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Epidemiological and clinical aspects of hepatitis B virus infection in Italy over the last 50 years

World Journal of Gastroenterology 2022年第26期28卷 3081-3091页

作者： Caterina sagnelli Antonello Sica Massimiliano Creta Armando Calogero Massimo Ciccozzi evangelista sagnelli Department of Mental Health and Public Medicine Section of Infectious DiseasesUniversity of Campania“Luigi Vanvitelli”Naples 80138Italy Department of Precision Medicine University of Campania“Luigi Vanvitelli”Naples 80131Italy Department of Neurosciences Reproductive Sciences and OdontostomatologyUniversity of Naples Federico IINaples 80138Italy Department of Advanced Biomedical Sciences-UO General Surgery University Federico II of NaplesNaples 80127Italy Medical Statistics and Molecular Epidemiology Unit Campus Bio-Medico UniversityRome 80138Italy

A relevant gradual reduction of both the incidence rate of acute hepatitis B(AHB)and prevalence of chronic hepatitis B has occurred in Italy in the last 50 years,due to substantial epidemiological changes:Improvement in socioeconomic and hygienic conditions,reduction of the family unit,accurate screening of blood donations,abolition of re-usable glass syringes,hepatitis B virus(HBV)-universal vaccination started in 1991,use of effective well tolerated nucleo(t)side analogues able to suppress HBV replication available from 1998,and educational mediatic campaigns against human immunodeficiency virus infection focusing on the prevention of sexual and parenteral transmission of *** an example,AHB incidence has gradually decreased from 10/100000 inhabitants in 1985 to 0.21 in ***,the coronavirus disease 2019(COVID-19)pandemic has interrupted the trend towards HBV *** fact,several HBV chronic carriers living in the countryside have become unable to access healthcare facilities for screening,diagnosis,clinical management,and nucleo(t)side analogue therapy in the COVID-19 pandemic,mainly for anxiety of becoming infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),movement restrictions,and reduced gains from job *** addition,one-third of healthcare facilities and personnel for HBV patients have been devolved to the COVID-19 assistance.

关键词： Hepatitis B virus Hepatitis B virus epidemiology Acute hepatitis B COVID-19

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Impact of comorbidities on the severity of chronic hepatitis B at presentation

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World Journal of Gastroenterology 2012年第14期18卷 1616-1621页

作者： evangelista sagnelli Tommaso Stroffolini Alfonso Mele Michele Imparato Caterina sagnelli Nicola Coppola Piero Luigi Almasio Department of Public Medicine Section of Infectious DiseasesSecond University of Naples80132 NaplesItaly Department of Infectious and Tropical Diseases Policlinico Umberto I00161 RomeItaly Laboratory of Epidemiology Clinical Epidemiology UnitIstituto Superiore di Sanità00161 RomeItaly Department of Clinical and Experimental Medicine and Surgery "F.Magrassi e A.Lanzara" Second University of Naples80132 NaplesItaly Gastroenterology Unit University of Palermo90127 PalermoItaly

AIM:To evaluate the clinical relevance of each cofactor on clinical presentation of chronic hepatitis ***:Out of 1366 hepatitis B surface antigen(HBsAg) positive subjects consecutively observed in 79 Italian hospitals,53(4.3%) showed as the only cofactor hepatitis D virus(HDV) infection [hepatitis B virus(HBV)/HDV group],130(9.5%) hepatitis C virus(HCV)(group HBV/HCV),6(0.4%) human immunodeficiencyvirus(HIV)(group HBV/HIV),138(10.2%) alcohol abuse(group HBV/alcohol);109(8.0%) subjects had at least two cofactors and 924 were in the cofactor-free(CF) ***:Compared with patients in group CF those in group HBV/alcohol were older and more frequently had cirrhosis(P < 0.001),those in group HBV/HDV were younger(P < 0.001),more frequently resided in the south of the country and had cirrhosis(P <0.001),those in group HBV/HCV were older(P < 0.001) and more frequently had cirrhosis(P < 0.001).These cofactors were all independent predictors of liver cirrhosis in HBsAg positive *** analysis showed that an older age [odds ratio(OR) 1.06,95% CI:1.05-1.08],alcohol abuse with more than 8 drinks daily(OR 2.89,95% CI:1.81-4.62) and anti-HDV positivity(OR 3.48,95% CI:2.16-5.58) are all independently associated with liver *** association was found also for anti-HCV positivity in univariate analysis,but it was no longer associated(OR 1.23,95% CI:0.84-1.80) at multivariate ***:Older age,HDV infection and alcohol abuse are the major determinants of severe liver disease in chronic HBV infection,while HCV replication plays a lesser role in the severity of hepatic damage.

