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Clinical perspectives,assessment,and mechanisms of metabolicassociated fatty liver disease in patients with COVID-19

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World Journal of Gastroenterology 2021年第33期27卷 5502-5519页

作者： Alejandro Campos-Murguía Berenice M Román-Calleja JoséA González-Regueiro Ivonne Hurtado-Díaz-de-León Alberto Adrián Solís-Ortega Nayelli C Flores-García Ignacio García-Juárez Astrid Ruiz-Margáin Ricardo Ulises Macías-Rodríguez Department of Gastroenterology Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico liver fibrosis and nutrition lab(LFNlab) MICTLÁN-Network(Mechanisms of Liver InjuryCell Death and Translational Nutrition in Liver Diseases-Research Network)Mexico City 14080Mexico

Metabolic diseases are highly prevalent worldwide and have been associated with adverse clinical outcomes,including mortality,in patients developing coronavirus disease(COVID-19).Because of the close relationship between metabolic diseases such as type 2 diabetes mellitus and obesity and the presence of metabolicassociated fatty liver disease(MAFLD),a high number of cases of patients affected by both MAFLD and COVID-19 would be expected,especially in highrisk *** studies have shown an increased risk of adverse clinical outcomes,viral shedding,and deep vein thrombosis,especially in patients with MAFLD-related liver *** predisposition to poor outcomes and severe acute respiratory syndrome coronavirus 2 infection in patients with MAFLD could be secondary to mechanisms common to both,including preexisting systemic chronic inflammation,endothelial dysfunction,and involvement of the renin-angiotensin *** of the increased risk of adverse outcomes,MAFLD should be screened in all patients admitted for *** computed tomography scans could be of help,assessment of liver fibrosis is also recommended,favoring noninvasive methods to limit the exposure of healthcare *** involvement in this population ranges from abnormalities in liver chemistry to hepatic steatosis in postmortem ***,preventive measures should be strongly advocated in patients already known to have MAFLD,including the use of telemedicine and vaccination in addition to general measures.

关键词： Metabolic-associated fatty liver disease COVID-19 Mortality fibrosis Histology Epidemiology

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nutritional therapy for hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2021年第10期13卷 1440-1452页

作者： Astrid Ruiz-Margáin Berenice M Román-Calleja Paulina Moreno-Guillén JoséA González-Regueiro DeyaniraKúsulas-Delint Alejandro Campos-Murguía Nayelli C Flores-García Ricardo Ulises Macías-Rodríguez liver nutrition Clinic Department of GastroenterologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico liver fibrosis and nutrition lab MICTLÁN-Network(Mechanisms of Liver InjuryCell Death and Translational Nutrition in Liver Diseases-Research Network)Mexico City 14080Mexico Department of Gastroenterology Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico

Hepatocellular carcinoma(HCC)is the most frequent primary liver cancer and presents together with cirrhosis in most *** addition to commonly recognized risk factors for HCC development,such as hepatitis B virus/hepatitis C virus infection,age and alcohol/tobacco consumption,there are nutritional risk factors also related to HCC development including high intake of saturated fats derived from red meat,type of cooking(generation of heterocyclic amines)and contamination of foods with *** the contrary,protective nutritional factors include diets rich in fiber,fruits and vegetables,n-3 polyunsaturated fatty acids and *** the patient is being evaluated for staging and treatment of HCC,special attention should be paid to nutritional support,including proper nutritional assessment and therapy by a multidisciplinary *** must be considered that these patients usually develop HCC on top of long-lasting cirrhosis,and therefore they could present with severe *** complications should be properly addressed and considered for nutritional *** addition to traditional methods,functional testing,phase angle and computed tomography scan derived skeletal muscle index-L3 are among the most useful tools for nutritional *** therapy should be centered on providing enough energy and protein to manage the increased requirements of both cirrhosis and *** with branched-chain amino acids is also recommended as it improves response to treatment,nutritional status and survival,and finally physical exercise must be encouraged and adapted to individual needs.

关键词： Sarcopenia liver Cancer Diet Branched-chain amino acids nutrition

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Serum ferritin in neonatal cholestasis: A specific and active molecule or a non-specific bystander marker?

