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World Journal of Gastroenterology 2022年第21期28卷 2251-2281页

作者： Leonardo Stella Francesco Santopaolo Antonio Gasbarrini Maurizio Pompili francesca romana ponziani Internal Medicine and Gastroenterology Hepatology UnitFondazione Policlinico Universitario Agostino Gemelli IRCCSRome 00168Italy

Hepatocellular carcinoma(HCC)is a global health *** to the high prevalence in low-income countries,hepatitis B virus(HBV)and hepatitis C virus infections remain the main risk factors for HCC occurrence,despite the increasing frequencies of non-viral *** addition,hepatitis D virus coinfection increases the oncogenic risk in patients with HBV *** molecular processes underlying HCC development are complex and various,either independent from liver disease etiology or *** reciprocal interlinkage among non-viral and viral risk factors,the damaged cellular microenvironment,the dysregulation of the immune system and the alteration of gutliver-axis are known to participate in liver cancer induction and *** mechanisms and pathways change throughout the natural history of viral hepatitis with the worsening of liver *** high risk of cancer incidence in chronic viral hepatitis infected patients compared to other liver disease etiologies makes it necessary to implement a proper surveillance,both through clinical-biochemical scores and periodic ultrasound *** review aims to outline viral and microenvironmental factors contributing to HCC occurrence in patients with chronic viral hepatitis and to point out the importance of surveillance programs recommended by international guidelines to promote early diagnosis of HCC.

关键词： Hepatitis C virus Hepatitis B virus Hepatitis D virus Hepatocellular carcinoma Cirrhosis Liver

Immunotherapy for nonalcoholic fatty liver disease-related hepatocellular carcinoma:Lights and shadows

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World Journal of Gastrointestinal Oncology 2022年第9期14卷 1622-1636页

作者： Federico Costante Carlo Airola Francesco Santopaolo Antonio Gasbarrini Maurizio Pompili francesca romana ponziani Internal Medicine and Gastroenterology-Hepatology Unit Fondazione Policlinico Universitario Agostino Gemelli IRCCSRoma 00168Italy Catholic University Largo Francesco Vito 100168 RomaItaly

About one-fourth of adults globally suffer from nonalcoholic fatty liver disease(NAFLD), which is becoming a leading cause of chronic liver disease worldwide. Its prevalence has rapidly increased in recent years, and is projected to increase even more. NAFLD is a leading cause of hepatocellular carcinoma(HCC), the sixth-most prevalent cancer worldwide and the fourth most common cause of cancer-related death. Although the molecular basis of HCC onset in NAFLD is not completely known, inflammation is a key player. The tumor microenvironment(TME) is heterogeneous in patients with HCC, and is characterized by complex interactions between immune system cells, tumor cells and other stromal and resident liver cells. The etiology of liver disease plays a role in controlling the TME and modulating the immune response. Markers of immune suppression in the TME are associated with a poor prognosis in several solid tumors. Immunotherapy with immune checkpoint inhibitors(ICIs) has become the main option for treating cancers, including HCC. However, meta-analyses have shown that patients with NAFLD-related HCC are less likely to benefit from therapy based on ICIs alone. Conversely, the addition of an angiogenesis inhibitor showed better results regarding the objective response rate and progression-free survival. Adjunctive diagnostic and therapeutic strategies, such as the application of novel biomarkers and the modulation of gut microbiota, should be considered in the future to guide personalized medicine and improve the response to ICIs in patients with NAFLD-related HCC.

关键词： Hepatocellular carcinoma Immunotherapy Liver cancer Nonalcoholic fatty liver disease Metabolic dysfunction-associated fatty liver disease Obesity

Immunotherapy for the treatment of hepatocellular carcinoma: finally in clinical practice

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Hepatobiliary Surgery and Nutrition 2023年第2期12卷 252-255页

作者： Ciro Celsa Lucia Cerrito Leonardo Stella Roberta Ciccia Giuseppe Cabibbo francesca romana ponziani Section of Gastroenterology&Hepatology Department of Health PromotionMother and Child CareInternal Medicine and Medical SpecialtiesPROMISEUniversity of PalermoPalermoItaly Department of Surgical Oncological and Oral Sciences(Di.Chir.On.S.)University of PalermoPalermoItaly Digestive Disease Center-CEMAD Fondazione Policlinico Universitario Agostino Gemelli IRCCSRomeItaly UniversitàCattolica del Sacro Cuore RomeItaly

Clinical guidelines for the prevention,diagnosis and management of human disease are evidence-based tools that rely on quality of clinical research,including data from randomized controlled clinical trials(RCTs)and real-world *** Society for Immunotherapy of Cancer(SITC)recently published a clinical practice guideline on immunotherapy for the treatment of hepatocellular carcinoma(HCC)(1).

