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Non-alcoholic fatty liver disease,non-alcoholic steatohepatitis,metabolic syndrome and hepatocellular carcinoma——a composite scenario

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Hepatobiliary Surgery and Nutrition 2018年第2期7卷 130-133页

作者： Luca Viganò ana lleo Alessio Aghemo Division of Hepatobiliary and General Surgery Department of SurgeryHumanitas Clinical and Research CenterHumanitas UniversityRozzanoMilanItaly Department of Biomedical Sciences Humanitas UniversityRozzanoMilanItaly Division of Internal Medicine and Hepatology Department of Internal MedicineHumanitas Clinical and Research CenterHumanitas UniversityRozzanoMilanItaly

Hepatocellular carcinoma(HCC)is the fifth most common cancer and the second leading cause of cancer-related death *** data suggest that the epidemiology of HCC is changing;while the frequencies of hepatitis B virus(HBV)-and hepatitis C virus(HCV)-related HCC are progressively decreasing owing to the development of nucleo(t)side-based therapies and directly acting antiviral agents,respectively,the frequency of cryptogenic HCC continues to increase(15–30%of cases)(1).The rise of cryptogenic HCC is mainly related to non-alcoholic fatty liver disease(NAFLD)(1,2).NAFLD encompasses a wide spectrum of liver injuries,ranging from steatosis to non-alcoholic steatohepatitis(NASH),which may progress to cirrhosis(1,3).

关键词： epidemiology liver NAFLD death

Etiopathogenesis of primary biliary cirrhosis

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World Journal of Gastroenterology 2008年第21期14卷 3328-3337页

作者： ana lleo Pietro Invernizzi Ian R Mackay Harry Prince Ren-Qian Zhong M Eric Gershwin Division of Internal Medicine and Liver Unit San Paolo Hospital School of Medicine University of Milan Milan 20142 Italy Division of Rheumatology Allergy and Clinical Immunology University of California at Davis Davis CA 95616 United States Department of Biochemistry & Molecular Biology Monash University Clayton Victoria 3800 Australia Focus Diagnostics 5785 Corporate Avenue Cypress CA 90630 United States Laboratory Diagnostics of Changzheng Hospital Second Military Medical University and Clinical Immunology Center of PLA Shanghai 200003 China

Primary biliary cirrhosis(PBC) is an autoimmune disease of the liver characterized by progressive bile duct destruction eventually leading to cirrhosis and liver *** 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 *** predisposition is indicated by the higher familial incidence of the disease particularly among siblings and the high concordance rate among monozygotic *** triggering events appear crucial to disrupt a pre-existing unstable immune tolerance of genetic origin allowing,after a long latency,the emergence of clinical *** 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 *** 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 *** 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.

关键词： Autoantibodies Autoreactive T cells 2-oxoacid dehydrogenase Biliary epithelial cells Primary biliary cirrhosis

Osteosarcopenia in autoimmune cholestatic liver diseases:Causes,management,and challenges

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World Journal of Gastroenterology 2022年第14期28卷 1430-1443页

作者： Nicola Pugliese Ivan Arcari Alessio Aghemo Andrea G Lania ana lleo Gherardo Mazziotti Department of Biomedical Sciences Humanitas UniversityPieve Emanuele 20090MilanItaly Division of Internal Medicine and Hepatology Department of GastroenterologyIRCCS Humanitas Research HospitalRozzano 20089MIItaly Department of Endocrinology Diabetology and Medical Andrology UnitIRCCS Humanitas Research HospitalRozzano 20089MIItaly

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 *** 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 *** is the most common bone disease in CLD,resulting in frequent fractures and leading to significant ***,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 *** mechanisms underlying osteoporosis and sarcopenia in CLD are still largely unknown and the association between these clinical conditions remains to be *** 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 *** guidelines recommend screening for bone disease at the time of diagnosis of ***,the optimal monitoring strategies and treatments have not been defined yet and vary among *** 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.

