M Viganò

University of Milan, Milano, Lombardy, Italy

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Publications (341)1005.69 Total impact

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    ABSTRACT: HBeAg negative chronic hepatitis B (CHB) is a frequent, progressive and difficult-to-cure phase of CHB. The end-point of therapy is to persistently suppress viral replication to halt progression of liver disease. Two different treatment strategies are currently available: a short-term course of pegylated interferon alpha (PEG-IFN) or long-term therapy with nucleot(s)ide analogues (NA), i.e. entecavir or tenofovir. Young patients with mild-to-moderate stages of liver disease can benefit from a 48-week course of PEG-IFN, while NA may be preferred in patients with more severe liver disease, in older patients, and in those who do not respond, are unwilling or have contraindications to PEG-IFN. Nucleot(s)ide analogues provide persistent viral suppression and biochemical normalization in almost all patients, together with the regression of fibrosis and the prevention of decompensation, but the effect on hepatocellular carcinoma rates is limited. Thus, NAs have become the most popular treatment strategy worldwide but lifelong administration is associated with high cost, unknown safety and adherence issues and an unknown risk of drug-resistance over time as well as limited rates of HBsAg seroclearance. On the other hand, PEG-IFN treatment may achieve a SVR in nearly a quarter of patients ultimately leading to HBsAg loss in almost 30–50%. Interestingly, response rates to PEG-IFN may further increase with more careful patient selection based on age, ALT and HBV DNA levels at baseline and by applying early on-treatment stopping rules based on HBV DNA and HBsAg kinetics. The combination of NA and PEG-IFN is not currently recommended but numerous studies are ongoing.
    Liver international: official journal of the International Association for the Study of the Liver 01/2015; 35(s1). · 3.87 Impact Factor
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    ABSTRACT: Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor widely used to treat patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infection. Despite the excellent safety records of this regimen, a few cases of acute renal failure and Fanconi syndrome have been reported among HIV patients exposed to TDF. In the HBV monoinfection scenario, only two cases of TDF-associated Fanconi syndrome have been reported thus far. Here, we describe two additional patients with chronic hepatitis B (CHB) who developed a TDF-induced Fanconi syndrome that reverted after TDF withdrawal and had viral replication fully suppressed upon switching to entecavir (ETV). Though the overall risk of TDF associated severe renal toxicity in HBV patients appears to be negligible, both glomerular and tubular function should be monitored in patients exposed to TDF, especially when other renal risk factors or a history of previous exposure to adefovir dipivoxil (ADV) are present.
    Journal of Clinical Virology. 10/2014;
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    ABSTRACT: Introduction: Rituximab (RTX), a chimeric mouse anti-human CD20 monoclonal antibody, is indicated for the treatment of patients with non-Hodgkin's lymphoma, chronic lymphocytic leukemia, granulomatosis with polyangiitis and microscopic polyangiitis, and rheumatoid arthritis, but nowadays it is increasingly used for the treatment of many other immune-mediated disorders. Hepatitis B virus (HBV) reactivation in RTX-treated patients, eventually leading to fatal liver failure, has been reported more often among hepatitis B surface antigen (HBsAg)-positive patients (overt infection) than in HBsAg-negative, antibody to hepatitis B core antigen (anti-HBc) seropositive patients (resolved infection). Areas covered: This paper reviews the safety of RTX in patients with overt or resolved HBV infection, providing recommendations for its safe use in such patients. Expert opinion: Prior to starting RTX treatment, all patients should be screened for HBV infection. While HBsAg-positive active carriers should receive long-term antiviral treatment with entecavir (ETV) or tenofovir, inactive carriers are candidates for universal prophylaxis with lamivudine, or ETV or tenofovir in selected cases, to prevent hepatitis reactivation. Conversely, for HBsAg-negative anti-HBc positive carriers, that is, those with resolved HBV infection, universal prophylaxis with lamivudine is recommended for those with onco-hematological diseases, whereas watchful monitoring of HBsAg/HBV DNA levels is advisable for all the other indications.
    Expert opinion on biological therapy. 07/2014; 14(7):1019-31.
