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

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 Hepatic flares in immunocompromised patients Immunocompromised patients Hepatitis A virus superinfection

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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 viral hepatitis Hepatitis B virus epidemiology Hepatitis delta virus epidemiology

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Role of genetic polymorphisms in hepatitis C virus chronic infection

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World Journal of Clinical Cases 2015年第9期3卷 807-822页

作者： Nicola Coppola mariantonietta pisaturo Caterina Sagnelli Lorenzo Onorato Evangelista Sagnelli Department of Mental Health and Public Medicine Section of Infectious DiseasesSecond University of Naples Department of Clinical and Experimental Medicine and Surgery "F.Magrassi e A.Lanzara" Second University of Naples

AIM: To analyze the host genetics factors influencing the clinical course and the response to antiviral treatment in patients with chronic hepatitis C(CHC).METHODS: We conducted an electronic search on the Pub Med and MEDLINE(2000-2014) databases and Cochrane library(2000-2014). A total of 73 articles were retrieved and their data were extensively evaluated and discussed by the authors and then analyzed in this review ***: Several studies associated polymorphisms in the interleukin 28 B gene on chromosome 19(19q13.13) with a spontaneous viral clearance in acute hepatitis C and with the response to pegylated interferon(PegIFN)-based treatment in chronic hepatitis C patients. Other investigations demonstrated that inosine triphosphate pyrophosphatase genetic variants protect hepatitis C virus-genotype-1 CHC patients from ribavirin-induced anemia, and other studies that a polymorphism in the patatin-like phospholipase domain-containing protein 3 was associated with hepatic steatosis in CHC patients. Although not conclusive, some investigations suggested that the vitamin D-associated polymorphisms play an important role in the achievement of sustained virologic response in CHC patients treated with Peg-IFN-based antiviral therapy. Several other polymorphisms have been investigated to ascertain their possible impact on the natural history and on the response to treatment in patients with CHC, but the data are preliminary and warrant confirmation. CONCLUSION: Several genetic polymorphisms seem to influence the clinical course and the response to antiviral treatment in patients with CHC, suggesting individualized follow up and treatment strategies.

关键词： Single nucleotide polymorphism Hepatitis C virus infection Interleukin 28B Inosine triphosphate pyrophosphatase Patatin-like phospholipase domaincontaining protein 3

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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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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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Role of occult hepatitis B virus infection in chronic hepatitis C

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World Journal of Gastroenterology 2015年第42期21卷 11931-11940页

作者： Nicola Coppola Lorenzo Onorato mariantonietta pisaturo Margherita Macera Caterina Sagnelli Salvatore Martini Evangelista Sagnelli Department of Mental Health and Public Medicine Section of Infectious Diseases Second 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

The development of sensitive assays to detect small amounts of hepatitis B virus(HBV) DNA has favored the identification of occult hepatitis B infection(OBI), a virological condition characterized by a low level of HBV replication with detectable levels of HBV DNA in liver tissue but an absence of detectable surface antigen of HBV(HBs Ag) in serum. The gold standard to diagnose OBI is the detection of HBV DNA in the hepatocytes by highly sensitive and specific techniques, a diagnostic procedure requiring liver tissue to be tested and the use of non-standardized non-commercially available techniques. Consequently, in everyday clinical practice, the detection of anti-hepatitis B core antibody(antiHBc) in serum of HBs Ag-negative subjects is used as a surrogate marker to identify patients with OBI. In patients with chronic hepatitis C(CHC), OBI has been identified in nearly one-third of these cases. Considerable data suggest that OBI favors the increase of liver damage and the development of hepatocellular carcinoma(HCC) in patients with CHC. The data from other studies, however, indicate no influence of OBI on the natural history of CHC, particularly regarding the risk of developing HCC.

关键词： Occult hepatitis B virus infection Silent hepatiti

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Clinical impact of occult hepatitis B virus infection in immunosuppressed patients

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World Journal of Hepatology 2014年第6期6卷 384-393页

作者： Evangelista Sagnelli mariantonietta pisaturo Salvatore Martini Pietro Filippini Caterina Sagnelli Nicola Coppola Department of Mental Health and Public Medicine Section of Infectious DiseasesSecond University of Naples Department of Clinical and Experimental Medicine and Surgery "F.Magrassi e A.Lanzara" Second University of Naples