关键词： Hepatocellular carcinoma immunotherapy immune-checkpoint inhibitors immune-related adverse events systemic therapies

Low ADAMTS-13/VWF ratio and altered gut–liver axis predict complications of advanced chronic liver disease:a pilot study

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Gastroenterology Report 2022年第1期10卷 671-673页

作者： francesca romana ponziani Monica Sacco Maira Tardugno Francesco Santopaolo Adriana Marsico Stefano Manna Stefano Lancellotti Antonio Gasbarrini Raimondo De Cristofaro Maurizio Pompili Internal Medicine and Gastroenterology–Hepatology Unit Fondazione Policlinico Universitario Agostino Gemelli IRCCSRomeItaly Translational Medicine and Surgery Department Catholic UniversityRomeItaly Hemorrhagic and Thrombotic Diseases Service Fondazione Policlinico Universitario Agostino Gemelli IRCCSRomeItaly

Introduction Liver cirrhosis is characterized by a delicate balance between thrombosis and *** extinction due to microvascular thrombosis is involved in disease progression and anticoagulant therapy with low-molecular-weight heparin has been shown to reduce the frequency of hepatic decompensation[1].Dysbiosis and bacterial translocation,which are hallmarks of liver cirrhosis,can influence the coagulation system through inflammation or by the activation of Toll-like receptors on endothelial cells and platelets[2].However,little is known about the connections between the coagulation system,the occurrence of liver cirrhosis complications,and the gut microbiome.

关键词： complications inflammation bleeding

What we should know about portal vein thrombosis in cirrhotic patients:A changing perspective

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World Journal of Gastroenterology 2012年第36期18卷 5014-5020页

作者： francesca romana ponziani Maria Assunta Zocco Matteo Garcovich francesca D'Aversa Davide Roccarina Antonio Gasbarrini Internal Medicine and Gastroenterology Policlinico A.GemelliCatholic University of Romelargo A.Gemelli800168 RomeItaly

Portal vein thrombosis(PVT) is one of the most common complications occurring during the natural course of liver *** though PVT is often asymptomatic,the worsening of liver function,an unexpected episode of gastrointestinal bleeding or ascitic decompensation may be landmarks of PVT *** these clinical manifestations,it is debated whether PVT really has an impact on liver cirrhosis natural history or rather represents only one of its *** PVT development should not only be considered as a matter of impaired blood flow or pro-coagulation *** one hand,PVT seems a consequence of the worsening in portal vein outflow due to the increased hepatic resistance in cirrhotic *** the other hand,vascular microthrombosis secondary to necroinflammation may cause liver ischemia and infarction,with loss of hepatic tissue(parenchymal extinction) which is replaced by fibrotic ***,PVT might also be considered as the overt manifestation of the liver fibrosing process evolution and anticoagulant therapy may thus have microscopic indirect effects also on the progression of liver *** present,a connection between PVT development and the progression of liver fibrosis/cirrhosis has not yet been ***,it is not clear if PVT development may worsen cirrhotic patients' outcome by *** authors tried to assess liver transplant benefit in PVT cirrhotic patients but data are *** this review,we will try to answer these questions,providing a critical analysis of data reported in literature.

关键词：血栓形成肝硬化门静脉患者肝纤维化 PVT 抗凝血剂标志性建筑

Eubiotic properties of rifaximin: Disruption of the traditional concepts in gut microbiota modulation

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World Journal of Gastroenterology 2017年第25期23卷 4491-4499页

作者： francesca romana ponziani Maria Assunta Zocco francesca D’Aversa Maurizio Pompili Antonio Gasbarrini Internal Medicine Gastroenterology and Hepatology Division Agostino Gemelli Hospital

