L E Adinolfi

University of Naples Federico II, Napoli, Campania, Italy

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Publications (139)749.59 Total impact

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    ABSTRACT: The inosine triphosphatase (ITPA) gene and interleukin 28B (IL28-B) gene variants have been associated to protection of anemia and sustained virological response, respectively, in patients with chronic hepatitis C (CHC) during antiviral therapy. Aim of this study was to evaluate the single and combined role of both polymorphisms in the management of peg-interferon-ribavirin treatment in CHC patients. We studied 79 Italian patients with histology proven CHC treated with pegylated interferon plus ribavirin for 6-12 months on the base of HCV genotype. Patients were carefully followed-up for anemia development which was classified as mild, moderate or severe in relation to levels of haemoglobin decreasing; ribavirin dosage reduction and/or epoietin administration were carried out, where needed. Sustained virological response (SVR) was considered for HCV-RNA clearance after 6 months of treatment stop. Decay of haemoglobin at month 1 of treatment significantly correlated with ITPA activity (p 0.0004) and at multivariate analysis ITPA activity was the only parameter associate with anemia (R - 0.4; p 0.0004). SVR was obtained in 47% of patients. IL28B CC variant was associated with SVR (p 0.01), but IL28B polymorphisms had no influence on the ITPA polymorphism. This study confirms the role of ITPA variants in the prediction of development of severe anemia during antiviral treatment for CHC and demonstrates the absence of influence of IL28B variant on ITPA polymorphisms. These two polymorphisms can be useful in the management of patients that need antiviral therapy for HCV chronic infection.
    Le infezioni in medicina: rivista periodica di eziologia, epidemiologia, diagnostica, clinica e terapia delle patologie infettive 06/2015; 23(2):134-9.
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    ABSTRACT: The patatin-like phospholipase domain-containing 3 gene (PNPLA3) has been associated with liver steatosis and disease progression in nonalcoholic steatohepatitis and chronic hepatitis C. The aim of the present study was to evaluate the influence of the PNPLA3 I148M polymorphisms on the clinical, histological, viral, and host parameters in Italian patients with chronic hepatitis B (CHB). Ninety-nine patients with CHB entered the study and underwent a clinical, histological, virological, and biochemical evaluation. PNPLA3 (p.I148M) variants were genotyped. PNPLA3 rare variant (148M) was significantly associated with liver steatosis (p = 0.0019) and cholesterol (p = 0.04) levels, but not with fibrosis or histological activity index. The 13 patients with severe liver steatosis (score > 3) (38 %) were more frequently homozygous for PNPLA3 148M variant than the 86 without (6 %, p = 0.003). At logistic regression analysis, severe steatosis was independently associated with the rare allele (p = 0.001) and waist circumference, but not with body mass index (BMI). In our CHB patients, the PNPLA3 polymorphisms influenced the development of liver steatosis, but not fibrosis status. The association of PNPLA3 p.I148M with liver steatosis increased with the greater amount of abdominal fat, irrespective of BMI.
    Digestive Diseases and Sciences 05/2015; DOI:10.1007/s10620-015-3716-7 · 2.61 Impact Factor
  • Tiziana Ciarambino · Luigi Elio Adinolfi · Mauro Giordano
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    ABSTRACT: Our patient is a 42 year old woman suffering from muscle paralysis, muscle weakness and fever. On admission, a neurological examination showed proximal and distal weakness in the leg. Serum CPK and serum myoglobina level were markedly increased (5600 UI/L and 5197 UI/L, respectively). There was no sign of renal failure. Nerve conduction study was negative. Serological studies for virus titers showed the antibody IgM-cytomegalovirus (CMV). Muscle weakness and its paralysis, fever and serum CPK level, gradually improved after the administration of methylprednisolone intravenous. CMV infection was thought to have played a central role in this case, leading to an acute but reversible peripheral muscle paralysis.
