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1.
Metabolism ; : 154911, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34648769

RESUMO

BACKGROUND: A significant proportion of the non-alcoholic fatty liver disease (NAFLD) population is non-obese. Prior studies reporting the severity of NAFLD amongst non-obese patients were heterogenous. Our study, using data from the largest biopsy-proven NAFLD international registry within Asia, aims to characterize the demographic, metabolic and histological differences between non-obese and obese NAFLD patients. METHODS: 1812 biopsy-proven NAFLD patients across nine countries in Asia assessed between 2006 and 2019 were pooled into a curated clinical registry. Demographic, metabolic and histological differences between non-obese and obese NAFLD patients were evaluated. The performance of Fibrosis-4 index for liver fibrosis (FIB-4) and NAFLD fibrosis score (NFS) to identify advanced liver disease across the varying obesity subgroups was compared. A random forest analysis was performed to identify novel predictors of fibrosis and steatohepatitis in non-obese patients. FINDINGS: One-fifth (21.6%) of NAFLD patients were non-obese. Non-obese NAFLD patients had lower proportions of NASH (50.5% vs 56.5%, p = 0.033) and advanced fibrosis (14.0% vs 18.7%, p = 0.033). Metabolic syndrome in non-obese individuals was associated with NASH (OR 1.59, 95% CI 1.01-2.54, p = 0.047) and advanced fibrosis (OR 1.88, 95% CI 0.99-3.54, p = 0.051). FIB-4 performed better than the NFS score (AUROC 81.5% vs 73.7%, p < 0.001) when classifying patients with F2-4 fibrosis amongst non-obese NAFLD patients. Haemoglobin, GGT, waist circumference and cholesterol are additional variables found on random forest analysis useful for identifying non-obese NAFLD patients with advanced liver disease. CONCLUSION: A substantial proportion of non-obese NAFLD patients has NASH or advanced fibrosis. FIB-4, compared to NFS better identifies non-obese NAFLD patients with advanced liver disease. Serum GGT, cholesterol, haemoglobin and waist circumference, which are neither components of NFS nor FIB-4, are important biomarkers for advanced liver disease in non-obese patients.

2.
Liver Int ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34619026

RESUMO

BACKGROUND: Despite substantial attention paid to the epidemic of nonalcoholic fatty liver disease (NAFLD) in adults, data on the burden and sexual dimorphism of NAFLD in Asian children have not yet been synthesized. METHODS: We conducted a literature search of 735 references up to April 2021. Pooled analyses, stratified analyses, and meta-regression were all performed. RESULTS: Thirty-three study populations were finally included. Nine of them comprising 20595 children showed an overall NAFLD prevalence of 5.53% (95% CI 3.46%-8.72%), in which, 36.64% (95% CI, 27.99%-46.26%) NAFLD subjects had elevated levels of ALT. The prevalence rate of NAFLD increased about 1.6-fold from 2004-2010 to the last decade. Male predominant trends were observed in pediatric NAFLD (boys: 8.18%, 95% CI 4.93%-13.26%; girls: 3.60%, 95% CI 1.60%-7.87%). Moreover, meta-analysis showed that after age 10 years, boys were more prone to have NAFLD than girls (OR=1.75; P = 0.0012). In addition, , the pooled prevalence of NAFLD increased sequentially in normal-weight (1.49%, 95% CI 0.88%-2.51%, n=2610 ), overweight (16.72%,95% CI 7.07%-34.65%,n=1265 ), and obese children (50.13%,95% CI 41.99%-58.27%, n=6434 individuals). After full covariate adjustment, the multivariate meta-regression also showed that boy percentage (p=0.0396) and body mass index (p<0.0001) were positively correlated with prevalent NAFLD. CONCLUSIONS: In Asia, pediatric NAFLD is becoming prevent over the recent decades, particularly among obese children and boys after 10 years old. The hormonal and chromosomal origins of pediatric NAFLD dimorphism need further investigation.

