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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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A new technique of combined endoscopic sclerotherapy and ligation for variceal bleeding

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World Journal of Gastroenterology 2003年第5期9卷 1090-1093页

作者： Radha K.Dhiman Yogesh K.Chawla Department of hepatology Postgraduate Institute of Medical Education & ResearchChandigarh 160012India

AIM: To develop a technique of combined endoscopic sclerotherapy and ligation (ESL) in which both techniques of endoscopic sclerotherapy (ES) and endoscopic variceal ligation (EVL) can be optimally ***: ESL was performed in 10 patients (age 46.4±7.9;9 males, 1 female) with cirrhosis of liver using sclerotherapy needle and Speedband, Superview multiple band ligater (Boston Scientific, Microvasive, Watertown, MA). A single band was placed 5-10 cm proximal to the gastro-esophageal junction over each varix from proximal to distal margin,followed by intravariceal injection of 1.5 % ethoxysclerol (4 ml each) 2 to 3 cm proximal to the gastroesophageal junction on the ligated varices distal to deployed band. EVL was then performed at the injection site. Similarly other varices were also injected and ligated from distal to proximally. In the subsequent sessions, ES alone was performed to sclerose small varices at the gastroesophageal ***: ESL was successfully performed in all patients.A median of 3 (ESL 1, ES 2) sessions (ranged 1-4) were required to eradicate the varices in 9 (90 %) of 10 *** of varices without bleed was seen in 1 patient during a mean follow-up of 10.3 months (ranged 6-15).Two patients died of liver failure. None died of variceal bleeding. None of the patients had procedure related ***: ESL may be useful in the fast eradication of esophageal varices. However, randomised controlled trials are required to find out its relative efficacy and impact on variceal recurrence in comparison to ES or EVL.

关键词： Adult Endoscopy, Digestive System Esophageal and Gastric Varices Female Gastrointestinal Hemorrhage Humans Ligation Liver Cirrhosis Male Middle Aged Pilot Projects Sclerotherapy

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Endoscopic management of postcholecystectomy biliary leakage

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Hepatobiliary & Pancreatic Diseases International 2010年第4期9卷 409-413页

作者： Virendra Singh Gurpreet Singh Ganga R Verma Rajesh Gupta Departments of hepatology Postgraduate Institute of Medical Education and Research Departments of Surgery Postgraduate Institute of Medical Education and Research

BACKGROUND: Biliary leak is an uncommon but significant complication following cholecystectomy. Endotherapy is an established method of treatment. However, the optimal intervention is not known. METHOD: Eighty-five patients with postcholecystectomy biliary leaks from July 2000 to March 2009 were retrospectively evaluated. RESULTS: The study population was 20 males and 65 females with a mean age of 42.47 years. Patients presented with abdominal pain (46), jaundice (23), fever (23), abdominal distension (42), or bilious abdominal drain (67). Endoscopic retrograde cholangiopancreatography detected a leak at the cystic duct stump in 45 patients, stricture with middle common bile duct leak in 4, leak from the right hepatic duct in 3, and a ligated common bile duct in 32. Twelve also had bile duct stones. One had a broken T-tube with stones Endotherapy was possible in 53 patients. Three patients with stones, one with a broken T-tube with stones, and 4 with stricture of the common bile duct with a leak were managed with sphincterotomy and stenting. Eight patients with a cystic duct stump leak with stones were managed with sphincterotomy and stone extraction. Three outpatients and 12 inpatients with a cystic duct stump leak were managed with sphincterotomy and stent and sphincterotomy and nasobiliary drain, respectively. Five patients with a cystic duct stump leak were managed with stenting. Sixteen with coagulopathy were managed with only nasobiliary drain (9) or stent (7). Leak closure was achieved in 100% patients Four developed mild pancreatitis which improved with conservative ***: Endoscopic intervention is a safe and effective method of treatment of postcholecystectomy biliary leaks. However, management should be individualized based on factors such as outpatients or inpatients, presence of stone, stricture, ligature, or coagulopathy.

关键词： biliary fistulae endoscopic retrograde cholangiopancreatography sphincterotomy biliary stent nasobiliary drain biliary strictures

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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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Cytokine Storm of COVID-19 and Its Impact on Patients with and without Chronic Liver Disease

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Journal of Clinical and Translational hepatology 2021年第2期9卷 256-264页

作者： Madhumita Premkumar Chandan Kumar Kedarisetty Departments of hepatology Postgraduate Institute of Medical Education and ResearchChandigarhIndia Department of hepatology and Liver transplantation Gleneagles Global HospitalHyderabadIndia

The coronavirus pandemic has resulted in increased rates of hepatic decompensation,morbidity and mortality in patients suffering from existing liver disease,and deranged liver biochemistries in those without liver *** patients with cirrhosis with coronavirus disease 2019(COVID-19),new onset organ failures manifesting as acute-onchronic liver failure have also been *** severe acute respiratory syndrome-coronavirus-2(SARS-CoV-2)also directly binds to enterocytes and cholangiocytes via the angiotensin converting enzyme receptor 2,although the lung remains the portal of *** with the COVID-19 related bystander hepatitis,a systemic inflammatory response is noted due to unregulated macrophage activation syndrome and cytokine ***,the exact definition and diagnostic criteria of the‘cytokine storm’in COVID-19 are yet *** addition,inflammatory markers like C-reactive protein,ferritin,D-dimer and procalcitonin are frequently *** in turn leads to disease progression,activation of the coagulation cascade,vascular microthrombi and immune-mediated injury in different organ *** liver chemistries are also noted due to the cytokine storm,and synergistic hypoxic or ischemic liver injury,drug-induced liver injury,and use of hepatotoxic antiviral agents all contribute to deranged liver *** of an unregulated cytokine storm at an early stage may avert disease morbidity and *** immunomodulator drugs and repurposed immunosuppressive agents have been used in COVID-19 with varying degrees of success.

