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Gastroenterology, Department of Medicine, University of Milan Bicocca, Milan, ItalyGastroenterology Hepatology and Transplantation, Papa Giovanni XXIII Hospital, Bergamo, Italy
Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, ItalyCRC “A. M. and A. Migliavacca” Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
Patients with chronic hepatitis B virus are older than in the past.
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About 22% of the patients are migrants; they are younger than Italians.
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The widespread use of effective antivirals contributes to the infection prevention.
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The cirrhosis likelihood was reduced by 40% than in the past.
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Hepatitis Delta co-infection is present in about one-quarter of cirrhosis cases.
Abstract
Objectives
The study measures trends in the profile of patients with chronic hepatitis B virus linked to care in Italy.
Methods
A cross-sectional, multicenter, observational cohort (PITER cohort) of consecutive patients with hepatitis B surface antigen (HBsAg) over the period 2019-2021 from 46 centers was evaluated. The reference was the MASTER cohort collected over the years 2012-2015. Standard statistical methods were used.
Results
The PITER cohort enrolled 4583 patients, of whom 21.8% were non-Italian natives. Compared with those in MASTER, the patients were older and more often female. The prevalence of hepatitis B e antigen (HBeAg) declined (7.2% vs 12.3; P <0.0001) and that of anti-hepatitis D virus (HDV) remained stable (9.3% vs 8.3%). In both cohorts, about 25% of the patients had cirrhosis, and those in the PITER cohort were older. HBeAg-positive was 5.0% vs 12.6% (P <0.0001) and anti-HDV positive 24.8% vs 17.5% (P <0.0017). In the logistic model, the variables associated with cirrhosis were anti-HDV-positive (odds ratio = 10.08; confidence interval 7.63-13.43), age, sex, and body mass index; the likelihood of cirrhosis was reduced by 40% in the PITER cohort. Among non-Italians, 12.3% were HBeAg-positive (vs 23.4% in the MASTER cohort; P <0.0001), and 12.3% were anti-HDV-positive (vs 11.1%). Overall, the adherence to the European Association for the Study of the Liver recommendations for antiviral treatment increased over time.
Conclusion
Chronic hepatitis B virus infection appears to be in the process of becoming under control in Italy; however, HDV infection is still a health concern in patients with cirrhosis and in migrants.
Hepatitis B virus (HBV) infection still accounts for an estimated 800,000 deaths worldwide, despite vaccination campaigns, which have been implemented in the majority of countries [
]. This reflects the impact of the compulsory national HBV vaccination program started in Italy in 1991, initially including all newborns and children aged 12 years (the latter for a period of 12 years) and then continued for all newborns [
]. As a consequence, at present, the population aged less than 40 years is protected by the vaccine, whereas chronic HBV infection still imposes an important clinical burden on the older population. Importantly, the prevalence of chronic hepatitis B surface antigen (HBsAg) carriers in the general population decreased from nearly 3% in the 1980s to an estimated less than 0.6% in the current year [
In the last 2 decades, Italy has been the site of an increasing immigration flow; at present, persons born abroad account for about 8.4% of the resident population [
, and attention to immigrants from geographical areas of high or moderate endemicity levels for HBV infection has increased. Indeed, among patients with chronic HBV infection, the proportion of non-Italian natives grew from 7% in the years 2006-2007 to 27% in 2012-2015 [
]. The high proportion of immigrants who are HBsAg carriers ± hepatitis D virus (HDV)/hepatitis C virus (HCV) co-infection or not vaccinated for HBV could not change the overall epidemiological profile of HBV infection in Italian natives; however, it could impact on the clinical burden of HBV and the need to care for individuals who are infected. On the other hand, during the last decade, the use of antivirals, such as tenofovir and entecavir, has been widely recommended [
European Association for the Study of the Liver Electronic address: [email protected], European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection.
], which has positively impacted the natural history of HBV infection.
Altogether, the factors mentioned previously have the potential to cause a rapid evolution in the profile of HBV infection and disease. In the current study, we aimed to cross-sectionally evaluate the clinical burden and to characterize the different phases of chronic HBV liver disease in health care centers in Italy based on the patients enrolled in the multicenter PITER HBV/HDV cohort. In addition, the updated data were compared with those obtained by the MASTER study conducted by the Italian Association for the Study of the Liver (AISF) during 2012-2015 [
]. The final aim was to contribute to the measurement of the achievement of the targets for HBV elimination defined by the World Health Organization.
