Hepatitis: Tocci G

Antonucci G, Antinori A, Boumis E, De Longis P, Gentile M, Girardi E, Lauria FN, Narciso P, Noto P, Palmieri F, Oliva A, Petrosillo N, Rosati S, Urso R, Tocci G, Tozzi V, Visco Comandini U, Ippolito G. · Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani, Istituto di Ricovero e Cura a Carattere Scientifico, Roma, Italy. · Infez Med. · Pubmed #15329524 links to  free full text

Abstract: It is crucial to ensure an optimal clinical management of HCV infection in HIV-co-infected persons. The reasons for the development of guidelines on HCV-infection treatment in HIV-infected persons arise from the need for a standardised management of HIV/HCV coinfection in our Institute. The aim of these guidelines are: to clarify principles of clinical management of HCV infection in HIV-infected patients to care-providers; to improve the awareness of HIV-infected patients cared for our Institute on current management of HCV infection; to improve the quality of care on this topic. These guidelines, based on Evidence based Medicine principles, have been developed by a panel of experts, who conducted a systematic review of the literature, mainly taking into account current international recommendations. In the present document, the most frequent clinical presentation occurring in the management of HIV/HCV co-infected patients at our Institution are discussed. The adherence to present guidelines and their effectiveness at our Institution, outcome indicators will be evaluated. The present guidelines cannot entirely substitute the judgement of an expert clinician. However, adherence to these guidelines will contribute to the improvement of the standard of care of HIV/HCV-co-infected persons.

Antonucci G, Longo MA, Angeletti C, Vairo F, Oliva A, Comandini UV, Tocci G, Boumis E, Noto P, Solmone MC, Capobianchi MR, Girardi E. · Clinical Department of Infectious Disease, National Institute for Infectious Disease, L. Spallanzani, Rome, Italy. · Am J Gastroenterol. · Pubmed #17403072 No free full text.

Abstract: OBJECTIVES: In many industrialized countries HCV infection is characterized by an increasing prevalence during ageing; however, data on the efficacy of treatment among older patients are scarce. This study was set up to evaluate the effect of age on the treatment of chronic HCV hepatitis with peginterferon alpha plus ribavirin. METHODS: We retrospectively reviewed medical records of 153 adult patients with chronic HCV hepatitis treated with combination therapy; 30 of them (19.6%) were 65 years of age or older. RESULTS: In multivariable analysis, age groups >/=40 years had similar odds of achieving sustained virologic response (P= 0.71) and significantly lower odds of sustained response compared with younger patients (odds ratio [OR] 0.16, 95% confidence interval [CI] 0.05-0.59, P= 0.006; OR 0.13, 95% CI 0.03-0.49, P= 0.002; OR 0.21, 95% CI 0.05-0.91, P= 0.037 for patients aged 40-49 years, 50-64 years, and older than 64 years, respectively). The effect of age was present in the 74 patients infected with genotype 1 or 4 (P= 0.04), while among the 79 patients with genotype 2 or 3 sustained virologic response rates were relatively uniform, with no statistically significant differences. CONCLUSIONS: The probability of good response to combination treatment with peginterferon alpha plus ribavirin is decreased for patients aged more than 40 years infected with genotype 1 or 4, but patients aged more than 65 had a similar rate of response to those aged 40-64 years. Combination treatment may be safely extended to elderly patients with no major contraindications.

Nisii C, Tempestilli M, Agrati C, Poccia F, Tocci G, Longo MA, D'Offizi G, Tersigni R, Lo Iacono O, Antonucci G, Oliva A. · National Institute for Infectious Diseases IRCCS L. Spallanzani, Via Portuense 292, 00149 Rome, Italy. · J Hepatol. · Pubmed #16426698 No free full text.

Abstract: BACKGROUND/AIMS: Hepatitis C virus (HCV) causes a chronic infection that can lead to fibrosis and carcinoma. Immune responses mediated by cytotoxic T lymphocytes (CTLs) could be involved in viral clearance or persistence, and therefore in determining the course of the disease. METHODS: Intrahepatic and peripheral blood CD8+T cells were obtained from 32 HCV-chronically infected patients and analysed by flow-cytometry for surface markers of differentiation, IFNgamma and TNFalpha production, degranulation capacity and perforin content, after CD3 triggering. Results were compared with those obtained from 13 patients with a non-viral liver disease. RESULTS: Intrahepatic CD8+T cells of HCV-infected patients, despite their phenotype of pre-terminally and terminally differentiated effectors (CCR7-CD45RA-/+), are poorly responsive to T cell receptor (TCR)-mediated stimulation compared with those obtained from uninfected subjects. This defect correlates with the severity of fibrosis, is more pronounced in patients with ALT<1.5xN than with ALT>1.5xNU/ml, and is not evident after mitogen stimulation. CONCLUSIONS: The present study describes the accumulation of hypo-responsive CD8+T cells in the liver of patients with chronic HCV infection. Understanding the mechanisms underlying this impairment may be helpful in the design of innovative strategies for HCV treatment.

Abbate I, Cappiello G, Rosati S, Tocci G, Antonucci G, Solmone M, Longo R, Spanò A, Capobianchi MR. · Laboratory of Virology, S. Pertini Hospital, Rome, Italy. · AIDS. · Pubmed #15090776 No free full text.

This publication has no abstract.

Nardacci R, Lo Iacono O, Ciccosanti F, Falasca L, Addesso M, Amendola A, Antonucci G, Craxì A, Fimia GM, Iadevaia V, Melino G, Ruco L, Tocci G, Ippolito G, Piacentini M. · Istituto Nazionale per le Malattie Infettive, IRCCS L. Spallanzani, Rome. · Am J Pathol. · Pubmed #12651621 links to  free full text

Abstract: The up-regulation of "tissue" transglutaminase (TG2) gene has been shown to occur in various pathologies and can lead to severe liver injury; however, its role in the onset of liver damage has not yet been clarified. To address this issue, we have used two experimental settings: carbon tetrachloride (CCl(4))-induced liver injury in wild-type and TG2 knockout mice; and liver biopsies obtained from a large cohort of hepatitis C virus (HCV)-infected patients. Mice lacking TG2 failed to clear the hepatic necrotic tissue formed in response to prolonged CCl(4) exposure (5 weeks) and 60% of them died before the end of the treatment. By contrast, wild-type mice were able to recover after the toxic insult. CCl(4)-treated TG2 null mice showed a derangement of the hepatic lobular architecture and a progressive accumulation of extracellular matrix (ECM) components and inflammatory cells which were not observed in the liver of control animals. Consistent with this protective role, we observed that TG2 levels were much higher (up to 15-fold) during the initial stages of liver fibrosis in HCV-infected individuals (METAVIR = F2) compared with uninfected controls, in which the enzyme protein localized in the hepatocytes facing the periportal infiltrate. By contrast, the enzyme levels decreased in the advanced stages (METAVIR = F3 and F4) and their localization was limited to the ECM. Our data demonstrate that TG2 plays a protective role in the liver injury by favoring tissue stability and repair.

Tocci G, Visco-Comandini U, Antonucci G. · No affiliation provided · N Engl J Med. · Pubmed #11936121 No free full text.

This publication has no abstract.