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BACKGROUND@#Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH.@*METHODS@#Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) ≥5 with a score of ≥1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS ≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL).@*RESULTS@#A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference [SMD]: 0.87 [0.69-1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension ( P < 0.001, P = 0.026 and P = 0.049, respectively). CK-18 M30 levels were positively associated with histological NAS in most centers. The area under the receiver operating characteristics (AUROC) for NASH was 0.750 (95% confidence intervals: 0.714-0.787), and CK-18 M30 at Youden's index maximum was 275.7 U/L. Both sensitivity (55% [52%-59%]) and positive predictive value (59%) were not ideal.@*CONCLUSION@#This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.
Subject(s)
Humans , Non-alcoholic Fatty Liver Disease/diagnosis , Keratin-18 , Biomarkers , Biopsy , Hepatocytes/pathology , Apoptosis , Liver/pathologyABSTRACT
Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in the world and seriously threatens human health. So far, change in unhealthy lifestyle is still the most important treatment method for NAFLD. However, traditional lifestyle intervention depends on hospital visits and follow-up, and patients tend to have poor execution and compliance. With the help of the Internet technology, digital therapeutics overcome these disadvantages and has achieved a certain clinical effect in NAFLD patients. This article reviews the application of digital therapeutics in medicine and NAFLD treatment, so as to provide a reference for the treatment of NAFLD.
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Metabolic associated fatty liver disease (MAFLD) is a hotspot in the field of fatty liver disease at present and it has become the most common chronic liver disease around the world. It is predicted that the incidence rates of MAFLD and related liver cirrhosis will continue to grow in the next 20 years and that they will become new global health issues. Acute-on-chronic liver failure (ACLF) is defined as a clinical syndrome of acute or subacute liver function decompensation within a short period of time in the presence of existing chronic liver diseases, with the main clinical manifestations of ascites, jaundice, coagulation disorder, and hepatic encephalopathy. Based on the existing data, this article discusses the epidemiology, pathogenesis, treatment and management strategies, and future prospects of MAFLD-ACLF.
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At present, the majority (＞80%) of hepatocellular carcinoma (HCC) cases in the world is mainly caused by chronic HBV or HCV infection, and in China, up to 80% of HCC cases are caused by HBV, but the mortality rate of HBV-related HCC has decreased by 30% recently. At the same time, obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD) gradually replace hepatitis virus infection and alcohol abuse and have become the important pathogenic factors for HCC, and there is also a tendency of increase in HCC cases caused by metabolic dysfunction and fatty liver disease in recent years. For this reason, it is particularly important to investigate the diagnosis, treatment, and possible pathogenesis of HCC associated with NAFLD.
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The terms nonalcoholic steatohepatitis and nonalcoholic fatty liver disease (NAFLD) were first used in the 1980s to describe a condition of similar liver histological changes to alcoholic liver disease, without excessive drinking nor other factors for liver injury. In-depth research on NAFLD has achieved rapid progress over the past 40 years; however, the unchanged nomenclature of the disease has become an obstacle for routine clinical practice and clinical trials. To overcome the shortcomings of the old term, the international consensus panel proposes to use the term metabolic associated fatty liver disease (MAFLD) to replace NAFLD and further puts forward the comprehensive and simple definition of MAFLD for clinical diagnosis, which makes MAFLD different from other liver diseases. Meanwhile, the panel suggests that MAFLD assessment and severity stratification should be extended beyond the simple dichotomous classification used at present. The new name MAFLD will become an important measure for optimizing clinical practice and improving clinical research and may bring benefits to physicians and patients.
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Objective@#To explore the relationship between liver controlled attenuation parameters (CAP) and body fat mass and its distribution.@*Methods@#From May to December 2018, 978 adult patients visited at the fatty liver center of the Third People's Hospital of Changzhou were treated. The patient's liver controlled attenuation parameters were measured by transient elastography and the body fat mass and its distribution were measured by bioelectrical impedance technology. Pearson’s correlation coefficient was adopted to describe the correlation between liver CAP value and body mass index (BMI), body fat mass index (BFMI), trunk fat mass index (TFMI), limbs fat mass index (LFMI) and visceral fat area (VFA). Receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate BMI, BFMI, TFMI, LFMI and VFA to differentiate the cut-off points and efficacy of CAP for diagnosing grading of fatty liver changes in S0-1 and S2-3.@*Results@#In 653 cases of male, S0 ~ S3 accounted for 4.90%, 3.37%, 22.36% and 69.37%, respectively, and in 325 cases of females, S0 ~ S3 accounted for 7.38%, 6.46%, 13.23% and 72.92%, respectively. Female patients had more visceral, trunk and limbs fat than male (P < 0.01). Body mass, body fat mass, body fat percentage, BMI, BFMI, TFMI, LFMI, and VFA were increased in male and female patients with increasing liver fat grade (P < 0.01). CAP values of male and female patients were positively correlated with BMI, BFMI, TFMI, LFMI and VFA. Percentage of body fat mass increased with increasing liver fat grade (male: F = 13.42, P < 0.001; female: F = 3.22, P = 0.023); while limb fat mass percentage did not increase with liver fat grade (Male: F = 1.13, P = 0.34; female: F = 1.05, P = 0.37). Hepatic steatosis grading (S0 ~ 1 or S2 ~ 3) diagnosed with CAP were distinguished through BMI, BFMI, TFMI, LFMI and VFA. AUC was 0.80 ~ 0.82 in males (P < 0.01), and 0.75 ~ 0.78 in females (P < 0.01).@*Conclusion@#The liver CAP value is positively correlated with the body's limbs, trunk and visceral fat, and has a strong correlation with trunk and visceral fat. BMI, BFMI, TFMI, LFMI and VFA up to some extent can identify the CAP diagnosis of grading of fatty liver changes in S0-1 and S2-3.
