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Dominating expression of negative regulatory factors downmodulates major histocompatibility complex Class-Ⅱexpression on dendritic cells in chronic hepatitis C infection

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World Journal of Gastroenterology 2016年第22期22卷 5173-5182页

作者： Shallu Tomer Yogesh K Chawla ajay duseja Sunil K Arora Department of Immunopathology Postgraduate Institute of Medical Education and Research Department of Hepatology Postgraduate Institute of Medical Education and Research

AIM: To elucidate the molecular mechanisms leading to development of functionally impaired dendritic cells(DCs) in chronic hepatitis C(CHC) patients infected with genotype 3 ***: This prospective study was conducted on the cohorts of CHC individuals identified as responders or non-responders to antiviral therapy. Myeloid DCs were isolated from the peripheral blood of each subject using CD1c(BDCA1)+ DC isolation Kit. Monocytes from healthy donor were cultured with DC growth factors such as IL-4 and GM-CSF either in the presence or absence of hepatitis C virus(HCV) viral proteins followed by LPS stimulation. Phenotyping was done by flowcytometry and gene expression profiling was evaluated by real-time ***: Non-responders [sustained virological response(SVR)-ve] to conventional antiviral therapy had significantly higher expression of genes associated with interferon responsive element such as IDO1 and PD-L1(6-fold) and negative regulators of JAK-STAT pathway such as SOCS(6-fold) as compared to responders(SVR+ve) to antiviral therapy. The downregulated genes in non-responders included factors involved in antigen processing and presentation mainly belonging to major histocompatibility complex(MHC) Class-Ⅱ family as HLA-DP, HLA-DQ(2-fold) and superoxide dismutase(2-fold). Cells grown in the presence of HCV viral proteins had genes downregulated for factors involved in innate response, interferon signaling, DC maturation and co-stimulatory signaling to T-cells, while the genes for cytokine signaling and Toll-like receptors(4-fold) were upregulated as compared to cells grown in absence of viral ***: Underexpressed MHC class-Ⅱ genes and upregulated negative regulators in non-responders indicate diminished capacity to present antigen and may constitute mechanism of functionally defective state of DCs.

关键词： Dendritic cells Hepatitis C Non-responders Negative regulators Major histocompatibility complex Class-Ⅱ genes

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Chronic Liver Failure-Sequential Organ Failure Assessment is better than the Asia-Pacific Association for the Study of Liver criteria for defining acute-on-chronic liver failure and predicting outcome

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World Journal of Gastroenterology 2014年第40期20卷 14934-14941页

作者： Radha K Dhiman Swastik Agrawal Tarana Gupta ajay duseja Yogesh Chawla Department of Hepatology Postgraduate Institute of Medical Education and Research Chandigarh 160012 India

AIM: To compare the utility of the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) and Asia-Pacific Association for the Study of Liver (APASL) definitions of acute-on-chronic liver failure (ACLF)... 详细信息

关键词： Cirrhosis Acute decompensation Mortality Prognosis Acute on chronic liver failure

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Non-alcoholic fatty liver disease development:A multifactorial pathogenic phenomena

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Liver Research 2022年第2期6卷 72-83页

作者： Aamir Bashir ajay duseja Arka De Manu Mehta Pramil Tiwari Department of Pharmacy Practice National Institute of Pharmaceutical Education and ResearchS.A.S.NagarMohaliPunjabIndia Department of Hepatology Post Graduate Institute of Medical Education and ResearchChandigarhIndia

Non-alcoholic fatty liver disease(NAFLD),characterized by the accumulation of excessive intrahepatic fat,is a leading metabolic disorder also considered as the hepatic manifestation of metabolic syndrome(MS).Though more commonly observed in obese individuals and those with metabolic risk factors,it also develops in a considerable number of non-obese individuals as well as participants without having any component of *** basic mechanism involved in the development of fatty liver is the imbalance between lipid uptake,synthesis,and metabolism in the liver,normally controlled by several mechanisms to maintain lipid *** a complex progressive liver disorder,the NAFLD pathogenesis is multifactorial,and several new pathogenic phenomena were discovered over *** available literature suggests the role of both genetic and environmental factors and associated metabolic factors;however,the mechanism of progression is not completely *** this review,we discuss different pathogenic mechanisms and their interplay to provide an elaborate idea regarding NAFLD development and *** understanding of pathogenic mechanisms will be useful in finding new treatment for patients with NAFLD.