    American Journal of Emergency Medicine 05/2015; DOI:10.1016/j.ajem.2015.04.040 · 1.27 Impact Factor
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    ABSTRACT: The impact of the cannabinoid receptor 2 (CB2) rs35761398 polymorphism on chronic hepatitis B (CHB) was evaluated in 106 consecutive biopsy proven CHB patients naive for antiviral therapy. A histological activity index (HAI) >9 (Ishak scoring) was more frequent in patients with CB2-63 RR than in those with CB2-63 QR or QQ (37% vs.16.7%, p<0.05). The logistic regression analysis identified CB2-63 RR (p<0.05) and a fibrosis score > 4 (p<0.005) as independently associated with an HAI >9. The observation that the CB2-63 RR variant is an independent predictor of extensive necroinflammation opens up new prospects in the study of CHB. Copyright © 2015. Published by Elsevier Ltd.
    Clinical Microbiology and Infection 03/2015; 21(6). DOI:10.1016/j.cmi.2015.02.021 · 5.77 Impact Factor
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    ABSTRACT: Hepatitis C virus (HCV) infection is considered a systemic disease because of involvement of other organs and tissues concomitantly with liver disease. Among the extrahepatic manifestations, neuropsychiatric disorders have been reported in up to 50% of chronic HCV infected patients. Both the central and peripheral nervous system may be involved with a wide variety of clinical manifestations. Main HCV-associated neurological conditions include cerebrovascular events, encephalopathy, myelitis, encephalomyelitis, and cognitive impairment, whereas "brain fog", depression, anxiety, and fatigue are at the top of the list of psychiatric disorders. Moreover, HCV infection is known to cause both motor and sensory peripheral neuropathy in the context of mixed cryoglobulinemia, and has also been recently recognized as an independent risk factor for stroke. These extrahepatic manifestations are independent of severity of the underlying chronic liver disease and hepatic encephalopathy. The brain is a suitable site for HCV replication, where the virus may directly exert neurotoxicity; other mechanisms proposed to explain the pathogenesis of neuropsychiatric disorders in chronic HCV infection include derangement of metabolic pathways of infected cells, alterations in neurotransmitter circuits, autoimmune disorders, and cerebral or systemic inflammation. A pathogenic role for HCV is also suggested by improvement of neurological and psychiatric symptoms in patients achieving a sustained virologic response following interferon treatment; however, further ad hoc trials are needed to fully assess the impact of HCV infection and specific antiviral treatments on associated neuropsychiatric disorders.
    World Journal of Gastroenterology 02/2015; 21(8):2269-2280. DOI:10.3748/wjg.v21.i8.2269 · 2.37 Impact Factor
  • Digestive and Liver Disease 02/2015; 47:e46. DOI:10.1016/j.dld.2015.01.101 · 2.96 Impact Factor
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    ABSTRACT: Background & AimA common non-synonymous polymorphism, E167K, in transmembrane 6 superfamily member 2 (TM6SF2) gene has been recently associated with an increased hepatic triglyceride content, dyslipidemia and liver fibrosis in NAFLD patients. We investigated possible associations between the TM6SF2 variants and liver lesions in chronic hepatitis C.Patients and Methods148 consecutive patients with biopsy proven anti-HCV/HCV-RNA-positive chronic hepatitis, naive for antiviral therapy, were genotyped for TM6SF2 E167K and PNAPL3 I148M variants.ResultsThe score of liver steatosis was higher in the 18 patients with TM6SF2 E167K variant (mean 1.9+1.3) than in the 130 homozygotes for TM6SF2 167E allele (1.1+1.1, p=0.02), and the prevalence of a steatosis score>3 was 33.3% vs. 12.3%, respectively (p=0.02). No difference in necroinflammatory or fibrosis scores was found between the two groups. A general linear model identified as independent predictors of steatosis TM6SF2 E167K and PNAPL3 M148M variants and waist circumference (p=0.0376, p=0.0069 and p=0.0273, respectively).Conclusions This is the first demonstration that TM6SF2 E167K variant is an independent predictor of liver steatosis in chronic hepatitis C.This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 01/2015; 35(8). DOI:10.1111/liv.12781 · 4.85 Impact Factor