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Hepatobiliary & Pancreatic Diseases International 2019年第2期18卷 173-180页

作者： Behairy El-Sayed Behairy Hatem Abd-Alsattar Konswa Hanaa Talaat Ahmed Dina Shehata El-Azab Nermin Mohamed Adawy Ahmad Mohamed Sira Department of Pediatric Hepatology Gastroenterology and Nutrition National Liver Institute Menofiya University Department of Pathology National Liver Institute Menofiya University

Background: Serum ferritin(SF) and consequently hepatic iron have long been considered important in liver fibrosis progression. They have been studied in different liver diseases with no previous reports in neonatal cholestasis(NC). This study aimed to measure SF in different etiologies of NC and investigate its relation to hepatic iron and fibrosis. Methods: SF was measured in 75 infants, including 50 with NC and 25 with sepsis. SF was compared between these two groups. Biochemical parameters, hepatic iron grades, and liver fibrosis and other histopathological characteristics and correlated with SF were assessed in NC group. Finally, a comparison between intrahepatic cholestasis and obstructive etiology was performed. Results: SF was elevated in NC(1598 ± 2405 ng/mL) with no significant difference from those with sepsis( P = 0.445). NC and sepsis constituted augmenting factors leading to more elevation of SF(2589 ± 3511 ng/mL). SF was significantly correlated with hepatic iron grades( r = 0.536, P liver fibrosis( P = 0.058). Conclusions: SF is non-specifically elevated in NC, with positive correlation to hepatic iron grades. SF ≥ 803.5 ng/mL can predict higher grades( ≥ grade 3) of hepatic iron. However, an active role of increased SF and hepatic iron in disease progression remains questionable.

关键词： Biliary atresia liver fibrosis Hepatic iron grade Intrahepatic cholestasis Iron

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Microbial metabolites in non-alcoholic fatty liver disease

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World Journal of Gastroenterology 2019年第17期25卷 2019-2028页

作者： Da Zhou Jian-Gao Fan Department of Gastroenterology and Hepatology Zhongshan HospitalFudan UniversityShanghai Institute of Liver Disease Center for Fatty liver Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Key Lab of Pediatric Gastroenterology and Nutrition

The prevalence of non-alcoholic fatty liver disease(NAFLD) is rising exponentially worldwide. The spectrum of NAFLD includes non-alcoholic fatty liver, non-alcoholic steatohepatitis, liver cirrhosis, and even hepatocellular carcinoma. Evidence shows that microbial metabolites play pivotal roles in the onset and progression of NAFLD. In this review, we discuss how microbederived metabolites, such as short-chain fatty acids, endogenous ethanol, bile acids and so forth, contribute to the pathogenesis of NAFLD.

关键词： Microbial metabolites Non-alcoholic steatohepatitis Short-chain fatty acids

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Efficacy of Intragastric Balloons in the Markers of Metabolic Dysfunction-associated Fatty liver Disease:Results from Meta-analyses

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Journal of Clinical and Translational Hepatology 2021年第3期9卷 353-363页

作者： Zi-Yuan Zou Jing Zeng Tian-Yi Ren Yi-Wen Shi Rui-Xu Yang Jian-Gao Fan Center for Fatty liver Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Key Lab of Pediatric Gastroenterology and NutritionShanghaiChina

Background and Aims:Nonalcoholic fatty liver disease,now renamed metabolic dysfunction-associated fatty liver disease(MAFLD),is common in obese *** balloon(IGB),an obesity management tool with low complication risk,might be used in MAFLD treatment but there is still unexplained heterogeneity in results across ***:We conducted a systematic search of 152 citations published up to September ***-analyses,stratified analyses,and meta-regression were performed to evaluate the efficacy of IGB on homeostasis model assessment of insulin resistance(HOMA-IR),alanine aminotransferase(ALT),aspartate aminotransferase(AST),and gamma-glutamyl transpeptidase(GGT),and to identify patients most appropriate for IGB ***:Thirteen observational studies and one randomized controlled trial met the inclusion criteria(624 participants in total).In the overall estimate,IGB therapy significantly improved the serum markers change from baseline to follow-up[HOMA-IR:1.56,95%confidence interval(CI)=1.16–1.95;ALT:11.53 U/L,95%CI=7.10–15.96;AST:6.79 U/L,95%CI=1.69–11.90;GGT:10.54 U/L,95%CI=6.32–14.75].In the stratified analysis,there were trends among participants with advanced age having less change in HOMA-IR(1.07 vs.1.82).The improvement of insulin resistance and liver biochemistries with swallowable IGB therapy was no worse than that with endoscopic *** meta-regression analyses showed that greater HOMA-IR loss was predicted by younger age(p=0.0107).Furthermore,effectiveness on ALT and GGT was predicted by basal ALT(p=0.0004)and GGT(p=0.0026),***:IGB is effective among the serum markers of *** patients had a greater decrease of HOMA-IR after IGB therapy.