Patients and methods
PITER is a structured network that benefits from an integrated collaboration involving Italy's National Institute of Public Health (Istituto Superiore di Sanità), the AISF, and the Italian Society for Infectious Diseases and their affiliated clinical centers [
PITER Collaborating Group PITER: an ongoing nationwide study on the real-life impact of direct acting antiviral based treatment for chronic hepatitis C in Italy.
]. The cohort enrolled consecutive patients who were HBsAg-positive who were seen in 46 infectious disease or gastroenterology/hepatology clinical centers from October 1, 2019; for the purpose of the current study, the database was frozen on December 31, 2021; the participating centers were well distributed over Italy (Supplementary Figure 1).
The inclusion criteria were consecutive patients with HBsAg positivity for at least 6 months with or without co-infection with HDV and/or HCV, independent of antiviral treatment. The exclusion criteria were patients with previous HBV infection who were HBsAg-negative at enrollment, patients with acute HBV hepatitis, and, for the purpose of the current study, patients with HIV co-infection. The virological and routine analyses were performed at each participating center using standard commercial kits.
For patients who were under antiviral treatment at the time of enrollment, the infection/disease stage was classified by each center, as recommended by the European Association for the Study of the Liver (EASL) clinical practice guidelines [
European Association for the Study of the Liver Electronic address: [email protected], European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection.
Liver cirrhosis was assessed either by liver biopsy (Metavir or Ishak score) or by transient elastography using a stiffness value equal to or higher than 12.5 kPa as the cut-off or by biochemical, image, and instrumental data. Specifically, the presence of esophageal or gastric varices and/or platelet count lower than 120,000/µl were considered indicative of cirrhosis. Liver stiffness measurements were considered valid if each patient had at least 10 stiffness measurements, with a success rate of at least 80%, an interquartile range of less than 30% of the median stiffness score, and a body mass index (BMI) of <30 kg/m2 [
Systematic review with meta-analysis: the diagnostic accuracy of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B.
The single patient data were collected using a specific electronic case report form. The data quality was checked through periodic remote monitoring using specific queries. Two expert clinical monitors and one physician were involved in ensuring data quality [
PITER Collaborating Group PITER: an ongoing nationwide study on the real-life impact of direct acting antiviral based treatment for chronic hepatitis C in Italy.
The data from the current cohort were compared with those of the multicenter Italian MASTER-B cohort, which enrolled patients using a similar enrollment and exclusion criteria, as previously reported [
]. Briefly, this was an independent AISF-endorsed study, which enrolled patients who were HBsAg-positive in 73 Italian centers from 2012 to the first quarter of 2015. The participating centers covered the entire country (Supplementary Figure 1); there was no difference from the PITER cohort as to the type of center (gastroenterology/infectious diseases/internal medicine). In both studies, the physicians at each center established the patient's HBV treatment regimen according to the current clinical practice guidelines.
For the aim of the present study, a unique dBase was prepared, codifying equally the variables present in both cohorts.
Statistical analysis
Continuous variables were described by the median and first and third quartiles; categorical variables were described by absolute frequencies and percentages. To compare the groups, we used the chi-square test for categorical variables (Fisher's exact test was preferred in the case of sparse tables) and Student's t-test for continuous variables (or Wilcoxon rank-sum test when a significant departure from normality was detected).
A multivariable analysis was undertaken using logistic regression. The odds ratio (OR) estimates were obtained by the method of maximum likelihood; 95% confidence intervals (CIs) were based on the profile likelihood. For the continuous predictors, linearity was assessed by plots of deviance residuals versus covariate values. The significance of the estimated effects was tested using the Wald chi-square statistic.
The statistical analyses were performed using the SAS statistical package, version 9.4 (SAS Institute Inc., Cary, NC, USA).