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Hepatocellular carcinoma (HCC) is a major disease with a high degree of malignancy, and poor prognosis, which seriously endangers human health. Chronic viral hepatitis (HBV, HCV)-cirrhosis-liver cancer patterns of pathogenesis has been widely accepted. However, the relationship between non-infectious liver disease and HCC is not completely clear; thereby how various non-infectious liver diseases develop through precancerous lesions has attracted widespread attention to HCC. A full understanding of these precancerous lesions is likely to provide new ideas and strategies for the prevention and treatment of non-infectious liver disease-related HCC.
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Worldwide increasing prevalence of obesity and lifestyle changes has put nonalcoholic fatty liver disease (NAFLD) as the most prevalent liver disease of the coming decade. NAFLD not only causes cirrhosis and hepatocellular carcinoma, but also acts as a component of metabolic syndrome together with obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and dyslipidemia. Consequently, its mutual cause-and-effect interactions have brought a huge clinical and financial burden to patients and society.
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For a long time, researchers and clinicians have strictly divided fatty liver diseases into alcoholic and non-alcoholic fatty liver disease. When one was diagnosed as alcoholic liver disease, the effects of non-alcoholic factors, including obesity, diabetes or metabolic syndrome, on liver diseases have been neglected. Conversely, when the patient was diagnosed as non-alcoholic fatty liver disease, the impacts of alcohol drinking are usually ignored. In the new era, physicians and scientific researchers need to pay more attention to the dual factors of alcohol and obesity, which often exist together and affect liver disease progression.This article elaborates on the clinical features of fatty liver disease in the new era from the aspects of changes in the clinical features of alcoholic liver disease, disease pattern of nonalcoholic fatty liver disease with drinking, and differential diagnosis of alcoholic and nonalcoholic fatty liver diseases.
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For a long time, researchers and clinicians have strictly divided fatty liver diseases into alcoholic and non-alcoholic fatty liver disease. When one was diagnosed as alcoholic liver disease, the effects of non-alcoholic factors, including obesity, diabetes or metabolic syndrome, on liver diseases have been neglected. Conversely, when the patient was diagnosed as non-alcoholic fatty liver disease, the impacts of alcohol drinking are usually ignored. In the new era, physicians and scientific researchers need to pay more attention to the dual factors of alcohol and obesity, which often exist together and affect liver disease progression.This article elaborates on the clinical features of fatty liver disease in the new era from the aspects of changes in the clinical features of alcoholic liver disease, disease pattern of nonalcoholic fatty liver disease with drinking, and differential diagnosis of alcoholic and nonalcoholic fatty liver diseases.
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Chronic hepatitis B and fatty liver disease are two most common chronic liver diseases in China, and with the increasing prevalence of obesity, chronic hepatitis B complicated by fatty liver disease is more and more common in clinical practice. The influence of chronic hepatitis B virus infection on fatty liver disease and lipid metabolism has gradually become a hot topic in clinical research, as well as the influence of fatty liver disease and metabolic factors on the course and treatment of chronic hepatitis B.
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Fatty liver is increasingly common in patients with chronic hepatitis B (CHB) in China. The impact of hepatitis B virus infection on fatty liver and metabolism , in turns the impact of fatty liver and metabolic factors on the development and treatment of patients with CHB are of great concern .The causes of abnormal elevation of serum aminotransferases in patients with CHB and fatty liver should be carefully determined to make appropriate therapeutic choices in these conditions.In order to make personalized treatment and follow-up measures, the non-invasive diagnosis for nonalcoholic steatohepatitis in patients with chronic hepatitis B virus infection requires further studies.
