BACKGROUND The global prevalence of non-alcoholic steatohepatitis(NASH)and its associated risk of adverse outcomes,particularly in patients with advanced liver fibrosis,underscores the importance of early and accurate...BACKGROUND The global prevalence of non-alcoholic steatohepatitis(NASH)and its associated risk of adverse outcomes,particularly in patients with advanced liver fibrosis,underscores the importance of early and accurate diagnosis.AIM To develop a machine learning-based diagnostic model for advanced liver fibrosis in NASH patients.METHODS A total of 749 patients who underwent liver biopsy at Beijing Ditan Hospital,Capital Medical University,between January 2010 and January 2020 were included.Patients were randomly divided into training(n=522)and validation(n=224)cohorts.Five machine learning models were applied to predict advanced liver fibrosis,with feature selection based on Shapley Additive Explanations(SHAP).The diagnostic performance of these models was compared to traditional scores such as the aspartate aminotransferase to platelet ratio index(APRI)and fibrosis index based on the 4 factors(FIB-4),using metrics including the area under the receiver operating characteristic curve(AUROC),decision curve analysis(DCA),and calibration curves.RESULTS The Extreme Gradient Boosting(XGBoost)model outperformed all other machine learning models,achieving an AUROC of 0.934(95%CI:0.914-0.955)in the training cohort and 0.917(95%CI:0.880-0.953)in the validation cohort(P<0.001).Incorporating liver stiffness measurement into the model further improved its performance,with an AUROC of 0.977(95%CI:0.966-0.980)in the training cohort and 0.970(95%CI:0.950-0.990)in the validation cohort,significantly surpassing APRI and FIB-4 scores(P<0.001).The XGBoost model also demonstrated superior clinical utility,as evidenced by DCA and calibration curve analysis in both cohorts.CONCLUSION The XGBoost model provides a highly accurate,non-invasive diagnosis of advanced liver fibrosis in NASH patients,outperforming traditional methods.An online tool based on this model has been developed to assist clinicians in evaluating the risk of advanced liver fibrosis.展开更多
AIM To assess the value of magnetic resonance elastography (MRE) in detecting advanced fibrosis/cirrhosis in autoimmune hepatitis (AIH). METHODS In this retrospective study, 36 patients (19 treated and 17 untreated) w...AIM To assess the value of magnetic resonance elastography (MRE) in detecting advanced fibrosis/cirrhosis in autoimmune hepatitis (AIH). METHODS In this retrospective study, 36 patients (19 treated and 17 untreated) with histologically confirmed AIH and liver biopsy performed within 3 mo of MRE were identified at a tertiary care referral center. Liver stiffness (LS) with MRE was calculated by a radiologist, and inflammation grade and fibrosis stage in liver biopsy was assessed by a pathologist in a blinded fashion. Two radiologists evaluated morphological features of cirrhosis on conventional magnetic resonance imaging (MRI). Accuracy of MRE was compared to laboratory markers and MRI for detection of advanced fibrosis/cirrhosis. RESULTS Liver fibrosis stages of 0, 1, 2, 3 and 4 were present in 4, 6, 7, 6 and 13 patients respectively. There were no significant differences in distribution of fibrosis stage and inflammation grade between treated and untreated patient groups. LS with MRE demonstrated stronger correlation with liver fibrosis stage in comparison to laboratory markers for chronic liver disease (r = 0.88 vs -0.48-0.70). A trend of decreased mean LS in treated patients compared to untreated patients was observed (3.7 kPa vs 3.84 kPa) but was not statistically significant. MRE had an accuracy/sensitivity/specificity/positive predictive value/negative predictive value of 0.97/90%/100%/100%/90% and 0.98/92.3%/96%/92.3%/96% for detection of advanced fibrosis and cirrhosis, respectively. The performance of MRE was significantly better than laboratory tests for detection of advanced fibrosis (0.97 vs 0.53-0.80, p < 0.01), and cirrhosis (0.98 vs 0.58-0.80, p < 0.01) and better than conventional MRI for diagnosis of cirrhosis (0.98 vs 0.78, p = 0.002). CONCLUSION MRE is a promising modality for detection of advanced fibrosis and cirrhosis in patients with AIH with superior diagnostic accuracy compared to laboratory assessment and MRI.展开更多
AIM:To evaluates the effectiveness and safety of the first generation,NS3/4A protease inhibitors(PIs) in clinical practice against chronic C virus,especially in patients with advanced fibrosis. METHODS:Prospective stu...AIM:To evaluates the effectiveness and safety of the first generation,NS3/4A protease inhibitors(PIs) in clinical practice against chronic C virus,especially in patients with advanced fibrosis. METHODS:Prospective study and non-experimental analysis of a multicentre cohort of 38 Spanish hospitals that includes patients with chronic hepatitis C genotype 1,treatment-na?ve(TN) or treatment-experienced(TE),who underwent triple therapy with the first generation NS3/4A protease inhibitors,boceprevir(BOC) and telaprevir(TVR),in combination with pegylated interferon and ribavirin. The patients were treatment in routine practice settings. Data on the study population and on adverse clinical and virologic effects were compiled during the treatment period and during follow up.RESULTS:One thousand and fifty seven patients were included,405(38%) were treated with BOC and 652(62%) with TVR. Of this total,30%(n = 319) were TN and the remaining were TE:28%(n = 298) relapsers,12%(n = 123) partial responders(PR),25%(n = 260) null-responders(NR) and for 5%(n = 57) with prior response unknown. The rate of sustained virologic response(SVR) by intention-to-treatment(ITT) was greater in those treated with TVR(65%) than in those treated with BOC(52%)(P < 0.0001),whereas by modified intention-to-treatment(m ITT) no were found significant differences. By degree of fibrosis,56% of patients were F4 and the highest SVR rates were recorded in the non-F4 patients,both TN and TE. In the analysis by groups,the TN patients treated with TVR by ITT showed a higher SVR(P = 0.005). However,by m ITT there were no significant differences between BOC and TVR. In the multivariate analysis by m ITT,the significant SVR factors were relapsers,IL28 B CC and non-F4; the type of treatment(BOC or TVR) was not significant. The lowest SVR values were presented by the F4-NR patients,treated with BOC(46%) or with TVR(45%). 