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    ABSTRACT: Hepatocellular carcinoma (HCC) is a development of severe liver disease frequently due to HBV and/or HCV infection. The aim of this retrospective study was to evaluate the development of HCC in patients with HBV-HCV chronic infection compared with patients with single HBV or HCV infection and the viral and host factors correlated to HCC in co-infected patients. We studied 268 patients with histology proven chronic hepatitis: 56 had HBV-HCV co-infection (HBV-HCV group), 46 had HBV infection (HBV group) and 166 had HCV infection (HCV group). Patients were followed up for at least 3 years. Viral and host factors were studied. HCC was more frequent in HBV-HCV group (14%) compared with HBV (2%, p = 0.006) and HCV monoinfected (4%, p = 0.006). The Mantel-Haenszel test used to investigate the relationship between HBV-HCV co-infection and development of HCC indicated an association between development of HCC and HBV-HCV co-infection (p < 0.001). In the HBV-HCV group, patients with HCC were significantly older (p = 0.000), had longer disease duration (p = 0.001), higher blood glucose levels (p = 0.001), lower levels of steatosis (p = 0.02), higher levels of fibrosis (p = 0.000), higher HCV RNA (p = 0.01) than those without HCC. ALT, lipid profile, PNPLA3 variant distribution and HBV viral load did not differ among co-infected patients with or without HCC. In conclusion HCC was more frequent in our patients with HBV-HCV co-infection, than in those with HBV or HCV mono-infection; possible associated risk factors for HCC development seem a long duration of disease, high levels of fibrosis and carbohydrate intolerance.
    Annals of hepatology: official journal of the Mexican Association of Hepatology 01/2015; 14(1):75-82. · 2.07 Impact Factor
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    ABSTRACT: Primary biliary cirrhosis (PBC) and multiple sclerosis (MS) are considered autoimmune diseases with a multifactorial aetiology which is thought to be due to a combination of genetic predisposition and environmental triggers. An association of both diseases has been previously described in sporadic case reports. Fingolimod, an antagonist of the sphingosine 1 phosphate receptor family (S1P1 3 4 5), is a promising and effective drug in the treatment of MS. Here we describe a case of PBC like syndrome that was unmasked, concomitantly or consequently to Epstein Barr virus (EBV) infection reactivation, in a 34 year old male patient with relapsing remitting multiple sclerosis who was receiving fingolimod treatment.
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    ABSTRACT: Aim: To evaluate steatosis, insulin resistance (IR) and patatin-like phospholipase domain-containing 3 (PNPLA3) and their relation to disease progression in hepatitis B and C viruses (HCV-HBV) co-infected patients. Methods: Three hundred and thirty patients with biopsy proven chronic hepatitis were enrolled: 66 had HBV-HCV, 66 HBV and 198 HCV infection. Prevalence of steatosis, IR and PNPLA3 polymorphisms and their relation to anthropometric, biochemical, virological and histological parameters were evaluated. Results: Prevalence of steatosis in group HBV-HCV was similar to that in HCV (47.0% vs 49.5%, respectively); group HBV showed the lowest steatosis (33.3%). Group HBV-HCV had a lesser degree of steatosis than HCV (P = 0.016), lower HCV RNA levels (P = 0.025) and lower prevalence and degree of IR (P = 0.01). PNPLA3 polymorphisms were associated with steatosis. Group HBV-HCV showed higher levels of liver fibrosis than group HCV (P = 0.001), but similar to that observed in HBV group. In HBV-HCV group, liver fibrosis was not associated with steatosis, IR or PNPLA3. HBV infection was the independent predictor of advanced liver fibrosis. Conclusion: HBV-HCV co-infected patients have lower degree of hepatic steatosis, IR and HCV RNA than HCV mono-infected; co-infected patients showed a more rapid liver fibrosis progression that seems to be due to the double infection and/or HBV dominance.