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    ABSTRACT: Background/Aims: Cryoglobulinemic vasculitis remains an uncommon complication of hepatitis B virus infection. Methods: We report the case of a 40-years old female Chinese patient with chronic hepatitis B developing cryoglobulinemic vasculitis with multiple organ involvement (liver, kidney, and skin) coupled with weakness, arthralgias, haemolytic anaemia, and autoimmune thyroiditis. She received entecavir mono-therapy at dose adjusted for estimated glomerular filtration rate. Results: Within five months of entecavir treatment, hepatitis B viraemia decreased below the limit of detection with normal serum amino-transferase levels, HBeAg clearance occurred, vasculitis regressed with disappearance of purpura and ascites; in addition, renal function normalized and nephritic syndrome remitted. After a five-year follow-up, the patient is asymptomatic with intact kidney function, proteinuria in the normal range, and normal liver biochemistry, despite the antiviral treatment was withdrawn and the patient remained HBsAg positive. Conclusions: This is the second case of hepatitis B virus-related cryoglobulinemic vasculitis successfully treated with entecavir suggesting that effective antiviral therapy may counteract both the hepatic and extra-hepatic manifestations of infection by hepatitis B virus. © 2014 S. Karger AG, Basel.
    Kidney and Blood Pressure Research 06/2014; 39(1):65-73. · 1.60 Impact Factor
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    E. Galmozzi, M. Viganò, P. Lampertico
    Alimentary Pharmacology & Therapeutics 05/2014; 39(10). · 4.55 Impact Factor
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    ABSTRACT: The aim of chronic hepatitis B (CHB) antiviral therapy is to persistently suppress HBV and improve survival by preventing the progression of liver damage to cirrhosis, end-stage liver disease or hepatocellular carcinoma (HCC), thus preventing early liver-related death. In HBeAg-negative patients who do not or will not respond to or be treated with pegylated interferon (PEG-IFN), the administration of third generation nucleot(s)ide analogues (NAs), i.e. entecavir (ETV) and tenofovir disoproxil fumarate (TDF), is the treatment of choice. Long-term administration of ETV or TDF suppresses HBV replication in >95% of patients after 5 years of treatment with high rates of biochemical normalization, regression of fibrosis and cirrhosis at histology as well as preventing clinical decompensation but not HCC, in compensated cirrhosis and improving survival. No major safety issues have been recorded with either drug. The need for long-term, perhaps indefinite, treatment is the main limitation of NA therapy with possible associated costs, unknown long-term safety and the low rates of HBsAg seroclearance. The latter is important since HBsAg seroclearance is still the best stopping rule for HBeAg-negative NA-treated patients, including those with cirrhosis. For this reason new trials based upon a combination of PEG-IFN and third generation NAs in both naïve and NA-responder HBeAg-negative patients are ongoing.
    Liver international: official journal of the International Association for the Study of the Liver 02/2014; 34 Suppl 1:120-6. · 3.87 Impact Factor
  • E Galmozzi, M Viganò, P Lampertico
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    ABSTRACT: Interferon lambda 3 (IFN-λ3) polymorphisms are the strongest genetic predictor of outcome of hepatitis C virus infection and of response to Pegylated interferon (PegIFN)-based therapy. Whether this holds true for hepatitis B virus (HBV) infection is matter of controversy. To review the association between host genomics and spontaneous or interferon-induced clearance of HBV with specific reference to the recently identified interleukin 28B gene now renamed IFN-λ3. A literature search was performed on MEDLINE, EMBASE and Web of Science for English articles and abstracts using free text words and combinations of the following terms 'IL28B', 'IFN lambda', 'genomics', 'hepatitis B virus', 'interferon' 'GWAS', 'treatment', 'SNPs', 'HLA', 'polymorphisms'. Genome-wide association studies convincingly demonstrated an association between SNPs in the HLA locus and spontaneous resolution of HBV infection in subgroups of Asian patients, yet no information is available for Caucasians. The preliminary observations of an association between IFN-λ3 SNP and virological and serological responses to IFN in both HBeAg-positive and -negative patients could not be replicated by subsequent studies. Yet, majority of studies performed so far suffer several limitations in terms of sample size, selection of the patients, endpoints of therapy, treatment strategies and duration of follow-up. While host genetics is associated with an increased likelihood of spontaneous clearance of HBV among genotype B/C patients, the relationship between IFN-λ3 polymorphisms and response to IFN has not been confirmed. Further studies in large cohorts of homogeneous patients are required, before this genetic test can be recommended in clinical practice.