28% of the patients interrupted the treatment,mainly by non-viral response(51%):this outcome was more frequent in the TE than in the TN patients(57% vs 40%,P = 0.01). With respect to severe haematological disorders,neutropaenia was more likely to affect the patients treated with BOC(33% vs 20%,P ≤ 0.0001),and thrombocytopaenia and anaemia,the F4 patients(P = 0.000,P = 0.025,respectively). CONCLUSION:In a real clinical practice setting with a high proportion of patients with advanced fibrosis,effectiveness of first-generation PIs was high except for NR patients,with similar SVR rates being achieved by BOC and TVR.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and type-2 diabetes mellitus(T2DM)have an intricate bidirectional relationship.Individuals with T2DM,not only have a higher prevalence of non-alcoholic steatosis,but a...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and type-2 diabetes mellitus(T2DM)have an intricate bidirectional relationship.Individuals with T2DM,not only have a higher prevalence of non-alcoholic steatosis,but also carry a higher risk of progression to nonalcoholic steatohepatitis.Experts still differ in their recommendations of screening for NAFLD among patients with T2DM.AIM To study the prevalence of NAFLD and advanced fibrosis among our patient population with T2DM.METHODS During the study period(November 2018 to January 2020),59 adult patients with T2DM and 26 non-diabetic control group individuals were recruited prospectively.Patients with known significant liver disease and alcohol use were excluded.Demographic data and lab parameters were recorded.Liver elastography was performed in all patients.RESULTS In the study group comprised of patients with T2DM and normal alanine aminotransferase levels(mean 17.8±7 U/L),81%had hepatic steatosis as diagnosed by elastography.Advanced hepatic fibrosis(stage F3 or F4)was present in 12%of patients with T2DM as compared to none in the control group.Patients with T2DM also had higher number of individuals with grade 3 steatosis[45.8%vs 11.5%,(P<0.00001)and metabolic syndrome(84.7%vs 11.5%,P<0.00001)].CONCLUSION A significant number of patients with T2DM,despite having normal transaminase levels,have NAFLD,grade 3 steatosis and advanced hepatic fibrosis as measured by liver elastography.展开更多
BACKGROUND The prevalence of nonalcoholic fatty liver disease(NAFLD) is significantly rising worldwide. Type-2 diabetes(T2D) is a major risk factor for NAFLD progression.AIM To assess the association of commonly used ...BACKGROUND The prevalence of nonalcoholic fatty liver disease(NAFLD) is significantly rising worldwide. Type-2 diabetes(T2D) is a major risk factor for NAFLD progression.AIM To assess the association of commonly used medications to advanced fibrosis(AF) in patients with biopsy-proven NAFLD and T2D.METHODS We used the International Classification of Disease 9 th Revision Clinical Modification coding system to identify patients with T2D and included patients who underwent liver biopsy for suspected NAFLD between January 1, 2000 to December 31, 2015. We compared demographics, clinical characteristics, and differences in pattern of medication use in patients who had biopsy-proven AF to those without it. A univariate and multivariate analysis was performed to assess the association of different classes of medication with the presence of AF.RESULTS A total of 1183 patients were included in the final analysis, out of which 32%(n =381) had AF on liver biopsy. Mean age of entire cohort was 52 years and majority were females(65%) and Caucasians(85%). Among patients with AF, 51% were on oral hypoglycemics, 30% were on insulin, 66% were on antihypertensives and 27% were on lipid lowering agents for the median duration of 19 mo, 10 mo, 26 mo, and 24 mo respectively. Medications associated with decreased risk of AF included metformin, liraglutide, lisinopril, hydrochlorothiazide, atorvastatin and simvastatin while the use of furosemide and spironolactone were associated with higher prevalence of AF.CONCLUSION In our cohort of T2D with biopsy proven NAFLD, the patients who were receiving metformin, liraglutide, lisinopril, hydrochlorothiazide, atorvastatin and simvastatin were less likely to have AF on biopsy, while patients who were receiving furosemide and spironolactone had a higher likelihood of having AF when they underwent liver biopsy. Future studies are needed to confirm these findings and to establish measures for prevention of NAFLD progression in patients with T2D.展开更多