3.
Acta Pharmacol Sin ; 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34341511

RESUMO

Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease that is increasingly prevalent worldwide. Liver inflammation is an important contributor to disease progression from nonalcoholic fatty liver (NAFL) to NASH, but there is a lack of efficient therapies. In the current study we evaluated the therapeutic potential of givinostat, a histone deacetylase (HDAC) inhibitor, in the treatment of NASH in vivo and in vitro. Liver inflammation was induced in mice by feeding a methionine- and choline-deficient diet (MCD) or a fructose, palmitate, cholesterol diet (FPC). The mice were treated with givoinostat (10 mg·kg-1·d-1, ip) for 8 or 10 weeks. At the end of the experiment, the livers were harvested for analysis. We showed that givoinostat administration significantly alleviated inflammation and attenuated hepatic fibrosis in MCD-induced NASH mice. RNA-seq analysis of liver tissues form MCD-fed mice revealed that givinostat potently blocked expression of inflammation-related genes and regulated a broad set of lipid metabolism-related genes. In human hepatocellular carcinoma cell line HepG2 and human derived fetal hepatocyte cell line L02, givinostat significantly decreased palmitic acid-induced intracellular lipid accumulation. The benefit of givinostat was further confirmed in FPC-induced NASH mice. Givinostat administration significantly attenuated hepatic steatosis, inflammation as well as liver injury in this mouse model. In conclusion, givinostat is efficacious in reversing diet-induced NASH, and may serve as a therapeutic agent for the treatment of human NASH.

4.
J Dig Dis ; 22(9): 536-544, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34374198

RESUMO

OBJECTIVES: The accelerated shedding of extracellular domains of syndecan-4 (SDC4) is associated with central obesity and insulin resistance, while the association between serum SDC4 and nonalcoholic fatty liver disease (NAFLD) is unknown. We aimed to examine the association between SDC4 and NAFLD. METHODS: Adults undergoing a health examination from 1 June 2019 to 31 December 2019 were enrolled. A diagnosis of NAFLD was made with an abdominal ultrasound. Logistic regression models and the receiver operating characteristic (ROC) curves were used to evaluate the role of SDC4 in predicting NAFLD. RESULTS: In total, 533 eligible participants were finally enrolled, among them 157 (29.46%) had NAFLD. The proportion of patients with NAFLD increased with the increasing quartiles of serum SDC4. With the increase of serum SDC4 levels, metabolic features including waist circumference, serum triglyceride, total cholesterol, fasting blood glucose, fasting insulin and homeostasis model assessment of insulin resistance were significantly increased. SDC4 was an independent factor for NAFLD (odds ratio 1.963, 95% confidence interval [CI] 1.628-2.367, P < 0.001). The area under the ROC curve of SDC4 for predicting NAFLD was 0.934 (95% CI 0.910-0.959). The optimal cut-off value was 6.575 ng/mL at Youden's index of 0.767. SDC4 had the highest diagnostic sensitivity (84.1%), positive predictive value (82.5%), negative predictive value (93.3%) and positive likelihood ratio (11.356) among all the variables. CONCLUSIONS: Elevated serum SDC4 level is associated with metabolic disorders and the prevalence of NAFLD among general population. Serum SDC4 may serve as a biomarker of NAFLD.

5.
Curr Opin Pharmacol ; 60: 170-176, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34455284

RESUMO

Despite the rising health burden of metabolic (dysfunction) associated fatty liver disease (MAFLD), there are no approved pharmacotherapies for MAFLD currently. This situation led to a significant escalation in drug development and randomized controlled trials for MAFLD, particularly as novel information about its molecular pathogenesis unfolds. Currently, there are numerous investigational candidate drugs for MAFLD in various stages of clinical development that act on different pathophysiological processes, such as metabolism/steatosis, inflammation or fibrosis. Here, we provide an update on drug development for the treatment of MAFLD and discuss the prospects and challenges for improving and accelerating the nonalcoholic fatty liver disease drug discovery pipeline.

