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| 1 | Role of liver biopsy in hepatocellular carcinoma显示文摘The role of liver biopsy in the diagnosis of hepatocellular carcinoma(HCC)has been challenged over time by the ability of imaging techniques to characterize liver lesions in patients with known cirrhosis.In fact,in the diagnostic algorithm for this tumor,histology is currently relegated to controversial cases.Furthermore,the risk of complications,such as tumor seeding and bleeding,as well as inadequate sampling have further limited the use of liver biopsy for HCC management.However,there is growing evidence of prognostic and therapeutic information available from microscopic and molecular analysis of HCC and,as the information content of the tissue sample increases,the advantages of liver biopsy might modify the current risk/benefit ratio.We herein review the role and potentiality of liver biopsy in the diagnosis and management of HCC.As the potentiality of precision medicine comes to the management of HCC,it will be crucial to have rapid pathways to define prognosis,and even treatment,by identifying the patients who could most benefit from target-driven therapies.All of the above reasons suggest that the current role of liver biopsy in the management of HCC needs substantial reconsideration. | Luca Di Tommaso Marco Spadaccini Matteo Donadon Nicola Personeni Abubaker Elamin Alessio Aghemo Ana Lleo | 2019 | World Journal of Gastroenterology2019，25，40： | 11 |
| 2 | Etiopathogenesis of primary biliary cirrhosis显示文摘Primary biliary cirrhosis(PBC) is an autoimmune disease of the liver characterized by progressive bile duct destruction eventually leading to cirrhosis and liver failure.The serological hallmark of the disease is the presence of circulating antimitochondrial antibodies(AMA).These reflect the presence of autoreactive T and B cells to the culprit antigens,the E2 subunits of mitochondrial 2-oxo-acid dehydrogenase enzymes,chiefly pyruvate dehydrogenase(PDC-E2).The disease results from a combination of genetic and environmental risk factors.Genetic predisposition is indicated by the higher familial incidence of the disease particularly among siblings and the high concordance rate among monozygotic twins.Environmental triggering events appear crucial to disrupt a pre-existing unstable immune tolerance of genetic origin allowing,after a long latency,the emergence of clinical disease.Initiating mimetopes of the vulnerable epitope of the PDC-E2 autoantigen can be derived from microbes that utilize the PDC enzyme or,alternatively,environmental xenobiotics/chemical compounds that modify the structure of native proteins to make them immunogenic.A further alternative as a source of antigen is PDC-E2 derived from apoptotic cells.In the effector phase the biliary ductular cell,by reason of itsproclivity to express the antigen PDC-E2 in the course of apoptosis,undergoes a multilineage immune attack comprised of CD4+ and CD8+ T cells and antibody.In this article,we critically review the available evidence on etiopathogenesis of PBC and present interpretations of complex data,new developments and theories,and nominate directions for future research. | Ana Lleo Pietro Invernizzi Ian R Mackay Harry Prince Ren-Qian Zhong M Eric Gershwin | 2008 | World Journal of Gastroenterology2008，14，21： | 9 |
| 3 | Tumor microenvironment in primary liver tumors: A challenging role of natural killer cells显示文摘In the last years,several studies have been focused on elucidate the role of tumor microenvironment(TME)in cancer development and progression.Within TME,cells from adaptive and innate immune system are one of the main abundant components.The dynamic interactions between immune and cancer cells lead to the activation of complex molecular mechanisms that sustain tumor growth.This important cross-talk has been elucidate for several kind of tumors and occurs also in patients with liver cancer,such as hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(iCCA).Liver is well-known to be an important immunological organ with unique microenvironment.Here,in normal conditions,the rich immune-infiltrating cells cooperate with non-parenchymal cells,such as liver sinusoidal endothelial cells and Kupffer cells,favoring self-tolerance against gut antigens.The presence of underling liver immunosuppressive microenvironment highlights the importance to dissect the interaction between HCC and iCCA cells with immune infiltrating cells,in order to understand how this cross-talk promotes tumor growth.Deeper attention is,in fact,focused on immune-based therapy for these tumors,as promising approach to counteract the intrinsic anti-tumor activity of this microenvironment.In this review,we will examine the key pathways underlying TME cell-cell communications,with deeper focus on the role of natural killer cells in primary liver tumors,such as HCC and iCCA,as new opportunities for immune-based therapeutic strategies. | Michela Anna Polidoro Joanna Mikulak Valentina Cazzetta Ana Lleo Domenico Mavilio Guido Torzilli Matteo Donadon | 2020 | World Journal of Gastroenterology2020，26，33： | 4 |
