luchinochessa

@aoucagliari.it/home

Department of Medical Sciences and Public Health, University of Cagliari
Unit Liver, University Hospital of Cagliari



              

https://researchid.co/luchessa
80

Scopus Publications

2025

Scholar Citations

21

Scholar h-index

30

Scholar i10-index

Scopus Publications

  • Humoral responses to wild type and ancient BA.1 SARS-CoV-2 variant after heterologous priming vaccination with ChAdOx1 nCoV-19 and BNT162b2 booster dose
    Giuseppina Sanna, Alessandra Marongiu, Davide Firinu, Cristina Piras, Vanessa Palmas, Massimiliano Galdiero, Luigi Atzori, Paola Caria, Marcello Campagna, Andrea Perra,et al.

    Springer Science and Business Media LLC
    AbstractSeveral countries have recommended a booster dose of Pfizer BNT162b2 vaccine for subjects under the age of 60, who have already received the first dose of ChAdOx1. This is due to several ChAdOx1 vaccine-associated adverse vascular events and thrombocytopenia. Neutralization assay and quantitative IgG anti-SARS-CoV-2 Spike antibody (anti-S-IgG) were conducted to investigate the long-term responses to vaccine treatment in a cohort of Sardinian participants, who have received heterologous Prime–Boost Vaccination via ChAdOx1 vector vaccine and a booster dose via BNT162b2. The obtained results were compared with those of a cohort of healthcare workers (HCW) who received homologous BNT162b2 (BNT/BNT/BNT) vaccination. One month (T2) and five months after the second and before the third dose (T3), anti-spike antibody or neutralizing titers in the subjects vaccinated with ChAdOx1-S/BNT162b2 were significantly higher than those who experienced the ChAdOx1-S/ChAdOx1-S or BNT162b2/BNT162b2 schedule. These results suggest that a ChAdOx1-S/BNT162b2 regimen provides a more robust antibody response than either of the homologous regimens. However, the anti-spike antibodies or neutralizing titers after the third injection (mRNA vaccine) of ChAdOx1-S as a second dose and BNT162b2 were not statistically different. Homologous and heterologous vaccination provided a strong antibody response. Neutralizing activities were also described against the Omicron BA.1 variant in a sub-group (40) representative of the three vaccination regimens among our cohort.

  • The Stability of Social and Behavioral Rhythms and Unexpected Low Rate of Relevant Depressive Symptoms in Old Adults during the COVID-19 Pandemic
    Federica Sancassiani, Giulia Cossu, Elisa Cantone, Ferdinando Romano, Alessandra Perra, Antonio Urban, Samantha Pinna, Stefano Del Giacco, Roberto Littera, Davide Firinu,et al.

    MDPI AG
    Background: The disruption of social rhythms was found to be associated with depressive disorders during the COVID-19 pandemic; lower rates of these disorders were surprisingly found in old adults. The present study aims to verify the stability of social rhythms during lockdown in a sample of elderly people. Methods: Controlled cohort study (secondary analyses) of a previous randomized-controlled trial with the first evaluation in April 2019 (T0) and then 48 weeks later (T1) during the lockdown. The regulation of social and behavioral rhythms was measured through the Brief Social Rhythms Scale (BSRS); the Patient Health Questionnaire-9 (PHQ9) was adopted to detect relevant depressive symptoms. Results: 93 elderlies (73.36 ± 4.97 years old, 50.5% females) were evaluated at T0 and T1. Neither the total score of BSRS nor any of the 10 items showed a statistically significant difference comparing the two survey periods. The frequency of relevant depressive symptoms was 5.3% at T0 and 6.4% at T1 (OR = 0.8, CI95% 0.2–24). Conclusions: Among elderlies who did not show an increased risk of depression during the lockdown, social and behavioral rhythms remained exceptionally stable during the same period. Considering previous evidence about rhythms dysregulation preceding depression, their stability may be considered a factor of resilience.

  • Further decompensation in cirrhosis: Results of a large multicenter cohort study supporting Baveno VII statements
    Gennaro D’Amico, Alexander Zipprich, Càndid Villanueva, Juan Antonio Sordà, Rosa Maria Morillas, Matteo Garcovich, Montserrat García Retortillo, Javier Martinez, Paul Calès, Mario D’Amico,et al.

    Ovid Technologies (Wolters Kluwer Health)
    Background and Aims: The prognostic weight of further decompensation in cirrhosis is still unclear. We investigated the incidence of further decompensation and its effect on mortality in patients with cirrhosis. Approach and Results: Multicenter cohort study. The cumulative incidence of further decompensation (development of a second event or complication of a decompensating event) was assessed using competing risks analysis in 2028 patients. A 4-state model was built: first decompensation, further decompensation, liver transplant, and death. A cause-specific Cox model was used to assess the adjusted effect of further decompensation on mortality. Sensitivity analyses were performed for patients included before or after 1999. In a mean follow-up of 43 months, 1192 patients developed further decompensation and 649 died. Corresponding 5-year cumulative incidences were 52% and 35%, respectively. The cumulative incidences of death and liver transplant after further decompensation were 55% and 9.7%, respectively. The most common further decompensating event was ascites/complications of ascites. Five-year probabilities of state occupation were 24% alive with first decompensation, 21% alive with further decompensation, 7% alive with a liver transplant, 16% dead after first decompensation without further decompensation, 31% dead after further decompensation, and <1% dead after liver transplant. The HR for death after further decompensation, adjusted for known prognostic indicators, was 1.46 (95% CI: 1.23–1.71) (p<0.001). The significant impact of further decompensation on survival was confirmed in patients included before or after 1999. Conclusions: In cirrhosis, further decompensation occurs in ~60% of patients, significantly increases mortality, and should be considered a more advanced stage of decompensated cirrhosis.

  • Predicting de-novo portal vein thrombosis after HCV eradication: A long-term competing risk analysis in the ongoing PITER cohort
    Loreta A. Kondili, Alberto Zanetto, Maria Giovanna Quaranta, Luigina Ferrigno, Valentina Panetta, Vincenza Calvaruso, Anna Linda Zignego, Maurizia R. Brunetto, Giovanni Raimondo, Elisa Biliotti,et al.