6.
World J Gastroenterol ; 27(25): 3863-3876, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34321850

RESUMO

BACKGROUND: The association between PPARGC1A rs8192678 and nonalcoholic fatty liver disease (NAFLD) requires further confirmation. In addition, it is still unknown whether PPARGC1A rs8192678 is associated with hepatic histological features in NAFLD in the Chinese population. AIM: To investigate the interaction between PPARGC1A rs8192678 and nonalcoholic steatohepatitis (NASH), and whether this polymorphism is associated with hepatic histological features. METHODS: Fifty-nine patients with liver biopsy-proven NAFLD and 93 healthy controls were recruited to a cohort representing the Chinese Han population. The SAF (steatosis, activity, and fibrosis) scoring system was used for hepatic histopathological evaluation. The polymorphisms of PPARGC1A rs8192678 and patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 were genotyped. The intrahepatic mRNA expression of PPARGC1A was evaluated by real-time polymerase chain reaction. RESULTS: Thirty-seven patients with NAFLD had NASH, of which 12 were nonobese. The PPARGC1A rs8192678 risk A allele (carrying GA and AA genotypes) had the lowest P value in the dominant model; the odds ratio (OR) for NAFLD was 2.321 [95% confidence interval (CI): 1.121-4.806]. After adjusting for age, sex, and the PNPLA3 rs738409 risk G allele, the PPARGC1A rs8192678 A allele was a risk factor for NAFLD (OR 2.202, 95%CI: 1.030-4.705, P = 0.042). The genetic analysis showed that patients with NAFLD, moderate-to-severe steatosis (S2-3), and Activity 2-4 (A ≥ 2) were more likely to carry A in PPARGC1A rs8192678 (OR 5.000, 95%CI: 1.343-18.620, P = 0.012; and OR 4.071, 95%CI: 1.076-15.402, P = 0.031). The multivariate logistic regression analysis showed that PPARGC1A rs8192678 risk A allele was also independently associated with S2-3, A ≥ 2, and NASH (OR 6.190, 95%CI: 1.508-25.410, P = 0.011; OR 4.506, 95%CI 1.070-18.978, P = 0.040; and OR 6.337, 95%CI: 1.135-35.392, P = 0.035, respectively) after adjusting for age, sex, body mass index, and PNPLA3 rs738409 risk G allele. The results also showed that this polymorphism was associated with nonobese NASH (OR 22.000, 95%CI: 1.540-314.292, P = 0.021). The intrahepatic expression of PPARGC1A mRNA was significantly lower in the group of patients who carried the risk A allele (P = 0.014). CONCLUSION: The PPARGC1A rs8192678 risk A allele is associated with NAFLD, and with S2-3, A ≥ 2 and NASH in NAFLD patients, independent of PNPLA3 rs738409, and may be associated with nonobese NASH.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Predisposição Genética para Doença , Humanos , Lipase/genética , Fígado/metabolismo , Proteínas de Membrana/genética , Hepatopatia Gordurosa não Alcoólica/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Polimorfismo de Nucleotídeo Único
7.
World J Gastroenterol ; 27(26): 3971-3983, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34326608

RESUMO

With the increasing incidence of obesity and metabolic syndrome worldwide, concomitant nonalcoholic fatty liver disease (NAFLD) in patients with chronic hepatitis B (CHB) has become highly prevalent. The risk of dual etiologies, outcome, and mechanism of CHB with concomitant NAFLD have not been fully characterized. In this review, we assessed the overlapping prevalence of metabolic disorders and CHB, assessed the risk of advanced fibrosis/hepatocellular carcinoma in CHB patients concomitant with NAFLD, and discussed the remaining clinical issues to be addressed in the outcome of such patients. We also explored the possible roles of hepatitis B virus in the development of steatosis and discussed difficultiesof histological evaluation. For CHB patients, it is important to address concomitant NAFLD through lifestyle management and disease screening to achieve better prognoses. The assessment of progressive changes and novel therapies for CHB patients concomitant with NAFLD deserve further research.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Carcinoma Hepatocelular/epidemiologia , Vírus da Hepatite B , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/epidemiologia , Humanos , Neoplasias Hepáticas/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia
8.
Artigo em Inglês | MEDLINE | ID: mdl-34229038