AIM: To study clinical and histopathological features of nonalcoholic fatty liver disease(NAFLD) in patients with and without type 2 diabetes mellitus(T2DM) using updated nonalcoholic steatohepatitis clinical research...AIM: To study clinical and histopathological features of nonalcoholic fatty liver disease(NAFLD) in patients with and without type 2 diabetes mellitus(T2DM) using updated nonalcoholic steatohepatitis clinical research network(NASH-CRN) grading system.METHODS: We retrospectively analyzed data of 235 patients with biopsy proven NAFLD with and without T2 DM.This database was utilized in the previously published study comparing ethnicity outcomes in NAFLD by the same corresponding author.The pathology database from University of Chicago was utilized for enrolling consecutive patients who met the criteria for NAFLD and their detailed clinical and histopathology findings were obtained for comparison.The relevant clinical profile of patients was collected from the Electronic Medical Records around the time of liver biopsy and the histology was read by a single well-trained histopathologist.The updated criteria for type 2 diabetes have been utilized for analysis.Background data of patients with NASH and NAFLD has been included.The mean differences were compared using χ2 and t-test along with regression analysis to evaluate the predictors of NASH and advanced fibrosis.RESULTS: Patients with NAFLD and T2 DM were significantly older(49.9 vs 43.0,P < 0.01),predominantly female(71.4 vs 56.3,P < 0.02),had higher rate of metabolic syndrome(88.7 vs 36.4,P < 0.01),had significantly higher aspartate transaminase(AST)/alanine transaminase(ALT) ratio(0.94 vs 0.78,P < 0.01) and Fib-4 index(1.65 vs 1.06,P < 0.01) as markers of NASH,showed higher mean NAFLD activity score(3.5 vs 3.0,P = 0.03) and higher mean fibrosis score(1.2 vs 0.52,P < 0.01) compared to patients with NAFLD without T2 DM.Furthermore,advanced fibrosis(32.5 vs 12.0,P < 0.01) and ballooning(27.3 vs 13.3,P < 0.01) was significantly higher among patients with NAFLD and T2 DM compared to patients with NAFLD without T2 DM.On multivariate analysis,T2 DM was independently associated with NASH(OR = 3.27,95%CI: 1.43-7.50,P < 0.01) and advanced fibrosis(OR = 3.45,95%CI: 1.53-7.77,P < 0.01) in all patients with NAFLD.There was a higher rate of T2DM(38.1 vs 19.4,P < 0.01) and cirrhosis(8.3 vs 0.0,P = 0.01) along with significantly higher mean Bilirubin(0.71 vs 0.56,P = 0.01) and AST(54.2 vs 38.3,P < 0.01) and ALT(78.7 vs 57.0,P = 0.01) level among patients with NASH when compared to patients with steatosis alone.The mean platelet count(247 vs 283,P < 0.01) and high-density lipoprotein cholesterol level(42.7 vs 48.1,P = 0.01) was lower among patients with NASH compared to patients with steatosis.CONCLUSION: Patients with NAFLD and T2 DM tend to have more advanced stages of NAFLD,particularly advanced fibrosis and higher rate of ballooning than patients with NAFLD without T2 DM.展开更多
The global burden of metabolic dysfunction-associated steatotic liver disease(MASLD),formerly termed nonalcoholic fatty liver disease(NAFLD),continues to rise alongside the epidemic of type 2 diabetes mellitus(T2DM)(1...The global burden of metabolic dysfunction-associated steatotic liver disease(MASLD),formerly termed nonalcoholic fatty liver disease(NAFLD),continues to rise alongside the epidemic of type 2 diabetes mellitus(T2DM)(1).Patients with T2DM are at particularly high risk for the progression of liver fibrosis and the development of liver-related events in MASLD.Accordingly,accurate,accessible,and noninvasive tools for early identification of advanced fibrosis(AF)are urgently needed to ensure appropriate clinical management of MASLD(2,3).Among these tools,the Fibrosis-4(FIB-4)index has emerged as one of the most widely used serum-based markers in clinical settings due to its simplicity and cost-effectiveness.However,its performance in high-risk subpopulations-especially those with T2DM-remains a concern(4).展开更多
Relevance of liver fibrosis amongst diabetic patients with metabolic-dysfunction associated steatotic liver disease(MASLD)and knowledge gaps Insulin resistance is paramount in the crosstalk between intrahepatic and ex...Relevance of liver fibrosis amongst diabetic patients with metabolic-dysfunction associated steatotic liver disease(MASLD)and knowledge gaps Insulin resistance is paramount in the crosstalk between intrahepatic and extrahepatic pathophysiological mechanisms leading to MASLD(1),hence gaining special relevance in patients diagnosed with type 2 diabetes(T2D).MASLD is the term that was recently endorsed by an international multidisciplinary consensus panel to replace non-alcoholic fatty liver disease[as non-alcoholic steatohepatitis(NASH)was replaced by metabolic dysfunction-associated steatohepatitis(MASH)](2).展开更多
Renal fibrosis is a common pathway of progressive renal diseases leading to end-stage renal disease regardless of the etiology. Accumulating evidence indicates that oxidative stress, resulting in generation of reactiv...Renal fibrosis is a common pathway of progressive renal diseases leading to end-stage renal disease regardless of the etiology. Accumulating evidence indicates that oxidative stress, resulting in generation of reactive oxygen species （ROS）, plays a critical role in the initiation and progression of fibrotic diseases. Nicotinamide adenine dinucleotide phosphate （NADPH） oxidase is the predominant enzyme source for ROS generation and is now recognized as a key mediator of cell proliferation and matrix accumulation in renal disease. Multiple stimuli and agonists, such as transforming growth factor , tumor necrosis factor, platelet derived growth factor, angiotensin II, hyperglycemia, oxidized low-density lipoprotein and albumin have been shown to alter the activity or expression of the NADPH oxidase and ultimately increase ROS production. ROS directly incites damage to biologically important macromolecules and leads to generation of the so-called advanced oxidation protein products （AOPPs） and advanced glycation end products, which are not only markers of oxidative stress but also cause renal injury. Targeting NADPH oxidase and/or reducing AOPPs production miaht be a novel strateav for the theraoeutic intervention of varietv of fibrotic kidney disorders.展开更多