关键词： Intragastric balloon Nonalcoholic fatty liver disease Insulin resistance Age groups Treatment outcome

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Chronic hepatitis B infection with concomitant hepatic steatosis:Current evidence and opinion

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World Journal of Gastroenterology 2021年第26期27卷 3971-3983页

作者： Yi-Wen Shi Rui-Xu Yang Jian-Gao Fan Center for Fatty liver Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Key Lab of Pediatric Gastroenterology and NutritionShanghai 200092China

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 *** risk of dual etiologies,outcome,and mechanism of CHB with concomitant NAFLD have not been fully *** 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 *** also explored the possible roles of hepatitis B virus in the development of steatosis and discussed difficultiesof histological *** CHB patients,it is important to address concomitant NAFLD through lifestyle management and disease screening to achieve better *** assessment of progressive changes and novel therapies for CHB patients concomitant with NAFLD deserve further research.

关键词： Nonalcoholic fatty liver disease Hepatitis B Metabolic disorders Steatosis Mechanism Disease burden

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Noninvasive biomarkers in non-alcoholic fatty liver disease:Current status and a glimpse of the future

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World Journal of Gastroenterology 2014年第31期20卷 10851-10863页

作者： Emer Fitzpatrick Anil Dhawan Paediatric liver GI and Nutrition Centre King’s College London School of Medicine at King’s College Hospital

The development of non invasive biomarkers of disease has become a major focus of interest in nonalcoholic fatty liver disease(NAFLD). The large prevalence of the disease and the invasive nature of the investigation means that screening with liver biopsy is *** addition to screening, the differentiation of those with simple steatosis vs steatohepatitis and fibrosis is clinically important as the prognosis of each *** biomarkers may be a combination of simple markers derived from large data sets or direct markers of disease activity. Serum markers of inflammation,apoptosis and oxidative stress in addition to fibrosis have been extensively studied in patients with *** techniques such as transient elastography,magnetic resonance elastography and acoustic radiation force imaging are becoming more established as noninvasive methods of detecting fibrosis in a variety of chronic liver conditions in addition to NAFLD. Newer high throughput methods such as proteomics and glycomics allow the nonhypothesis-driven identification of novel markers and may also potentially contribute to our understanding of the pathogenesis of the *** review addresses some of the methodological issues which need to be considered in the search for the ideal biomarker. It is likely that a combination of serum biomarkers and techniques such as transient elastography may provide the optimal diagnostic discrimination however this remains to be proven in large studies.

关键词： Noninvasive biomarkers Nonalcoholic fatty liver disease fibrosis

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SOX9 in biliary atresia: New insight for fibrosis progression

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Hepatobiliary & Pancreatic Diseases International 2021年第2期20卷 154-162页

作者： Hanaa Ahmed El-Araby Magdy Anwar Saber Noha Mohamed Radwan Doha Maher Taie Nermin Mohamed Adawy Ahmad Mohamed Sira Department of Pediatric Hepatology Gastroenterologyand NutritionNational Liver InstituteMenoufia University32511 Shebin El-koomMenoufiaEgypt Department of Pathology National Liver InstituteMenoufia University32511 Shebin El-koomMenoufiaEgypt

Background:liver fibrosis is a hallmark determinant of morbidity in biliary atresia(BA)even in successfully operated *** factors for this rapid progression of fibrosis are not completely *** expression of the transcription factor SOX9 and hepatic progenitor cells(HPCs)proliferation have roles in fibrogenesis in cholestatic ***,they were not investigated sufficiently in *** aimed to delineate the relation of SOX9 and HPCs to fibrosis and its progression in ***:Forty-eight patients with BA who underwent an initial diagnostic liver biopsy(LB)and consequent intraoperative LB were recruited and compared to 28 cases with non-BA cholestasis that had an LB in their diagnostic *** fibrosis,tissue SOX9 and HPC expressions were studied in both BA and non-BA-cholestasis *** fibrosis,SOX9,and HPCs’dynamic changes in BA cases were *** of fibrosis and its progression to SOX9 and HPCs in BA was ***:SOX9 and HPCs in ductular reaction(DR)form were expressed in 100%of BA and their grades increased significantly in the second *** rapidly progressive fibrosis in BA,represented by fibrosis grade of the intraoperative LB,correlated significantly to SOX9-DR and HPC-DR at the diagnostic(r=0.420,P=0.003 and r=0.405,P=0.004,respectively)and the intraoperative(r=0.460,P=0.001 and r=0.467,P=0.001,respectively)*** the other hand,fibrosis,SOX9-DR,and HPC-DR were significantly lower in non-BA cases at a comparable age(Pfibrosis in BA is rapidly progressive within a short time and is significantly correlated to SOX9 and *** of targeting SOX9 and HPCs on fibrosis progression is warranted.