RESUMO

BACKGROUND & AIMS: Despite rapidly increasing nonalcoholic fatty liver disease (NAFLD) prevalence, providers' knowledge may be limited. We assessed NAFLD knowledge and associated factors among physicians of different specialties globally. METHODS: NAFLD knowledge surveys containing 54 and 59 questions covering 3 domains (epidemiology/pathogenesis, diagnostics, and treatment) were completed electronically by hepatologists, gastroenterologists (GEs), endocrinologists (ENDOs), and primary care physicians (PCPs) from 40 countries comprising 5 Global Burden of Disease super-regions. Over 24 months, 2202 surveys were completed (488 hepatologists, 758 GEs, 148 ENDOs, and 808 PCPs; 50% high-income Global Burden of Disease super-region, 27% from North Africa and Middle East, 12% Southeast Asia, and 5% South Asian and Latin America). RESULTS: Hepatologists saw the greatest number of NAFLD patients annually: median 150 (interquartile range, 60-300) vs 100 (interquartile range, 35-200) for GEs, 100 (interquartile range, 30-200) for ENDOs, and 10 (interquartile range, 4-50) for PCPs (all P < .0001). The primary sources of NAFLD knowledge acquisition for hepatologists were international conferences (33% vs 8%-26%) and practice guidelines for others (39%-44%). The Internet was the second most common source of NAFLD knowledge for PCPs (28%). NAFLD knowledge scores were higher for hepatologists than GEs: epidemiology, 62% vs 53%; diagnostics, 80% vs 73%; and treatment, 61% vs 58% (P < .0001), and ENDOs scores were higher than PCPs: epidemiology, 70% vs 60%; diagnostics, 71% vs 64%; and treatment, 79% vs 68% (P < .0001). Being a hepatologist or ENDO was associated with higher knowledge scores than a GE or PCP, respectively (P < .05). Higher NAFLD knowledge scores were associated independently with a greater number of NAFLD patients seen (P < .05). CONCLUSIONS: Despite the growing burden of NAFLD, a significant knowledge gap remains for the identification, diagnosis, and management of NAFLD.

9.
Hepatobiliary Pancreat Dis Int ; 20(5): 426-432, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34246549

RESUMO

BACKGROUND: This study aimed to assess the association between metabolic syndrome (MetS) and severity of nonalcoholic fatty liver disease (NAFLD), and to discuss the pathological relevance of the diagnostic criteria in metabolic (dysfunction) associated fatty liver disease (MAFLD). METHODS: This was a multicenter, cross-sectional study. Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China. Anthropometric and metabolic parameters were collected to assess the pathological relevance. RESULTS: Of 246 enrolled patients with NAFLD, 150 (61.0%) had the comorbidity of MetS. With the increase of metabolic components, the proportions of nonalcoholic steatohepatitis (NASH) and significant fibrosis were notably increased. The comorbid three metabolic components significantly increased the proportion of NASH, and further increase of metabolic components did not increase the proportion of NASH. However, the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis. Among the 246 patients, 239 (97.2%) met the diagnostic criteria of MAFLD. Although non-MAFLD patients had less NASH, they present with similar proportion of significant fibrosis and cirrhosis. In the diagnostic criteria of MAFLD, BMI ≥ 23 kg/m2 was related to NASH (Mantel-Haenszel Common Estimate OR: 2.975; 95% CI: 1.037-8.538; P = 0.043), and T2DM was related to significant fibrosis (Mantel-Haenszel Common Estimate OR: 2.531; 95% CI: 1.388-4.613; P = 0.002). The homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 2.5 was the most significant factor for NASH (OR: 4.100; 95% CI: 1.772-9.487; P = 0.001) and significant factor for liver fibrosis (OR: 2.947; 95% CI: 1.398-6.210; P = 0.004) after the adjustments of the BMI and diabetes. CONCLUSIONS: Metabolic dysregulations are important risk factors in NAFLD progression. The insulin resistance status may play a predominant role in the progression in MAFLD patients.