    Alimentary Pharmacology & Therapeutics 01/2014; · 4.55 Impact Factor
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    ABSTRACT: Steatosis is a common histopathological feature of chronic hepatitis B (CHB) and has been associated with severity of liver disease. Recently, the rs738409 I148M patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism has been demonstrated to influence steatosis susceptibility and fibrosis progression in patients with different liver diseases, but no data are yet available for CHB. The aim of this study was to evaluate whether PNPLA3 I148M influences steatosis susceptibility in a large series of patients with CHB. We enrolled 235 treatment-naïve CHB patients consecutively examined by percutaneous liver biopsy. In ≥2-cm-long liver tissue cores, steatosis and fibrosis were staged by Kleiner and METAVIR scores, respectively. The I148M polymorphism was determined by Taqman assays. Steatosis was present in 146 (62%) patients, of whom 24 (10%) had severe (>33% of hepatocytes) steatosis. Steatosis was independently associated with age (odds ratio [OR]: 2.67; confidence interval [CI]: 1.50-4.92; for age ≥50 years), body mass index (BMI; OR, 2.84; CI, 1.30-6.76; for BMI ≥27.5 kg/m2), diabetes or impaired fasting glucose (OR, 4.45; CI, 1.10-30.0), and PNPLA3 148M allele (OR, 1.62; CI, 1.00-7.00; for each 148M allele). Independent predictors of severe steatosis were BMI (OR, 3.60; CI, 1.39-9.22; for BMI ≥27.5 kg/m2) and PNPLA3 148M allele (OR, 6.03; CI, 1.23-5.0; for each 148M allele). PNPLA3 148M alleles were associated with a progressive increase in severe steatosis in patients with acquired cofactors, such severe overweight and a history of alcohol intake (P = 0.005). Conclusion: In CHB patients, the PNPLA3 I148M polymorphism influences susceptibility to steatosis and, in particular, when associated with severe overweight and alcohol intake, severe steatosis. (Hepatology 2013;58:1245–1252)
    Hepatology 10/2013; 58(4). · 12.00 Impact Factor
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    ABSTRACT: Assessment of liver fibrosis is important in determining prognosis, disease progression and need for treatment in patients with chronic hepatitis B (CHB). Limitations to the use of liver biopsy in assessing fibrosis are well recognized, and noninvasive tests are being increasingly evaluated including transient elastography (TE) and serum markers such as the Enhanced Liver Fibrosis (ELF) test. We assessed performance of ELF and TE in detecting liver fibrosis with reference to liver histology in a cohort of patients with CHB (n = 182), and compared the performance of these modalities. Median age was 46 and mean AST 70 IU/L. Cirrhosis was reported in 20% of liver biopsies. Both modalities performed well in assessing fibrosis at all stages. Area under receiver operator characteristic (AUROC) curves for detecting METAVIR fibrosis stages F ≥ 1, F ≥ 2, F ≥ 3 and F4 were 0.77, 0.82, 0.80 and 0.83 for ELF and 0.86, 0.86, 0.90 and 0.95 for TE. TE performed significantly better in the assessment of severe fibrosis (AUROC 0.80 for ELF and 0.90 for TE, P < 0.01) and cirrhosis (0.83 for ELF and 0.95 for TE, P < 0.01). This study demonstrates that ELF has good performance in detection of liver fibrosis in patients with CHB, and when compared, TE performs better in detection of severe fibrosis/cirrhosis.