关键词：慢性乙型肝炎合并症乙肝表面抗原乙型肝炎病毒丙型肝炎病毒病毒感染多元统计分析临床意义

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Reactivation of hepatitis B virus infection in patients with hemolymphoproliferative diseases, and its prevention

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World Journal of Gastroenterology 2019年第26期25卷 3299-3312页

作者： Caterina sagnelli Mariantonietta Pisaturo Federica Calò Salvatore Martini evangelista sagnelli Nicola Coppola Department of Mental Health and Public Medicine Section of Infectious Diseases University of Campania Luigi Vanvitelli

Reactivation of hepatitis B virus(HBV)replication is characterized by increased HBV-DNA serum values of about 1 log or by HBV DNA turning positive if previously undetectable in serum,possibly associated with liver damage and seldom *** to HBV reactivation,hepatitis B surface antigen(HBsAg)-negative/anti-HBc-positive subjects may revert to *** patients with hemo-lymphoproliferative disease,the frequency of HBV reactivation depends on the type of lymphoproliferative disorder,the individual's HBV serological status and the potency and duration of *** particular,it occurs in 10%-50%of the HBsAg-positive and in 2%-25%of the HBsAg-negative/anti-HBc-positive,the highest incidences being registered in patients receiving rituximab-based *** reactivation can be prevented by accurate screening of patients at risk and by a pharmacological prophylaxis with anti-HBV nucleo(t)sides starting 2-3 wk before the beginning of immunosuppressive treatment and covering the entire period of administration of immunosuppressive drugs and a long subsequent period,the duration of which depends substantially on the degree of immunodepression *** with significant HBV replication before immunosuppressive therapy should receive anti-HBV nucleo(t)sides as a long-term(may be life-long)*** review article is mainly directed to doctors engaged every day in the treatment of patients with onco-lymphoproliferative diseases,so that they can broaden their knowledge on HBV infection and on its reactivation induced by the drugs with high immunosuppressive potential that they use in the care of their patients.

关键词： Hepatitis B virus reactivation Hepatitis B virus infection Hemolymphoproliferative diseases Immunosuppressive therapy Hepatitis B virus therapy Hepatitis B virus prophylasis

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Hepatitis B virus/hepatitis D virus epidemiology: Changes over time and possible future influence of the SARS-CoV-2 pandemic

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World Journal of Gastroenterology 2021年第42期27卷 7271-7284页

作者： Caterina sagnelli Mariantonietta Pisaturo Caterina Curatolo Alessio Vinicio Codella Nicola Coppola evangelista sagnelli Department of Mental Health and Public Medicine Section of Infectious DiseasesUniversity of Campania Luigi VanvitelliNaples 80131Italy Department of Mental Health and Public Medicine University of CampaniaNaples 80135Italy

Hepatitis D virus(HDV)is a defective liver-tropic virus that needs the helper function of hepatitis B virus(HBV)to infect humans and *** is transmitted sexually or by a parenteral route,in co-infection with HBV or by super-infection in HBV chronic *** infection causes acute hepatitis that may progress to a fulminant form(7%-14%by super-infection and 2%-3%by HBV/HDV co-infection)or to chronic hepatitis(90%by HDV super-infection and 2%-5%by HBV/HDV co-infection),frequently and rapidly progressing to cirrhosis or hepatocellular carcinoma(HCC).Peg-interferon alfa the only recommended therapy,clears HDV in only 10%-20%of cases and,consequently,new treatment strategies are being *** endemicity progressively decreased over the 50 years from the identification of the virus,due to improved population lifestyles and economic levels,to the use of HBV nuclei(t)side analogues to suppress HBV replication and to the application of universal HBV vaccination *** changes are expected during the severe acute respiratory syndrome coronavirus-2 pandemic,unfortunately towards increased endemicity due to the focus of healthcare towards coronavirus disease 2019 and the consequently lower possibility of screening and access to treatments,lower care for patients with severe liver diseases and a reduced impulse to the HBV vaccination policy.

