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MARZIA MARGOTTI

Assegnista di ricerca
Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto

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Pubblicazioni

2022 - Predictors of solid extra-hepatic non-skin cancer in liver transplant recipients and analysis of survival: a long-term follow-up study [Articolo su rivista]
Gitto, Stefano; Magistri, Paolo; Marzi, Luca; Mannelli, Nicolò; De Maria, Nicola; Mega, Andrea; Vitale, Giovanni; Valente, Giovanna; Vizzutti, Francesco; Villa, Erica; Marra, Fabio; Andreone, Pietro; Di Benedetto, Fabrizio; Falcini, Margherita; Catellani, Barbara; Guerrini, Gian Piero; Serra, Valentina; Di Sandro, Stefano; Ballarin, Roberto; Piai, Guido; Schepis, Filippo; Margotti, Marzia; Cursaro, Carmela; De Simone, Paolo; Petruccelli, Stefania; Carrai, Paola; Forte, Paolo; Campani, Claudia; Zoller, Heinz
abstract

Introduction and objectives: De novo malignancies represent an important cause of death for liver transplant recipients. Our aim was to analyze predictors of extra-hepatic non-skin cancer (ESNSC) and the impact of ESNSC on the long-term outcome. Patients: We examined data from patients transplanted between 2000 and 2005 and followed-up in five Italian transplant clinics with a retrospective observational cohort study. Cox Regression was performed to identify predictors of ESNSC. A 1:2 cohort sub-study was developed to analyze the impact of ESNSC on 10-year survival. Results: We analyzed data from 367 subjects (median follow-up: 15 years). Patients with ESNSC (n=47) more often developed post-LT diabetes mellitus (DM) (57,4% versus 35,9%, p=0,004). At multivariate analysis, post-LT DM independently predicted ESNSC (HR 1.929, CI 1.029-3.616, p=0.040). Recipients with ESNSC showed a lower 10-year survival than matched controls (46,8% versus 68,1%, p=0,023). Conclusions: Post-LT DM seems to be a relevant risk factor for post-LT ESNSC. ESNSC could have a noteworthy impact on the long-term survival of LT recipients.

