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Evaluation of the prognostic value of liver stiffness in patients with hepatitis C virus treated with triple or dual antiviral therapy:A prospective pilot study

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World Journal of Gastroenterology 2015年第10期21卷 3013-3019页

作者： Cristina Stasi Alessia Piluso Umberto Arena Elena Salomoni Paolo Montalto Monica Monti Barbara Boldrini Giampaolo Corti Fabio Marra Giacomo Laffi Stefano Milani Anna Linda Zignego Department of Experimental and Clinical Medicine University of Florence Health Agency of Tuscany Gastrointestinal Endoscopy Unit Ospedale SS Cosma e Damiano Department of Biomedical Experimental and Clinical sciencesUniversity of Florence

AIM:To evaluate the association between liver stiffness(LS) prior to the initiation of dual/triple therapy and viral response.METHODS:LS was measured in all patients before treatment was administered.The therapeutic approach was based on hepatic,virological,and immunological evaluations and considered the fact that patients with severe fibrosis(F3)or compensated cirrhosis(F4)in Child-Pugh class A are the primary candidates for triple therapy.In total,65 hepatitis C virus(HCV)patients were treated with Peg-interferon/ribavirin(Peg-IFN/RBV);24patients were classified as genotypes 1/4(36.92%),and41 patients were classified as genotypes 2/3(63.08%)(dual therapy).In addition,20 HCV treatment-experienced genotype 1 patients were treated with Peg IFN-RBV and boceprevir(triple therapy).Wilcoxon rank-sum tests were used to compare the groups.RESULTS:LS significantly differed between dual therapy and triple therapy(P=0.002).The mean LS value before dual therapy treatment was 8.61±5.79k Pa and was significantly different between patients achieving a sustained virologic response(SVR)24weeks after therapy and those who did not(7.23±5.18 k Pa vs 11.72±5.99 k Pa,respectively,P=0.0003).The relative risk of non-response to therapy was 4.45(95%CI:2.32-8.55).The attributable risk of non-response to therapy was 49%.The mean LSvalue before triple therapy treatment was 13.29±8.57k Pa and was significantly different between patients achieving and not achieving SVR24(9.41±5.05 vs19.11±9.74,respectively;P=0.008).The relative risk of non-response to therapy was 5.57%(95%CI:1.50-20.65).The attributable risk of non-response to therapy(70%)was increased compared with dual therapy patients.Pre-treatment stiffness>12 k Pa was significantly associated with non-SVR(P<0.025)in both groups.CONCLUSION:Pre-treatment liver stiffness may be useful for predicting the response to treatment in patients treated with either dual or triple anti-HCV therapy.

关键词： Antiviral therapy Chronic hepatitis C Fibrosis Liv

Hepato-splenic lymphoma:a rare entity mimicking acute hepatitis:A case report

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World Journal of Gastroenterology 2003年第6期9卷 1381-1384页

作者： Federico Perfetto Roberto Tarquini Francesco Mancuso Simonetta di Lollo Silvia Tozzini Giampiero Bellesi Giacomo Laffi Department of Internal Medicine University of FlorenceItaly Department of Human Pathology and Oncology University of FlorenceItaly Department of Hematology University of FlorenceItaly

We reported a case of non-Hodgkin's lymphoma where liver involvement was the predominant clinical manifestation. A 27-year old man presented wiht markedly elevated serum aspartate aminotrasferase, alanine aminotransferase and lactate dehydrogenase, reduced prothrombin activity, thrombocytopenic purpura and hepato-splenomegaly without adenopathy. Viral, toxic,autoimmune and metabolic liver diseases were excluded.Bone marrow biopsy showed an intracapillary infiltration of T-lymphocytes with no evidence of lipid storage disease.Because of a progressive spleen enlargement, splenectomy was performed. Histological examination showed lymphomatous intrasinuses invasion of the spleen.Immunohistochemical investigation revealed the T phenotype of the neoplastic cells: CD45+, CD45RO+,CD3+, CD4-, CD8-, TIA1-. About 50 % of the lymphoid cells expressed CD56 antigen. The diagnosis of hepatosplenic T cell lymphoma was done. The patient was treated with chemotherapy, which induced a complete remission. Eighteen months later, he had a first relapse with increased aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase,thrombocytopenic purpura and blast in the peripheral blood.In spite of autologous bone marrow transplantation, he died twenty months after the diagnosis. Even in the absence of a mass lesion or lymphoadenopathy, hepatosplenic Tcell lymphoma should be considered in the differential diagnosis of a patient whose clinical course is atypical for acute hepatic dysfunction.