Occult hepatitis B infection(OBI), is characterized by low level hepatitis B virus(HBV) DNA in circulating blood and/or liver tissue. In clinical practice the presence of antibody to hepatitis B core antigen in hepatitis B surface antigen(HBsAg)-/anti-HBs-negative subjects is considered indicative of OBI. OBI is mostly observed in the window period of acute HBV infection in blood donors and in recipients of blood and blood products, in hepatitis C virus chronic carriers, in patients under pharmacological immunosuppression, and in those with immunodepression due to HIV infection or cancer. Reactivation of OBI mostly occurs in anti-HIV-positive subjects, in patients treated with immunosuppressive therapy in onco-hematological settings, in patients who undergo hematopoietic stem cell transplantation, in those treated with anti-CD20 or anti-CD52 monoclonal antibody, or anti-tumor necrosis factors antibody for rheumatological diseases, or chemotherapy for solid tumors. Under these conditions the mortality rate for hepatic failure or progression of the underlying disease due to discontinuation of specific treatment can reach 20%. For patients with OBI, prophylaxis with nucleot(s)ide analogues should be based on the HBV serological markers, the underlying diseases and the type of immunosuppressive treatment. Lamivudine prophylaxis is indicated in hemopoietic stem cell transplantation and in onco-hematological diseases when high dose corticosteroids and rituximab are used; monitoring may be indicated when rituximab-sparing schedules are used, but early treatment should be applied as soon as HBsAg becomes detectable. This review article presents an up-to-date evaluation of the current knowledge on OBI.

关键词： Occult hepatitis B virus infection Silent hepatitis B virus infection Hepatitis C virus infection Liver fibrosis

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Hepatitis B virus infection in immigrant populations

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World Journal of Hepatology 2015年第30期7卷 2955-2961页

作者： Nicola Coppola Loredana Alessio mariantonietta pisaturo Margherita Macera Caterina Sagnelli Rosa Zampino 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 Internal Medicine and Hepatology Second University of Naples

Hepatitis B virus(HBV) is the most common cause of hepatitis worldwide, with nearly 350 million people chronically infected and 600000 deaths per year due to acute liver failure occurring during acute hepatitis or, more frequently, in HBV-related liver cirrhosis or hepatocellular carcinoma. Ongoing immigration from countries with a high HBV endemicity to those with a low HBV endemicity warrants particular attention to prevent the spread of HBV infection to the native population. This review article analyzes the epidemiology and virological and clinical characteristics of HBV infection in immigrant populations and in their host countries, and suggests prophylactic measures to prevent the spread of this infection. Among the immigrants from different geographical areas, those from South East Asia and sub-Saharan Africa show the highest prevalences of hepatitis B surface antigen(HBs Ag) carriers, in accordance with the high endemicity of the countries of origin. The molecular characteristics of HBV infection in immigrants reflect those of the geographical areas of origin: HBV genotype A and D predominate in immigrants from Eastern Europe, B and C in those from Asia and genotype E in those from Africa. The literature data on the clinical course and treatment of HBs Agpositive immigrants are scanty. The management of HBV infection in immigrant populations is difficult and requires expert personnel and dedicated structures for their assistance. The social services, voluntary operators and cultural mediators are essential to achieve optimized psychological and clinical intervention.

关键词： Hepatitis B virus infection Chronic hepatitisB Immigration Immigrants Developing countries

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Liver fibrosis in human immunodeficiency virus/hepatitis C virus coinfection: Diagnostic methods and clinical impact

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World Journal of Hepatology 2015年第24期7卷 2510-2521页

作者： Caterina Sagnelli Salvatore Martini mariantonietta pisaturo Giuseppe Pasquale Margherita Macera Rosa Zampino Nicola Coppola Evangelista Sagnelli Department of Clinical and Experimental Medicine and Surgery "F.Magrassi e A.Lanzara Second University of Naples 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 Azienda Ospedaliera Universitaria Second University of Naples Department of Medical SurgicalNeurologicalMetabolic and Geriatric SciencesSecond University of Naples

Several non-invasive surrogate methods have recently challenged the main role of liver biopsy in assessing liver fibrosis in hepatitis C virus(HCV)-monoinfected and human immunodeficiency virus(HIV)/HCV-coinfected patients, applied to avoid the well-known side effects of liver puncture. Serological tests involve the determination of biochemical markers of synthesis or degradation of fibrosis, tests not readily available in clinical practice, or combinations of routine tests used in chronic hepatitis and HIV/HCV coinfection. Several radiologic techniques have also been proposed, some of which commonly used in clinical practice. The studies performed to compare the prognostic value of noninvasive surrogate methods with that of the degree of liver fibrosis assessed on liver tissue have not as yet provided conclusive results. Each surrogate technique has shown some limitations, including the risk of over- or under-estimating the extent of liver fibrosis. The current knowledge on liver fibrosis in HIV/HCVcoinfected patients will be summarized in this review article, which is addressed in particular to physicians involved in this setting in their clinical practice.

关键词： Human immunodeficiency virus/hepatitis C virus coi

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