关键词： Hepatitis B virus/hepatitis delta virus SARS-CoV-2 COVID-19 Hepatitis delta virus infection Hepatitis D Hepatitis delta virus epidemiology

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Micro-RNAs in hepatitis B virus-related chronic liver diseases and hepatocellular carcinoma

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World Journal of Hepatology 2018年第9期10卷 558-570页

作者： evangelista sagnelli Nicoletta Potenza Lorenzo Onorato Caterina sagnelli Nicola Coppola Aniello Russo Department of Mental Health and Public Medicine Section of Infectious DiseasesUniversity of Campania Luigi Vanvitelli DISTABIF University of Campania "Luigi Vanvitelli"

MicroRNAs(miRNAs) are small non-coding RNAs that modulate gene expression at the post-transcriptional level by affecting both the stability and translation of complementary mRNAs. Several studies have shown that mi RNAs are important regulators in the conflicting efforts between the virus(to manipulate the host for its successful propagation) and the host(to inhibit the virus),culminating in either the elimination of the virus or its persistence. An increasing number of studies report a role of miRNAs in hepatitis B virus(HBV) replication and pathogenesis. In fact,HBV is able to modulate different host miRNAs,particularly through the transcriptional transactivator HBx protein and,conversely,different cellular miRNAs can regulate HBV gene expression and replication by a direct binding to HBV transcripts or indirectly targeting host factors. The present review will discuss the role of miRNAs in the pathogenesis of HBVrelated diseases and their role as a biomarker in the management of patients with HBV-related disease and as therapeutic targets.

关键词： Hepatitis B virus infection MicroRNAs Hepatitis B virus pathogenesis Molecular mechanisms

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TM6SF2 E167K variant predicts severe liver fibrosis for human immunodeficiency/hepatitis C virus co-infected patients, and severe steatosis only for a non-3 hepatitis C virus genotype

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World Journal of Gastroenterology 2016年第38期22卷 8509-8518页

作者： Caterina sagnelli Marco Merli Caterina Uberti-Foppa Hamid Hasson Anna Grandone Grazia Cirillo Stefania Salpietro Carmine Minichini Mario Starace Emanuela Messina Patrizia Morelli Emanuele Miraglia Del Giudice Adriano Lazzarin Nicola Coppola evangelista sagnelli Department of Clinical and Experimental Medicine and Surgery F. Magrassi e A. LanzaraSecond University of Naples 80131 Naples Italy Department of Infectious Diseases Vita-Salute University San Raffaele Scientific Institute 20127 Milan Italy Department of Pediatrics Second University of Naples 80131 Naples Italy Department of Mental Health and Public Medicine Section of Infectious Diseases Second University of Naples 80131 Naples Italy

AIM To evaluate the impact of the Glu167Lys(E167K) transmembrane 6 superfamily member 2(TM6SF2) variant on the biochemical and morphologic expression of liver lesions in human immunodeficiency virus(HIV)/hepatitis C virus(HCV) co-infected *** The study comprised 167 consecutive patients with HIV/HCV coinfection and biopsy-proven chronic hepatitis. A pathologist graded liver fibrosis and necroinflammation using the Ishak scoring system, and steatosis using Kleiner's scoring system. Patients were genotyped for TM6SF2 E167K(rs58542926) by real-time Polymerase chain reaction. The 167 patients, 35 therapy-naive and 132 receiving ART, were prevalently males(73.6%), the median age was 40.7 years and the immunological condition good(median CD4+ cells/mm3 = 505.5).RESULTS The 17 patients with the TM6SF2 E167 K variant, compared with the 150 with TM6SF2-E/E, showed higher AST(P = 0.02) and alanine aminotransferase(P = 0.02) and higher fibrosis score(3.1 ± 2.0 vs 2.3 ± 1.5, P = 0.05). In a multivariate analysis, TM6SF2 E167 K was independently associated with severe fibrosis. The same analysis showed that HCV-genotype 3, present in 42.2% of patients was an independent predictor of severe steatosis. The association of TM6SF2 E167 K with severe steatosis, absent for the whole group of 167 patients, was re-evaluated separately for HCVgenotype 3 and non-3 patients: No factor was independently associated with severe steatosis in the HCV-genotype-3 subgroup, whereas an independent association was observed between severe steatosis and TM6SF2 E167 K in non-3 HCV genotypes. No association between the TM6SF2 E167 K variant and severe liver necroinflammation was *** In HIV/HCV coinfection the TM6SF2 E167 K variant is an independent predictor of severe fibrosis, but appears to be independently associated with severe steatosis only for patients with a non-3 HCV genotype.