10.
Hepatobiliary Pancreat Dis Int ; 20(5): 416-425, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34275749

RESUMO

BACKGROUND: Although concomitant nonalcoholic steatohepatitis (NASH) is common in chronic hepatitis B (CHB), the impact of viral factors on NASH and the outcome of CHB patients concomitant with NASH remain unclear. We aimed to investigate the outcomes of NASH in CHB patients receiving antiviral treatment. METHODS: In the post-hoc analysis of a multicenter trial, naïve CHB patients receiving 72-week entecavir treatment were enrolled. We evaluated the biochemical, viral and histopathological responses of these patients. The histopathological features of NASH were also evaluated, using paired liver biopsies at baseline and week 72. RESULTS: A total of 1000 CHB patients were finally enrolled for analysis, with 18.2% of whom fulfilling the criteria of NASH. A total of 727 patients completed entecavir antiviral treatment and received the second biopsy. Serum HBeAg loss, HBeAg seroconversion and HBV-DNA undetectable rates were similar between patients with or without NASH (P > 0.05). Among patients with NASH, the hepatic steatosis, ballooning, lobular inflammation scores and fibrosis stages all improved during follow-up (all P < 0.001), 46% (63/136) achieved NASH resolution. Patients with baseline body mass index (BMI) ≥ 23 kg/m2 (Asian criteria) [odds ratio (OR): 0.414; 95% confidence interval (95% CI): 0.190-0.899; P = 0.012] and weight gain (OR: 0.187; 95% CI: 0.050-0.693; P = 0.026) were less likely to have NASH resolution. Among patients without NASH at baseline, 22 (3.7%) developed NASH. Baseline BMI ≥ 23 kg/m2 (OR: 12.506; 95% CI: 2.813-55.606; P = 0.001) and weight gain (OR: 5.126; 95% CI: 1.674-15.694; P = 0.005) were predictors of incident NASH. CONCLUSIONS: Lower BMI and weight reduction but not virologic factors determine NASH resolution in CHB. The value of weight management in CHB patients during antiviral treatment deserves further evaluation.

11.
Cell Mol Gastroenterol Hepatol ; 12(3): 857-871, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33989817

RESUMO

BACKGROUND AND AIMS: Butyric acid is an intestinal microbiota-produced short-chain fatty acid, which exerts salutary effects on alleviating nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanism of butyrate on regulating hepatic lipid metabolism is largely unexplored. METHODS: A mouse model of NAFLD was induced with high-fat diet feeding, and sodium butyrate (NaB) intervention was initiated at the eighth week and lasted for 8 weeks. Hepatic steatosis was evaluated and metabolic pathways concerning lipid homeostasis were analyzed. RESULTS: Here, we report that administration of NaB by gavage once daily for 8 weeks causes an augmentation of insulin-induced gene (Insig) activity and inhibition of lipogenic gene in mice fed with high-fat diet. Mechanistically, NaB is sufficient to enhance the interaction between Insig and its upstream kinase AMP-activated protein kinase (AMPK). The stimulatory effects of NaB on Insig-1 activity are abolished in AMPKα1/α2 double knockout (AMPK-/-) mouse primary hepatocytes. Moreover, AMPK activation by NaB is mediated by LKB1, as evidenced by the observations showing NaB-mediated induction of phosphorylation of AMPK, and its downstream target acetyl-CoA carboxylase is diminished in LKB1-/- mouse embryonic fibroblasts. CONCLUSIONS: These studies indicate that NaB serves as a negative regulator of hepatic lipogenesis in NAFLD and that NaB attenuates hepatic steatosis and improves lipid profile and liver function largely through the activation of LKB1-AMPK-Insig signaling pathway. Therefore, NaB has therapeutic potential for treating NAFLD and related metabolic diseases.