关键词：肝脾淋巴瘤临床表现急性肝炎病例报告

在姿势的挑战以后的肝脏硬化症的病人的非侵略的连续血液动力学的评估

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World Journal of Hepatology 2012年第4期4卷 149-153页

作者： Roberto Tarquini Gianluigi Mazzoccoli Fulvio Fusi Giacomo Laffi Gian Franco Gensini Salvatore Mario Romano Department of Internal Medicine School of Medicine 50134 Florence Italy Department of Internal Medicine and Chronobiology Unit Scientific Institute and Regional General Hospital Casa Sollievo della Sofferenza 71013 San Giovanni Rotondo (FG) Italy Heart and Vessel Department School of Medicine 50134 Florence Italy

AIM: To assess whether Most Care is able to detect the cardiovascular alterations in response to physiological stress (posture). METHODS: Non invasive hemodynamic was assessed in 26 cirrhotic patients compared to healthy subjects, both in the supine and standing positions. RESULTS: In baseline conditions, when compared to healthy subjects, cirrhotic patients showed significantly lower values of dicrotic and diastolic pressures and systemic vascular resistance. While in the standing position, cirrhotic patients showed higher values of cardiac index, stroke volume index and cardiac cycle efficiency. When returning to the supine position, cirrhotic patients exhibited lower values of dicrotic and diastolic pressures and systemic vascular resistance in the presence of higher values of cardiac index, stroke volume index and cardiac cycle efficiency.

关键词： Liver cirrhosis Non-invasive hemodynamic Pressure recording analytical method Posture

Long-term albumin infusion improves survival in patients with cirrhosis and ascites: An unblinded randomized trial

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World Journal of Gastroenterology 2006年第9期12卷 1403-1407页

作者： Roberto Giulio Romanelli Giorgio La Villa Giuseppe Barletta Francesco Vizzutti Fabio Lanini Umberto Arena Vieri Boddi Roberto Tarquini Pietro Pantaleo Paolo Gentilini Giacomo Laffi Department of Internal Medicine University of Florence School of Medicine FlorenceItaly Department of Heart and Vessels University of Florence School of Medicine FlorenceItaly Department of Public Health University of Florence School of Medicine FlorenceItaly Giacomo Laffi Department of Internal Medicine University of Florence School of Medicine Florence Italy

瞄准：在幸存上调查长期的白朊管理的效果，腹水的复发和另外的复杂并发症的发作。方法：为第一发作的腹水招收的 100 个连续病人被使随机化加人的白朊收到利尿剂第一年和 25 g 里的 25 g/wk 每二 wk 此后(组 1 ) 或利尿剂独自一个(组 2... 详细信息

瞄准：在幸存上调查长期的白朊管理的效果，腹水的复发和另外的复杂并发症的发作。方法：为第一发作的腹水招收的 100 个连续病人被使随机化加人的白朊收到利尿剂第一年和 25 g 里的 25 g/wk 每二 wk 此后(组 1 ) 或利尿剂独自一个(组 2 ) 。没有肝移植，主要端点是幸存。第二等的端点是腹水的复发和另外的复杂并发症的出现。结果：中部的后续是 84 (2-120 ) 瞬间。对待白朊的病人有显著地更大的累积幸存率(Breslow test=7.05， P=0.0078 ) 并且腹水复发的更低的概率(51% 对 94% ， P<0.0001 ) 。长期的白朊注入导致了 16 瞬间的幸存的吝啬的增加。结论：在第一发作的腹水以后的长期的白朊管理显著地改进病人的幸存并且减少腹水复发的风险。