关键词： Human immunodeficiency virus/hepatitis C virus co-infection TM6SF2 Liver histology Liver steatosis Liver biopsy

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Hepatic flares in chronic hepatitis C: Spontaneous exacerbation vs hepatotropic viruses superinfection

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World Journal of Gastroenterology 2014年第22期20卷 6707-6715页

作者： evangelista sagnelli Caterina sagnelli Mariantonietta Pisaturo Nicola Coppola Section of Infectious Diseases Department of Mental Health and Public MedicineSecond University of Naples80131 NaplesItaly Mariantonietta Pisaturo Division of Infectious DiseasesAORN Sant’Anna e San Sebastiano di Caserta81100 CasertaItaly Department of Clinical and Experimental Medicine and Surgery "F Magrassi e A Lanzara" Second University of Naples80131 NaplesItaly

The hepatitis C virus(HCV)causes an acute infection that is frequently asymptomatic,but a spontaneous eradication of HCV infection occurs only in one-third of *** remaining two-thirds develop a chronic infection that,in most cases,shows an indolent course and a slow progression to the more advanced stagesof the *** a quarter of cases with chronic hepatitis C(CHC)develop liver cirrhosis with or without hepatocellular *** indolent course of the illness may be troubled by the occurrence of a hepatic flare,i.e.,a spontaneous acute exacerbation of CHC due to changes in the immune response,immunosuppression and subsequent restoration,and is characterized by an increase in serum aminotransferase values,a frequent deterioration in liver fibrosis and necroinflammation but also a high frequency of sustained viral response to pegylated interferon plus ribavirin treatment.A substantial increase in serum aminotransferase values during the clinical course of CHC may also be a consequence of a superinfection by other hepatotropic viruses,namely hepatitis B virus(HBV),HBV plus hepatitis D virus,hepatitis E virus,cytomegalovirus,particularly in geographical areas with high endemicity *** etiology of a hepatic flare in patients with CHC should always be defined to optimize follow-up procedures and clinical and therapeutic decisions.

关键词： Chronic hepatitis C virus infection Hepatic flares

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Epidemiology of acute and chronic hepatitis B and delta over the last 5 decades in Italy

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World Journal of Gastroenterology 2014年第24期20卷 7635-7643页

作者： evangelista sagnelli Caterina sagnelli Mariantonietta Pisaturo Margherita Macera Nicola Coppola Department of Mental Health and Public Medicine Section of Infectious DiseasesSecond University of Naples80131 NaplesItaly Department of Clinical and Experimental Medicine and Surgery "F.Magrassi e A.Lanzara" Second University of Naples80131 NaplesItaly

The spread of hepatitis B virus(HBV)infection has gradually decreased in Italy in the last 5 decades as shown by the steady reduction in the incidence rates of acute hepatitis B,from 10/100000 inhabitants in1984 to 0.85/100000 in 2012,and by the reduced prevalence of hepatitis B surface antigen(HBsAg)-positive cases among chronic hepatitis patients with different etiologies,from 60%in 1975 to about 10%in *** prevalence of HBsAg chronic carriers in the general population also decreased from nearly 3%in the 1980s to 1%in *** to HBV by its characteristics of defective virus,the hepatitis delta virus(HDV)has shown a similar epidemiological impact on the Italian population over *** incidence of acute HDV infection decreased from 3.2/100000 inhabitants in 1987 to 0.8/100000 in 2010 and the prevalence of HDV infection in HBsAg chronic carriers decreased from24%in 1990 to 8.5%in *** the beneficial effects of HBV mass vaccination introduced in 1991,the decreased endemicity of HBV and HDV infection in Italy paralleled the improvement in screening blood donations,the higher standard of living and impressive reduction in the birth rate associated with a marked reduction in the family size.A further contribution to the decline in HBV and HDV infections most probably came from the media campaigns to prevent the spread of human immunodeficiency virus infection by focusing the attention of the general population on the same routes of transmission of viral infections such as unsafe sexual intercourse and parenteral exposures of different kinds.