    World Journal of Hepatology 09/2014; 6(9):677-684. DOI:10.4254/wjh.v6.i9.677
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    ABSTRACT: Hepatitis C virus (HCV) is a successful pathogen on the grounds that it exploits its host's metabolism to build up viral particles; moreover it favours its own survival by inducing chronic disease and the development of specific anatomic changes in the infected organ. Steatosis, therefore, is associated with HCV infection by necessity rather than by chance alone. Approximately 6% of HCV patients have steatohepatitis. Interestingly, HCV steatosis occurs in the setting of multiple metabolic abnormalities (hyperuricemia, reversible hypocholesterolemia, insulin resistance, arterial hypertension and expansion of visceral adipose tissue) collectively referred to as "hepatitis C-associated dysmetabolic syndrome" (HCADS). General, nonalcoholic fatty liver disease (NAFLD)-like, mechanisms of steatogenesis (including increased availability of lipogenic substrates and de novo lipogenesis; decreased oxidation of fatty substrates and export of fatty substrates) are shared by all HCV genotypes. However, genotype 3 seemingly amplifies such steatogenic molecular mechanisms reported to occur in NAFLD via more profound changes in microsomal triglyceride transfer protein; peroxisome proliferator-activated receptor alpha; sterol regulatory element-binding proteins and phosphatase and tensin homologue. HCV steatosis has a remarkable clinical impact in as much as it is an acknowledged risk factor for accelerated fibrogenesis; for impaired treatment response to interferon and ribavirin; and development of hepatocellular carcinoma. Recent data, moreover, suggest that HCV-steatosis contributes to premature atherogenesis via both direct and indirect mechanisms. In conclusion, HCV steatosis fulfills all expected requirements necessary to perpetuate the HCV life cycle. A better understanding of the physiology of HCADS will likely result in a more successful handling of disease with improved antiviral success rates.
    World Journal of Gastroenterology 06/2014; 20(23):7089-7103. DOI:10.3748/wjg.v20.i23.7089 · 2.37 Impact Factor
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    ABSTRACT: Hepatitis C virus (HCV) infection represents a major health issue worldwide due to its burden of chronic liver disease and extrahepatic manifestations including cardiovascular diseases, which are associated with excess mortality. Analysis of published studies supports the view that HCV infection should be considered a risk factor for the development of carotid atherosclerosis, heart failure and stroke. In contrast, findings from studies addressing coronary artery disease and HCV have yielded conflicting results. Therefore, meta-analytic reviews and prospective studies are warranted. The pathogenic mechanisms connecting HCV infection, chronic liver disease, and atherogenesis are not completely understood. However, it has been hypothesized that HCV may promote atherogenesis and its complications through several direct and indirect biological mechanisms involving HCV colonization and replication within arterial walls, liver steatosis and fibrosis, enhanced and imbalanced secretion of inflammatory cytokines, oxidative stress, endotoxemia, mixed cryoglobulinemia, perturbed cellular and humoral immunity, hyperhomocysteinemia, hypo-adiponectinaemia, insulin resistance, type 2 diabetes and other components of the metabolic syndrome. Understanding these complex mechanisms is of fundamental importance for the development of novel therapeutic approaches to prevent and to treat vascular complications in patients with chronic HCV infection. Currently, it seems that HCV clearance by interferon and ribavirin treatment significantly reduces non-liver-related mortality; moreover, interferon-based treatment appears to decrease the risk of ischemic stroke.