Background and Aims:The clinicopathological features and long-term outcomes of patients with vanishing bile duct syndrome(VBDS)have yet to be elucidated.The study aims to investigate these features and identify factor...Background and Aims:The clinicopathological features and long-term outcomes of patients with vanishing bile duct syndrome(VBDS)have yet to be elucidated.The study aims to investigate these features and identify factors associated with poor prognosis.Methods:This multicenter retrospective study recruited patients with liver biopsy-proven VBDS who were followed up at five hospitals in northern China from January 2003 to April 2022.Clinical and pathological data at time of biopsy were reviewed.Clinical outcomes including cirrhosis,decompensation events,liver transplantation(LT),and liver-related death were recorded.Cox regression analysis was used to identify the risk factors associated with poor outcomes.Results:A total of 183 patients were included.The median age was 47 years,with 77.6%being women.During a median follow-up of 4.8 years,88 patients developed compensated or decompensated cirrhosis,27 died,and 15 received LT.Multivariate Cox regression analysis showed that hepatocellular cholestasis(HR 2.953,95%CI:1.437–6.069),foam cells(HR 2.349,95%CI:1.092–5.053),and advanced fibrosis(HR 2.524,95%CI:1.313–4.851)were independent predictors of LT or liver-related deaths.A nomogram formulated with the above factors showed good consistency with a concordance index of 0.746(95%CI:0.706–0.785).Conclusions:Nearly half of VBDS patients studied progressed to end-stage liver disease and 23%of them had LT or liver-related death within two years of diagnosis.Hepatocellular cholestasis,foam cells and advanced fibrosis rather than the degree of bile duct loss or underlying etiologies were independently associated with poor prognosis in VBDS patients.展开更多
Achieving a sustained virologic response(SVR)through direct-acting antivirals for hepatitis C virus(HCV)infection significantly reduces the long-term risk of hepatocellular carcinoma(HCC),particularly in patients with...Achieving a sustained virologic response(SVR)through direct-acting antivirals for hepatitis C virus(HCV)infection significantly reduces the long-term risk of hepatocellular carcinoma(HCC),particularly in patients with advanced fibrosis(F3)or cirrhosis(F4).However,despite this improvement,the risks associated with HCC and the optimal surveillance strategies for patients who have achieved SVR remain topics of debate.This controversy is compounded by challenges in reliably staging liver fibrosis non-invasively,especially at advanced fibrosis(F3),and the unclear cost-effectiveness,modality,frequency,and duration of HCC surveillance in individuals with SVR but without cirrhosis.These factors contribute to significant variations in surveillance guidelines recommended by different professional societies.Therefore,there is a pressing need for an optimal surveillance strategy that is both simplified and cost-effective to facilitate wider adoption by clinicians.This review article evaluates the existing data,addresses ongoing controversies,and aims to provide new perspectives on HCC surveillance strategies for patients who have achieved SVR from HCV.展开更多
Background and Aims:Disease severity across the different diagnostic categories of metabolic dysfunction-associated fatty liver disease(MAFLD)remains elusive.This study assessed the fibrosis stages and features of MAF...Background and Aims:Disease severity across the different diagnostic categories of metabolic dysfunction-associated fatty liver disease(MAFLD)remains elusive.This study assessed the fibrosis stages and features of MAFLD between different items.We also aimed to investigate the associations between advanced fibrosis and risk factors.Methods:This multicenter cross-sectional study enrolled adults participating in liver disease screening in the community.Patients were stratified following MAFLD diagnostic criteria,to group A(395 patients)for type 2 diabetes,group B(1,818 patients)for body mass index(BMI)>23 kg/m^(2),and group C(44 patients)for BMI≤23kg/m^(2) with at least two metabolic factors.Advanced fibrosis was defined as a fibrosis-4 index>2.67.Results:Between 2009 and 2020,1,948 MAFLD patients were recruited,including 478 with concomitant liver diseases.Advanced fibrosis was observed in 125 patients.A significantly larger proportion of patients in group C(25.0%)than in group A(7.6%)and group B(5.8%)had advanced fibrosis (p<0.01).Logistic regression analysis found that hepatitis B virus(HBV)/hepatitis C virus(HCV)coinfection(odds ratio[OR]:12.14,95%confidence interval[CI]:4.04-36.52;p<0.01),HCV infection(OR:7.87,95%CI:4.78-12.97;p<0.01),group C(OR:6.00,95%CI:2.53-14.22;p<0.01),and TC/LDL-C(OR:1.21,95%CI:1.06-1.38;p<0.01)were significant predictors of advanced fibrosis.Conclusions:A higher proportion of lean MAFLD patients with metabolic abnormalities had advanced fibrosis.HCV infection was significantly associated with advanced fibrosis.展开更多
基金Supported by the Natural Science Foundation of China,No.81970512the Beijing Hospitals Authority Youth Programme,No.QMl220201802+1 种基金the Beijing Traditional Chinese Medicine Science and Technology Development Fund Project,No.Qn-2020-25High-Level Public Health Technical Personnel Construction Project.