关键词： Acute hepatitis B Acute hepatitis delta Chronic vi

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Treatment of chronic hepatitis C in patients with HIV/HCV coinfection

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World Journal of Virology 2015年第1期4卷 1-12页

作者： Nicola Coppola Salvatore Martini Mariantonietta Pisaturo Caterina sagnelli Pietro Filippini evangelista sagnelli Department of Mental Health and Public Medicine Section of Infectious DiseasesSecond University of Naples Division of Infectious Diseases AORN Sant’Anna e San Sebastiano di Caserta Department of Clinical and Experimental Medicine and Surgery "F.Magrassi e A.Lanzara" Second University of Naples

Hepatitis C virus(HCV) infection is one of the mostfrequent causes of comorbidity and mortality in the human immunodeficiency virus(HIV) population, and liver-related mortality is now the second highest cause of death in HIV-positive patients, so HCV infection should be countered with adequate antiviral therapy. In 2011 began the era of directly acting antivirals(DAAs) and the HCV NS3/4A protease inhibitors telaprevir and boceprevir were approved to treat HCV-genotype-1 infection, each one in combination with pegylated interferon alfa(Peg-IFN) + ribavirin(RBV). The addition of the first generation DAAs, strongly improved the efficacy of antiviral therapy in patients with HCVgenotype 1, both for the HCV-monoinfected and HIV/HCV coinfected, and the poor response to Peg-IFN + RBV in HCV/HIV coinfection was enhanced. These treatments showed higher rates of sustained virological response than Peg-IFN + RBV but reduced tolerability and adherence due to the high pill burden and the several pharmacokinetic interactions between HCV NS3/4A protease inhibitors and antiretroviral drugs. Then in 2013 a new wave of DAAs arrived, characterized by high efficacy, good tolerability, a low pill burden and shortened treatment duration. The second and third generation DAAs also comprised IFN-free regimens, which in small recent trials on HIV-positive patients have shown comforting preliminary results in terms of efficacy, tolerability and adherence.

关键词： Hepatitis C virus infection Human immunodeficiency virus infection Anti-hepatitis C virus treatment Directly acting antivirals HIV/HCV coinfection Chronic hepatitis C

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Hepatitis c virus markers in infection by hepatitis c virus: In the era of directly acting antivirals

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World Journal of Gastroenterology 2015年第38期21卷 10749-10759页

作者： Nicola Coppola Mariantonietta Pisaturo Rosa Zampino Margherita Macera Caterina sagnelli evangelista sagnelli Department of Mental Health and Public Medicine Section of Infectious DiseasesSecond University of Naples Division of Infectious Diseases AORN Sant’Anna e San Sebastiano di Caserta Internal Medicine and Hepatology Second University of Naples Department of Clinical and Experimental Medicine and Surgery "F. Magrassi e A. Lanzara" Second University of Naples

About 130-170 million people are infected with the hepatitis C virus(HCV) worldwide and more than 350000 people die each year of HCV-related liver diseases. The combination of pegylated interferon(Peg-IFN) and ribavirin(RBV) was recommended as the treatment of choice for chronic hepatitis C for nearly a decade. In 2011 the directly acting antivirals(DAA) HCV NS3/4A protease inhibitors,telaprevir and boceprevir,were approved to treat HCV-genotype-1 infection,each in triple combination with Peg-IFN and RBV. These treatments allowed higher rates of SVR than the double Peg-IFN + RBV,but the low tolerability and high pill burden of these triple regimes were responsible for reduced adherence and early treatment discontinuation. The second and third wave DAAs introduced in 2013-2014 enhanced the efficacy and tolerability of anti-HCV treatment. Consequently,the traditional indicators for disease management and predictors of treatment response should be revised in light of these new therapeutic options. This review article will focus on the use of the markers of HCV infection and replication,of laboratory and instrumental data to define the stage of the disease and of predictors,if any,of response to therapy in the DAA era. The article is addressed particularly to physicians who have patients with hepatitis C in care in their everyday clinical practice.

关键词： Chronic hepatitis C Hepatitis C virus replication

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