different imaging conditions.It suggests directions for future research,with insights into technological advancements that can enhance surgical planning and diagnostic accuracy by comparing popular methods.This paper contributes to a comprehensive understanding of current liver tumor detection techniques,provides a roadmap for future innovations,and improves diagnostic and therapeutic outcomes for liver cancer by integrating recent progress with remaining challenges.
基金supported by grants from Capital’s Funds for Health Improvement and Research (2024–1–2022)Beijing Nat-ural Science Foundation (7244318)。
文摘Liver transplantation is hindered by organ shortage. The potential way to relieve this issue is to expand the donor pool via extending the donor criteria and make full use of all available grafts. The concept of “no-donor” liver transplantation allows grafts to be recovered from other liver recipients. This review summarizes the current clinical practice of “no-donor” liver transplantation, focusing on the experiences of Chinese transplant teams. Domino liver transplantation was introduced by Furtado in 1995 and implemented later in 2013 in China, and novel donor indications including some essential-to-treat inherited metabolic liver-based diseases have emerged. The concept of cross-auxiliary domino liver transplantation brings a further expansion of the domino liver graft pool, and the first pair of liver transplantation performed “rigorously without donation” was accomplished in our center in 2018. Our experience with this original transplantation procedure is hereby reviewed. In order to further promote and make successful “no-donor” liver transplantation, close co-operation between researchers, surgeons, physicians, organ procurement organizations, as well as ethical committees is required.
文摘BACKGROUND The Streptococcus salivarius(S.salivarius)group,which produces the enzyme urease has been identified as a potential contributor to ammonia production in the gut.Researchers have reported that patients with minimal HE had an increased abundance of the S.salivarius group,which is a specific change in the gut microbiota that distinguishes them from healthy individuals.The correlation between the aggregation of specific bacterial species and fibrosis progression in chronic liver disease(CLD)is yet to be fully elucidated.AIM To quantify S.salivarius using digital PCR(dPCR)as a liver fibrosis marker of CLD.METHODS This study retrospectively analysed 52 patients with CLD.To quantify S.salivarius in patients with CLD using dPCR,we evaluated the specificity and sensitivity of S.salivarius bacterial load using dPCR for a type strain.Next,we evaluated the clinical usefulness of dPCR for S.salivarius load quantification for detecting liver fibrosis in patients with CLD.The liver fibrosis stage was categorized into mild and advanced fibrosis based on pathological findings.RESULTS The dPCR assay revealed that S.salivarius was highly positive for the tnpA gene.The lower limit of quantification for dPCR using the tnpA gene with a 1μL template comprising 1.28×102 CFU/mL was 4.3 copies.After considering the detection range in dPCR,we adjusted the extracted DNA concentration to 5.0×10-4 ng/μL from 200 mg stool samples.The median bacterial loads of S.salivarius in stool sample from patients with mild and advanced fibrosis were 1.9 and 7.4 copies/μL,respectively.The quantification of S.salivarius load was observed more frequently in patients with advanced fibrosis than in those with mild fibrosis(P=0.032).CONCLUSION Quantifying of S.salivarius load using digital PCR is a useful biomarker for liver fibrosis in patients with CLD.