2021 - Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort [Articolo su rivista]
Quaranta, M. G.; Ferrigno, L.; Tata, X.; D'Angelo, F.; Massari, M.; Coppola, C.; Biliotti, E.; Giorgini, A.; Laccabue, D.; Ciancio, A.; Blanc, P. L.; Margotti, M.; Ieluzzi, D.; Brunetto, M. R.; Barbaro, F.; Russo, F. P.; Beretta, I.; Morsica, G.; Verucchi, G.; Saracino, A.; Galli, M.; Kondili, L. A.; Mazzaro, C.; Bertola, M.; Benedetti, A.; Schiada, L.; Cucco, M.; Giacometti, A.; Brescini, L.; Castelletti, S.; Fiorentini, A.; Angarano, G.; Milella, M.; Leo, A. D.; Rendina, M.; Salvatore D'ABRAMO, F.; Lillo, C.; Iannone, A.; Piazzolla, M.; Badia, L.; Piscaglia, F.; Benevento, F.; Serio, I.; Castelli, F.; Zaltron, S.; Spinetti, A.; Odolini, S.; Bruno, R.; Mondelli, M.; Chessa, L.; Loi, M.; Torti, C.; Costa, C.; Mazzitelli, M.; Pisani, V.; Scaglione, V.; Trecarichi, E. M.; Zignego, A. L.; Monti, M.; Madia, F.; Attala, L.; Pierotti, P.; Salomoni, E.; Mariabelli, E.; Santantonio, T. A.; Bruno, S. R.; Cela, E. M.; Bassetti, M.; Mazzarello, G.; Alessandrini, A. I.; Biagio, A. D.; Nicolini, L. A.; Raimondo, G.; Filomia, R.; Aghemo, A.; Meli, R.; Lazzarin, A.; Salpietro, S.; Fracanzani, A. L.; Fatta, E.; Lombardi, R.; Lampertico, P.; Borghi, M.; D'Ambrosio, R.; Degasperi, E.; Puoti, M.; Baiguera, C.; D'Amico, F.; Vinci, M.; Rumi, M. G.; Zuin, M.; Zermiani, P.; Andreone, P.; Caraceni, P.; Guarneri, V.; Villa, E.; Bernabucci, V.; Bristot, L.; Paradiso, M. L.; Migliorino, G.; Gambaro, A.; Lapadula, G.; Spolti, A.; Soria, A.; Invernizzi, P.; Ciaccio, A.; Luca, M.; Malinverno, F.; Ratti, L.; Amoruso, D. C.; Pisano, F.; Scarano, F.; Staiano, L.; Morisco, F.; Cossiga, V.; Gentile, I.; Buonomo, A. R.; Foggia, M.; Zappulo, E.; Federico, A.; Dallio, M.; Coppola, N.; Sagnelli, C.; Martini, S.; Monari, C.; Nardone, G.; Sgamato, C.; Chemello, L.; Cavalletto, L.; Sterrantino, D.; Zanetto, A.; Zanaga, P.; Brancaccio, G.; Craxi, A.; Petta, S.; Calvaruso, V.; Crapanzano, L.; Madonia, S.; Cannizzaro, M.; Bruno, E. M.; Licata, A.; Amodeo, S.; Capitano, A. R.; Ferrari, C.; Negri, E.; Orlandini, A.; Pesci, M.; Gulminetti, R.; Pagnucco, L.; Parruti, G.; Stefano, P. D.; Coco, B.; Corsini, R.; Garlassi, E.; Andreoni, M.; Teti, E.; Cerva, C.; Baiocchi, L.; Grassi, G.; Gasbarrini, A.; Pompili, M.; Siena, M. D.; Taliani, G.; Spaziante, M.; Persico, M.; Masarone, M.; Aglitti, A.; Calvanese, G.; Anselmo, M.; Leo, P. D.; Marturano, M.; Saracco, G. M.
abstract

Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively. Conclusion: Compared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted.

2021 - Hepatitis C Virus Core Antigen (HCVAg): An affordable assay to monitor the efficacy of treatment in DAAs era [Articolo su rivista]
Rossetti, B.; Loggi, E.; Raffaelli, C. S.; Mercinelli, S.; Gandolfo, C.; Savellini, G. G.; Galli, S.; Vitale, G.; Di Donato, R.; Vukotic, R.; Grandini, E.; Margotti, M.; Guarneri, V.; Furlini, G.; Re, M. C.; de Luca, A.; Andreone, P.; Galli, C.; Cusi, M. G.
abstract

Hepatitis C virus (HCV) Core Antigen (HCVAg) and HCV-RNA were tested in 962 plasma/serum samples from 180 patients during Direct Antiviral Agents (DAAs) treatment and at follow-up. One hundred and eighty individuals were included: 71% carried advanced fibrosis and 43% were treatment-experienced. A Sustained Virological Response (SVR) was achieved in 166/180 (92%) individuals: 96/102 (94.1%) naïve and 70/78 (89.7%) treatment-experienced (p=0.20). The baseline median levels of HCV-RNA and HCVAg were not significantly different between individuals achieving SVR (5.92 x 105 IU/mL, IQR 5.4-6.4, and 3,417 fmol/L, 2,900-3,795) and those without SVR (6.06 x 105 IU/mL, 5.63-6.57, and 3,391 fmol/L, 2,828-4,077). The HCV-RNA vs. HCVAg assays results showed a fair correlation with an overall moderate qualitative agreement (kappa=0.52). Among treatment-failed individuals, at failure 100% of the assays results were positive for both techniques, with HCV-RNA median value 3.09 x 105 IU/mL (2.10-29.09) and HCVAg median value 1570.28 fmol/L (360.15-9317.67). Undetectable HCV-RNA at EOT showed sensitivity 54%, specificity 100%, negative predictive value (NPV) 93% and positive predictive value (PPV) 100%. Undetectable HCVAg at EOT showed sensitivity 74%, specificity 100%, NPV 97% and PPV 100%. The operative and economic advantages of the HCVAg support the alternative use of HCVAg to monitor DAAs treatment outcome.