| 4 | Y chromosome loss in male patients with primary biliary cirrhosis显示文摘 | Ana Lleo Sabine Oertelt-Prigione Ilaria Bianchi Lisa Caliari Palma Finelli Monica Miozzo Roberta Lazzari Annarosa Floreani Francesca Donato Massimo Colombo M. Eric Gershwin Mauro Podda Pietro Invernizzi | 2013 | Journal of Autoimmunity2013，，： | 2 |
| 5 | Osteosarcopenia in autoimmune cholestatic liver diseases:Causes,management,and challenges显示文摘Primary biliary cholangitis and primary sclerosing cholangitis(PSC)are the most common cholestatic liver diseases(CLD)in adults and are both characterized by an immune pathogenesis.While primary biliary cholangitis is a model autoimmune disease,with over 90%of patients presenting very specific autoantibodies against mitochondrial antigens,PSC is considered an immune mediated disease.Osteoporosis is the most common bone disease in CLD,resulting in frequent fractures and leading to significant morbidity.Further,sarcopenia is emerging as a frequent complication of chronic liver diseases with a significant prognostic impact and severe implications on the quality of life of patients.The mechanisms underlying osteoporosis and sarcopenia in CLD are still largely unknown and the association between these clinical conditions remains to be dissected.Although timely diagnosis,prevention,and management of osteosarcopenia are crucial to limit the consequences,there are no specific guidelines for management of osteoporosis and sarcopenia in patients with CLD.International guidelines recommend screening for bone disease at the time of diagnosis of CLD.However,the optimal monitoring strategies and treatments have not been defined yet and vary among centers.We herein aim to comprehensively outline the pathogenic mechanisms and clinical implications of osteosarcopenia in CLD,and to summarize expert recommendations for appropriate diagnostic and therapeutic approaches. | Nicola Pugliese Ivan Arcari Alessio Aghemo Andrea G Lania Ana Lleo Gherardo Mazziotti | 2022 | World Journal of Gastroenterology2022，28，14： | 2 |
| 6 | Cell wall chemical composition of Enterococcus faecalis in the viable but nonculturable state 显示文摘 | Signoretto C Lleo MD Tafi MC Canepari P | 2000 | ApplEnviron Microbiol2000，66，5： | 1 |
| 7 | Current pharmacotherapy for Alzheimer's disease显示文摘 | Lleo A Greenberg SM Growdon JH | 2006 | Annu Rev Med2006，57，： | 1 |
| 8 | B cell depletion therapy exacerbates murine primary biliary cirrhosis显示文摘 | DHIRAPONG A LLEO A YANG GX | 2011 | Hep- atology2011，53，2： | 1 |
| 9 | The limitations and hidden gems of the epidemiology of primary biliary cirrhosis显示文摘 | Mauro Podda Carlo Selmi Ana Lleo Luca Moroni Pietro Invernizzi | 2013 | Journal of Autoimmunity2013，，： | 1 |
| 10 | Effect of different thawing temperaturos on the viability, in vitro fertilizing capacity and chromgttin condensation of frozen boar semen packaged in 5mL straws 显示文摘 | Cordova-lzquierdo A Oliva J H Lleo B etal | 2006 | Animal Reproduetion Science2006，92，12： | 1 |
| 11 | Apolipoprotein E modulates gamma-secretase cleavage of the amyloid precursor protein显示文摘 | Irizarry MC Deng A Lleo A | | 0，，05： | 1 |
| 12 | Biliary apotopes and anti- mitochondrial antibodies activate innate immune responses in primary biliary cirrhosis显示文摘 | Lleo A Bowlus CL Yang GX5 | 2010 | Hepatology2010，52，3： | 1 |
| 13 | Interpreting serological tests in diagnosing autoimmune liver diseases显示文摘 | Invernizzi P Lleo A Podda M | 2007 | Semin Liver Dis2007，27，： | 1 |
| 14 | Geoepidemiology,gender and autoimmune disease 显示文摘 | Moroni L Bianchi I Lleo A | 2012 | AutoimmunRev2012，11，67： | 1 |
| 15 | gamma-Secretase as a therapeutic target in Alzheimer's disease 显示文摘 | GUARDIA-LAGUARTA C PERA M LLEO A | 2010 | Curt Drug Targets2010，11，4： | 1 |
| 16 | Advances in pharmacotherapy for primary biliary cirrhosis 显示文摘 | MOUSA HS LLEO A INVERNIZZl P | 2015 | Expert Opin Pharmacother2015，16，5： | 1 |
| 17 | Lipoteichoic acid as a new target for activity of antibiotics: mode of action of daptomycin (LY146032) 显示文摘 | Canepari P Boaretti M Lleo MM | 1990 | Antimicrob Agents Chemother1990，34，6： | 1 |
| 18 | The viable but nonculturable state and starvation are different stress responses of Enterococcusfaecalis as determined by proteome analysis 显示文摘 | Heim S Maria Del Mar Lleo Barbara Bonato Guzman CA Canepari P | 2002 | Bacteriology2002，184，23： | 1 |
| 19 | Nonsteroidal anti-inflammatory drugs lower Abeta42 and change presenilin 1 conformation显示文摘 | Lleo A Berezovska O Herl L | 2004 | Nat Med2004，10，10： | 1 |
| 20 | Cell wall chemical composition of Enterococcus faecalis in the viable but noneulturable state 显示文摘 | Signoretto C Lleo MD Tafi MC Canepari P | 2000 | Appl Environ Microbiol2000，66，5： | 1 |
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