    Journal of Viral Hepatitis 08/2013; · 3.08 Impact Factor
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    ABSTRACT: Persistent viral eradication or suppression through a defined course of Pegylated-interferon (PegIFN) or the administration of a long-term potent nucleot(s)ide analogues (NUCs) can impact positively the natural course of HBV infection by preventing disease progression. Despite the higher rates of off-therapy response achieved with PegIFN compared with NUC, its benefits are restricted to a subgroup of patients only. To increase the rates of patients who may benefit from PegIFN treatment, minimizing the adverse events, careful patient selections based on baseline features and on treatment HBsAg kinetics for individual treatment optimization are required.
    Clinics in liver disease 08/2013; 17(3):425-43.
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    ABSTRACT: Chronic HBV and HCV are progressive diseases leading to cirrhosis and liver transplantation. Persistent viral eradication or suppression can positively affect the natural course of the infection, by preventing disease progression. Since its introduction more than 30 years ago, IFN-α has represented the foundation of HBV and, lately, anti-HCV treatment. Pegylation of the IFN-α molecule (PegIFN-α2a) has provided improvements in both efficacy and administration schedule, thus becoming part of the standard-of-care regimen for HCV and HBV therapy in the last 10 years. Currently, treatment of finite duration with PegIFN-α2a may achieve a sustained virological response off-treatment and HBsAg seroconversion. PegIFN-α2a will most likely remain the backbone of HCV treatment for the next few years, despite the availability of direct-acting antivirals that are expected to improve cure rates. However, many efforts are concentrated on developing new compounds, with the goal of administrating all oral regimens and eliminating PegIFN from anti-HCV treatment.
    Expert Review of Anticancer Therapy 05/2013; 11(5):459-74. · 3.22 Impact Factor
  • Journal of Hepatology 04/2013; 45:S10–S11. · 9.86 Impact Factor
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    Mauro Viganò, Pietro Lampertico
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    ABSTRACT: Watch a video presentation of this article Watch the interview with the author Answer questions and earn CME
    Clinical Liver Disease. 02/2013; 2(1).
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    ABSTRACT: Chronic hepatitis B (CHB) in serum HBeAg negative patients is a difficult to cure, progressive disease leading to end-stage liver disease and hepatocellular carcinoma. Currently, there are two different treatment strategies for such patients: a finite course of Pegylated interferon (PEG-IFN) or long-term administration of the more potent and less resistance-prone nucleot(s)ide analogues (NUC), i.e. entecavir and tenofovir. Although NUC may ensure persistent viral suppression by preventing disease progression in most patients, they require lifelong administration with the hypothetical disadvantages of cost, lack of long-term safety data and, most important, the null rates of HBsAg seroclearance. On the other hand, 1 year of PEG-IFN has the advantage of providing an immune-mediated control of hepatitis B virus (HBV) infection, with the possibility of achieving a sustained off-treatment response in 20% of the patients, ultimately leading to HBsAg loss in approximately 50% of these. However, these sustained response rates can be significantly increased by carefully selecting candidates for PEG-IFN therapy based upon baseline ALT and HBV DNA levels, viral genotype and IL28B polymorphisms, by extending PEG-IFN therapy beyond 48 weeks and, most importantly, by applying early on-treatment stopping rules based upon HBsAg kinetics. Overall, PEG-IFN is an ideal treatment strategy in selected patients with HBeAg-negative CHB, because of its well-recognized and predictable safety profile and a unique mechanism of antiviral activity leading to long-lasting immune control. Because of these features, new therapeutic trials based upon a combination of PEG-IFN and third generation NUC such as entecavir and tenofovir, in both naïve and NUC-exposed patients, are ongoing to further increase the rates of HBsAg seroclearance, which remains the ‘ideal end-point’ in all HBeAg-negative CHB subjects.