关键词： Metabolic syndrome(MS) Non-alcoholic fatty liver disease(NAFLD) Non-alcoholic steatohepatitis(NASH) Fatty liver Steatohepatitis Insulin resistance(IR) Lysosomal acid lipase(LAL)

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Genetic polymorphism in CD14 gene, a co-receptor of TLR4 associated with non-alcoholic fatty liver disease

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World Journal of Gastroenterology 2016年第42期22卷 9346-9355页

作者： Shweta Kapil ajay duseja Bal Krishan Sharma Bhupesh Singla Anuradha Chakraborti Ashim Das Pallab Ray Radha K Dhiman Yogesh Chawla Department of Hepatology Postgraduate Institute of Medical Education and Research Experimental Medicine and Biotechnology Postgraduate Institute of Medical Education and Research Histopathology Postgraduate Institute of Medical Education and Research Microbiology Postgraduate Institute of Medical Education and Research

AIM To evaluate the pathogenic role of toll-like receptor(TLR) gene polymorphisms in patients with nonalcoholic fatty liver disease(NAFLD).METHODS Two hundred and fifty subjects(NAFLD = 200, healthy volunteers = 50) underwent polymerase chain reaction and restriction fragment length polymorphism to assess one polymorphism in the toll-like receptor 2(TLR2) gene(A753G), two polymorphisms in the TLR4 gene(TLR4 Asp299 Gly and Thr399 Ile allele), and two polymorphisms in the cluster of differentiation 14(CD14)(C-159 T and C-550T) gene, a co-receptor of TLR4. Association of TLR gene polymorphisms with NAFLD and its severity was evaluated by genetic models of *** On both multiplicative and recessive models of gene polymorphism association, there was significant association of CD14 C(-159) T polymorphism with NAFLD; patients with TT genotype had a 2.6 fold increased risk of developing NAFLD in comparison to CC genotype. There was no association of TLR2 Arg753 Gln, TLR4 Asp299 Gly, Thr399 Ile, and CD14 C(-550) T polymorphisms with NAFLD. None of the TLR gene polymorphisms had an association with histological severity of *** Patients with CD14 C(-159) T gene polymorphism, a co-receptor of TLR4, have an increased risk of NAFLD development.

关键词： Non-alcoholic steatohepatitis Nonalcoholic fatty liver disease Toll-like receptors Obesity Cirrhosis Insulin resistance Bacterial overgrowth

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Clinical Validation of Global Coagulation Tests to Guide Blood Component Transfusions in Cirrhosis and ACLF

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Journal of Clinical and Translational Hepatology 2021年第2期9卷 210-219页

作者： Madhumita Premkumar Rohit Mehtani Smita Divyaveer Kamal Kajal Anand VKulkarni Syed Ahmed Harmanpreet Kaur Harpreet Kaur Radhakrishna Dhiman ajay duseja Arka De Departments of Hepatology Postgraduate Institute of Medical Education and ResearchChandigarhIndia Nephrology Postgraduate Institute of Medical Education and ResearchChandigarhIndia Anesthesia and Intensive CarePostgraduate Institute of Medical Education and ResearchChandigarhIndia Department of Hepatology Asian Institute of GastroenterologyHyderabadIndia Medicine Postgraduate Institute of Medical Education and ResearchChandigarhIndia