    Wiley
    AbstractBackground & AimsSustained virological response (SVR) by direct‐acting antivirals (DAAs) may reverse the hypercoagulable state of HCV cirrhosis and the portal vein thrombosis (PVT) risk. We evaluated the incidence and predictive factors of de novo, non‐tumoral PVT in patients with cirrhosis after HCV eradication.MethodsPatients with HCV‐related cirrhosis, consecutively enrolled in the multi‐center ongoing PITER cohort, who achieved the SVR using DAAs, were prospectively evaluated. Kaplan‐Meier and competing risk regression analyses were performed.ResultsDuring a median time of 38.3 months (IQR: 25.1–48.7 months) after the end of treatment (EOT), among 1609 SVR patients, 32 (2.0%) developed de novo PVT. A platelet count ≤120,000/μL, albumin levels ≤3.5 mg/dL, bilirubin >1.1 mg/dL, a previous liver decompensation, ALBI, Baveno, FIB‐4, and RESIST scores were significantly different (p < 0.001), among patients who developed PVT versus those who did not. Considering death and liver transplantation as competing risk events, esophageal varices (subHR: 10.40; CI 95% 4.33–24.99) and pre‐treatment ALBI grade ≥2 (subHR: 4.32; CI 95% 1.36–13.74) were independent predictors of PVT. After HCV eradication, a significant variation in PLT count, albumin, and bilirubin (p < 0.001) versus pre‐treatment values was observed in patients who did not develop PVT, whereas no significant differences were observed in those who developed PVT (p > 0.05). After the EOT, esophageal varices and ALBI grade ≥2, remained associated with de novo PVT (subHR: 9.32; CI 95% 3.16–27.53 and subHR: 5.50; CI 95% 1.67–18.13, respectively).ConclusionsIn patients with HCV‐related cirrhosis, a more advanced liver disease and significant portal hypertension are independently associated with the de novo PVT risk after SVR.

  • Prevalence of Apical Periodontitis in Patients with Autoimmune Liver Diseases on Immune Suppressants and Immune Modulators: A Cross-sectional Study
    Francesca Ideo, Sadia Niazi, Luchino Chessa, Michela Miglianti, Giulia Bardini, Francesco Mannocci, and Elisabetta Cotti

    Elsevier BV

  • Impact of Exposure to Vaccination and Infection on Cellular and Antibody Response to SARS-CoV-2 in CVID Patients Through COVID-19 Pandemic
    Giulia Anna Maria Luigia Costanzo, Carla Maria Deiana, Giuseppina Sanna, Andrea Perra, Marcello Campagna, Andrea Giovanni Ledda, Ferdinando Coghe, Vanessa Palmas, Riccardo Cappai, Aldo Manzin,et al.

    Springer Science and Business Media LLC

  • Combined Salivary Proteome Profiling and Machine Learning Analysis Provides Insight into Molecular Signature for Autoimmune Liver Diseases Classification
    Giulia Guadalupi, Cristina Contini, Federica Iavarone, Massimo Castagnola, Irene Messana, Gavino Faa, Simona Onali, Luchino Chessa, Rui Vitorino, Francisco Amado,et al.

    MDPI AG
    Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) are autoimmune liver diseases that target the liver and have a wide spectrum of presentation. A global overview of quantitative variations on the salivary proteome in presence of these two pathologies is investigated in this study. The acid-insoluble salivary fraction of AIH and PBC patients, and healthy controls (HCs), was analyzed using a gel-based bottom-up proteomic approach combined with a robust machine learning statistical analysis of the dataset. The abundance of Arginase, Junction plakoglobin, Desmoplakin, Hexokinase-3 and Desmocollin-1 decreased, while that of BPI fold-containing family A member 2 increased in AIHp compared to HCs; the abundance of Gelsolin, CD14, Tumor-associated calcium signal transducer 2, Clusterin, Heterogeneous nuclear ribonucleoproteins A2/B1, Cofilin-1 and BPI fold-containing family B member 2 increased in PBCp compared to HCs. The abundance of Hornerin decreased in both AIHp and PBCp with respect to HCs and provided an area under the ROC curve of 0.939. Machine learning analysis confirmed the feasibility of the salivary proteome to discriminate groups of subjects based on AIH or PBC occurrence as previously suggested by our group. The topology-based functional enrichment analysis performed on these potential salivary biomarkers highlights an enrichment of terms mostly related to the immune system, but also with a strong involvement in liver fibrosis process and with antimicrobial activity.

  • Profiling the risk of hepatocellular carcinoma after long-term HCV eradication in patients with liver cirrhosis in the PITER cohort
    Loreta A. Kondili, Maria Giovanna Quaranta, Luisa Cavalletto, Vincenza Calvaruso, Luigina Ferrigno, Roberta D'Ambrosio, Ilaria Simonelli, Giuseppina Brancaccio, Giovanni Raimondo, Maurizia R. Brunetto,et al.

    Elsevier BV

  • Trends in chronic hepatitis B virus infection in Italy over a 10-year period: Clues from the nationwide PITER and MASTER cohorts toward elimination
    Giuseppina Brancaccio, Barbara Coco, Alessandra Nardi, Maria Giovanna Quaranta, Maria Elena Tosti, Luigina Ferrigno, Irene Cacciola, Vincenzo Messina, Luchino Chessa, Filomena Morisco,et al.

    Elsevier BV

  • COVID-19 Vaccine Hesitancy among Italian Healthcare Workers: Latent Profiles and Their Relationships to Predictors and Outcome
    Igor Portoghese, Melinda Siddi, Luchino Chessa, Giulia Costanzo, Vanessa Garcia-Larsen, Andrea Perra, Roberto Littera, Giada Sambugaro, Stefano Del Giacco, Marcello Campagna,et al.