关键词：白蛋白硬化腹水病理机制

慢性肝病的血小板减少症：来自移植患者的经验

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传染病网络动态 2007年第12期 27-29页

作者： giacomo laffi 董培玲（编译）杨月（审校）

晚期肝硬化病人止血障碍，原因复杂，其中血小板减少症是一常见表现。这一现象的发病机制很复杂，脾的血池储存、血小板的消耗增加和／或产生减少被认为是发病因素。采用放射性同位素示踪标记血小板的动力学研究显示血小板汇集增加、平... 详细信息

晚期肝硬化病人止血障碍，原因复杂，其中血小板减少症是一常见表现。这一现象的发病机制很复杂，脾的血池储存、血小板的消耗增加和／或产生减少被认为是发病因素。采用放射性同位素示踪标记血小板的动力学研究显示血小板汇集增加、平均血小板寿命下降。而且发现轻度肝硬化患者平均血小板计数几乎正常，因为骨髓产生血小板较正常情况增加两倍。几项研究证实这一假说：当肝脏功能进行性衰竭时，TPO（血小板生成因子）合成减少导致对骨髓刺激不当，低血小板血症随之发生。

关键词：血小板减少症慢性肝病血小板生成因子移植放射性同位素肝硬化病人血小板计数肝硬化患者

Uveitis in autoimmune hepatitis:A case report

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World Journal of Gastroenterology 2006年第10期12卷 1637-1640页

作者： Roberto Giulio Romanelli Giorgio La Villa Fabio Almerigogna Francesco Vizzutti Elena Di Pietro Valentina Fedi Paolo Gentilini Giacomo Laffi Department of Internal Medicine University of Florence-School of Medicine Viale Morgagni85-50134 FlorenceItaly

在这份病案报告，我们第一次描述在自体免疫的肝炎(AIH ) 和眼色素层炎之间的一个协会，没有关于另外的可能的病原学的任何疑问，例如 HCV，自从在为 HCV 相关的肝炎的测试能是可得到的以前，所有旧报告与虹膜睫状体炎描述 AIH 的协会... 详细信息

在这份病案报告，我们第一次描述在自体免疫的肝炎(AIH ) 和眼色素层炎之间的一个协会，没有关于另外的可能的病原学的任何疑问，例如 HCV，自从在为 HCV 相关的肝炎的测试能是可得到的以前，所有旧报告与虹膜睫状体炎描述 AIH 的协会。有反常的肝功能测试和球结膜的充血的一个 38 岁的商人进入医院。在承认，与坚持的发烧介绍的病人，关节痛，结膜充血，白细胞增多和增加的 ESR 前的六年，指了尖锐风湿热。系统病的存在，通常与眼色素层炎联系的大多数，没有结果，被调查，病人然后与热门 corticosteroids 被对待。他解决的症状。为反原子的抗体的测试是阳性的，在 1:320 的一个效价，与一个有斑点、核仁的染色的模式。肝超声与肝的增加的回响结构显示出温和肝肿大。经皮的肝活体检视在超声帮助下面被执行。组织学的检查在门，仙子门和小叶片的区域上显示出 necroinflammation，纤维变性门道与仙子门纤维变性和偶尔的 portal-to-portal bridgings，但是未经触动的肝的建筑学。某 hepatocytes 在小叶片的区域显示出含铁血黄素的恰好看得清的小粒。胆小管没有任何重要词法改变。METAVIR 分数是 A2-F3，根据修改 HAI 等级 / 纤维变性阶段。病人被诊断与温和活动和纤维变性有 AIH 并且在 25 mg 泼尼松上被解除，进入临床、生物化学的宽恕，进一步的证实诊断。在分泌物以后，病人继续在 5 mg 的剂量作为一个门诊病人与 corticosteroids 有治疗。在 2002 年 1 月，病人被重新接纳到医院。为反原子的抗体的测试是阳性的，在 1:320 的一个效价，与一个有斑点、核仁的染色的模式。反光滑的肌肉抗体测试也是阳性的(1:160 ) ，当 anti-LKM 抗体是否定的时。眼科学检查在角膜在左眼，和基质损害的前房揭示了煽动性的房间和 proteinaceous 闪光。他在抑制免疫力的治疗(加为二个星期的热门抗菌素治疗的 5 mg 泼尼松) 上被维持然后排出。症状的完全的宽恕在后续上被登记。目前(2005 年 7 月) ，病人在泼尼松(5 mg ) 上并且没有症状。肝功能测试也在正常范围以内。