关键词： Cholestatic liver diseases Primary biliary cholangitis Primary sclerosing cholangitis Osteoporosis Sarcopenia

Role of liver biopsy in hepatocellular carcinoma

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World Journal of Gastroenterology 2019年第40期25卷 6041-6052页

作者： Luca Di Tommaso Marco Spadaccini Matteo Donadon Nicola Personeni Abubaker Elamin Alessio Aghemo ana lleo Pathology Unit Humanitas Clinical and Research Center IRCCSRozzano 20089Italy Department of Biomedical Sciences Humanitas UniversityPieve Emanuele 20090Italy Division of Hepatobiliary and General Surgery Department of General SurgeryHumanitas Clinical and Research Center IRCCSRozzano 20089Italy Division of Medical Oncology and Hematology Humanitas Cancer CenterHumanitas Clinical and Research Center IRCCSRozzano 20089Italy Division of Internal Medicine and Hepatology Department of GastroenterologyHumanitas Clinical and Research Center IRCCSRozzano 20089Italy

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 *** fact,in the diagnostic algorithm for this tumor,histology is currently relegated to controversial ***,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 ***,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 *** herein review the role and potentiality of liver biopsy in the diagnosis and management of *** 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 *** of the above reasons suggest that the current role of liver biopsy in the management of HCC needs substantial reconsideration.

关键词： Hepatocellular carcinoma Liver biopsy Prognostic factors Liver cancer Recurrence Liquid biopsy

Tumor microenvironment in primary liver tumors: A challenging role of natural killer cells

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World Journal of Gastroenterology 2020年第33期26卷 4900-4918页

作者： Michela Anna Polidoro Joanna Mikulak Valentina Cazzetta ana lleo Domenico Mavilio Guido Torzilli Matteo Donadon Hepatobiliary Immunopathology Laboratory Humanitas Clinical and Research Center–IRCCSRozzano 20089MilanItaly Laboratory of Clinical and Experimental Immunology Humanitas Clinical and Research Center-IRCCSRozzano 20089MilanItaly Department of Medical Biotechnologies and Translational Medicine(BioMeTra) University of MilanRozzano 20089MilanItaly Department of Biomedical Science Humanitas UniversityPieve Emanuele 20090MilanItaly Department of Internal Medicine Humanitas Clinical and Research Center–IRCCSRozzano 20089MilanItaly Department of Hepatobiliary and General Surgery Humanitas Clinical and Research Center-IRCCSRozzano 20089MilanItaly

In the last years,several studies have been focused on elucidate the role of tumor microenvironment(TME)in cancer development and *** TME,cells from adaptive and innate immune system are one of the main abundant *** dynamic interactions between immune and cancer cells lead to the activation of complex molecular mechanisms that sustain tumor *** 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 ***,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 *** 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 *** attention is,in fact,focused on immune-based therapy for these tumors,as promising approach to counteract the intrinsic anti-tumor activity of this *** 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.

关键词： Primary liver cancer Natural killer cells Tumor microenvironment Hepatocellular carcinoma Intrahepatic cholangiocarcinoma Immune cells

Alpha-fetoprotein screening in patients with hepatitis C-induced cirrhosis who achieved a sustained virologic response in the direct-acting antiviral agents era

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Hepatobiliary & Pancreatic Diseases International 2018年第6期17卷 570-574页

作者： Marco Spadaccini ana lleo Roberto Ceriani Giovanni Covini Lorenza Rimassa Guido Torzilli Luca Di Tommaso Alessio Aghemo Internal Medicine and Liver Unit Humanitas Research Hospital Department of Biomedical Sciences Humanitas University Medical Oncology and Hematology Unit Humanitas Clinical and Research Center Humanitas University Division of Hepatobiliary and General Surgery Department of Surgery Humanitas Clinical and Research Center - IRCCS Humanitas University Pathology Unit Humanitas Research Hospital

To the Editor:Hepatocellular carcinoma (HCC) is the most common primary livertumorandthethirdcauseofcancer-relateddeathsworldwide. HCC is the consequence of malignant transformation of hepatocytes and mainly occurs in patients with cirrhosis. Hepatitis C virus (HCV) chronic infection is a leading cause of end-stage liver diseaseandHCCintheWesterncountries[1].Theapprovalof direct-acting antiviral agents (DAAs) for the treatment of HCV has revolutionized the management of the disease, as no absolute contraindication to treatment exists and sustained virological response

关键词： HCC AFP SVR Alpha-fetoprotein screening in patients with hepatitis C-induced cirrhosis who achieved a sustained virologic response in the direct-acting antiviral agents era