Results
The PITER study enrolled 4583 patients with plasma positivity for HBsAg, who were observed throughout Italy from October 1, 2019 to December 31, 2021. The main patient characteristics were compared with those recorded in the MASTER-B cohort, which enrolled 2920 patients who were HBsAg-positive from June 1, 2012 to the end of enrollment on March 30, 2015 (Table 1). Overall, the patients in the PITER cohort were older (median age difference + 8.97 years): 21.8% of them were aged ≤40 years versus 28% in the MASTER cohort. The proportion of Italian patients aged <40 years decreased from 14.6% in the MASTER to 3.8% in the PITER study. In addition, the most recent cohort showed a greater proportion of females and a lower percentage of non-Italian natives (21.8% vs 26.8%), the majority (76.3%) of whom had been in Italy for more than 10 years. The proportion of patients who tested positive for hepatitis B e antigen (HBeAg) decreased sharply (7.2% vs 12.3%) from the MASTER to the PITER cohort; the majority of the cases in the PITER cohort had an undetectable serum HBV DNA, which mirrors the increased percentage of subjects under antiviral therapy compared with the MASTER cohort. Anti-HDV antibodies were present in 9.3% versus 8.3% in the MASTER cohort (P = 0.2329); of note, anti-HDV antibodies were not tested in 26.1% in the PITER cohort versus 33.6% in the MASTER cohort (P <0.0001). No difference between the cohorts was observed in the prevalence of cirrhosis, hepatocellular carcinoma (HCC), and anti-HCV antibodies. Moreover, patients without cirrhosis (Supplementary Table 1) were significantly older in the PITER cohort (median age difference + 10.4 years) and less frequently male (58.6% vs 64.8%); about one-third of them reported alcohol use. Notably, the proportion of HBeAg-positive cases was 7.9% versus 12.2% in the MASTER study (P <0.0001), and anti-HDV antibodies were detected in 4.0% versus 5.0% (P = 0.1303).
Table 1Main characteristics of the patients at enrollment.
Variables Median (Q1, Q3) or n (%)
PITER n = 4583
MASTER n = 2920
P-value
Age (years)
58.80 (47.92-68.22)
49.83 (38.59-60.25)
<0.0001
Sex (male)
2850 (62.27)
2003 (68.60)
<0.0001
Body mass index Missing 20.0%
24.14 (22.07-26.70)
23.83 (21.91-26.22)
0.0049
Body mass index ≥30
472 (13.18)
272 (11.24)
0.0248
Origin
<0.0001
Italian natives
3419 (78.20)
2136 (73.25)
East Europe
547 (12.51)
386 (13.24)
Africa
162 (3.71)
173 (5.93)
Asia
221 (5.05)
194 (6.65)
South and Central America
13 (0.30)
15 (0.51)
Central Western Europe
10 (0.23)
12 (0.41)
Alcohol use Missing 11.6%
1408 (34.21)
783 (31.13)
0.0098
Hepatitis B e antigen Missing 5.2%
322 (7.17)
323 (12.31)
<0.0001
Hepatitis B virus-DNA IU/ml Missing 6.1%
<0.0001
0
2629 (61.25)
958 (34.81)
(0, 2000)
1115 (25.98)
691 (25.11)
(>2000, 20000)
277 (6.45)
355 (12.90)
>20000
271 (6.31)
748 (27.18)
Cirrhosis
1107 (24.15)
722 (24.75)
0.5572
Anti-hepatitis D virus Missing 29.1%
314 (9.28)
161 (8.31)
0.2329
Anti-hepatitis C virus Missing 21.7%
169 (4.56)
81 (3.73)
0.1283
Hepatocellular carcinoma
210 (4.64)
110 (3.80)
0.0827
Previous therapy (mainly interferon based)
1354 (31.84)
983 (33.66)
0.1046
Ongoing therapy
3043 (66.56)
1000 (34.25)
<0.0001
Missing data were reported when >5%. Differences in missing data between the two cohorts ranged from 3.6 to 8.3%, except for anti-HDV which was not tested in 26.1% in the PITER cohort versus 33.6% in the MASTER cohort (P <0.0001).
According to the EASL classification, patients in the PITER cohort were classified as 1.9% e+ infection, 5.6% e+ chronic hepatitis, 20.0% e- infection, and 72.5% e- chronic hepatitis; the corresponding percentages for the MASTER cohort were 0.6%, 11.6%, 18.9%, and 68.9%, respectively.