2019 - Economic Consequences of Investing in Anti-HCV Antiviral Treatment from the Italian NHS Perspective: A Real-World-Based Analysis of PITER Data [Articolo su rivista]
Marcellusi, A.; Viti, R.; Kondili, L. A.; Rosato, S.; Vella, S.; Mennini, F. S.; Kondili, L. A.; Vella, S.; Quaranta, M. G.; Rosato, S.; Tosti, M. E.; Weimer, L. E.; Ferrigno, L.; D'Angelo, F.; Falzano, L.; Benedetti, A.; Schiada, L.; Cucco, M.; Giacometti, A.; Brescini, L.; Castelletti, S.; Drenaggi, D.; Mazzaro, C.; Angarano, G.; Milella, M.; Dileo, A.; Rendina, M.; Contaldo, A.; Iannone, A.; La Fortezza, F.; Rizzi, M.; Cologni, G.; Bolondi, L.; Benevento, F.; Serio, I.; Andreone, P.; Caraceni, P.; Guarneri, V.; Margotti, M.; Simonetti, G.; Mazzella, G.; Verucchi, G.; Donati, V.; Mian, P.; Rimenti, G.; Rossini, A.; Contessi, G. B.; Castelli, F.; Zaltron, S.; Spinetti, A.; Odolini, S.; Leandro, G.; Cozzolongo, R.; Zappimbulso, M.; Russello, M.; Benigno, R.; Coco, C.; Torti, C.; Costa, C.; Greco, G.; Mazzitelli, M.; Pisani, V.; Cosco, L.; Quintieri, F.; Desiena, M.; Giancotti, F.; Vecchiet, J.; Falasca, K.; Mastroianni, A.; Apuzzo, G.; Chidichimo, L.; Foschi, F. G.; Dall'Aglio, A. C.; Libanore, M.; Segala, D.; Sighinolfi, L.; Bartolozzi, D.; Salomoni, E.; Blanc, P.; Baragli, F.; Delpin, B.; Mariabelli, E.; Mazzotta, F.; Poggi, A.; Zignego, A. L.; Monti, M.; Madia, F.; Xheka, A.; Cela, E. M.; Santantonio, T. A.; Bruno, S. R.; Viscoli, C.; Alessandrini, A. I.; Curti, C.; Dibiagio, A.; Nicolini, L. A.; Balletto, E.; Mastroianni, C.; Blerta, K.; Prati, D.; Raffaele, L.; Andreoletti, M.; Perboni, G.; Costa, P.; Manzini, L.; Raimondo, G.; Filomia, R.; Lazzarin, A.; Morsica, G.; Salpietro, S.; Puoti, M.; Baiguera, C.; Vassalli, S.; Rumi, M. G.; Labanca, S.; Zuin, M.; Giorgini, A.; Orellana, D.; D'Arminiomonforte, A.; Debona, A.; Solaro, S.; Fargion, S.; Valenti, L.; Periti, G.; Pelusi, S.; Galli, M.; Calvi, E.; Milazzo, L.; Peri, A.; Lampertico, P.; Borghi, M.; D'Ambrosio, R.; Degasperi, E.; Vinci, M.; Villa, E.; Bernabucci