关键词： Chronic liver disease COVID-19 Cytokines Hepatitis Gut-liver axis

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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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Contrast-free air cholangiography-assisted unilateral plastic stenting in malignant hilar biliary obstruction

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Hepatobiliary & Pancreatic Diseases International 2010年第1期9卷 88-92页

作者： Virendra Singh Gurpreet Singh Vikas Gupta Rajesh Gupta Rakesh Kapoor Departments of hepatology Postgraduate Institute of Medical Education and Research Departments of Surgery Postgraduate Institute of Medical Education and Research Departments of Radiotherapy Postgraduate Institute of Medical Education and Research

BACKGROUND:Endoscopic palliation in malignant hilar biliary obstruction requires endoscopic retrograde cholangiopancreatography (ERCP),whereas contrast injection leads to ***-free metal stenting with or without magnetic resonance cholangiopancreatography (MRCP) has shown encouraging results,but MRCP and metal stents are *** have been no reports on the use of air ***:We prospectively evaluated the role of air cholangiography-assisted unilateral plastic stenting in 10 patients with type Ⅱ malignant hilar biliary obstruction.A retrospectively analysed group of 10 patients treated with contrast-free unilateral metal stenting served as historical ***:Ten patients with unresectable type Ⅱ malignant hilar biliary obstruction were *** cholangiography detected type Ⅱ obstruction in all patients,similar to *** patients underwent unilateral *** endoscopic drainage was achieved in all *** mean patency of the stent was 95.8±17.5 days in the study group and 143.9±115.1 days in the control group (P=0.20).The mean survival was 121.8±41.6 days in the study group and 154.9±122.5 days in the control group (P=0.42).KaplanMeier analysis showed an estimated median survival of 100:95% CI (65.9,134.1) days in the study group and 98:95% CI (84.1,111.9) days in the control group (P=0.62).Cholangitis occurred in none of the patients and there were no 30-day deaths nor major *** cholangiographyassisted unilateral plastic stenting was cheaper than contrastfree unilateral metal ***:Air cholangiography-assisted unilateral plastic stenting is as safe and effective as contrast-free unilateral metal stenting in type Ⅱ malignant hilar biliary obstruction for palliating patients,but it is cheaper.

关键词： air cholangiogram hilar obstruction malignant plastic stent metal stent unilateral

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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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The roles of anurans in antagonistic networks are explained by life-habit and body-size

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Integrative Zoology 2022年第4期17卷 530-542页

作者： Amanda Caroline DUDCZAK Gabriel Massaccesi DE LA TORRE Lorena EUCLYDES Karla Magalhães CAMPIÃO Department of Zoology Federal University of ParanáCuritibaBrazil postgraduate program in Zoology Federal University of ParanáCuritibaBrazil postgraduate program in Ecology and Conservation Federal University of ParanáCuritibaBrazil

Interactions among living beings are the structuring basis of ecosystems,and studies of networks allow us to identify the patterns and consistency of such *** networks reflect the energy flow of communities,and identifying network structure and the biological aspects that influence its stability is crucial to understanding ecosystem *** used antagonistic anuran interactions-predator-prey and host-parasite-to assess structural patterns and to identify the key anuran species structuring these *** tested whether anuran body-size and life-habit are related to their roles in these *** collected individuals of 9 species of anurans from an area of the Atlantic Forest in Brazil and identified their prey and helminth *** used network(modularity,specialization,and nestedness)and centrality metrics(degree,closeness,and betweenness)to identify the role of anuran species in both *** then evaluated whether anuran body-size or life-habit were related to anuran centrality using generalized linear mixed *** networks formed specialized interactions in compartments composed by key species from different *** our networks,anurans with rheophilic and cryptozoic habit are central in predator-prey networks,and those with larger body size and arboreal and cryptozoic habit in the host-parasite *** study represents a step towards a better understanding of the influential factors that affect the structure of anuran antagonist networks,as well as to recognize the functioning roles of anuran species.

关键词： diet disease food web helminth infection network centrality

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Immunology of hepatocellular carcinoma

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World Journal of hepatology 2015年第17期7卷 2080-2090页

作者： Meenakshi Sachdeva Yogesh K Chawla Sunil K Arora Department of Immuno- pathology Postgraduate Institute of Medical Education and Research Department of hepatology Postgraduate Institute of Medical Education and Research

Hepatocellular carcinoma(HCC) is primarily a malignancy of the liver, advancing from a damaged, cirrhotic liver to HCC. Globally, HCC is the sixth most prevalent cancer and the third-most prevalent reason for neoplastic disease-related deaths. A diverse array of infiltrating immunocytes regulates the development and progression of HCC, as is the case in many other cancers. An understanding of the various immune components during HCC becomes necessary so that novel therapeutic strategies can be designed to combat the disease. A dysregulated immune system(including changes in the number and/or function of immune cells, cytokine levels, and the expression of inhibitory receptors or their ligands) plays a key role in the development of HCC. Alterations in either the innate or adaptive arm of the immune system and cross-talk between them make the immune system tolerant to tumors, leading to disease progression. In this review, we have discussed the status and roles of various immune effector cells(e.g., dendritic cells, natural killer cells, macrophages, and T cells), their cytokine profile, and the chemokine-receptor axis in promoting or impeding HCC.

关键词： Hepatocellular carcinoma Immune cells Immune-dysregulation Adaptive immunity Innateimmunity

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