Background and Aims:Patients with cirrhosis and acuteon-chronic liver failure(ACLF)may have bleeding complications and need for invasive ***-of-care(POC)coagulation tests like thromboelastography(TEG)and Sonoclot may be better for guiding patient management than the standard coagulation tests(SCTs),like prothrombin time,platelet count and international normalized ***:We prospectively compared and validated the POC tests and SCTs in 70 persons with ACLF and 72 persons with decompensated cirrhosis who had clinical bleeding and checked for episodes of re-bleeding and transfusion *** assessed pre-procedure requirement of blood components when correction was done based on an SCT or POC ***:Episodes of bleeding were seen in 45%and 28%of ACLF and cirrhosis patient,respectively(p=0.036),with the major site of bleeding being gastrointestinal(31%and 16%,respectively).Platelet counts correlated with TEG-maximum amplitude in cirrhosis(p=0.045)and prothrombin time correlated positively with TEG-reaction(R)time(p=0.032),TEG-Clot kinetics(K)time(p=0.042),Son-activated clotting time(p=0.038)and negatively with clot rate(p=0.043)in ACLF,making these correctable target variables in POC transfusion *** 223 procedures,transfusion of fresh frozen plasma and platelet concentrate was reduced by 25%(p=0.035)and 20.8%(p=0.045)by using a POC strategy in 76 *** of deranged Son-activated clotting time and TEG-reaction time was noted in 68%and 72%after 24 h of fresh frozen plasma transfusion in ACLF and 85%and 80%in cirrhosis,***:Our study clinically validates that POC tests can better detect coagulation defects and transfusion thresholds in ACLF and cirrhosis,whereas use of conventional tests appear to be less suitable in patients with clinical *** Registration:NCT04332484.

关键词： Coagulation Cirrhosis ACLF Validation Sonoclot Thromboelastography

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Indian patients with nonalcoholic fatty liver disease presenting with raised transaminases are different at presentation

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World Journal of Gastroenterology 2007年第4期13卷 649-650页

作者： ajay duseja Ashim Das Radha Krishan Dhiman Yogesh Kumar Chawla Reena Das Sanjay Bhadada Ravinder Sialy Kiran Kumar Thumburu Anil Bhansali Naveen Kalra Department of Hepatology Postgraduate Institute of Medical Education and Research Chandigarh India Department of Histopathology Postgraduate Institute of Medical Education and Research Chandigarh India Department of Hematology Postgraduate Institute of Medical Education and Research Chandigarh India Department of Endocrinology Postgraduate Institute of Medical Education and Research Chandigarh India Department of Radiodiagnosis and Imaging Postgraduate Institute of Medical Education and Research Chandigarh India

We read with great interest the article, ＂Non-alcoholic fatty liver disease may not be a severe disease at presentation among Asian Indians＂ by Madan et at in the recent issue of WJG. Twenty-eight （55%） out of 51 patients with nonalcoholic fatty liver disease （NAFLD） who presented with abnormal transaminases had histological evidence of nonalcoholic steatohepatitis （NASH）. The majority of patients had grade 1 [32 （63%）] or grade 2 [16 （31%）] inflammation and either had no [23 （45%）] fibrosis or stage I [19 （37%）] fibrosis. None of the patients had cirrhosisf11. We agree with Madan et al that Asian Indians with NAFLD who present with unexplained increase in transaminases may have mild disease at presentation on the basis of similar observations made by us. NAFLD has a spectrum which includes patients with only steatosis and NASH that can progress to cirrhotic and hepatocellular carcinoma.

关键词： Gastroenterology

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Nonalcoholic steatohepatitis in Asian Indians is neither associated with iron overload nor with HFE gene mutations

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World Journal of Gastroenterology 2005年第3期11卷 393-395页

作者： ajay duseja Reena Das Mohit Nanda Ashim Das Gurjeewan Garewal Yogesh Chawla Department of Hepatology Department of Hematology Department of Histopathology

AIM: The pathogenesis of occurrence of liver inflammation and fibrosis in patients with nonalcoholic steatohepatitis (NASH) is not completely understood. Other than insulin resistance, iron abnormalities have been thought to be one of the triggering factors. Therefore, our aim was to study the role of iron abnormalities and HFE gene mutations in patients with NASH. METHODS: Thirty-one patients of NASH diagnosed on the basis of clinical examination biochemistry, ultrasonography and liver biopsy (n = 14) were included in the study. Serum iron parameters (n = 23) (iron, ferritin, total iron-binding capacity and transferrin saturation), Perls' iron staining on liver biopsies (n = 14) and HFE gene mutations (C282Y and H63D) (n = 16) were studied in these patients. The association between iron staining, necroinflammatory activity and fibrosis stage on liver biopsies was also determined. RESULTS: Elevated serum iron, ferritin and transferrin saturation above 55% were observed in 4.3% of patients. On histology, 71% of the patients had negative iron staining, 21.4% had 1+ staining, 7.2% had 2+ staining and none had 3+ or 4+ staining. There was no association between the degree of iron staining and necroinflammatory activity (P=0.55) and fibrosis stage (P= 0.09) on histology. None of the patients had C282Y HFE gene mutation and four patients (25%) were found to be heterozygotes for H63D gene mutation. CONCLUSION: Our study does not favor iron overload and HFE gene mutations as major factors in the pathogenesis of NASH in Asian Indians.