Cirrhosis
Patients with cirrhosis (Table 2) were older in the PITER cohort (median age difference + 6.4 years); 86.4% of the patients were Italians versus 80.1% in the MASTER cohort. The proportion of HBeAg-positive cases was 5.0% versus 12.6% in the past (P <0.0001); by contrast, anti-HDV antibodies were detected in 24.8% of the cases versus 17.5% of those in the past (P <0.0017); anti-HCV antibodies were present in 7.9% versus 6.1%, respectively, and HCC in 16.6% versus 14.0%.
Table 2Characteristics of the patients with cirrhosis in the two study cohorts.
The crude percentage of patients with cirrhosis was almost identical in the two study cohorts (24.8% vs 24.2%). A logistic model was fitted to compare the presence of cirrhosis in the two cohorts, taking their different features into account (Table 3). The presence of anti-HDV antibodies was by far the most significant factor (OR = 10.09; 95% CI = 7.63, 13.43). Other significant predictors were age, sex, and BMI; for age and BMI, residual analysis confirmed a linear effect. Notably, after the adjustment for significant predictors, the likelihood of cirrhosis in the PITER cohort was reduced by about 40% compared with the MASTER cohort (OR = 0.61; 95% CI = 0.51, 0.72); in addition, being non-Italian was associated with an increased risk of cirrhosis (OR = 1.56; 95% CI = 1.22, 1.99).
Table 3Factors associated to the likelihood of cirrhosis. Results from the fitted logistic models.
As expected, within each cohort, non-Italian patients were younger and showed a higher prevalence of females, the positivity for HBeAg or anti-HDV was more frequent among immigrants, and the proportion of patients on treatment was lower among non-Italians (these comparisons are not shown). Interestingly, the profiles of the non-Italian patients showed remarkable changes between the two cohorts (Table 4); they were now older (median age difference + 6.4 years) and showed an increased prevalence of females, alcohol use became more frequent, the HBeAg prevalence was almost halved (12.2% vs 23.5%), whereas the prevalence of anti-HDV antibodies (12.3%) remained stable. Cirrhosis among foreigners was less frequent in the PITER cohort, whereas no difference was present in the prevalence of HCC. Similarly, the patients of Italian origin were older in the PITER cohort (median age difference + 7.7 years) and more frequently female than in the past; of note, the proportion of the patients positive for HBeAg declined (5.9% vs 8.2%; P = 0.0014). The prevalence of anti-HDV positivity remained almost stable (8.0% vs 7.3%), as did the proportion of patients with cirrhosis or HCC.
Table 4Characteristics of the patients enrolled in PITER and MASTER cohorts, by Italian and non-Italian origin.
We examined the patients who were not on treatment with nucleos(t)ide analogs (NUCs) at the time of enrollment in the PITER (n = 1456) and MASTER cohorts (n = 1860), categorized by HBV DNA concentration (Figure 1). Overall, only 5.6% in the PITER cohort with a HBV DNA >20,000 IU/ml were not under antiviral therapy; this percentage was 35.9% in the MASTER cohort. Among patients with cirrhosis, in the PITER cohort, 10.6% with an HDV DNA value >2000 did not receive treatment; in the MASTER cohort, the corresponding percentage was 62%.
Figure 1Distribution of untreated patients according to HBV DNA plasma concentrations.
The rapid evolution of the clinical and epidemiological burden of HBV infection in Italy is primarily due to three factors: (i) the ongoing effect of systematic anti-HBV vaccination; (ii) the widespread use of antiviral drugs that block the progression of the liver disease and abolish the infectivity of patients, and (iii) immigration from areas where HBV is endemic.
The role of each factor and the modification of its weight over time appear clearly in the current study. As recalled from the Introduction section, the compulsory vaccination program has raised a barrier against HBV infection in younger Italian residents. In the PITER cohort, only 3.8% of Italian patients were aged below 40 years compared with 44.3% among foreigners. The small residual number of the Italian cases is consistent with the acceleration of the vaccination campaign during the first years [
] and corroborates the concept that the elimination of HBV infection is imminent among patients born in Italy; a further indicator of the reduction of new chronic infections is the dramatic reduction of HBeAg-positive cases compared with the period 2012-2015. Although their proportion remains the same as in the past cohort, the mean age of patients with cirrhosis is increasing as a consequence of the lack of renewal with new younger patients; we can expect a drop in the number of cirrhosis and then of HCC cases in the coming years, at least among patients with HBV monoinfection. A further contribution to the reduction in the burden of advanced liver disease will come from the extended use of antiviral therapy, mainly NUCs, which can stop the progression of liver disease to advanced stages and even cause the regression of fibrosis in patients with cirrhosis [
. In the PITER cohort, 66.6% of the patients were under therapy, which is a proportion almost double that of the MASTER cohort. It is reassuring that there was an increase over time in adherence to the treatment indication according to the EASL recommendations, as shown in Figure 1, with only 5.6% of the patients not being on treatment at the time of enrollment, despite an HBV DNA value >20,000 IU/ml; the corresponding percentage in the MASTER cohort was 35.6%, i.e., more than six times higher.