文摘BACKGROUND The global prevalence of non-alcoholic steatohepatitis(NASH)and its associated risk of adverse outcomes,particularly in patients with advanced liver fibrosis,underscores the importance of early and accurate diagnosis.AIM To develop a machine learning-based diagnostic model for advanced liver fibrosis in NASH patients.METHODS A total of 749 patients who underwent liver biopsy at Beijing Ditan Hospital,Capital Medical University,between January 2010 and January 2020 were included.Patients were randomly divided into training(n=522)and validation(n=224)cohorts.Five machine learning models were applied to predict advanced liver fibrosis,with feature selection based on Shapley Additive Explanations(SHAP).The diagnostic performance of these models was compared to traditional scores such as the aspartate aminotransferase to platelet ratio index(APRI)and fibrosis index based on the 4 factors(FIB-4),using metrics including the area under the receiver operating characteristic curve(AUROC),decision curve analysis(DCA),and calibration curves.RESULTS The Extreme Gradient Boosting(XGBoost)model outperformed all other machine learning models,achieving an AUROC of 0.934(95%CI:0.914-0.955)in the training cohort and 0.917(95%CI:0.880-0.953)in the validation cohort(P<0.001).Incorporating liver stiffness measurement into the model further improved its performance,with an AUROC of 0.977(95%CI:0.966-0.980)in the training cohort and 0.970(95%CI:0.950-0.990)in the validation cohort,significantly surpassing APRI and FIB-4 scores(P<0.001).The XGBoost model also demonstrated superior clinical utility,as evidenced by DCA and calibration curve analysis in both cohorts.CONCLUSION The XGBoost model provides a highly accurate,non-invasive diagnosis of advanced liver fibrosis in NASH patients,outperforming traditional methods.An online tool based on this model has been developed to assist clinicians in evaluating the risk of advanced liver fibrosis.
基金Supported by National Institutes of Health,No.EB001981 to Ehman RL and No.EB017197 to Yin Mthe National Natural Science Foundation of China,No.81271562 to Wang J
文摘AIM To assess the value of magnetic resonance elastography (MRE) in detecting advanced fibrosis/cirrhosis in autoimmune hepatitis (AIH). METHODS In this retrospective study, 36 patients (19 treated and 17 untreated) with histologically confirmed AIH and liver biopsy performed within 3 mo of MRE were identified at a tertiary care referral center. Liver stiffness (LS) with MRE was calculated by a radiologist, and inflammation grade and fibrosis stage in liver biopsy was assessed by a pathologist in a blinded fashion. Two radiologists evaluated morphological features of cirrhosis on conventional magnetic resonance imaging (MRI). Accuracy of MRE was compared to laboratory markers and MRI for detection of advanced fibrosis/cirrhosis. RESULTS Liver fibrosis stages of 0, 1, 2, 3 and 4 were present in 4, 6, 7, 6 and 13 patients respectively. There were no significant differences in distribution of fibrosis stage and inflammation grade between treated and untreated patient groups. LS with MRE demonstrated stronger correlation with liver fibrosis stage in comparison to laboratory markers for chronic liver disease (r = 0.88 vs -0.48-0.70). A trend of decreased mean LS in treated patients compared to untreated patients was observed (3.7 kPa vs 3.84 kPa) but was not statistically significant. MRE had an accuracy/sensitivity/specificity/positive predictive value/negative predictive value of 0.97/90%/100%/100%/90% and 0.98/92.3%/96%/92.3%/96% for detection of advanced fibrosis and cirrhosis, respectively. The performance of MRE was significantly better than laboratory tests for detection of advanced fibrosis (0.97 vs 0.53-0.80, p < 0.01), and cirrhosis (0.98 vs 0.58-0.80, p < 0.01) and better than conventional MRI for diagnosis of cirrhosis (0.98 vs 0.78, p = 0.002). CONCLUSION MRE is a promising modality for detection of advanced fibrosis and cirrhosis in patients with AIH with superior diagnostic accuracy compared to laboratory assessment and MRI.