Antibiotics are usually prescribed to cure infections but they also have significant modulatory effects on the gut microbiota. Several alterations of the intestinal bacterial community have been reported during antibiotic treatment, including the reduction of beneficial bacteria as well as of microbial alpha-diversity. Although after the discontinuation of antibiotic therapies it has been observed a trend towards the restoration of the original condition, the new steady state is different from the previous one, as if antibiotics induced some kind of irreversible perturbation of the gut microbial community. The poorly absorbed antibiotic rifaximin seem to be different from the other antibiotics, because it exerts non-traditional effects additional to the bactericidal/bacteriostatic activity on the gut microbiota. Rifaximin is able to reduce bacterial virulence and translocation, has anti-inflammatory properties and has been demonstrated to positively modulate the gut microbial composition. Animal models, culture studies and metagenomic analyses have demonstrated an increase in Bifidobacterium, Faecalibacterium prausnitzii and Lactobacillus abundance after rifaximin treatment, probably consequent to the induction of bacterial resistance, with no major change in the overall gut microbiota composition. Antibiotics are therefore modulators of the symbiotic relationship between the host and the gut microbiota. Specific antibiotics, such as rifaximin, can also induce eubiotic changes in the intestinal ecosystem; this additional property may represent a therapeutic advantage in specific clinical settings.

关键词：肠的细菌抗菌素 Rifaximin 内脏 microbiota Eubiosis Dysbiosis 毁坏 microbiota 调整

Prevention and treatment of hepatic encephalopathy: Focusing on gut microbiota

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World Journal of Gastroenterology 2012年第46期18卷 6693-6700页

作者： Matteo Garcovich Maria Assunta Zocco Davide Roccarina francesca romana ponziani Antonio Gasbarrini Department of Internal Medicine Catholic University of Sacred Heart

The gut flora plays an important role in the pathogenesis of the complications of cirrhosis. Hepatic encephalopathy (HE) represents a broad continuum of neuropsychological dysfunction in patients with acute or chronic liver disease and/or porto-systemic shunting of blood flow and it manifests with progressive deterioration of the superior neurological functions. The pathophysiology of this disease is complex, as it involves overproduction and reduced metabolism of various neurotoxins, particularly ammonia. Management of HE is diversified and requires several steps: elimination of precipitating factors, removal of toxins, proper nutritional support, modulation of resident fecal flora and downregulation of systemic and gut-derived inflammation. This review will provide an overview of gut barrier function and the influence of gut-derived factors on HE, focusing on the role of gut microbiota in the pathogenesis of HE and the recent literature findings on its therapeutic manipulation.

关键词：肠道菌群肝性脑病治疗预防发病机制神经功能肝脏疾病功能障碍

Treatment of hepatocellular carcinoma in patients with portal vein tumor thrombosis: Beyond the known frontiers

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World Journal of Gastroenterology 2019年第31期25卷 4360-4382页

作者： Lucia Cerrito Brigida Eleonora Annicchiarico Roberto Iezzi Antonio Gasbarrini Maurizio Pompili francesca romana ponziani Division of Internal Medicine Gastroenterology and Hepatology UnitFondazione Policlinico Universitario Agostino Gemelli IRCCSUniversitàCattolica del Sacro CuoreRome 00168Italy Department of Bioimaging and Radiological Sciences Institute of RadiologyFondazione Policlinico Universitario Agostino Gemelli IRCCSUniversitàCattolica del Sacro CuoreRome 00168Italy

Hepatocellular carcinoma is one of the most frequent malignant tumors worldwide:Portal vein tumor thrombosis(PVTT)occurs in about 35%-50%of patients and represents a strong negative prognostic factor,due to the increased risk of tumor spread into the bloodstream,leading to a high recurrence *** this reason,it is a contraindication to liver transplantation and in several prognostic scores sorafenib represents its standard of care,due to its antiangiogenetic action,although it can grant only a poor prolongation of life *** scientific evidences lead to consider PVTT as a complex anatomical and clinical condition,including a wide range of patients with different prognosis and new treatment possibilities according to the degree of portal system involvement,tumor biological aggressiveness,complications caused by portal hypertension,patient’s clinical features and tolerance to antineoplastic *** median survival has been reported to range between 2.7 and 4 mo in absence of therapy,but it can vary from 5 mo to 5 years,thus depicting an extremely variable *** this reason,it is extremely important to focus on the most adequate strategy to be applied to each group of PVTT patients.