    Liver international: official journal of the International Association for the Study of the Liver 02/2013; 33(s1). · 3.87 Impact Factor
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    ABSTRACT: OBJECTIVE: Treatment with peginterferon α-2a (PegIFN) for 48 weeks is the standard of care for selected HBeAg-negative patients chronically infected with hepatitis B virus (HBV), but with limited treatment efficacy. A study was undertaken to investigate whether treatment extension to 96 weeks improves the outcome in this patient population. METHODS: 128 HBeAg-negative patients (120 genotype D) were randomised to weekly 180 μg PegIFN for 48 weeks (group A, n=51), 180 μg PegIFN for 48 weeks followed by 135 μg weekly for an additional 48 weeks (group B, n=52) or 180 μg PegIFN plus lamivudine (100 mg/day) for 48 weeks then 135 μg PegIFN for 48 weeks (group C, n=25). Endpoints were alanine aminotransferase normalisation plus HBV DNA <3400 IU/ml (primary), HBV DNA <2000 IU/ml and HBsAg clearance at 48 weeks after treatment. RESULTS: Forty-eight weeks after treatment, six patients in group A and 13 in group B achieved alanine aminotransferase normalisation plus HBV DNA <3400 IU/ml (11.8% vs 25.0%, p=0.08), 6 vs 15 patients had HBV DNA <2000 IU/ml (11.8% vs 28.8%, p=0.03), 0 vs 3 achieved HBsAg clearance (0% vs 5.8%, p=0.24) and 0 vs 5 had HBsAg <10 IU/ml (0% vs 9.6%, p=0.06). While extended PegIFN treatment was the strongest independent predictor of response, the combination with lamivudine did not improve responses. Discontinuation rates were similar among the groups (19.6%, 23.1%, 32.0%, p=0.81) and were mostly due to PegIFN-related adverse events. CONCLUSIONS: In HBeAg-negative genotype D patients with chronic hepatitis B, PegIFN treatment for 96 weeks was well tolerated and the post-treatment virological response improved significantly compared with 48 weeks of treatment. TRIAL REGISTRATION NUMBER: http://ClinicalTrials.gov registration number: NCT01095835.
    Gut 08/2012; · 10.73 Impact Factor
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    ABSTRACT: In patients with chronic hepatitis B virus (HBV) infection, persistent exposure to high concentrations of antigen can disrupt T-cell functions. It is not clear to what extent long-term suppression of HBV by nucleos(t)ide analogues can restore antiviral T-cell functions. We compared HBV-specific T-cell responses of patients treated with nucleos(t)ide analogues with those detected in other conditions of HBV control. We analyzed intracellular levels of interferon gamma, interleukin-2, and tumor necrosis factor α in HBV-specific T cells after 10 days of stimulation with peptides covering the overall HBV genotype D sequence and ex vivo with selected CD8 epitopes and the corresponding HLA-A2 dextramers. Findings from patients treated with nucleos(t)ide analogues who had complete (HBV DNA negative/antibody to hepatitis B surface antigen positive) or partial (HBV DNA negative/hepatitis B surface antigen positive) control of their infections were compared with those of patients with spontaneous or interferon alfa-induced resolution of acute or chronic infections, inactive HBV carriers, or untreated hepatitis B e antigen-negative patients with chronic infections. Although HBV-specific T cells from nucleos(t)ide analogue-treated patients with complete control of infection were dysfunctional ex vivo, they had efficient responses after in vitro expansion. These responses were comparable to those of patients who spontaneously resolved acute HBV infection. Nucleos(t)ide analogue-treated patients who were HBV DNA negative but hepatitis B surface antigen positive had lower levels of T-cell responses but responses greater than those of untreated patients with chronic infection. In vitro reactivity can be restored to T cells from patients with suppressed HBV infection following long-term treatment with nucleos(t)ide analogues, despite prolonged exposure to large loads of antigen. Immune therapies that increase the antiviral T-cell response might increase the likelihood of complete HBV control in patients undergoing long-term nucleos(t)ide analogue treatment.
    Gastroenterology 07/2012; 143(4):963-973.e9. · 12.82 Impact Factor
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    ABSTRACT: Background / Purpose: The aim of the study was to assess the effectiveness and safety of long-term Tenofovir (TDF) monotherapy in a European cohort of NUC-naive patients with chronic hepatitis B. Main conclusion: TDF suppressed hepatitis B virus suppression in most NUC-naive patients in field practice up to 30 months, leading to increasing rates of HBeAg seroconversion and HBsAg clearance.The safety profile of TDF was as good as that in registration studies, with few patients discontinuing the medication.