    World Journal of Gastroenterology 04/2014; 20(13):3410-3417. DOI:10.3748/wjg.v20.i13.3410 · 2.37 Impact Factor
  • Journal of Hepatology 04/2014; 60(1):S288. DOI:10.1016/S0168-8278(14)60822-9 · 11.34 Impact Factor
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    ABSTRACT: Background and Aim To evaluate in anti-HCV-positive patients the clinical impact of the rs35761398 variant of the CNR2 gene leading to the substitution of Gln (Q) of codon 63 of the cannabinoid receptor 2 (CB2) with Arg (R). Patients and Methods 253 consecutive anti-HCV-/HCV-RNA-positive patients were enrolled, of whom 53 were HCV carriers with persistently normal ALT (PNALT group) and 200 had a history of steadily abnormal serum ALT values (abnormal ALT group). All patients were naive for antiviral therapy and were screened for the CNR2 rs35761398 polymorphism by a TaqMan assay. Results Subjects in the PNALT group, compared with those in the abnormal ALT group were older (58.5±12 vs. 50.7±12.4 years, p = 0.001), more frequently female (66% vs. 42%, p = 0.003), with lower body massindex (BMI) (24.5±3.1 vs. 26.6±4.6, p = 0.003), and more frequently with HCV genotype 2 (43.1% vs 17.7%, p = 0.0002) and CB2-63 QQ variant (34% vs. 11%, p = 0.0001). Considering all 253 patients, no difference in the demographic, biochemical, or virological data was observed between patients in the different CB2-63 variants. The logistic regression analysis identified CB2-63 QQ, HCV genotype 2, older age and lower BMI as independent predictors of PNALT (p<0.00001). Discussion The CB2-63 QQ variant in HCV patients was independently associated with the PNALT status.
    PLoS ONE 02/2014; 9(6):e99450. DOI:10.1371/journal.pone.0099450 · 3.23 Impact Factor
  • International journal of cardiology 01/2014; 172(1). DOI:10.1016/j.ijcard.2013.12.231 · 4.04 Impact Factor
  • C Romano · A Sellitto · L Restivo · L E Adinolfi
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    ABSTRACT: Diagnosis of small-vessel vasculitides (granulomatosis with polyangiitis, microscopic polyangiitis, Churg-Strauss syndrome, and their localized forms) is aided by the detection of serum antineutrophil cytoplasmic antibodies (ANCA). However, serum ANCA positivity does not always mean vasculitis. Here, we report on a 61-year-old female patient with very high serum levels of proteinase 3 ANCA, marked hypergammaglobulinemia, low complement levels, and a 16-mm lung nodule on chest CT scan, who was referred to our Institution with a provisional diagnosis of possible granulomatosis with polyangiitis. On admission, history-taking disclosed two recent episodes of viral reactivation (namely, cytomegalovirus and Varicella-Zoster virus), while physical examination revealed lingual and nail involvement suggestive of Candida infection. An immunodeficiency disorder was eventually suspected. Search for antibodies against human immunodeficiency virus (HIV) 1 and 2 turned positive. Western blot analysis confirmed HIV infection. Thus, although ANCA detection may be helpful in diagnosing small-vessel vasculitis in the appropriate clinical scenario, screening for HIV infection should sometimes be considered to discriminate clinically irrelevant serum ANCA positivity.
    International journal of immunopathology and pharmacology 12/2013; 26(4):957-9. · 1.62 Impact Factor
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    ABSTRACT: Cerebrovascular diseases are leading cause of death worldwide. Plaque rupture and embolization account for one-third of ischemic stroke. The causes are not fully known, but inflammation plays a pathogenic role. Recently, HCV infection has been identify as risk of atherosclerosis. HCV replicates within carotid plaques and brain endothelia cells; moreover, HCV patients showed higher levels of inflammation. Thus, we hypothesized that subjects carrying HCV are at higher risk of stroke. Accordingly, we evaluated prevalence and role of HCV infection in patients with stroke. A priori sample size was calculated. Overall, 820 consecutive patients were enrolled, 123 with stroke and, as control, 697 age- and gender-matched (295 with COPD; 402 with diseases other than HCV-associated). Patients were evaluated for HCV and conventional risk of stroke. Prevalence of HCV was higher in patients with stroke than that observed in control (26.8% vs. 6.6%, p = 0.0001). An analysis of stroke patients showed that those HCV positive were younger (p = 0.017) had lower serum levels of cholesterol (p = 0.001), triglycerides (p = 0.045), and higher serum levels of inflammation markers (ESR, p = 0.001; CRP, p = 0.0001; fibrinogen, p = 0.012). A multivariate analysis showed that HCV infection was an independent risk factor of stroke (O.R. 2.04, 95% C.I. 1.69-2.46; p = 0.0001). A secondary analysis showed that HCV patients had higher (p = 0.031) prevalence of past ischemic heart disease. HCV infected patients are at higher and earlier risk of stroke. Inflammation is a key mediator. Clinicians in clinical practice and researchers in future trials should take into account these new findings.