关键词：葡萄膜炎自体免疫肝炎病理机制治疗

Predictors of survival in patients with established cirrhosis and hepatocellular carcinoma treated with sorafenib

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World Journal of Gastroenterology 2014年第3期20卷 786-794页

作者： Andrea L Inghilesi Donatella Gallori Lorenzo Antonuzzo Paolo Forte Daniela Tomcikova Umberto Arena Stefano Colagrande Silvia Pradella Bernardo Fani Elena Gianni Luca Boni Giacomo Laffi Francesco Di Costanzo Fabio Marra Dipartimento di Medicina Sperimentale e Clinica Università degli Studi di Firenze Oncologia Medica Azienda Ospedaliero-Universitaria Careggi Gastroenterologia 2 Azienda Ospedaliero-Universitaria Careggi Centro per il Coordinamento delle Sperimentazioni Cliniche Istituto Toscano Tumoriand Azienda Ospedaliero-Universitaria Careggi Dipartimento di Scienze Biomediche Sperimentali e ClinicheUniversità degli Studi di Firenze

AIM:To investigate in greater detail the efficacy and safety of sorafenib for the treatment of hepatocellular carcinoma(HCC)in patients with established cirrhosis.METHODS:From October 2009 to July 2012 patients with an established diagnosis of cirrhosis and HCC treated with sorafenib were consecutively enrolled.According to the Barcelona Clinic Liver Cancer(BCLC)classification,patients were in the advanced stage(BCLC-C)or in the intermediate stage(BCLC-B)but unfit or unresponsive to other therapeutic strategies.Treatment was evaluated performing a 4-phase computed tomography or magnetic resonance imaging scan every 2-3 mo,and analyzed according to the modified Response Evaluation Criteria in Solid Tumors.Sorafenib was administered at 800 mg/d,until radiological progression or occurrence of unacceptable adverse events(AEs).Univariate and multivariate analyses identified predictors of 16-wk clinical benefit and overall survival.RESULTS:Forty-four patients were enrolled,15 had intermediate HCC and 14 a Child-Pugh score of B7.AEs caused treatment interruption in 19 patients(43%),and median treatment duration was shorter in this subset(5 wk vs 19 wk,P<0.001)and in the BCLC-C subgroup(13 wk vs 40 wk,P=0.015).No significant differences in the reason for treatment interruption or in treatment duration were found comparing patients in Child-Pugh class A vs B or in patients older or younger than 70 years.After 16 wk of treatment,18 patients(41%)had stable disease or partial response.Patients with viral infection or BCLC-C were at higher risk of disease progression.ECOG,extrahepatic spread,macrovascular invasion,alpha-fetoprotein or alkaline phosphatase levels at admission were independent predictors of overall survival.CONCLUSION:In patients with cirrhosis and HCC treated with sorafenib,AEs are a common cause of early treatment withdrawal.Vascular invasion and extrahepatic spread condition early response to treatment and survival.Baseline biochemical parameters may be helpful to identify patients at higher risk of shorter

关键词： Hepatocellular carcinoma Sorafenib Cirrhosis Adver

Clinical epidemiology of chronic viral hepatitis B:A Tuscany real-world large-scale cohort study

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World Journal of Hepatology 2018年第5期10卷 409-416页