12.
Health Qual Life Outcomes ; 19(1): 140, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33962617

RESUMO

BACKGROUND: Health Related Quality of Life (HRQL) is a multi-dimensional construct that can comprehensively evaluate the patient's health status, including physical, emotional, mental and social well-being. In this study, we aimed to evaluate the impact of non-alcoholic fatty liver disease (NAFLD) on HRQL in a Chinese population. METHODS: In this national multicenter cross-sectional survey, patients with NAFLD were enrolled. Chronic Liver Disease Questionnaire (CLDQ)-NAFLD was used to qualify HRQL. Univariate and multivariate analysis were used to identify independent risk factors of HRQL. RESULTS: A total of 5181 patients with NAFLD from 90 centers were enrolled in this study (mean age, 43.8 ± 13.3 years; male, 65.8%). The overall CLDQ score was 5.66 ± 0.89. Multivariate logistic regression analysis showed that body mass index (BMI: HR, 1.642; 95% CI, 1.330-2.026), alanine transaminase (ALT: HR, 1.006; 95% CI, 1.001-1.011), triglyceride (HR, 1.184; 95% CI, 1.074-1.305), disease severity (HR, 3.203; 95% CI, 1.418-7.232) and cardiovascular disease (HR, 4.305; 95% CI, 2.074-8.939) were independent risk factors for overall CLDQ score. In the logistic analyses of individual domain, BMI and triglyceride were independent risk factors of all domains. ALT, disease severity, diabetes, depression and cardiovascular disease were influencing factors for the CLDQ score of several domains. CONCLUSIONS: This national multicenter cross-sectional survey in China indicated that the HRQL in patients with NAFLD was impaired. HRQL was found to be significantly associated with sociodemographic and clinical factors. Attention should be paid to the optimally managing care of patients with NAFLD to improve their HRQL.


Assuntos
Grupo com Ancestrais do Continente Asiático/psicologia , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Nível de Saúde , Hepatopatia Gordurosa não Alcoólica/psicologia , Qualidade de Vida/psicologia , Índice de Gravidade de Doença , Inquéritos e Questionários/normas , Adolescente , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
13.
Clin Transl Gastroenterol ; 12(4): e00323, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33848277

RESUMO

INTRODUCTION: To evaluate the diagnostic performance of ultrasound attenuation parameter (UAP) and liver stiffness measurement (LSM) by FibroTouch for diagnosis of hepatic steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: We recruited 237 patients undergoing FibroTouch and liver biopsy within 2 weeks. The pathological findings of liver biopsy were scored by Nonalcoholic Steatohepatitis Clinical Research Network, and the diagnostic accuracy of UAP for steatosis and LSM for fibrosis was evaluated by area under the receiver operating characteristic curve (AUROC). The impacts of histological parameters on UAP and LSM were analyzed, and diagnostic performance of FibroTouch UAP and LSM was compared with other noninvasive biomarkers. RESULTS: The success rate of FibroTouch examination was 96.51%. The AUROC of UAP for diagnosis of steatosis ≥S1, ≥S2, and S3 was 0.88, 0.93, and 0.88, and the cutoff values were 244, 269, and 296 dB/m, respectively. The AUROC of LSM for the diagnosis of fibrosis stages ≥F2, ≥F3, and F4 was 0.71, 0.71, and 0.77, and the cutoff values were 9.4, 9.4, and 11 kPa, respectively. Multiple regression analysis showed that LSM was positively correlated with degree of fibrosis and NAFLD activity score. UAP was positively correlated with liver steatosis. The diagnostic performance of UAP for steatosis was significantly superior to that of the hepatic steatosis index. DISCUSSION: FibroTouch has a low failure rate with moderate to high diagnostic performance for discriminating the steatosis degree and fibrosis stage and is suitable for clinical evaluation and monitoring of patients with NAFLD.