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Objective To explore the application value of transient elastography (TE)by using transient elas-tography(FibroScan)for the noninvasive diagnosis of hepatic fibrosis and steatosis by measuring liver stiffness (LS)and controlled attenuation parameter (CAP)in the preschool children in Shanghai for their health check - up. Methods A total of 410 children,who underwent health screening in Xinhua Hospital,Affiliated to Shanghai Jiaotong University School of Medicine,from April to November 2017 were collected. LS and CAP values were obtained by the FibroScan device with M - probe. The differences in LS and CAP values between different genders were analyzed,as well as the in-fluencing factors for LS and CAP values. Results A total of 410 preschool healthy children were enrolled. The success rate of valid TE measurements by M - probe in the participating children was 96. 5％ . The LS and CAP values were (3. 22 ± 0. 86)kPa and (176. 74 ± 20. 84)dB/ m,respectively. LS and CAP values didn′t differ significantly in gender (all P > 0. 05). In univariate analysis,the CAP values were significantly associated with height (r = 0. 112,P =0. 026),weight(r = 0. 145,P = 0. 004),body mass index(r = 0. 114,P = 0. 023),waist circumference(r = 0. 178,P =0. 000)and hip circumference(r = 0. 148,P = 0. 003). Conclusions FibroScan equipped with M - probe is feasible for LS and hepatic steatosis measurement in preschool children.
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Recent studies have found that non-alcoholic fatty liver disease(NAFLD) has great impact on the development of biliary tract diseases. Here in this review, we summarized the relationship between NAFLD and the occurrence and development, risk factors and severity of cholestasis, gallstones, intrahepatic cholangiocarcinoma, primary biliary cirrhosis and bile microbiota, so as to further illuminate the pathogenesis of NAFLD and biliary tract diseases, obtain better diagnostic and therapeutic outcomes on NAFLD and biliary tract diseases.
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Objective@#To investigate the association between hepatic controlled attenuation parameter (CAP) and metabolic syndrome (MetS) and the correlation of CAP and its changes with the incidence of MetS.@*Methods@#A total of 2461 subjects who underwent physical examination from July 2013 to September 2015 were enrolled. Spearman correlation analysis was used to investigate the correlation of CAP with the number of MetS components and each MetS component, and the chi-square test was used to investigate the prevalence rates of MetS and each component under different CAP levels. Logistic regression analysis was used to analyze the odds ratio (95% confidence interval (CI)) of MetS under different CAP levels. A total of 230 subjects without baseline MetS were selected; in a prospective cohort study, these subjects were divided into groups according to the baseline CAP, change in CAP, and percent change in CAP, and the chi-square test was performed to compare the incidence of MetS. The Cox regression analysis was used to analyze the values of baseline CAP, change in CAP, and percent change in CAP in predicting MetS.@*Results@#CAP was positively correlated with the number of MetS components (r = 0.309, P < 0.01) and significantly correlated with all components. There were significant differences in the prevalence rates of MetS and its components under different CAP levels (< 238 dB/m, 238-258 dB/m, 259-291 dB/m, and ≥292 dB/m) (P < 0.05). After the adjustment for sex and age, with < 238 dB/m as a reference, the odds ratios (95% CI) of MetS in patients with CAP levels of 238-258 dB/m, 259-291 dB/m, and ≥292 dB/m were 1.784 (1.369-2.325), 2.936 (2.292-3.760), and 4.363 (3.435-5.543), respectively (all P < 0.05). Follow-up data showed that 28 patients (12.2%) developed MetS. After the adjustment for related factors, the hazard ratios (95% CI) of MetS in patients with baseline CAP > 238 dB/m, change in CAP > 30 dB/m, and percent change in CAP > 25.0% were 3.337 (1.163-9.569), 7.732 (2.453-24.366), and 11.656 (3.329-40.813), respectively (all P < 0.05).@*Conclusion@#CAP is closely associated with MetS and its components. CAP and its change can be used to predict the risk of MetS.