The improvement in the treatment rate observed in the PITER cohort, other than the individual benefit discussed previously, may acquire the value of treatment as prevention at the community level. Indeed, abating viremia would be an effective means of stopping the transmission from young persons with a high level of plasma HBV DNA to susceptible individuals, which occurs mainly through sexual intercourse or within the family. To date, the role of treatment as prevention has been thoroughly assessed for persons with HIV who achieve optimal viral suppression while under therapy [
]. Because young persons with HBV are predominantly of non-Italian origin, once again, programs to reduce the barriers to access to therapy are needed.
Overall, co-infection with HDV was detected in 9.3% of study participants, with a higher prevalence among non-Italian natives. There was a positive trend compared with the MASTER study toward testing patients who were HBsAg-positive for anti-HDV; although, 26.1% of the patients remained untested. The availability of new therapies against HDV [
] should act as a potent incentive for screening. The presence of anti-HDV maintains a significant role as a driver of cirrhosis, being present in 24.8% of cirrhosis cases, a proportion higher than that in the MASTER study (17.5%). Clearly, the increase in this proportion might be influenced by the increase in testing; however, it seems likely that a relative increment in the proportion of HDV cases is due to the reduction of cirrhosis cases among patients with HBV monoinfection for the reasons discussed previously. Indeed, the prevalence of anti-HDV remained stable over time in the subset of patients of Italian origin, patients without cirrhosis, and patients of non-Italian origin. This interpretation is supported by the disproportionate role of HDV as the cause of decompensation and liver cancer leading to transplant in two Italian studies [
. The major role of HDV infection in cirrhosis was confirmed by the logistic model, together with those of age, sex, and BMI. Interestingly, the model showed that being part of the PITER cohort, with other characteristics being equal, lowered the likelihood of cirrhosis by about 40% compared with the MASTER cohort. We can hypothesize that the patient management improved in the period between the two studies, particularly due to the increasing use of antivirals, whereas some patients died or underwent liver transplant. Similarly, when the confounders were controlled, non-Italian natives showed a high likelihood of cirrhosis. The prevalence of more aggressive HBV/HDV genotypes or subtypes, the acquisition of the infection at birth, or the exposure to environmental factors in their countries of origin are potential causes not explored by the current studies. In any case, the analysis suggests caution in interpreting the crude prevalence in clinical/epidemiological studies.
Non-Italian natives account for 22-27% of the patients in the current and in the MASTER cohort, respectively. Migrants were definitely younger than Italian patients in both cohorts but older in the current cohort than in the past one. The PITER study enrolled participants during the peaks of the COVID-19 epidemic, when there were restrictions on immigration flows and barriers to access to in- and out-patient clinics [
Assessing the impact of COVID-19 on the management of patients with liver diseases: a national survey by the Italian association for the study of the Liver.
; so, it is likely that new waves of younger patients diminished. Indeed, 76% of non-Italian natives were subjects who had been in Italy for more than 10 years. Because enrollment in the PITER study is ongoing, it would be interesting to monitor this aspect.
A further point is the increasing prevalence of females among non-Italian natives which, coupled with their young age, leads to a high number of women of childbearing age [
]. Screening pregnant women for HBV infection is a consolidated habit in public and private hospitals in Italy and should help in preventing mother-to-child transmission by adequate prophylaxis. However, the adherence to prophylaxis may be suboptimal among non-Italian women [
]; so, the continuity in the care of mothers and neonates should be pursued by offering dedicated assistance points, particularly in disadvantaged areas, which are sites of undocumented immigration. At present, there are around 5.5 million non-Italian natives officially residing in Italy, to which should be added an estimated 500,000 illegal residents or waiting for asylum [
], whose characteristics are not included in this study.