文摘AIM:To evaluates the effectiveness and safety of the first generation,NS3/4A protease inhibitors(PIs) in clinical practice against chronic C virus,especially in patients with advanced fibrosis. METHODS:Prospective study and non-experimental analysis of a multicentre cohort of 38 Spanish hospitals that includes patients with chronic hepatitis C genotype 1,treatment-na?ve(TN) or treatment-experienced(TE),who underwent triple therapy with the first generation NS3/4A protease inhibitors,boceprevir(BOC) and telaprevir(TVR),in combination with pegylated interferon and ribavirin. The patients were treatment in routine practice settings. Data on the study population and on adverse clinical and virologic effects were compiled during the treatment period and during follow up.RESULTS:One thousand and fifty seven patients were included,405(38%) were treated with BOC and 652(62%) with TVR. Of this total,30%(n = 319) were TN and the remaining were TE:28%(n = 298) relapsers,12%(n = 123) partial responders(PR),25%(n = 260) null-responders(NR) and for 5%(n = 57) with prior response unknown. The rate of sustained virologic response(SVR) by intention-to-treatment(ITT) was greater in those treated with TVR(65%) than in those treated with BOC(52%)(P < 0.0001),whereas by modified intention-to-treatment(m ITT) no were found significant differences. By degree of fibrosis,56% of patients were F4 and the highest SVR rates were recorded in the non-F4 patients,both TN and TE. In the analysis by groups,the TN patients treated with TVR by ITT showed a higher SVR(P = 0.005). However,by m ITT there were no significant differences between BOC and TVR. In the multivariate analysis by m ITT,the significant SVR factors were relapsers,IL28 B CC and non-F4; the type of treatment(BOC or TVR) was not significant. The lowest SVR values were presented by the F4-NR patients,treated with BOC(46%) or with TVR(45%). 28% of the patients interrupted the treatment,mainly by non-viral response(51%):this outcome was more frequent in the TE than in the TN patients(57% vs 40%,P = 0.01). With respect to severe haematological disorders,neutropaenia was more likely to affect the patients treated with BOC(33% vs 20%,P ≤ 0.0001),and thrombocytopaenia and anaemia,the F4 patients(P = 0.000,P = 0.025,respectively). CONCLUSION:In a real clinical practice setting with a high proportion of patients with advanced fibrosis,effectiveness of first-generation PIs was high except for NR patients,with similar SVR rates being achieved by BOC and TVR.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and type-2 diabetes mellitus(T2DM)have an intricate bidirectional relationship.Individuals with T2DM,not only have a higher prevalence of non-alcoholic steatosis,but also carry a higher risk of progression to nonalcoholic steatohepatitis.Experts still differ in their recommendations of screening for NAFLD among patients with T2DM.AIM To study the prevalence of NAFLD and advanced fibrosis among our patient population with T2DM.METHODS During the study period(November 2018 to January 2020),59 adult patients with T2DM and 26 non-diabetic control group individuals were recruited prospectively.Patients with known significant liver disease and alcohol use were excluded.Demographic data and lab parameters were recorded.Liver elastography was performed in all patients.RESULTS In the study group comprised of patients with T2DM and normal alanine aminotransferase levels(mean 17.8±7 U/L),81%had hepatic steatosis as diagnosed by elastography.Advanced hepatic fibrosis(stage F3 or F4)was present in 12%of patients with T2DM as compared to none in the control group.Patients with T2DM also had higher number of individuals with grade 3 steatosis[45.8%vs 11.5%,(P<0.00001)and metabolic syndrome(84.7%vs 11.5%,P<0.00001)].CONCLUSION A significant number of patients with T2DM,despite having normal transaminase levels,have NAFLD,grade 3 steatosis and advanced hepatic fibrosis as measured by liver elastography.
文摘BACKGROUND The prevalence of nonalcoholic fatty liver disease(NAFLD) is significantly rising worldwide. Type-2 diabetes(T2D) is a major risk factor for NAFLD progression.AIM To assess the association of commonly used medications to advanced fibrosis(AF) in patients with biopsy-proven NAFLD and T2D.METHODS We used the International Classification of Disease 9 th Revision Clinical Modification coding system to identify patients with T2D and included patients who underwent liver biopsy for suspected NAFLD between January 1, 2000 to December 31, 2015. We compared demographics, clinical characteristics, and differences in pattern of medication use in patients who had biopsy-proven AF to those without it. A univariate and multivariate analysis was performed to assess the association of different classes of medication with the presence of AF.RESULTS A total of 1183 patients were included in the final analysis, out of which 32%(n =381) had AF on liver biopsy. Mean age of entire cohort was 52 years and majority were females(65%) and Caucasians(85%). Among patients with AF, 51% were on oral hypoglycemics, 30% were on insulin, 66% were on antihypertensives and 27% were on lipid lowering agents for the median duration of 19 mo, 10 mo, 26 mo, and 24 mo respectively. Medications associated with decreased risk of AF included metformin, liraglutide, lisinopril, hydrochlorothiazide, atorvastatin and simvastatin while the use of furosemide and spironolactone were associated with higher prevalence of AF.CONCLUSION In our cohort of T2D with biopsy proven NAFLD, the patients who were receiving metformin, liraglutide, lisinopril, hydrochlorothiazide, atorvastatin and simvastatin were less likely to have AF on biopsy, while patients who were receiving furosemide and spironolactone had a higher likelihood of having AF when they underwent liver biopsy. Future studies are needed to confirm these findings and to establish measures for prevention of NAFLD progression in patients with T2D.