, V.; Bristot, L.; Pereira, F.; Chessa, L.; Pasetto, M. C.; Loi, M.; Gori, A.; Beretta, I.; Pastore, V.; Soria, A.; Strazzabosco, M.; Ciaccio, A.; Gemma, M.; Borgia, G.; Foggia, A.; Zappulo, E.; Gentile, I.; Buonomo, A. R.; Abrescia, N.; Maddaloni, A.; Caporaso, N.; Morisco, F.; Camera, S.; Donnarumma, L.; Coppola, C.; Amoruso, D. C.; Staiano, L.; Saturnino, M. R.; Coppola, N.; Martini, S.; Monari, C.; Federico, A.; Dallio, M.; Loguercio, C.; Gaeta, G. B.; Brancaccio, G.; Nardone, G.; Sgamato, C.; D'Adamo, G.; Alberti, A.; Gonzo, M.; Piovesan, S.; Chemello, L.; Buggio, A.; Cavalletto, L.; Barbaro, F.; Castelli, E.; Floreani, A.; Cazzagon, N.; Franceschet, I.; Russo, F. P.; Zanetto, A.; Franceschet, E.; Madonia, S.; Cannizzaro, M.; Montalto, G.; Licata, A.; Capitano, A. R.; Craxi, A.; Petta, S.; Calvaruso, V.; Rini, F.; Ferrari, C.; Negri, E.; Orlandini, A.; Pesci, M.; Bruno, R.; Lombardi, A.; Zuccaro, V.; Gulminetti, R.; Asti, A.; Villaraggia, M.; Mondelli, M.; Ludovisi, S.; Baldelli, F.; Di Candilo, F.; Parruti, G.; Di Stefano, P.; Sozio, F.; Gizzi, M. C.; Brunetto, M. R.; Colombatto, P.; Coco, B.; Surace, L.; Foti, G.; Pellicano, S.; Fornaciari, G.; Schianchi, S.; Vignoli, P.; Massari, M.; Corsini, R.; Garlassi, E.; Ballardini, G.; Andreoni, M.; Cerva, C.; Angelico, M.; Gasbarrini, A.; Siciliano, M.; De Siena, M.; Nosotti, L.; Taliani, G.; Biliotti, E.; Santori, M.; Spaziante, M.; Tamburini, F.; Vullo, V.; D'Ettorre, G.; Cavallari, E. N.; Gebremeskel, T. S.; Pavone, P.; Cauda, R.; Cingolani, A.; Lamonica, S.; D'Offizi, G.; Lionetti, R.; Visco Comandini, U.; Grieco, A.; D'Aversa, F.; Picardi, A.; De Vincentis, A.; Galati, G.; Gallo, P.; Dell'Unto, C.; Aghemo, A.; Gatti Comini, A.; Persico, M.; Masarone, M.; Anselmo, M.; De Leo, P.; Marturano, M.; Brunelli, E.; Ridolfi, F.; Schimizzi, A. M.; Ayoubi Khajekini, M.; Framarin, L.; Di Perri, G.; Cariti, G.; Boglione, L.; Cardellino, C.; Marinaro, L.; Saracco, G. M.; Ciancio, A.; Toniutto, P.; Alterini, G.; Capra, F.; Ieluzzi, D.
abstract