关键词： Biliary atresia fibrosis Hepatic progenitor cells Immunohistochemistry Neonatal cholestasis SOX9

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Trimethylamine N-oxide attenuates high-fat high-cholesterol dietinduced steatohepatitis by reducing hepatic cholesterol overload in rats

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World Journal of Gastroenterology 2019年第20期25卷 2450-2462页

作者： Ze-Hua Zhao Feng-Zhi Xin Da Zhou Ya-Qian Xue Xiao-Lin Liu Rui-Xu Yang Qin Pan Jian-Gao Fan Center for Fatty liver Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China CAS Key laboratory of nutrition Metabolism and Food SafetyShanghai Institute of Nutrition and HealthShanghai Institutes for Biological SciencesUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China Shanghai Key lab of Pediatric Gastroenterology and nutrition Shanghai 200092China

BACKGROUND Trimethylamine N-oxide (TMAO) has been shown to be involved in cardiovascular disease (CVD). However, its role in nonalcoholic steatohepatitis (NASH) is unknown. AIM To determine the effect of TMAO on the progression of NASH. METHODS A rat model was induced by 16-wk high-fat high-cholesterol (HFHC) diet feeding and TMAO was administrated by daily oral gavage for 8 wk. RESULTS Oral TMAO intervention attenuated HFHC diet-induced steatohepatitis in rats. Histological evaluation showed that TMAO treatment significantly alleviated lobular inflammation and hepatocyte ballooning in the livers of rats fed a HFHC diet. Serum levels of alanine aminotransferase and aspartate aminotransferase were also decreased by TMAO treatment. Moreover, hepatic endoplasmic reticulum (ER) stress and cell death were mitigated in HFHC diet-fed TMAOtreated rats. Hepatic and serum levels of cholesterol were both decreased by TMAO treatment in rats fed a HFHC diet. Furthermore, the expression levels of intestinal cholesterol transporters were detected. Interestingly, cholesterol influxrelated Niemann-Pick C1-like 1 was downregulated and cholesterol efflux-related ABCG5/8 were upregulated by TMAO treatment in the small intestine. Gut microbiota analysis showed that TMAO could alter the gut microbial profile and restore the diversity of gut flora. CONCLUSION These data suggest that TMAO may modulate the gut microbiota, inhibit intestinal cholesterol absorption, and ameliorate hepatic ER stress and cell death under cholesterol overload, thereby attenuating HFHC diet-induced steatohepatitis in rats. Further studies are needed to evaluate the influence on CVD and define the safe does of TMAO treatment.

关键词： Gut microbiota Trimethylamine N-oxide Nonalcoholic steatohepatitis Endoplasmic reticulum stress Cholesterol

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Etiology and management of liver injury in patients with COVID-19

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World Journal of Gastroenterology 2020年第32期26卷 4753-4762页

作者： Rui-Xu Yang Rui-Dan Zheng Jian-Gao Fan Center for Fatty liver Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Diagnosis and Treatment Center for liver Diseases Zhengxing HospitalZhangzhou 363000Fujian ProvinceChina Center for Fatty liver Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Key Lab of Pediatric Gastroenterology and NutritionShanghai 200092China

The outbreak of novel coronavirus disease 2019(COVID-19)has resulted in global *** the expansion of related research,in addition to respiratory symptoms,digestive system involvement such as nausea,vomiting,and diarrhea have also been reported with ***,abnormal liver function is also frequent in biochemical tests of COVID-19 patients,which is correlated with the severity and mortality of the disease *** 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 *** 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 *** article reviews the epidemiological characteristics,etiology,management,and preventive strategies for liver injury in patients with COVID-19.

关键词： COVID-19 SARS-CoV-2 Coronavirus liver injury Function test,liver Etiology

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