    MDPI AG
    Vaccine hesitancy and conspiracy beliefs among healthcare workers (HCWs) represent operational priorities that require urgent attention. Identifying and classifying specific subpopulation of hesitancy is crucial to customize educational and intervention strategies to enhance the acceptance and uptake rate of vaccination. Thus, the main purpose of our study was to empirically identify latent profiles of vaccine hesitancy among Italian HCWs adopting a person-centered approach and investigating their relationships with antecedents and intention to get a fourth dose of COVID-19 vaccine. We conducted latent profile analyses (LPA) to identify different configurations of vaccine hesitancy based on five antecedents of vaccination: confidence, complacency, constraints, calculation, and collective responsibility among a sample of Italian HCWs (n = 573). LPA revealed four distinct profiles: believer (61.5%), middler (24.7%), hesitant (9.00%), and rejecter (4.7%). Having conspiracy beliefs was associated with a greater likelihood of membership in all but believer. Finally, the likelihood of intention to get a fourth dose of COVID-19 vaccine was lowest in the rejector and hesitant profiles. Theoretical contributions and implications for practice are discussed.

  • Direct-acting antivirals used in HCV-related liver disease do not affect thyroid function and autoimmunity
    R. Rodia, P. E. Meloni, C. Mascia, C. Balestrieri, V. Ruggiero, G. Serra, M. Conti, M. Loi, F. Pes, S. Onali,et al.



  • Comparing the responses of countries and National Health Systems to the COVID-19 pandemic: a critical analysis with a case-report series
    M. G. Carta, G. Orrù, R. Littera, D. Firinu, L. Chessa, G. Cossu, D. Primavera, S. Del Giacco, E. Tramontano, N. Manocchio,et al.


    This review aimed to compare the different responses of countries to the pandemic, their National Health Systems, and their impact on citizens' health. This work aimed to create a narrative plot that connects different discussion points and suggests organizational solutions and strategic choices in the face of the pandemic. In particular, this work focused on public health organizations, specifically the European Union and vaccination politics. It is also based on a case report series (about the United States, Germany, Vietnam, New Zealand, Cuba, and Italy), where each country has responded differently to the pandemic in terms of political decisions such as vaccination type, information to citizens, dealings with independent experts, and other specific country factors. In comparing the various models of care systems response to the pandemic, it emerges that: we have found some (few) good practices, but without global coordination, and this is obviously not enough. It is now quite clear that there cannot be a "good answer" in a single nation. Uncoordinated local responses cannot counter a global phenomenon. The second point is that the general context must be considered from a strategic point of view. With the threat of new pandemics (but also of health disasters linked to climate change, pollution, and wars), humanity finds itself at the crossroads between investing in a "democratic" management of international bodies but without power (and at the mercy of the need for funds with consequent conflicts) or in some new leadership proposals that advocate efficiency and problem-solving (and that would probably be able to implement it) but that would place processes totally outside of the public's control.

  • Decision trees for early prediction of inadequate immune response to coronavirus infections: a pilot study on COVID-19
    Fabio Pisano, Barbara Cannas, Alessandra Fanni, Manuela Pasella, Beatrice Canetto, Sabrina Rita Giglio, Stefano Mocci, Luchino Chessa, Andrea Perra, and Roberto Littera

    Frontiers Media SA
    IntroductionFew artificial intelligence models exist to predict severe forms of COVID-19. Most rely on post-infection laboratory data, hindering early treatment for high-risk individuals.MethodsThis study developed a machine learning model to predict inherent risk of severe symptoms after contracting SARS-CoV-2. Using a Decision Tree trained on 153 Alpha variant patients, demographic, clinical and immunogenetic markers were considered. Model performance was assessed on Alpha and Delta variant datasets. Key risk factors included age, gender, absence of KIR2DS2 gene (alone or with HLA-C C1 group alleles), presence of 14-bp polymorphism in HLA-G gene, presence of KIR2DS5 gene, and presence of KIR telomeric region A/A.ResultsThe model achieved 83.01% accuracy for Alpha variant and 78.57% for Delta variant, with True Positive Rates of 80.82 and 77.78%, and True Negative Rates of 85.00% and 79.17%, respectively. The model showed high sensitivity in identifying individuals at risk.DiscussionThe present study demonstrates the potential of AI algorithms, combined with demographic, epidemiologic, and immunogenetic data, in identifying individuals at high risk of severe COVID-19 and facilitating early treatment. Further studies are required for routine clinical integration.

  • A review of the main genetic factors influencing the course of COVID-19 in Sardinia: the role of human leukocyte antigen-G
    Stefano Mocci, Roberto Littera, Luchino Chessa, Marcello Campagna, Maurizio Melis, Carla Maria Ottelio, Ignazio S. Piras, Sara Lai, Davide Firinu, Stefania Tranquilli,et al.

    Frontiers Media SA
    IntroductionA large number of risk and protective factors have been identified during the SARS-CoV-2 pandemic which may influence the outcome of COVID-19. Among these, recent studies have explored the role of HLA-G molecules and their immunomodulatory effects in COVID-19, but there are very few reports exploring the genetic basis of these manifestations. The present study aims to investigate how host genetic factors, including HLA-G gene polymorphisms and sHLA-G, can affect SARS-CoV-2 infection.Materials and MethodsWe compared the immune-genetic and phenotypic characteristics between COVID-19 patients (n = 381) with varying degrees of severity of the disease and 420 healthy controls from Sardinia (Italy).ResultsHLA-G locus analysis showed that the extended haplotype HLA-G*01:01:01:01/UTR-1 was more prevalent in both COVID-19 patients and controls. In particular, this extended haplotype was more common among patients with mild symptoms than those with severe symptoms [22.7% vs 15.7%, OR = 0.634 (95% CI 0.440 – 0.913); P = 0.016]. Furthermore, the most significant HLA-G 3’UTR polymorphism (rs371194629) shows that the HLA-G 3’UTR Del/Del genotype frequency decreases gradually from 27.6% in paucisymptomatic patients to 15.9% in patients with severe symptoms (X2 = 7.095, P = 0.029), reaching the lowest frequency (7.0%) in ICU patients (X2 = 11.257, P = 0.004). However, no significant differences were observed for the soluble HLA-G levels in patients and controls. Finally, we showed that SARS-CoV-2 infection in the Sardinian population is also influenced by other genetic factors such as β-thalassemia trait (rs11549407C>T in the HBB gene), KIR2DS2/HLA-C C1+ group combination and the HLA-B*58:01, C*07:01, DRB1*03:01 haplotype which exert a protective effect [P = 0.005, P = 0.001 and P = 0.026 respectively]. Conversely, the Neanderthal LZTFL1 gene variant (rs35044562A>G) shows a detrimental consequence on the disease course [P = 0.001]. However, by using a logistic regression model, HLA-G 3’UTR Del/Del genotype was independent from the other significant variables [ORM = 0.4 (95% CI 0.2 – 0.7), PM = 6.5 x 10-4].ConclusionOur results reveal novel genetic variants which could potentially serve as biomarkers for disease prognosis and treatment, highlighting the importance of considering genetic factors in the management of COVID-19 patients.