Assuntos
Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/patologia , Ultrassonografia/métodos , Adulto , Área Sob a Curva , Biomarcadores , Biópsia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
15.
J Gastroenterol Hepatol ; 36(7): 1754-1768, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33569851

RESUMO

BACKGROUND AND AIM: There is debate among the hepatology community regarding the simple non-invasive scoring systems and histological scores (even it was developed for histological classification) in predicting clinical outcomes in patients with non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether the presence of simple non-invasive scoring systems and histological scores could predict all-cause mortality, liver-related mortality, and liver disease decompensation (liver failure, cirrhosis, hepatocellular carcinoma, or decompensated liver disease). METHODS: The pooled hazard ratio of prognostic factors and incidence rate per 1000 person-years in patients with NAFLD was calculated and further adjusted by two different models of handling the duplicated data. RESULTS: A total of 19 longitudinal studies were included. Most simple non-invasive scoring systems (Fibrosis-4 Score, BARD, and aspartate aminotransferase-to-platelet ratio index ) and histological scores (NAFLD activity score, Brunt, and "steatosis, activity, and fibrosis" ) failed in predicting mortality, and only the NAFLD fibrosis score > 0.676 showed prognostic ability to all-cause mortality (four studies, 7564 patients, 118 352 person-years followed up, pooled hazard ratio 1.44, 95% confidence interval [CI] 1.05-1.96). The incidence rate per 1000 person-years of all-cause mortality, liver-related mortality, cardiovascular-related mortality, and liver disease decompensation resulted in a pooled incidence rate per 1000 person-years of 22.65 (14 studies, 95% CI 9.62-53.31), 3.19 (7 studies, 95% CI 1.14-8.93), 6.02 (6 studies, 95% CI 4.69-7.74), and 11.46 (4 studies, 95% CI 5.33-24.63), respectively. CONCLUSION: Non-alcoholic fatty liver disease fibrosis score showed promising prognostic value to all-cause mortality. Most present simple non-invasive scoring systems and histological scores failed to predict clinical outcomes.

16.
J Gastroenterol ; 56(1): 1-11, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33151407

RESUMO

The human gut microbiome (bacteria, fungi, viruses, and archaea) is a complex and diverse ecosystem. It plays an important role in human health, but is involved in several intestinal and extraintestinal diseases. Most research to date has focused on the role of bacteria, while studies focusing on fungi (also referred to as "mycobiome" or "fungome") are still in its infancy. In this review, we focus on the existing literature available about the gut mycobiome with an emphasis on compositional mycobiome changes associated with liver diseases, the impact on pathogenesis of disease, and its potential use as therapeutic targets. We also provide insights into current methodologies of studying mycobiome, and we highlight the interkingdom interactions in the context of disease and how they affect health of the host. Herein, by focusing on the gut mycobiome, this review provides novel insights and directions for liver research.