作者： Cristina Stasi Caterina Silvestri Roberto Berni Maurizia Rossana Brunetto Anna Linda Zignego Cristina Orsini Stefano Milani Liana Ricciardi Andrea De Luca Pierluigi Blanc Cesira Nencioni Donatella Aquilini Alessandro Bartoloni Giampaolo Bresci Santino Marchi Franco Filipponi Piero Colombatto Paolo Forte Andrea Galli Sauro Luchi Silvia Chigiotti Alessandro Nerli Giampaolo Corti Rodolfo Sacco Paola Carrai Angelo Ricchiuti Massimo Giusti Paolo Almi Andrea Cozzi Silvia Carloppi Giacomo Laffi Fabio Voller Francesco Cipriani Observatory of Epidemiology Regional Health Agency of TuscanyFlorence 50141Italy Center for Systemic Manifestations of Hepatitis Viruses(MaSVE) Internal Medicine and Liver UnitDepartment of Experimental and Clinical MedicineCareggi University HospitalFlorence 50134Italy Web Solutions Data Visualization and Scientific DocumentationRegional Health Agency of TuscanyFlorence 50141Italy Hepatology Unit Department of Clinical and Experimental MedicineUniversity Hospital of PisaPisa 56100Italy Gastroenterology Research Unit Department of Experimental and Clinical Biomedical Sciences“Mario Serio”Careggi University HospitalFlorence 50134Italy Infectious Disease Unit Hospital of LuccaLucca 55100Italy Infectious Diseases Unit Department of Medical BiotechnologiesSiena University HospitalSiena 53100Italy Infectious Disease Unit “S.Maria Annunziata”HospitalPonte a Niccheri 50012Italy Infectious Disease Unit Hospital of GrossetoGrosseto 58100Italy Infectious Disease Unit Hospital of PratoPrato 59100Italy Infectious and Tropical Diseases Unit Department of Experimental and Clinical MedicineCareggi University HospitalFlorence 50134Italy Gastroenterology and Metabolic Disorders Department of SurgeryCisanello University HospitalPisa 56100Italy Gastroenterology Unit Department of Translational Research and New Technologies in Medicine and SurgeryCisanello University Hospital of PisaPisa 56100Italy Liver Surgery and Transplantation Unit Department of Surgical PathologyMedicineMolecular and Critical AreaCisanello University HospitalPisa 56100Italy Internal Medicine Unit “San Jacopo”HospitalPistoia 51100Italy Infectious Diseases and Hepatology Unit Department of Internal and Specialized MedicineUniversity Hospital of SienaSiena 53100Italy Gastroenterology Unit San Giuseppe HospitalEmpoli 50053Italy Internal Medicine and Liver Unit Department of Experimental and Clinical MedicineCareggi University HospitalFlorence 50135Italy Department of Prevention Central Tuscany Local UnitFlorence 5

AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus(HBV)-infected patients in the Tuscan public health care system.METHODS This study used a cross-sectional cohort design. We evaluated chronic viral hepatitis patients with HBV referred to the outpatient services of 16 hospital units. Information in the case report forms included main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations, and eligibility for treatment or ongoing therapy and liver transplantation. RESULTS Of 4015 chronic viral hepatitis patients, 1096(27.3%) were HBV infected. The case report form was correctly completed for only 833 patients(64% males, 36% females; mean age 50.1 ± 15.4). Of these HBV-infected patients, 73% were Caucasian, 21% Asian, 4% Central African, 1% North African and 1% American. Stratifying patients by age and nationality, we found that 21.7% of HBV-infected patients were aged < 34 years(only 2.8% were Italian). The most represented routes of transmission were nosocomial/dental procedures(23%), mother-to-child(17%) and sexual transmission(12%). The most represented HBV genotypes were D(72%) and A(14%). Of the patients, 24.7% of patients were HBe Ag positive, and 75.3% were HBe Ag negative. Of the HBV patients 7% were anti-HDV positive. In the whole cohort, 26.9% were cirrhotic(35.8% aged < 45 years), and 47% were eligible for or currently undergoing treatment, of whom 41.9 % were cirrhotic. CONCLUSION Only 27.3% of chronic viral hepatitis patients were HBV infected. Our results provide evidence of HBV infection in people aged < 34 years, especially in the foreign population not protected by vaccination. In our cohort of patients, liver cirrhosis was also found in young adults.

关键词： Hepatitis B virus infection Liver fibrosis Cirrhosis Public health Epidemiology