  • Top-Down Proteomics Detection of Potential Salivary Biomarkers for Autoimmune Liver Diseases Classification
    Alessandra Olianas, Giulia Guadalupi, Tiziana Cabras, Cristina Contini, Simone Serrao, Federica Iavarone, Massimo Castagnola, Irene Messana, Simona Onali, Luchino Chessa,et al.

    MDPI AG
    (1) Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) are autoimmune liver diseases characterized by chronic hepatic inflammation and progressive liver fibrosis. The possible use of saliva as a diagnostic tool has been explored in several oral and systemic diseases. The use of proteomics for personalized medicine is a rapidly emerging field. (2) Salivary proteomic data of 36 healthy controls (HCs), 36 AIH and 36 PBC patients, obtained by liquid chromatography/mass spectrometry top-down pipeline, were analyzed by multiple Mann—Whitney test, Kendall correlation, Random Forest (RF) analysis and Linear Discriminant Analysis (LDA); (3) Mann—Whitney tests provided indications on the panel of differentially expressed salivary proteins and peptides, namely cystatin A, statherin, histatin 3, histatin 5 and histatin 6, which were elevated in AIH patients with respect to both HCs and PBC patients, while S100A12, S100A9 short, cystatin S1, S2, SN and C showed varied levels in PBC with respect to HCs and/or AIH patients. RF analysis evidenced a panel of salivary proteins/peptides able to classify with good accuracy PBC vs. HCs (83.3%), AIH vs. HCs (79.9%) and PBC vs. AIH (80.2%); (4) RF appears to be an attractive machine-learning tool suited for classification of AIH and PBC based on their different salivary proteomic profiles.

  • What do young people know about HIV? Results of a cross sectional study on 18-24-year-old students
    A. Mereu, A. Liori, Luca Fadda, Massimiliano Puddu, L. Chessa, P. Contu and C. Sardu


    Introduction Increasing people's knowledge of transmission, prevention, early diagnosis, and available treatments is a key step toward HIV control; it means setting the conditions for empowerment and enabling individuals to make aware choices about the prevention strategy best suited to their needs. This study aims to identify unmet needs on HIV knowledge among freshman students. Methods A cross sectional study was carried out at the University of Cagliari, which is an Italian public state university. Data were collected by means of an anonymous questionnaire; the final sample included 801 students. Results Results offer a detailed picture of students' knowledge and perceptions of HIV. Several topics deserve to be better understood by students, but the main gaps relate to the pre-exposure prophylaxis and the decreased likelihood of sexually transmitting HIV due to early treatments. Students' vision of the quality of life of people living with HIV was negatively affected by perceiving as relevant the effects of HIV on physical health or on sexual/affective domains, while conversely, it seemed positively affected by knowing that current treatments are useful for counteracting physical symptoms and decreasing the possibility of transmitting HIV. Conclusion Being aware of the potential benefits of current therapies could favour a less negative view, in line with the current state of the beneficial effects of HIV treatment. Universities are a valuable setting to bridge the HIV knowledge gap and thus also contribute to tackling stigma and actively promoting HIV testing.

  • Predictors of serious adverse events and non-response in cirrhotic patients with primary biliary cholangitis treated with obeticholic acid
    Antonio De Vincentis, Daphne D'Amato, Laura Cristoferi, Alessio Gerussi, Federica Malinverno, Ana Lleo, Francesca Colapietro, Fabio Marra, Andrea Galli, Cecilia Fiorini,et al.

    Wiley
    BACKGROUND & AIMS Obeticholic acid (OCA) has recently been restricted in patients with primary biliary cholangitis (PBC) with "advanced cirrhosis" because of its narrow therapeutic index. We aimed at better defining the predicting factors of hepatic serious adverse events (SAEs) and non-response in cirrhotic patients undergoing OCA therapy. METHODS Safety and efficacy of treatment were evaluated in a cohort of consecutive PBC cirrhotic patients started with OCA. OCA response was evaluated according to the Poise criteria. Risk factors for hepatic SAEs and non-response were reported as risk ratios (RR) with 95% confidence intervals (CIs). RESULTS One-hundred PBC cirrhotics were included, 97 Child-Pugh class A and 3 class B. Thirty-one had esophageal varices, 5 had history of ascites. Thirty-three% and 32% of patients achieved a biochemical response at 6 and 12 months, respectively. Male-sex (adjusted-RR 1.75, 95%CI 1.42-2.12), INR (1.37,1.00-1.87), Child-Pugh score (1.79,1.28-2.50), MELD (1.17,1.04-1.30), and bilirubin (1.83,1.11-3.01) were independently associated with non-response to OCA. Twenty-two patients discontinued OCA within 12 months: 10 for pruritus, 9 for hepatic SAEs (5 for jaundice and/or ascitic decompensation; 4 for upper digestive bleeding). INR (adjusted-RR 1.91,95%CI 1.10-3.36), lower albumin levels (0.18,0.06-0.51), Child-Pugh score (2.43,1.50-4.04), history of ascites (3.5,1.85-6.5), and bilirubin (1.30,1.05-1.56), were associated with hepatic SAEs. A total bilirubin≥1.4mg/dL at baseline was the most accurate biochemical predictor of hepatic SAEs under OCA. CONCLUSIONS An accurate baseline assessment is crucial to select cirrhotic patients who can benefit from OCA. Although OCA is effective in one third of cirrhotics, bilirubin level≥1.4mg/dL should discourage from its use.