18.
Biomed Res Int ; 2020: 8869674, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33294458

RESUMO

Single-nucleotide polymorphisms (SNPs) of apolipoprotein C3 (APOC3) play important role in lipid metabolism, and dyslipidemia underlies nonalcoholic fatty liver disease (NAFLD). But the correlation of serum lipidomics, APOC3 SNPs, and NAFLD remains limited understood. Enrolling thirty-four biopsy-proven NAFLD patients from Tianjin, Shanghai, Fujian, we investigated their APOC3 genotype and serum lipid profile by DNA sequencing and ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), respectively. Scoring of hepatocyte steatosis, ballooning, lobular inflammation, and liver fibrosis was then performed to reveal the role of lipidomics-affecting APOC3 SNPs in NAFLD-specific pathological alterations. Here, we reported that APOC3 SNPs (rs4225, rs4520, rs5128, rs2070666, and rs2070667) intimately correlated to serum lipidomics in NAFLD patients. A allele instead of G allele at rs2070667, which dominated the SNPs underlying lipidomic alteration, exhibited downregulatory effect on triacylglycerols (TGs: TG 54 : 7, TG 54 : 8, and TG 56 : 9) containing polyunsaturated fatty acid (PUFA). Moreover, subjects with low-level PUFA-containing TGs were predisposed to high-grade lobular inflammation (TG 54 : 7, rho = -0.454 and P = 0.007; TG 54 : 8, rho = -0.411 and P =0.016; TG 56 : 9, rho = -0.481 and P = 0.004). The significant correlation of APOC3 rs2070667 and inflammation grading [G/G vs. G/A+A/A: 0.00 (0.00 and 1.00) vs. 1.50 (0.75 and 2.00), P = 0.022] further confirmed its pathological action on the basis of lipidomics-impacting activity. These findings suggest an inhibitory effect of A allele at APOC3 rs2070667 on serum levels of PUFA-containing TGs, which are associated with high-grade lobular inflammation in NAFLD patients.


Assuntos
Apolipoproteína C-III/genética , Predisposição Genética para Doença , Inflamação/sangue , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/genética , Polimorfismo de Nucleotídeo Único/genética , Triglicerídeos/sangue , Adulto , Regulação para Baixo/genética , Feminino , Estudos de Associação Genética , Humanos , Inflamação/patologia , Lipidômica , Masculino
19.
Hepatol Int ; 14(6): 889-919, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33006093

RESUMO

Metabolic associated fatty liver disease (MAFLD) is the principal worldwide cause of liver disease and affects nearly a quarter of the global population. The objective of this work was to present the clinical practice guidelines of the Asian Pacific Association for the Study of the Liver (APASL) on MAFLD. The guidelines cover various aspects of MAFLD including its epidemiology, diagnosis, screening, assessment, and treatment. The document is intended for practical use and for setting the stage for advancing clinical practice, knowledge, and research of MAFLD in adults, with specific reference to special groups as necessary. The guidelines also seek to improve patient care and awareness of the disease and assist stakeholders in the decision-making process by providing evidence-based data. The guidelines take into consideration the burden of clinical management for the healthcare sector.

20.
World J Gastroenterol ; 26(32): 4753-4762, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32921955

RESUMO

The outbreak of novel coronavirus disease 2019 (COVID-19) has resulted in global emergence. With the expansion of related research, in addition to respiratory symptoms, digestive system involvement such as nausea, vomiting, and diarrhea have also been reported with COVID-19. Besides, abnormal liver function is also frequent in biochemical tests of COVID-19 patients, which is correlated with the severity and mortality of the disease course. The etiology of liver injury in patients with COVID-19 might include viral immunologic injury, drug-induced liver injury, the systemic inflammatory response, hypoxic hepatitis, and the exacerbation of preexisting liver disease. Although liver injuries in COVID-19 are often transient and reversible, health workers need to pay attention to preexisting liver disease, monitor liver function, strengthen supportive treatment, and reduce the chance of drug-induced liver injury. This article reviews the epidemiological characteristics, etiology, management, and preventive strategies for liver injury in patients with COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Hepatopatias/virologia , Pneumonia Viral/complicações , COVID-19 , Infecções por Coronavirus/virologia , Gerenciamento Clínico , Feminino , Humanos , Fígado/virologia , Hepatopatias/epidemiologia , Testes de Função Hepática , Masculino , Pandemias , Pneumonia Viral/virologia , SARS-CoV-2
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