Objective: We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy. Methods: A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered. Results: The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively. Conclusions: This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV.

2017 - Monitoring the treatment of hepatitis C with directly acting antivirals by serological and molecular methods [Articolo su rivista]
Loggi, Elisabetta; Galli, Silvia; Vitale, Giovanni; Donato, Roberto Di; Vukotic, Ranka; Grandini, Elena; Margotti, Marzia; Guarneri, Valeria; Furlini, Giuliano; Galli, Claudio; Re, Maria Carla; Andreone, Pietro
abstract

Aim: To evaluate the potential value of using a serological assay to quantitate the hepatitis C virus core antigen (HCV-Ag) when monitoring patients with chronic hepatitis C being treated with direct-acting antivirals (DAAs). Methods: Ninety-six patients treated with DAAs, either alone (91) or in combination with PEG interferon (5), were tested for HCV-RNA and for HCV-Ag at baseline and at weeks 2, 4, 8 and 12 during treatment and 12 weeks after completion. The concordance and correlation between the viral parameters as well as the respective kinetics during and after treatment were evaluated. Results: A sustained viral response (SVR) was achieved in 82 patients (91%), whereas 11 relapsed (R) and 1 showed a virological breakthrough while receiving treatment. HCV-RNA and HCV-Ag showed good concordance (kappa = 0.62) and correlation. No significant differences between SVR and R was observed in either assay at 2 and 4 weeks after the start of treatment. At 8 weeks, HCV-Ag showed higher accuracy than HCV-RNA (AUC: 0.74 vs. 0.55) and there was a significantly greater decrease from baseline in SVR than in R (4.01 vs. 3.36 log10; p<0.05). Conclusions: Monitoring during treatment with DAAs by using either HCV-RNA or HCV-Ag has only a limited predictive value for SVR. Since those assays are equivalent for identifying a virological relapse, HCV-Ag may be preferred from an economical and organizational perspective.

2014 - Calcineurin inhibitors levels reduction during treatment with Sofosbuvir in liver transplanted patients [Articolo su rivista]
Vukotic, Ranka; Morelli, M; Pinna, Antonio Daniele; Margotti, Marzia; Foschi, Fg; Loggi, Elisabetta; Bernardi, Mauro; Andreone, Pietro
abstract

In liver transplant, during anti-viral therapy for hepatitis C virus (HCV) recurrence, the immunosuppressant levels should be monitored to prevent both toxicity and rejection. Sofosbuvir (SOF) has been used within compassionate programs for HCV recurrence and, according to pharmacokinetic analyses, is not supposed to have significant pharmacological interactions with tacrolimus (Tac) or ciclosporin.1 This was reported in the review article by Koff recently published.2 We treated eight transplant recipients with SOF/ribavirin (RBV) for a severe HCV recurrence, and observed unexpected Tac/ciclosporin reduction during SOF.

2012 - Antibodies against pegylated interferon-alpha affect response to treatment in patients with chronic hepatitis C [Abstract in Rivista]
Loggi, Elisabetta; Scuteri, Alessandra; MARTELLO PANNO, Arianna; Grandini, Elena; Cursaro, C.; Margotti, Marzia; Foglianti, G.; Bernardi, Mauro; Brillanti, Stefano; Andreone, Pietro
abstract

2010 - Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis [Articolo su rivista]
Liu, X; Invernizzi, P; Lu, Y; Kosoy, R; Lu, Y; Bianchi, I; Podda, M; Xu, C; Xie, G; Macciardi, F; Selmi, C; Lupoli, S; Shigeta, R; Ransom, M; Lleo, A; Lee, At; Mason, Al; Myers, Rp; Peltekian, Km; Ghent, Cn; Bernuzzi, F; Zuin, M; Rosina, F; Borghesio, E; Floreani, A; Lazzari, R; Niro, G; Andriulli, A; Muratori, Luigi; Muratori, Paolo; Almasio, Pl; Andreone, Pietro; Margotti, Marzia; Brunetto, M; Coco, B; Alvaro, D; Bragazzi, Mc; Marra, F; Pisano, A; Rigamonti, C; Colombo, M; Marzioni, M; Benedetti, A; Fabris, L; Strazzabosco, M; Portincasa, P; Palmieri, Vo; Tiribelli, C; Croce, L; Bruno, S; Rossi, S; Vinci, M; Prisco, C; Mattalia, A; Toniutto, P; Picciotto, A; Galli, A; Ferrari, C; Colombo, S; Casella, G; Morini, L; Caporaso, N; Colli, A; Spinzi, G; Montanari, R; Gregersen, Pk; Heathcote, Ej; Hirschfield, Gm; Siminovitch, Ka; Amos, Ci; Gershwin, Me; Seldin, M. F.
abstract

A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 × 10−11, odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 × 10−10, OR = 1.63) and 17q12-21 (P = 1.7 × 10−10, OR = 1.38).