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Objective@#To investigate the serum lipidomic profile in patients with nonalcoholic fatty liver disease (NAFLD), and to analyze the lipid metabolism characteristics of NAFLD.@*Methods@#The subjects were divided into control group (23 patients) and pathologically confirmed NAFLD group (42 patients), and ultra-high-performance liquid chromatography-tandem mass spectrometry was used to measure serum lipidomic metabolites. The partial least squares-discriminant analysis (PLS-DA) model was established to analyze the differences in lipid metabolism with reference to the univariate analysis. The t-test and Mann-Whitney U test were used for data analysis.@*Results@#A total of 239 lipids were identified and qualitative and quantitative analyses were performed. The PLS-DA model (R2 = 0.753, Q2 = 0.456) and the univariate analysis showed that 77 lipids were metabolized differentially between the NAFLD group and the control group (VIP > 1, P < 0.05), including free fatty acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, lysophosphatidylcholine, lysophosphatidylinositol (LPI), choline plasmalogen (PlsCho), ethanolamine plasmalogen (PlsEtn), ceramide (Cer), sphingomyelin, and triglyceride (TG). Compared with the control group, the NAFLD group had significant increases in monounsaturated fatty acids (increased by 39%, t = -3.954, P < 0.05) and TGs (increased by 36%, Z = -2.662, P < 0.05), mainly TGs with low numbers of carbon atoms and unsaturated bonds, while there were reductions in TGs with high numbers of carbon atoms and unsaturated bonds. In addition, compared with the control group, the NAFLD group had significant increases in the levels of LPI (increased by 223%, t = -3.858, P < 0.05) and Cer (increased by 21%, t = -2.481, P < 0.05) and significant reductions in PlsCho (reduced by 18%, t = 3.184, P < 0.05) and PlsEtn (reduced by 20%, t = 2.363, P < 0.05).@*Conclusion@#There is a significant difference in lipid metabolism profile between NAFLD patients and healthy people, and a serum lipidomic analysis of NAFLD helps to further clarify the characteristics of lipid metabolism in patients with NAFLD.
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Nonalcoholic fatty liver disease (NAFLD) is a multi-system disease, and metabolic syndrome, type 2 diabetes, and NAFLD interact as both cause and effect. Deaths caused by cardiovascular diseases and malignant tumors are the adverse outcome of patients with NAFLD and nonalcoholic steatohepatitis (NASH), and increased deaths caused by liver disease is mainly seen in NASH patients. There is a causal relationship between NASH and hepatocellular carcinoma, and almost 50% of patients with NASH-associated hepatocellular carcinoma do not have liver cirrhosis. At present, cohort studies on the natural history of NAFLD in China should be enhanced in order to provide a basis for the development of health strategies and prevention and treatment measures. This editorial elaborates on the association of NAFLD with diabetes, cardiovascular disease, liver cirrhosis, and hepatocellular carcinoma from the perspective of clinical epidemiology, in order to emphasize the importance of the natural history of NAFLD.
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There is a close relationship of metabolic syndrome (MS) with chronic liver disease, especially fatty liver. There have been many studies on the clinical features, pathogenesis, diagnosis, and treatment of MS with fatty liver, but controversy still exists. This article reviews the latest progress and difficulties in the clinical studies of MS and related fatty liver, alcoholic liver disease, and chronic viral hepatitis, so as to help physicians improve the management of MS and fatty liver.
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Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease seen in patients with obesity, diabetes, and metabolic syndrome. Metabolic syndrome is an important predictor of the severe form of NAFLD, nonalcoholic steatohepatitis (NASH), and NASH patients with diabetes have an increased risk of liver cirrhosis and hepatocellular carcinoma. With the prevalence of obesity and diabetes around the world, NAFLD has become a global public health problem. NAFLD is not only one of the most important causes of liver-related disability and mortality, but also associated with the increasing incidence of diabetes and cardiovascular disease. The effective prevention and treatment of NAFLD is expected to reduce the burden of liver disease and cardiovascular disease. Therefore, this article overviews the advances in the diagnosis, prevention, and treatment of NAFLD.
Subject(s)
Humans , Carcinoma, Hepatocellular , Epidemiology , Cardiovascular Diseases , Epidemiology , Diabetes Mellitus , Epidemiology , Liver Cirrhosis , Epidemiology , Liver Neoplasms , Epidemiology , Metabolic Syndrome , Epidemiology , Non-alcoholic Fatty Liver Disease , Diagnosis , Epidemiology , Therapeutics , Obesity , Epidemiology , PrevalenceABSTRACT
Objective To investigate the effect and mechanism of AngⅡ on collagen in hepatic stellate cell. Methods HSCs were isolated and cultured, 3H-pro incorporation method was used to evaluate the effects of different doses of AngⅡ on the proline syntheses. RT-PCR assay were used to assess changes in mRNA expression levels of type Ⅰ and Ⅲ procollagen. PDGFR-β mRNA and protein were determined by in situ hybridization and immunocytochemistry. Results 10-8~ 10-5 mol/L AngⅡ could significantly increase the 3H-pro incorporation rate of HSC in a dose-dependent style, 10-6 mol/L AngⅡis the most effective dose. The cultured HSC showed a little expression of type Ⅰ and Ⅲ procollagen mRNAs, while 10-6 mol/L AngⅡwas able to enhance the expression for type Ⅰ and Ⅲ procollagen mRNAs significantly(P < 0.01). AngⅡalso could enhance both mRNA and protein expression of PDGFR-β on HSC(P < 0.01). Conclusion These results suggest that AngⅡ could promote HSC collagen synthesis by enhancing the expressions of PDGFR-β.