  • The double-sided of human leukocyte antigen-G molecules in type 1 autoimmune hepatitis
    Roberto Littera, Andrea Perra, Michela Miglianti, Ignazio S. Piras, Stefano Mocci, Sara Lai, Maurizio Melis, Teresa Zolfino, Cinzia Balestrieri, Maria Conti,et al.

    Frontiers Media SA
    The immunomodulatory effects of HLA-G expression and its role in cancers, human liver infections and liver transplantation are well documented, but so far, there are only a few reports addressing autoimmune liver diseases, particularly autoimmune hepatitis (AIH).Method and materialsWe analyzed the genetic and phenotypic characteristics of HLA-G in 205 type 1 AIH patients (AIH-1) and a population of 210 healthy controls from Sardinia (Italy).ResultsAnalysis of the HLA-G locus showed no substantial differences in allele frequencies between patients and the healthy control population. The HLA-G UTR-1 haplotype was the most prevalent in both AIH-1 patients and controls (40.24% and 34.29%). Strong linkage was found between the HLA-G UTR-1 haplotype and HLA-DRB1*03:01 in AIH-1 patients but not controls (D’ = 0.92 vs D’ = 0.50 respectively; P = 1.3x10-8). Soluble HLA-G (sHLA-G) levels were significantly lower in AIH-1 patients compared to controls [13.9 (11.6 – 17.4) U/mL vs 21.3 (16.5 – 27.8) U/mL; P = 0.011]. Twenty-four patients with mild or moderate inflammatory involvement, as assessed from liver biopsy, showed much higher sHLA-G levels compared to the 28 patients with severe liver inflammation [33.5 (23.6 – 44.8) U/mL vs 8.8 (6.1 – 14.5) U/mL; P = 0.003]. Finally, immunohistochemistry analysis of 52 liver biopsies from AIH-1 patients did not show expression of HLA-G molecules in the liver parenchyma. However, a percentage of 69.2% (36/52) revealed widespread expression of HLA-G both in the cytoplasm and the membrane of plasma cells labeled with anti-HLA-G monoclonal antibodies.ConclusionThis study highlights the positive immunomodulatory effect of HLA-G molecules on the clinical course of AIH-1 and how this improvement closely correlates with plasma levels of sHLA-G. However, our results open the debate on the ambiguous role of HLA-G molecules expressed by plasma cells, which are pathognomonic features of AIH-1.

  • Evaluation of antibody response to BNT162b2 mRNA COVID-19 vaccine in patients affected by immune-mediated inflammatory diseases up to 5 months after vaccination
    Davide Firinu, Andrea Perra, Marcello Campagna, Roberto Littera, Giuseppe Fenu, Federico Meloni, Selene Cipri, Francesca Sedda, Maria Conti, Michela Miglianti,et al.

    Springer Science and Business Media LLC
    AbstractSARS-CoV-2 vaccination with mRNA product BNT162b2 elicited high immunogenicity in healthy subjects in trials. This study aims to better understand the factors that influence the humoral immune response to vaccination against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs). We enrolled patients and healthy healthcare workers control group (HCW) that underwent mRNA BNT162b2 vaccination and measured the serum IgG anti-S-RBD response at booster dose (T1), one month after booster dose (T2) and up to 5 months (T3). Demographic, disease-specific and vaccination data were recorded. Vaccination response of 551 participants naïve to SARS-CoV-2 infection were included in HCW and 102 in the IMID group, analyzing separately those on anti-CD20. At T2 all naïve HCW developed anti-S-RBD-IgG, while 94% of IMID responded (p < 0.001). IMID patients had a significantly different level of IgG than HCW at both T1 (p = 0.031), T2 (p < 0.001), while there was no significant difference at T3. There were no statistically significant differences according to the IMID type or to ongoing treatment with immunosuppressants, corticosteroids or biological drugs other than anti-CD20. The proportion and magnitude of response was significantly lower in IMID treated with anti-CD20 drugs. There was a correlation with age at T1 and at T2 but not at T3, stronger in patients than in HCW. Immune response close after BNT162b2 vaccination is reduced in patients with IMID, but there is no significant difference at 5 months. The measured reduction is related to age and the disease itself rather than treatments, with the exception of anti-CD20 drugs.

  • Differences in lethality and diffusion of Covid-19 in countries using different kinds of vaccines
    Mauro Giovanni Carta, Germano Orrù, Ambra Peracchia, Giulia Cossu, Fernanda Velluzzi, Laura Atzori, Caterina Ferreli, Cesar Ivan Aviles Gonzalez, Ferdinando Romano, Roberto Littera,et al.

    SAGE Publications
    To verify if lethality and diffusivity of Covid-19 correlated with percentage of people vaccinated in different countries and whether results on these indicators were comparable under different types of vaccines. A linear regression analysis was conducted between vaccines/inhabitant, new cases/inhabitants and ratio deaths/cases. A comparison between the three indicators was carried out in countries subdivided by kind of vaccine. The proportion of vaccinations/inhabitants correlates negatively with proportion of deaths × 100 cases ( R = −3.90, p < 0.0001), but didn’t on incidence of new cases. Countries with prevalence of mRNA vaccines were similar to others on incidence of new cases; but a lower lethality of Sars-Cov2 was found than in countries with prevalence of viral vehicle vaccines ( F = 6.064, p = 0.0174) but didn’t against countries with prevalence of inactivated vaccines. The higher is the proportion of vaccine/inhabitant in a given country, the less is the fraction of infected people who die.

  • Evaluation of humoral and cellular response to third dose of BNT162b2 mRNA COVID-19 vaccine in patients treated with B-cell depleting therapy
    Davide Firinu, Giuseppe Fenu, Giuseppina Sanna, Giulia A. Costanzo, Andrea Perra, Marcello Campagna, Roberto Littera, Carlotta Locci, Alessandra Marongiu, Riccardo Cappai,et al.