2009 - Ketoprofen, peginterferon-alpha2a and ribavirin for genotype 1 chronic hepatitis C: a phase II study [Articolo su rivista]
Gramenzi, Annagiulia; Cursaro, C; Margotti, Marzia; Balsano, C; Spaziani, A; Anticoli, S; Loggi, Elisabetta; Salerno, M; Galli, S; Furlini, G; Bernardi, Mauro; Andreone, Pietro
abstract

2008 - In vitro effect of thymosin-alpha1 and interferon-alpha on Th1 and Th2 cytokine synthesis in patients with eAg-negative chronic hepatitis B [Articolo su rivista]
Loggi, Elisabetta; Gramenzi, Annagiulia; Margotti, Marzia; Cursaro, C; Galli, S; Vitale, Giovanni; Grandini, Elena; Scuteri, Alessandra; Vukotic, Ranka; Andreone, Pietro; Bernardi, Mauro
abstract

2005 - Cytokine profile of peripheral blood mononuclear cells from patients with different outcomes of hepatitis C virus infection [Articolo su rivista]
Gramenzi, Annagiulia; Andreone, Pietro; Loggi, Elisabetta; Foschi, F. G.; Cursaro, C.; Margotti, Marzia; Biselli, Maurizio; Bernardi, Mauro
abstract

2005 - Genetic variability of hepatitis C virus in HBV/HCV co-infection and HCV single-infection [Articolo su rivista]
De Mitri, Maria Stella; Morsica, G.; Cassini, Romina; Bagaglio, S.; Andreone, Pietro; Bianchi, Giampaolo; Margotti, Marzia; Bernardi, Mauro
abstract

2004 - Genetic heterogeneity of hepatitis C virus in HBV/HCV co-infection [Abstract in Atti di Convegno]
DE MITRI, MARIA STELLA; G., Morsica; Cassini, Romina; S., Bagaglio; Andreone, Pietro; Bianchi, Giampaolo; Margotti, Marzia; Bernardi, Mauro
abstract

2004 - In vitro effect of indomethacin and interferon-alpha on Th1 and Th2 cytokine synthesis in patients with chronic hepatitis C [Articolo su rivista]
Andreone, Pietro; Gramenzi, Annagiulia; Loggi, Elisabetta; Favarelli, L.; Cursaro, C.; Margotti, Marzia; Biselli, Maurizio; Lorenzini, S.; Bernardi, Mauro
abstract

Current evidences suggest that non-steroidal anti-inflammatory drugs could enhance the antiviral activity of interferon-α in chronic HCV infection. In this study, we investigated the effect of indomethacin, a non-steroidal anti-inflammatory drug, and interferon-α on cytokine production by peripheral blood mononuclear cells from 12 untreated patients with chronic hepatitis C. We evaluated the effect of incubation with indomethacin, interferon-α or both on synthesis of Th1- (interleukin-2, interferon-γ) and Th2-associated cytokines (interleukin-4, interleukin-10), and of the antiviral protein 2′,5′-oligoadenylate synthetase. Interferon-α induced a significant increase in production of interleukin-2. Smaller increases were also seen in the presence of indomethacin, while incubation with both indomethacin and interferon-α leads to a synergistic effect. Incubation with indomethacin decreased both interleukin-4 and interleukin-10, whereas interferon-α increased these cytokines. The addition of indomethacin to interferon-α significantly reversed this interferon-induced increase. Finally, both indomethacin and the association interferon-α plus indomethacin determined a significant increase in 2′,5′-oligoadenylate synthetase production compared to both baseline and interferon-α alone. In conclusion, indomethacin was able to enhance the antiviral activity of interferon-α and to modulate the interferon-induced Th1 and Th2 cytokine response by increasing the Th1-response, fundamental for sustained clearance of HCV, and by decreasing the Th-2 type response, associated with HCV persistence