关键词： Portal vein tumor thrombosis Sorafenib Systemic chemotherapy Transarterial chemoembolization Transarterial radioembolization Percutaneous ablation therapies Combined therapies Surgery Liver transplantation

Subclinical atherosclerosis is linked to small intestinal bacterial overgrowth via vitamin K2-dependent mechanisms

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World Journal of Gastroenterology 2017年第7期23卷 1241-1249页

作者： francesca romana ponziani Maurizio Pompili Enrico Di Stasio Maria Assunta Zocco Antonio Gasbarrini Roberto Flore Internal Medicine Gastroenterology and HepatologyAgostino Gemelli Hospital Biochemistry Agostino Gemelli Hospital Internal Medicine and Vascular Medicine Agostino Gemelli Hospital

AIM To assess the rate of matrix Gla-protein carboxylation in patients with small intestinal bacterial overgrowth(SIBO) and to decipher its association with subclinical *** Patients with suspected SIBO who presented with a low risk for cardiovascular disease and showed no evidence of atherosclerotic plaques were included in the study. A glucose breath test was performed in order to confirm the diagnosis of SIBO and vascular assessment was carried out by ultrasound examination. Plasma levels of the inactive form of MGP(dephosphorylateduncarboxylated matrix Gla-protein) were quantified by ELISA and vitamin K2 intake was estimated using a food frequency *** Thirty-nine patients were included in the study. SIBO was confirmed in 12/39(30.8%) patients who also presented with a higher concentration ofdephosphorylated-uncarboxylated matrix Gla-protein(9.5 μg/L vs 4.2 μg/L; P = 0.004). Arterial stiffness was elevated in the SIBO group(pulse-wave velocity 10.25 m/s vs 7.68 m/s; P = 0.002) and this phenomenon was observed to correlate linearly with the levels of dephosphorylated-uncarboxylated matrix Gla-protein(β = 0.220, R2 = 0.366, P = 0.03). Carotid intima-media thickness and arterial calcifications were not observed to be significantly elevated as compared to *** SIBO is associated with reduced matrix Gla-protein activation as well as arterial stiffening. Both these observations are regarded as important indicators of subclinical atherosclerosis. Hence, screening for SIBO, intestinal decontamination and supplementation with vitamin K2 has the potential to be incorporated into clinical practice as additional preventive measures.

关键词：小肠的细菌的增生维生素 K Dysbiosis 动脉粥样硬化心血管的疾病风险

COVID-19 as a trigger of irritable bowel syndrome:A review of potential mechanisms

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World Journal of Gastroenterology 2021年第43期27卷 7433-7445页

作者： Carlo Romano Settanni Gianluca Ianiro francesca romana ponziani Stefano Bibbò Jonathan Philip Segal Giovanni Cammarota Antonio Gasbarrini UnitàOperativa Complessa Medicina Interna e Gastroenterologia Dipartimento di Scienze Mediche e ChirurgicheFondazione Policlinico Universitario"A.Gemelli"IRCCSRome 00168Italy Istituto di Patologia Speciale Medica UniversitàCattolica del Sacro CuoreRome 00168Italy Department of Gastroenterology and Hepatology Hillingdon HospitalUxbridge HA13UJUnited Kingdom

In December 2019 a novel coronavirus disease 2019(COVID-19),caused by the severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),started spreading from Wuhan city of Chinese Hubei province and rapidly became a global *** symptoms of the disease range from paucisymptomatic disease to a much more severe *** symptoms of the initial phase include fever and cough,with possible progression to acute respiratory distress *** manifestations such as diarrhoea,vomiting and abdominal pain are reported in a considerable number of affected individuals and may be due to the SARS-CoV-2 tropism for the peptidase angiotensin receptor *** intestinal homeostasis and microenvironment appear to play a major role in the pathogenesis of COVID-19 and in the enhancement of the systemic inflammatory ***-term consequences of COVID-19 include respiratory disturbances and other disabling manifestations,such as fatigue and psychological *** date,there is a paucity of data on the gastrointestinal sequelae of SARS-CoV-2 *** COVID-19 can directly or indirectly affect the gut physiology in different ways,it is plausible that functional bowel diseases may occur after the recovery because of potential pathophysiological alterations(dysbiosis,disruption of the intestinal barrier,mucosal microinflammation,post-infectious states,immune dysregulation and psychological stress).In this review we speculate that COVID-19 can trigger irritable bowel syndrome and we discuss the potential mechanisms.

关键词： SARS-CoV-2 COVID-19 Irritable bowel syndrome Microbiota Dysbiosis Gut-brain axis