As usual, the study has some limitations and strengths. While its multicenter design allows a realistic view of the health status of the patients with HBV who are somehow linked to care, it may suffer from potential heterogeneity of methods and evaluations; regardless, the strict connections of the centers with the reference scientific societies might have counteracted this potential bias. The PITER and MASTER cohorts were enrolled using the same criteria, and the participating centers were distributed over the entire Italian territory, had the same specialization, and enrolled consecutive patients, which makes them representative of the Italian epidemiological burden in the two periods. The number of centers participating in PITER was smaller, and each enrolled a higher number of patients than the MASTER study; this could reflect the national policy in recent years of combining the regional centers allowed to prescribe antiviral therapies. In addition, in the same period, data were published that reinforced the concept that NUCs could reverse cirrhosis and avoid the progression of liver disease when given at an early stage [
; these findings enhanced awareness among general practitioners and specialists and possibly caused a higher number of patients to be sent to specialist centers. A further limitation of the current data was that more detailed virological analyses remained outside the scope of the study.
In conclusion, the data depict a rapidly evolving scenario for HBV infection in Italy, mainly due to the progressive exhaustion of HBV infection among Italian natives and highlight new needs to meet health demands.
Declaration of Competing Interest
The authors have no competing interests to declare.
Funding
This study was supported by Italian Ministry of Health (“Attività Istituzionale di ricerca scientifica e terza missione dell’Istituto Superiore di Sanità – anno 2022”. Fasc. BDC2/1).
Ethical approval
This study was conducted in accordance with the Helsinki Declaration of 1975, as revised in 2008, and the principles of Good Clinical Practice. The protocol of the PITER study was approved by the Ethics Committee of the Istituto Superiore di Sanit.ß ISS on 24th July 2019, and by the Ethics Committees of each participating institution that are listed in the PITER Collaborating Group available at www.iss.it/piter. All patients included in the database signed an informed consent prior to enrolment. The patients' data were evaluated through an anonymous analysis, adopting codes generated by the electronic case-report form. The MASTER study followed similar ethic procedures.
Acknowledgments
The authors wish to thank all PITER collaborating group and all participating centers, investigators and research staff (available in www progettopiter.it) who are involved in the study on a voluntary basis, for their time and effort. We also thank and Giampaolo La Terza (Medisoft Informatic Services) for Database maintenance and implementation. We additionally acknowledge Federica Magnani, Rosangela Duranti, Erika Olivieri, Alessandra Mattei for secretarial and administrative assistance.
Authors' contribution
GB: Investigation, Resources, Writing ... original draft, Visualization, Writing ... review & editing. BC: Investigation, Resources, Writing ... original draft, Writing ... review & editing. AN: Investigation, Methodology, Validation, Formal analysis, Data curation, Writing ... review & editing. MGQ: Resources, Visualization, Writing ... review & editing. MET: Investigation, Formal analysis, Data curation. LF: Data curation. IC, VM, LC, FM, MM, FB, ACi, FPR, NC, PB, EC, GV, MP, ALZ, LC, RSM, SF, AM, CF, PL, VDM, ACr, TAS, GR: Resources, Writing ... review & editing. MRB: Investigation, Resources, Writing ... review & editing. GBG: Conceptualization, Supervision, Writing ... original draft, Writing ... review & editing. LAK: Conceptualization, Supervision, Funding acquisition, Writing ... original draft, Writing ... review & editing. PITER Collaborating Investigators contributed to data collection and data quality check. All authors approved the final version of the manuscript.