    Elsevier BV

  • A prospective study of direct-acting antiviral effectiveness and relapse risk in HCV cryoglobulinemic vasculitis by the Italian PITER cohort
    Loreta A. Kondili, Monica Monti, Maria Giovanna Quaranta, Laura Gragnani, Valentina Panetta, Giuseppina Brancaccio, Cesare Mazzaro, Marcello Persico, Mario Masarone, Ivan Gentile,et al.

    Wiley
    Mixed cryoglobulinemia is the most common HCV extrahepatic manifestation. We aimed to prospectively evaluate the cryoglobulinemic vasculitis (CV) clinical profile after a sustained virologic response (SVR) over a medium‐term to long‐term period.

  • A Protective HLA Extended Haplotype Outweighs the Major COVID-19 Risk Factor Inherited From Neanderthals in the Sardinian Population
    Stefano Mocci, Roberto Littera, Stefania Tranquilli, Aldesia Provenzano, Alessia Mascia, Federica Cannas, Sara Lai, Erika Giuressi, Luchino Chessa, Goffredo Angioni,et al.

    Frontiers Media SA
    Sardinia has one of the lowest incidences of hospitalization and related mortality in Europe and yet a very high frequency of the Neanderthal risk locus variant on chromosome 3 (rs35044562), considered to be a major risk factor for a severe SARS-CoV-2 disease course. We evaluated 358 SARS-CoV-2 patients and 314 healthy Sardinian controls. One hundred and twenty patients were asymptomatic, 90 were pauci-symptomatic, 108 presented a moderate disease course and 40 were severely ill. All patients were analyzed for the Neanderthal-derived genetic variants reported as being protective (rs1156361) or causative (rs35044562) for severe illness. The β°39 C>T Thalassemia variant (rs11549407), HLA haplotypes, KIR genes, KIRs and their HLA class I ligand combinations were also investigated. Our findings revealed an increased risk for severe disease in Sardinian patients carrying the rs35044562 high risk variant [OR 5.32 (95% CI 2.53 - 12.01), p = 0.000]. Conversely, the protective effect of the HLA-A*02:01, B*18:01, DRB*03:01 three-loci extended haplotype in the Sardinian population was shown to efficiently contrast the high risk of a severe and devastating outcome of the infection predicted for carriers of the Neanderthal locus [OR 15.47 (95% CI 5.8 – 41.0), p < 0.0001]. This result suggests that the balance between risk and protective immunogenetic factors plays an important role in the evolution of COVID-19. A better understanding of these mechanisms may well turn out to be the biggest advantage in the race for the development of more efficient drugs and vaccines.

  • Neutralizing Antibodies Responses against SARS-CoV-2 in a Sardinian Cohort Group Up to 9 Months after BNT162b2 Vaccination
    Giuseppina Sanna, Alessandra Marongiu, Davide Firinu, Cristina Piras, Gianluigi Franci, Massimiliano Galdiero, Giuseppe Pala, Vanessa Palmas, Fabrizio Angius, Roberto Littera,et al.

    MDPI AG
    Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, has caused over 460 million cases of infection and over 6 million deaths worldwide. The pandemic has called for science, technology, and innovation to provide solutions and, due to an incredible scientific and financial global effort, several prophylactic and therapeutic apparatuses such as monoclonal antibodies and vaccines were developed in less than one year to address this emergency. After SARS-CoV-2 infection, serum neutralizing antibodies are produced by B cells and studies on virus-neutralizing antibodies’ kinetics are pivotal. The process of protective immunity and the duration of this kind of protection against COVID-19 remain to be clarified. We tested 136 sera from 3 groups of individuals, some of them providing multiple sequential sera (1—healthy, no previous CoV2-infected, vaccinated; 2—healthy, previous CoV2 infected, vaccinated; 3—healed, previous CoV2-infected, not vaccinated) to assess the kinetics of antibodies (Abs) neutralizing activity. We found that SARS-CoV-2 infection elicits moderate neutralizing antibody activity in most individuals; neither age nor gender appear to have any influence on Abs responses. The BNT162b2 vaccine, when administered in two doses, induces high antibodies titre endowed with potent neutralizing activity against bare SARS-CoV-2 in in vitro neutralizing assay. The residual neutralization capability and the kinetic of waning immunity were also evaluated over 9 months after the second dose in a reference group of subjects. Neutralization titre showed a decline in all subjects and the median level of S-protein IgG, over 270 days after the second vaccination dose, was below 10 AU/mL in 53% of serum tested.

  • Covid-19 vaccines work but other factors play a relevant role: A data analysis on spread and mortality in 24 countries
    Mauro Giovanni Carta, Germano Orrù, Giulia Cossu, Fernanda Velluzzi, Laura Atzori, Cesar Ivan Aviles Gonzalez, Ferdinando Romano, Roberto Littera, Luchino Chessa, Davide Firinu,et al.

    SAGE Publications
    Background The aim was to outline a methodology to monitor the impact of vaccinations in different countries comparing in two different time within countries and between countries the frequency of new cases and Covid-19 related deaths and the percentage of vaccinations conducted. Design and methods The 25 countries with the largest increase in SARS-CoV-2 cases on 8 August 2021 were evaluated. In each nation was calculated the proportion of Covid-19 deaths divided per new cases x 100 and the proportion of new cases per 1.000 inhabitant on 10 January 2021 (before vaccinations’ distribution) and 8 August 2021 (when large percentage of the population had been vaccinated in many countries). Results The study shows that in the countries with the highest number of cases as of 8 August 2021, the proportion of vaccinations carried out in the population correlates negatively with both the proportion between Covid-19 dead people x100 infected people and with the rate of new cases. However, the proportion of vaccinations does not correlate with the differences in the two same indicators considered in the weeks observed, thus additional factors seem to play an important role. Conclusions This work indicates that mass vaccination is associated with a lower spread of the pandemic and, to greater extent, with a lowering of mortality in infected people.