关键词： Nonalcoholic steatohepatitis Iron overload HFE gene Mutation

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Frequency of primary iron overload and HFE gene mutations (C282Y,H63D and S65C) in chronic liver disease patients in north India

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World Journal of Gastroenterology 2007年第21期13卷 2956-2959页

作者： Barjinderjit Kaur Dhillon Reena Das Gurjeewan Garewal Yogesh Chawla RK Dhiman Ashim Das ajay duseja GR Chandak Department of Haematology Postgraduate Institute of Medical Education & ResearchChandigarhIndia Department of Hepatology India Department of Histopathology Postgraduate Institute of Medical Education & ResearchChandigarhIndia CCMB HyderabadIndia

AIM:To identify the frequency of iron overload and study the three mutations in the HFE gene (C282Y,H63D,and S65C) in patients with chronic liver disorders (CLD) and controls. METHODS:To identify patients with iron overload (transferrin saturation > 45% in females and > 50% in males and serum ferritin > 1000 ng/mL) we evaluated 236 patients with CLD,including 59 with non-alcoholic steatohepatitis (NASH),22 with alcoholic liver disease (ALD),19 of cirrhosis due to viruses (HBV,HCV),and 136 with cryptogenic cirrhosis. Mutations of the HFE gene were analyzed by PCR-RE. hundred controls were screened for iron status and the mutations. RESULTS:Seventeen patients with CLD showed evidence of iron overload. Fifteen cases of iron overload had cryptogenic cirrhosis and two had ALD. None of the controls showed iron overload. We did not find any individual with 282Y or 65C either in the cases or in the controls. The prevalence of H63D heterozygosity was 12% in normal individuals,14.8% in 236 patients (16.9% in NASH,13.6% in ALD,26.3% in viral and 12.5% in cryptogenic cirrhosis) and the overall prevalence was 13.98%. Only two of the 17 patients with primary iron overload were heterozygous for H63D. One patient with NASH and one normal individual who were homozygous for H63D showed no iron ***:Primary iron overload in Indians is nonHFE type,which is different from that in Europeans and further molecular studies are required to determine the defect in various iron regulatory genes.

关键词： HFE gene mutations C282Y H63D S65C Population genetics

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Gamma-glutamyl transferase and cardiovascular risk in nonalcoholic fatty liver disease:The Gut and Obesity Asia initiative

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World Journal of Gastroenterology 2020年第19期26卷 2416-2426页

作者： Panyavee Pitisuttithum Wah-Kheong Chan George Boon-Bee Goh Jian-Gao Fan Myeong Jun Song Phunchai Charatcharoenwitthaya ajay duseja Yock-Young Dan Kento Imajo Atsushi Nakajima Khek-Yu Ho Khean-Lee Goh Vincent Wai-Sun Wong Sombat Treeprasertsuk Department of Medicine Faculty of MedicineChulalongkorn UniversityBangkok 10330Thailand Department of Medicine University of MalayaKuala Lumpur 50603Malaysia Department of Gastroenterology&Hepatology Singapore General HospitalSingapore 169608Singapore Department of Gastroenterology Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of Internal Medicine The Catholic University of KoreaDaejeon 301-723South Korea Division of Gastroenterology Faculty of Medicine Siriraj HospitalMahidol UniversityBangkok 10700Thailand Department of Hepatology Post Graduate Institute of Medical Education and ResearchChandigarh 160012India Department of Medicine National University of Singapore 119228Singapore Department of Gastroenterology and Hepatology Yokohama City University Graduate School of MedicineYokohama 236-0004Japan Department of Medicine and Therapeutics The Chinese University of Hong KongHong Kong 999077China