文摘AIM: To study clinical and histopathological features of nonalcoholic fatty liver disease(NAFLD) in patients with and without type 2 diabetes mellitus(T2DM) using updated nonalcoholic steatohepatitis clinical research network(NASH-CRN) grading system.METHODS: We retrospectively analyzed data of 235 patients with biopsy proven NAFLD with and without T2 DM.This database was utilized in the previously published study comparing ethnicity outcomes in NAFLD by the same corresponding author.The pathology database from University of Chicago was utilized for enrolling consecutive patients who met the criteria for NAFLD and their detailed clinical and histopathology findings were obtained for comparison.The relevant clinical profile of patients was collected from the Electronic Medical Records around the time of liver biopsy and the histology was read by a single well-trained histopathologist.The updated criteria for type 2 diabetes have been utilized for analysis.Background data of patients with NASH and NAFLD has been included.The mean differences were compared using χ2 and t-test along with regression analysis to evaluate the predictors of NASH and advanced fibrosis.RESULTS: Patients with NAFLD and T2 DM were significantly older(49.9 vs 43.0,P < 0.01),predominantly female(71.4 vs 56.3,P < 0.02),had higher rate of metabolic syndrome(88.7 vs 36.4,P < 0.01),had significantly higher aspartate transaminase(AST)/alanine transaminase(ALT) ratio(0.94 vs 0.78,P < 0.01) and Fib-4 index(1.65 vs 1.06,P < 0.01) as markers of NASH,showed higher mean NAFLD activity score(3.5 vs 3.0,P = 0.03) and higher mean fibrosis score(1.2 vs 0.52,P < 0.01) compared to patients with NAFLD without T2 DM.Furthermore,advanced fibrosis(32.5 vs 12.0,P < 0.01) and ballooning(27.3 vs 13.3,P < 0.01) was significantly higher among patients with NAFLD and T2 DM compared to patients with NAFLD without T2 DM.On multivariate analysis,T2 DM was independently associated with NASH(OR = 3.27,95%CI: 1.43-7.50,P < 0.01) and advanced fibrosis(OR = 3.45,95%CI: 1.53-7.77,P < 0.01) in all patients with NAFLD.There was a higher rate of T2DM(38.1 vs 19.4,P < 0.01) and cirrhosis(8.3 vs 0.0,P = 0.01) along with significantly higher mean Bilirubin(0.71 vs 0.56,P = 0.01) and AST(54.2 vs 38.3,P < 0.01) and ALT(78.7 vs 57.0,P = 0.01) level among patients with NASH when compared to patients with steatosis alone.The mean platelet count(247 vs 283,P < 0.01) and high-density lipoprotein cholesterol level(42.7 vs 48.1,P = 0.01) was lower among patients with NASH compared to patients with steatosis.CONCLUSION: Patients with NAFLD and T2 DM tend to have more advanced stages of NAFLD,particularly advanced fibrosis and higher rate of ballooning than patients with NAFLD without T2 DM.
文摘The global burden of metabolic dysfunction-associated steatotic liver disease(MASLD),formerly termed nonalcoholic fatty liver disease(NAFLD),continues to rise alongside the epidemic of type 2 diabetes mellitus(T2DM)(1).Patients with T2DM are at particularly high risk for the progression of liver fibrosis and the development of liver-related events in MASLD.Accordingly,accurate,accessible,and noninvasive tools for early identification of advanced fibrosis(AF)are urgently needed to ensure appropriate clinical management of MASLD(2,3).Among these tools,the Fibrosis-4(FIB-4)index has emerged as one of the most widely used serum-based markers in clinical settings due to its simplicity and cost-effectiveness.However,its performance in high-risk subpopulations-especially those with T2DM-remains a concern(4).
文摘Relevance of liver fibrosis amongst diabetic patients with metabolic-dysfunction associated steatotic liver disease(MASLD)and knowledge gaps Insulin resistance is paramount in the crosstalk between intrahepatic and extrahepatic pathophysiological mechanisms leading to MASLD(1),hence gaining special relevance in patients diagnosed with type 2 diabetes(T2D).MASLD is the term that was recently endorsed by an international multidisciplinary consensus panel to replace non-alcoholic fatty liver disease[as non-alcoholic steatohepatitis(NASH)was replaced by metabolic dysfunction-associated steatohepatitis(MASH)](2).
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 30830056 and No. U0932002）. Conflict of interests： None.
文摘Renal fibrosis is a common pathway of progressive renal diseases leading to end-stage renal disease regardless of the etiology. Accumulating evidence indicates that oxidative stress, resulting in generation of reactive oxygen species （ROS）, plays a critical role in the initiation and progression of fibrotic diseases. Nicotinamide adenine dinucleotide phosphate （NADPH） oxidase is the predominant enzyme source for ROS generation and is now recognized as a key mediator of cell proliferation and matrix accumulation in renal disease. Multiple stimuli and agonists, such as transforming growth factor , tumor necrosis factor, platelet derived growth factor, angiotensin II, hyperglycemia, oxidized low-density lipoprotein and albumin have been shown to alter the activity or expression of the NADPH oxidase and ultimately increase ROS production. ROS directly incites damage to biologically important macromolecules and leads to generation of the so-called advanced oxidation protein products （AOPPs） and advanced glycation end products, which are not only markers of oxidative stress but also cause renal injury. Targeting NADPH oxidase and/or reducing AOPPs production miaht be a novel strateav for the theraoeutic intervention of varietv of fibrotic kidney disorders.