RECENT SCHOLAR PUBLICATIONS

  • Humoral responses to wild type and ancient BA. 1 SARS-CoV-2 variant after heterologous priming vaccination with ChAdOx1 nCoV-19 and BNT162b2 booster dose
    G Sanna, A Marongiu, D Firinu, C Piras, V Palmas, M Galdiero, L Atzori, ...
    Clinical and Experimental Medicine 24 (1), 1-9 2024

  • Further decompensation in cirrhosis: Results of a large multicenter cohort study supporting Baveno VII statements
    G D’Amico, A Zipprich, C Villanueva, JA Sord, RM Morillas, M Garcovich, ...
    Hepatology 79 (4), 869-881 2024

  • Prevalence of apical periodontitis in patients with autoimmune liver diseases under immune suppressants and immune modulators: a cross-sectional study.
    F Ideo, S Niazi, L Chessa, M Miglianti, G Bardini, F Mannocci, E CottiDDS
    Journal of Endodontics 2024

  • Does HLA-G play a role in PBC?
    M Miglianti, R Littera, S Mocci, C Sanna, A Mascia, M Serra, M Conti, ...
    Digestive and Liver Disease 56, S26 2024

  • Longer transplant-free and liver-related event-free survival in obeticholic acid-treated patients with primary biliary cholangitis compared to external controls from two large
    F Terracciani, A De Vincentis, D D'Amato, P Invernizzi, A Morgando, ...
    Digestive and Liver Disease 56, S3-S5 2024

  • Biochemical response to obeticholic acid drives liver stiffness variation over time and the risk of liver-related events in patients with primary biliary cholangitis
    A De Vincentis, F Terracciani, D D'Amato, M Scaravaglio, P Invernizzi, ...
    Digestive and Liver Disease 56, S21-S22 2024

  • Determinants of worse liver‐related outcome according to HDV infection among HBsAg positive persons living with HIV: Data from the ICONA cohort
    A d’Arminio Monforte, A Tavelli, R Salpini, L Piermatteo, S D'Anna, ...
    Liver International 44 (2), 603-613 2024

  • The Stability of Social and Behavioral Rhythms and Unexpected Low Rate of Relevant Depressive Symptoms in Old Adults during the COVID-19 Pandemic
    F Sancassiani, G Cossu, E Cantone, F Romano, A Perra, A Urban, ...
    Journal of Clinical Medicine 13 (7), 2005 2024

  • Impact of Exposure to Vaccination and Infection on Cellular and Antibody Response to SARS-CoV-2 in CVID Patients Through COVID-19 Pandemic
    GAML Costanzo, CM Deiana, G Sanna, A Perra, M Campagna, AG Ledda, ...
    Journal of Clinical Immunology 44 (1), 12 2024

  • The effect of exposure to SARS-CoV-2 vaccination and infection on humoral and cellular immunity in a cohort of patients with immune-mediated inflammatory diseases
    G Costanzo, CM Deiana, M Miglianti, G Sanna, M Ennas, A Perra, ...
    ALLERGY 78 2023

  • Impact of SARS-CoV-2 exposure to vaccination and infection on cellular and antibody response among CVID patients during COVID-19 pandemics
    CM Deiana, G Costanzo, G Sanna, A Perra, M Campagna, R Littera, ...
    ALLERGY 78 2023

  • Predicting de‐novo portal vein thrombosis after HCV eradication: A long‐term competing risk analysis in the ongoing PITER cohort
    LA Kondili, A Zanetto, MG Quaranta, L Ferrigno, V Panetta, V Calvaruso, ...
    United European Gastroenterology Journal 2023

  • PREDICTION OF BIOCHEMICAL RESPONSE IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS TREATED WITH OBETICHOLIC ACID: DERIVATION AND EXTERNAL VALIDATION OF THE OCA RESPONSE SCORE (ORS)
    A De Vincentis, J Ampuero, F Terracciani, D D'Amato, P Invernizzi, ...
    HEPATOLOGY 78, S2060-S2062 2023

  • INCIDENCE AND PREDICTIVE FACTORS OF PORTAL VEIN THROMBOSIS IN PATIENTS WITH HCV-RELATED CIRRHOSIS AFTER SUSTAINED VIROLOGICAL RESPONSE: LONG TERM COMPETING RISK ANALYSIS IN THE
    L Kondili, A Zanetto, MG Quaranta, L Ferrigno, V Panetta, V Calvaruso, ...
    HEPATOLOGY 78, S693-S694 2023

  • Is HCV elimination among persons living with HIV feasible? Data from the NoCo study in the setting of the ICONA cohort
    A d’Arminio Monforte, A Tavelli, R Rossotti, R Gagliardini, A Saracino, ...
    Liver International 43 (10), 2130-2141 2023

  • Comparing the responses of countries and National Health Systems to the COVID-19 pandemic: a critical analysis with a case-report series.
    MG Carta, G Orr, R Littera, D Firinu, L Chessa, G Cossu, D Primavera, ...
    European Review for Medical & Pharmacological Sciences 27 (16) 2023

  • Combined Salivary Proteome Profiling and Machine Learning Analysis Provides Insight into Molecular Signature for Autoimmune Liver Diseases Classification
    G Guadalupi, C Contini, F Iavarone, M Castagnola, I Messana, G Faa, ...
    International Journal of Molecular Sciences 24 (15), 12207 2023

  • Profiling the risk of hepatocellular carcinoma after long-term HCV eradication in patients with liver cirrhosis in the PITER cohort
    LA Kondili, MG Quaranta, L Cavalletto, V Calvaruso, L Ferrigno, ...
    Digestive and Liver Disease 55 (7), 907-917 2023

  • A review of the main genetic factors influencing the course of COVID-19 in Sardinia: the role of human leukocyte antigen-G
    S Mocci, R Littera, L Chessa, M Campagna, M Melis, CM Ottelio, IS Piras, ...
    Frontiers in Immunology 14, 1138559 2023

  • Further decompensation as a new prognostic stage in cirrhosis. Results of a large multicenter cohort study supporting Baveno VII statements
    G D’Amico, G Garcia-Tsao, A Zipprich, C Villanueva, JA Sorda, ...
    Journal of Hepatology 78, S105-S106 2023