BACKGROUND Gamma-glutamyl transferase(GGT)is associated with the risk of cardiovascular disease(CVD)in the general *** To identify the association of baseline GGT level and QRISK2 score among patients with biopsy-proven nonalcoholic fatty liver disease(NAFLD).METHODS This was a retrospective study involving 1535 biopsy-proven NAFLD patients from 10 Asian centers in 8 countries using data collected by the Gut and Obesity in Asia(referred to as“GO ASIA”)*** patients with available baseline GGT levels and all 16 variables for the QRISK2 calculation(QRISK2-2017;developed by researchers at the United Kingdom National Health Service;https://***/2017/;10-year cardiovascular risk estimation)were included and compared to healthy controls with the same age,sex,and *** risk was ***2 score>10%was defined as the high-CVD-risk *** stages 3 and 4(F3 and F4)were considered advanced *** A total of 1122 patients(73%)had complete data and were included in the final analysis;314(28%)had advanced *** median age(interquartile range[IQR])of the study population was 53(44-60)years,532(47.4%)were females,and 492(43.9%)were of Chinese *** median 10-year CVD risk(IQR)was 5.9%(2.6-10.9),and the median relative risk of CVD over 10 years(IQR)was 1.65(1.13-2.2)compared to healthy individuals with the same age,sex,and *** high-CVD-risk group was significantly older than the low-risk group(median[IQR]:63[59-67]vs 49[41-55]years;P<0.001).Higher fibrosis stages in biopsy-proven NAFLD patients brought a significantly higher CVD risk(P<0.001).Median GGT level was not different between the two groups(GGT[U/L]:Median[IQR],high risk 60[37-113]vs low risk 66[38-103],P=0.56).There was no correlation between baseline GGT level and 10-year CVD risk based on the QRISK2 score(r=0.02).CONCLUSION The CVD risk of NAFLD patients is higher than that of healthy *** GGT level cannot predict CVD ri

关键词： Nonalcoholic fatty liver disease Gamma glutamyl transferase QRISK Cardiovascular risk Gut and Obesity in Asia

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Geochemistry and mineral chemistry of the armoor granitoids,eastern dharwar craton: implications for the redox conditions and tectono-magmatic environment

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Acta Geochimica 2024年第1期43卷 110-133页

作者： A.ajay Kumar Ch.Ashok Department of Geology Osmania UniversityHyderabad 500007India CSIR-National Geophysical Research Institute UppalHyderabad 500007India

The mineralogical and geochemical characteristics of the K-rich granites from the Armoor granitic rocks in the northeastern portion of the Eastern Dharwar Craton(EDC) are *** order to understand its physicochemical conditions,the petrogenesis of the granitoid was explained from biotite chemistry and geochemical *** of mineral chemistry expose that compositionally,K-feldspar and plagioclase in Armoor granite rocks range from An0,Ab_(3-5.9),Or_(94-96.9) and An_(5-29,-Ab71.9-94.9),Or_(0-1.5),*** mineral chemistry of biotite crystals exhibits composition that varies from primary to re-equilibrated primary *** biotites from the Armoor granites generally exhibit an I-type trend,with calc-alkaline parental magma in a subduction *** chemistry of granites displays magnetite(oxidized)series nature,which has oxygen fugacity(fO_(2))=-15.1 to-16.7(log_(10) bar),under high oxidizing *** and pressure estimates for the crystallization of Armoor granites based on biotite composition are T=612-716 ℃ and 1.0-0.4 kbar,***,these rocks are metaluminous to slightly peraluminous and magnesian,with calc-alkaline potassiumrich *** the chondrite normalized REE diagram,the granites have positive europium anomalies;rich Sr/Y,(Dy/Yb)_(N) ratios and reduced Mg#,Rb/Sr,Rb,Sr indicate that the melting of earlier rocks,crystal accumulation and residual garnet source formed at high *** examined granites show that they are produced from the melting of crustal ***,the extensive analyses of the described Armoor granite suggest that they were produced by crust sources and developed under oxidizing conditions in subduction setting.

关键词： Armoor granites Oxygen fugacity Crystal accumulation Remelting Subduction

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