    Atherosclerosis 11/2013; 231(1):22-26. DOI:10.1016/j.atherosclerosis.2013.08.003 · 3.99 Impact Factor
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    ABSTRACT: Hepatitis C virus core antigen (HCVcoreAg) may be measured in serum with a sensitive, recently validated assay. Beyond its value as a marker of viral infection, there are little data on its relation with clinical, histological, and virological parameters. In this study, the significance of HCVcoreAg levels was studied in a prospective cohort of 114 patients with chronic hepatitis C. HCVcoreAg was measured by a commercial chemiluminescent microparticle immunoassay. Clinical and virological data included quantitative HCV-RNA, HCV genotype, ALT, GGT, IL28B rs12979860 polymorphism as well as liver histology parameters. HCVcoreAg levels were correlated significantly with HCV-RNA (r = 0.56; P < 0.0001) but also with ALT levels (r = 0.258; P < 0.01) and liver necroinflammatory activity (r = 0.205; P < 0.04). Patients harbouring HCV genotype 3 showed lower levels of HCVcoreAg than both genotype 1 and two patients. In genotype 3, a direct correlation between steatosis and HCVcoreAg was found. Levels of HCVcoreAg also varied according to the IL28B genotype. These data suggest that the evaluation of HCVcoreAg serum levels may provide relevant data for the baseline clinical evaluation of chronic hepatitis C patients. HCVcoreAg serum levels may be a useful tool to further the understanding of chronic hepatitis C pathobiology. J. Med. Virol. © 2013 Wiley Periodicals, Inc.
    Journal of Medical Virology 11/2013; 85(11). DOI:10.1002/jmv.23672 · 2.35 Impact Factor
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    ABSTRACT: The liver has a central role in regulating inflammation by its capacity to secrete a number of proteins that control both local and systemic inflammatory responses. Chronic inflammation or an exaggerated inflammatory response can produce detrimental effects on target organs. Chronic hepatitis C virus (HCV) infection causes liver inflammation by complex and not yet well-understood molecular pathways, including direct viral effects and indirect mechanisms involving cytokine pathways, oxidative stress and steatosis induction. An increasing body of evidence recognizes the inflammatory response in chronic hepatitis C as pathogenically linked to the development of both liver-limited injury (fibrosis, cirrhosis and hepatocellular carcinoma) and extrahepatic HCV-related diseases (lymphoproliferative disease, atherosclerosis, cardiovascular and brain disease). Defining the complex mechanisms of HCV-induced inflammation could be crucial to determine the global impact of infection, to estimate progression of the disease, and to explore novel therapeutic approaches to avert HCV-related diseases. This review focuses on HCV-related clinical conditions as a result of chronic liver and systemic inflammatory states.
    World Journal of Hepatology 10/2013; 5(10):528-540. DOI:10.4254/wjh.v5.i10.528
  • Ultraschall in der Medizin 10/2013; 34(S 01). DOI:10.1055/s-0033-1354999 · 4.92 Impact Factor

Publication Stats

3k Citations
749.59 Total Impact Points


  • 1996–2015
    • University of Naples Federico II
      • • Department of Clinical Medicine and Surgery
      • • Department of Molecular Medicine and Medical Biotechnology
      Napoli, Campania, Italy
  • 1982–2015
    • Second University of Naples
      • Faculty of Medicine and Surgery
      Caserta, Campania, Italy
  • 2003–2014
    • Università degli Studi di Modena e Reggio Emilia
      • Department of Biomedical, Metabolical and Neurosciences
      Modène, Emilia-Romagna, Italy
  • 2006–2009
    • Università degli Studi di Napoli L'Orientale
      Napoli, Campania, Italy
  • 2000–2009
    • Naples Eastern University
      Napoli, Campania, Italy
  • 1989
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, MA, United States
  • 1988–1989
    • Georgia Health Sciences University
      Augusta, Georgia, United States