Appendix A
PITER collaborating investigators Luisa Pasulo (Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, Italy), Carmine Coppola, Federica Pisano (Department of Hepatology, Gragnano Hospital, Gragnano (NA), Italy), Mariarosaria Romano (Department of Infectious Diseases, Sant'Anna Hospital, Caserta, Italy), Carmen Porcu (Liver Unit, University Hospital, Monserrato, Cagliari, Italy), Irene Francesca Bottalico (Infectious Diseases Unit, Ospedali Riuniti, Foggia, Italy), Valentina Cossiga (Gastroenterology Unit, Federico II University, Naples, Italy), Xhimi Tata (Center for Global Health, Istituto Superiore di Sanità, Rome, Italy), Caterina Sagnelli (Infectious Diseases Unit, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Naples, Italy), Piera Pierotti (Infectious Disease Unit, Santa Maria Annunziata Hospital, Florence, Italy), Elisabetta Degasperi (Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy), Valerio Rosato (Hepatology Unit, Betania Hospital, Naples, Italy), Lorenzo Badia (Clinic of Infectious Diseases and Microbiology Unit, Alma Mater Studiorum Bologna University, Bologna, Italy), Donatella Ieluzzi (Liver Unit, University Hospital of Verona, Verona, Italy), Monica Monti (Center for Systemic Manifestations of Hepatitis Viruses, Department of Experimental and Clinical Medicine, , University of Florence, Florence, Italy), Maria Grazia Bavetta (Department of Internal Medicine, Villa Sofia-Cervello Hospital, Palermo, Italy), Luisa Cavalletto (Department of Medicine, Unit of Internal Medicine & Hepatology, University of Padua, Padua, Italy), Pierluigi Toniutto, Ezio Fornasiere (Hepatology and Liver Transplant Unit, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy), Antonio Colecchia, Alberto Ferrarese (Gastroenterology Unit, University Hospital Borgo Trento, Verona, Italy), Gerardo Nardone, Alba Rocco (Department of Clinical Medicine and Surgery, Hepato-Gastroenterology Unit, University of Napoli “Federico II”, Napoli, Italy), Mauro Viganò (Hepatology Unit, San Giuseppe Hospital, Milan, Italy), Francesco Giuseppe Foschi, Fabio Conti (Internal Medicine, Hospital of Faenza, A.U.S.L. of Romagna, Faenza, RA, Italy), Giulia Morsica, Stefania Salpietro (Department of Infectious Diseases, San Raffaele Hospital, Milan, Italy), Carlo Torti, Chiara Costa (Department of Medical and Surgical Sciences, Infectious and Tropical Diseases Unit, “Magna Graecia” University, Catanzaro, Italy), Alessandro Federico, Marcello Dallio (Department of Hepato-Gastroenterology, University of Campania Luigi Vanvitelli, Naples, Italy), Alessia Giorgini (Gastroenterology and Hepatology Unit, San Paolo Hospital, University of Milan, Milan, Italy), Marco Anselmo, Pasqualina De Leo (Infectious Disease Unit, San Paolo Hospital, Savona, Italy), Serena Zaltron, Anna Cambianica (Department of Infectious and Tropical Diseases, Spedali Civili and University of Brescia, Brescia, Italy), Fabio Piscaglia, Ilaria Serio (Division of Internal Medicine Unit, Sant'Orsola Malpighi Hospital, Bologna, Italy), Simona Schivazappa (Department of Medicine and Surgery, University of Parma, Unit of Hematology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy), Antonio Mastroianni, Luciana Chidichimo (Department of Infectious and Tropical Diseases, SS Annunziata Hospital, Cosenza Italy), Marco Massari (Malattie Infettive, Azienda Unità Sanitaria Locale, IRCCS di Reggio Emilia, Reggio Emilia, Italy), Cesare Mazzaro (Unit of Clinical of Experimental Onco-Hematology, IRCCS Centro di Riferimento Oncologico, Aviano, Pordenone, Italy), Aldo Marrone, Francesca Maria D'Amore (Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy), Gianpiero D'Offizi (National Institute for Infectious Diseases, Lazzaro Spallanzani-IRCCS, Rome, Italy), Anna Licata (Infectious Diseases Clinic, Department of Biomedical Sciences and Public Health, DIBIMIS, University of Palermo, Palermo, Italy), Grazia Anna Niro (Unità Operativa di Gastroenterologia ed Endoscopia Digestiva, Fondazione Casa Sollievo della Sofferenza IRCCS, San Giovanni Rotondo (FG), Italy), Teresa Pollicino (Department of Internal Medicine, University Hospital of Messina, Messina, Italy), Alessio Aghemo (Department of Gastroenterology, IRCCS Humanitas Research Hospital IRCCS, Rozzano, Italy).
Electronic address: [email protected], European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection.
Systematic review with meta-analysis: the diagnostic accuracy of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B.
Assessing the impact of COVID-19 on the management of patients with liver diseases: a national survey by the Italian association for the study of the Liver.
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