MOST CITED SCHOLAR PUBLICATIONS

  • Long-term benefit of interferon α therapy of chronic hepatitis D: regression of advanced hepatic fibrosis
    P Farci, T Roskams, L Chessa, G Peddis, AP Mazzoleni, R Scioscia, ...
    Gastroenterology 126 (7), 1740-1749 2004
    Citations: 373

  • Early changes in hepatitis C viral quasispecies during interferon therapy predict the therapeutic outcome
    P Farci, R Strazzera, HJ Alter, S Farci, D Degioannis, A Coiana, G Peddis, ...
    Proceedings of the National Academy of Sciences 99 (5), 3081-3086 2002
    Citations: 269

  • Randomised study comparing 48 and 96 weeks peginterferon α-2a therapy in genotype D HBeAg-negative chronic hepatitis B
    P Lampertico, M Vigan, GG Di Costanzo, E Sagnelli, M Fasano, ...
    Gut 62 (2), 290-298 2013
    Citations: 154

  • Association of chronic hepatitis C with major depressive disorders: irrespective of interferon-alpha therapy
    MG Carta, MC Hardoy, A Garofalo, E Pisano, V Nonnoi, G Intilla, G Serra, ...
    Clinical Practice and Epidemiology in Mental Health 3, 1-4 2007
    Citations: 134

  • Human leukocyte antigen complex and other immunogenetic and clinical factors influence susceptibility or protection to SARS-CoV-2 infection and severity of the disease course
    R Littera, M Campagna, S Deidda, G Angioni, S Cipri, M Melis, D Firinu, ...
    Frontiers in immunology 11, 605688 2020
    Citations: 113

  • Association of chronic hepatitis C with recurrent brief depression
    MG Carta, J Angst, MF Moro, G Mura, MC Hardoy, C Balestrieri, L Chessa, ...
    Journal of affective disorders 141 (2-3), 361-366 2012
    Citations: 54

  • Treatment of chronic hepatitis D
    P Farci, L Chessa, C Balestrieri, G Serra, ME Lai
    Journal of viral hepatitis 14, 58-63 2007
    Citations: 54

  • Real-world experience with obeticholic acid in patients with primary biliary cholangitis
    D D’Amato, A De Vincentis, F Malinverno, M Vigan, D Alvaro, M Pompili, ...
    JHEP Reports 3 (2), 100248 2021
    Citations: 53

  • Modeling cost‐effectiveness and health gains of a “universal” versus “prioritized” hepatitis C virus treatment policy in a real‐life cohort
    LA Kondili, F Romano, FR Rolli, M Ruggeri, S Rosato, MR Brunetto, ...
    Hepatology 66 (6), 1814-1825 2017
    Citations: 49

  • Incidence of DAA failure and the clinical impact of retreatment in real-life patients treated in the advanced stage of liver disease: Interim evaluations from the PITER network
    LA Kondili, GB Gaeta, MR Brunetto, A Di Leo, A Iannone, TA Santantonio, ...
    PLoS One 12 (10), e0185728 2017
    Citations: 46

  • Forecasting Hepatitis C liver disease burden on real‐life data. Does the hidden iceberg matter to reach the elimination goals?
    LA Kondili, S Robbins, S Blach, I Gamkrelidze, AL Zignego, MR Brunetto, ...
    Liver International 38 (12), 2190-2198 2018
    Citations: 45

  • Premature ovarian senescence and a high miscarriage rate impair fertility in women with HCV
    A Karampatou, X Han, LA Kondili, G Taliani, A Ciancio, F Morisco, ...
    Journal of Hepatology 68 (1), 33-41 2018
    Citations: 42

  • Natural killer-cell immunoglobulin-like receptors trigger differences in immune response to SARS-CoV-2 infection
    R Littera, L Chessa, S Deidda, G Angioni, M Campagna, S Lai, M Melis, ...
    PloS One 16 (8), e0255608 2021
    Citations: 41

  • Gastrointestinal coronavirus disease 2019: epidemiology, clinical features, pathogenesis, prevention, and management
    S Deidda, L Tora, D Firinu, S Del Giacco, M Campagna, F Meloni, G Orru, ...
    Expert Review of Gastroenterology & Hepatology 15 (1), 41-50 2021
    Citations: 38

  • Exploring the role of killer cell immunoglobulin-like receptors and their HLA class I ligands in autoimmune hepatitis
    R Littera, L Chessa, S Onali, F Figorilli, S Lai, L Secci, G La Nasa, ...
    PLoS One 11 (1), e0146086 2016
    Citations: 30

  • Add‐on peginterferon alfa‐2a to nucleos (t) ide analogue therapy for Caucasian patients with hepatitis B ‘e’antigen‐negative chronic hepatitis B genotype D
    P Lampertico, MR Brunetto, A Crax, GB Gaeta, M Rizzetto, A Rozzi, ...
    Journal of Viral Hepatitis 26 (1), 118-125 2019
    Citations: 28

  • Severe autoimmune hemolytic anemia in a patient with chronic hepatitis C during treatment with peginterferon alfa-2a and ribavirin
    C Cauli, G Serra, L Chessa, C Balestrieri, R Scioscia, ME Lai, P Farci
    Haematologica 91 (6_Suppl), ECR26-ECR26 2006
    Citations: 27

  • Interferon-alpha-induced psychiatric side effects in patients with chronic viral hepatitis: a prospective, observational, controlled study
    MG Orr, A Baita, R Sitzia, A Costa, E Muntoni, S Landau, L Chessa, ...
    Epidemiology and Psychiatric Sciences 14 (3), 145-153 2005
    Citations: 26

  • Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS): a
    S Petta, M Marzioni, P Russo, A Aghemo, A Alberti, A Ascione, A Antinori, ...
    The Lancet Gastroenterology & Hepatology 2 (6), 427-434 2017
    Citations: 23

  • Hepatitis C in the elderly: a multicentre cross-sectional study by the Italian Association for the Study of the Liver.
    AP Gramenzi A, Conti F, Camm C, Grieco A, Picciotto, AHES Group.
    Digestive and Liver Disease 44 (8), 674-680 2012
    Citations: 22