基金supported by National Natural Science Foundation of China(No.82100633 to LTT).
文摘Background and Aims:The clinicopathological features and long-term outcomes of patients with vanishing bile duct syndrome(VBDS)have yet to be elucidated.The study aims to investigate these features and identify factors associated with poor prognosis.Methods:This multicenter retrospective study recruited patients with liver biopsy-proven VBDS who were followed up at five hospitals in northern China from January 2003 to April 2022.Clinical and pathological data at time of biopsy were reviewed.Clinical outcomes including cirrhosis,decompensation events,liver transplantation(LT),and liver-related death were recorded.Cox regression analysis was used to identify the risk factors associated with poor outcomes.Results:A total of 183 patients were included.The median age was 47 years,with 77.6%being women.During a median follow-up of 4.8 years,88 patients developed compensated or decompensated cirrhosis,27 died,and 15 received LT.Multivariate Cox regression analysis showed that hepatocellular cholestasis(HR 2.953,95%CI:1.437–6.069),foam cells(HR 2.349,95%CI:1.092–5.053),and advanced fibrosis(HR 2.524,95%CI:1.313–4.851)were independent predictors of LT or liver-related deaths.A nomogram formulated with the above factors showed good consistency with a concordance index of 0.746(95%CI:0.706–0.785).Conclusions:Nearly half of VBDS patients studied progressed to end-stage liver disease and 23%of them had LT or liver-related death within two years of diagnosis.Hepatocellular cholestasis,foam cells and advanced fibrosis rather than the degree of bile duct loss or underlying etiologies were independently associated with poor prognosis in VBDS patients.
文摘Achieving a sustained virologic response(SVR)through direct-acting antivirals for hepatitis C virus(HCV)infection significantly reduces the long-term risk of hepatocellular carcinoma(HCC),particularly in patients with advanced fibrosis(F3)or cirrhosis(F4).However,despite this improvement,the risks associated with HCC and the optimal surveillance strategies for patients who have achieved SVR remain topics of debate.This controversy is compounded by challenges in reliably staging liver fibrosis non-invasively,especially at advanced fibrosis(F3),and the unclear cost-effectiveness,modality,frequency,and duration of HCC surveillance in individuals with SVR but without cirrhosis.These factors contribute to significant variations in surveillance guidelines recommended by different professional societies.Therefore,there is a pressing need for an optimal surveillance strategy that is both simplified and cost-effective to facilitate wider adoption by clinicians.This review article evaluates the existing data,addresses ongoing controversies,and aims to provide new perspectives on HCC surveillance strategies for patients who have achieved SVR from HCV.
基金supported in part by grants from The Ministry of Science and Technology,Taiwan(MOST 110-2314-B-03-073-MY3)The Ministry of Health and Welfare,Taiwan(MOHW,112-TDU-B-221-124007)+1 种基金National Yang Ming Chiao Tung University-Kaohsiung Medical University Joint Research Project(NYCU-KMU-111-I001,NYCU-KMU-112-I001)Kaohsiung Medical University Hospital(KMUH SA10907,KMUH110-0R05).
文摘Background and Aims:Disease severity across the different diagnostic categories of metabolic dysfunction-associated fatty liver disease(MAFLD)remains elusive.This study assessed the fibrosis stages and features of MAFLD between different items.We also aimed to investigate the associations between advanced fibrosis and risk factors.Methods:This multicenter cross-sectional study enrolled adults participating in liver disease screening in the community.Patients were stratified following MAFLD diagnostic criteria,to group A(395 patients)for type 2 diabetes,group B(1,818 patients)for body mass index(BMI)>23 kg/m^(2),and group C(44 patients)for BMI≤23kg/m^(2) with at least two metabolic factors.Advanced fibrosis was defined as a fibrosis-4 index>2.67.Results:Between 2009 and 2020,1,948 MAFLD patients were recruited,including 478 with concomitant liver diseases.Advanced fibrosis was observed in 125 patients.A significantly larger proportion of patients in group C(25.0%)than in group A(7.6%)and group B(5.8%)had advanced fibrosis (p<0.01).Logistic regression analysis found that hepatitis B virus(HBV)/hepatitis C virus(HCV)coinfection(odds ratio[OR]:12.14,95%confidence interval[CI]:4.04-36.52;p<0.01),HCV infection(OR:7.87,95%CI:4.78-12.97;p<0.01),group C(OR:6.00,95%CI:2.53-14.22;p<0.01),and TC/LDL-C(OR:1.21,95%CI:1.06-1.38;p<0.01)were significant predictors of advanced fibrosis.Conclusions:A higher proportion of lean MAFLD patients with metabolic abnormalities had advanced fibrosis.HCV infection was significantly associated with advanced fibrosis.