    47th Annual International Liver Congress 2012; 06/2012
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    ABSTRACT: Background / Purpose: This study was conducted to assess the long-term effectiveness and safety of entecavir (ETV) in a large cohort of NUC-naive patients with chronic hepatitis B. Main conclusion: ETV monotherapy was safe and effective for up to four years in clinical practice, providing high rates of virological suppression and increasing rates of HBeAg and HBsAg seroconversion.
    47th Annual International Liver Congress 2012; 06/2012
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    ABSTRACT: BACKGROUND.: Interleukin(IL)28B polymorphisms have been associated to interferon(IFN)-induced viral clearance in patients with chronic hepatitis C. Whether this is also true for patients with the difficult to cure HBeAg-negative chronic hepatitis B, is unknown. METHODS.: 101 HBeAg-negative patients (92% genotype D) with compensated chronic hepatitis B (84% males, 46 years, HBV DNA 6.0 log cp/ml, ALT 136 IU/L, 42% with cirrhosis) were followed for a median of 11 (1-17) years after median 23 (10-48) months of either standard or pegylated (Peg)IFN alfa therapy. A post-treatment response was defined as HBsAg clearance with or without anti HBs seroconversion. The rs12979860 (C>T) genotype in the IL28B locus was assessed in serum samples by using Custom TaqMan SNP Genotyping Assays. RESULTS.: During a median of 11 years of post-treatment follow-up, 21 (21%) patients cleared serum HBsAg, including 15 who developed >10 IU/ml anti-HBs titers. Forty-eight patients (47%) had CC genotype, 42 (42%) CT and 11 (11%) TT, the allelic frequency being 68% for C allele and 32% for T allele. The rate of serum HBsAg clearance was 29% (n=14) in CC compared to 13% (n=7) in non-CC genotype carriers (p=0.039). Baseline HBV DNA levels <6 log cp/ml (OR 11.9, CI 2.8-50.6, p=0.001), ALT levels >136 IU/ml (OR 6.5, CI 1.8-22.5, p=0.003), duration of IFN (OR 1.16, CI 1.02-1.31, p=0.021) and genotype CC (OR 3.9, CI 1.1-13.2, p=0.025) independently predicted HBsAg clearance. CONCLUSIONS.: IL28B polymorphism is an additional predictor of off-therapy IFN-related HBsAg seroclearance to be used in pretreatment stratification of HBeAg-negative patients chronically infected by genotype D of hepatitis B virus. (HEPATOLOGY 2012.).
    Hepatology 04/2012; · 12.00 Impact Factor
  • Journal of Hepatology 04/2012; 44:S19. · 9.86 Impact Factor

Publication Stats

3k Citations
1,005.69 Total Impact Points

Institutions

  • 2003–2014
    • University of Milan
      • Department of Internal Medicine
      Milano, Lombardy, Italy
  • 2010–2013
    • Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
      • Gastroenterology 3
      Milano, Lombardy, Italy
    • Istituto Clinico Humanitas IRCCS
      Rozzano, Lombardy, Italy
  • 2011
    • Ospedale Maggiore Carlo Alberto Pizzardi di Bologna
      Bolonia, Emilia-Romagna, Italy
    • San Giuseppe Hospital
      Ареццо, Tuscany, Italy
  • 1989–2011
    • University of Pavia
      • Department of Diagnostic, Paediatric, Clinical and Surgical Science
      Ticinum, Lombardy, Italy
  • 1990–2008
    • Policlinico San Matteo Pavia Fondazione IRCCS
      • s.c. Cardiologia
      Ticinum, Lombardy, Italy
  • 2001
    • Università degli Studi dell'Insubria
      Varese, Lombardy, Italy
  • 1997–2000
    • Fondazione Salvatore Maugeri IRCCS
      Ticinum, Lombardy, Italy
  • 1988–1998
    • Ospedale di San Raffaele Istituto di Ricovero e Cura a Carattere Scientifico
      Milano, Lombardy, Italy
  • 1991–1997
    • Università degli Studi del Sannio
      Benevento, Campania, Italy
  • 1991–1993
    • Istituto di Cura e Cura a Carattere Scientifico Basilicata
      Rionero in Vulture, Basilicate, Italy