Hepatitis: Galeazzi M

Giannitti C, Bellisai F, Ferri C, Galeazzi M. · University of Siena, Department of Clinical Medicine and Immunological Science, Rheumatology Section, Policlinico Le Scotte, Siena, Italy. · Expert Opin Pharmacother. · Pubmed #19284361 No free full text.

Abstract: BACKGROUND: The poor prognosis of rheumatoid arthritis (RA) can be aggravated by the concomitant presence of chronic hepatitis C virus (HCV) infection and there are no guidelines for the treatment of patients affected by both conditions. OBJECTIVE: To propose new therapeutic strategies for patient affected by RA and concomitant HCV chronic infection. METHODS: Review of the literature on the usage of cyclosporine-A (CsA) and anti-tumour-necrosis-factor (TNF)-alpha agents for the treatment of patients affected by RA and HCV. RESULTS/CONCLUSION: CsA exerts an inhibitory effect on HCV replication and it is safe in patients affected by RA and HCV. Anti-TNF-alpha agents are safe and efficacious in patient with RA and HCV. Anti-TNF-alpha and CsA can be safely given in combination in RA patients with HCV infection.

Galeazzi M, Giannitti C, Manganelli S, Benucci M, Scarpato S, Bazzani C, Caporali R, Sebastiani GD. · Sezione di Reumatologia, Dipartimento di Medicina Clinica e Scienze Imunologiche, Università di Siena, Italy. · Autoimmun Rev. · Pubmed #18694850 No free full text.

Abstract: A wide variety of rheumatic diseases has been documented in the presence of hepatitis C virus (HCV) infection and in human immunodeficiency virus (HIV) infection. In this conditions, physicians are refrained from using corticosteroids and/or immunosuppressants agents because of the risk of favouring viral replication and the progression of the underlying viral disease. In the present review we have focused our attention on the possible role of cyclosporine A (CsA), anti-Tumour Necrosis Factor (TNF) alpha agents in the treatment of HIV or HCV infected autoimmune patients. The results drown from the literature and from our personal experience confirm the safety of CsA and anti-TNF alpha agents, in terms of viral load and liver toxicity. A limited experience also suggest that both therapies can be given in combination in rheumatoid arthritis patients without increasing the risk of adverse events.

Antonelli A, Ferri C, Galeazzi M, Giannitti C, Manno D, Mieli-Vergani G, Menegatti E, Olivieri I, Puoti M, Palazzi C, Roccatello D, Vergani D, Sarzi-Puttini P, Atzeni F. · University of Pisa School of Medicine, Pisa, Italy. · Clin Exp Rheumatol. · Pubmed #18570753 No free full text.

Abstract: Chronic hepatitis C virus (HCV) infection is a worldwide public health problem with a global prevalence of 2-3%. It is believed that about 170 million people are currently infected (about 3% of the world's population), and a further 3-4 million are infected each year. HCV is the main reason for liver transplantation in the developed world, and the main cause of liver-related morbidity and mortality in a number of countries, including Italy. It is not only a frequent cause of chronic liver diseases such as hepatitis, cirrhosis and hepatocellular carcinoma, but is also involved in the pathogenesis of various autoimmune and rheumatic disorders (arthritis, vasculitis, sicca syndrome, porphyria cutanea tarda, lichen planus, nephropathies, thyroid diseases, and lung fibrosis), as well as in the development of B-cell lymphoproliferative diseases. Furthermore, patients suffering from C hepatitis tend to produce rheumatoid factor, cryoglobulins and a large series of autoantibodies (ANA, anti-SSA/SSB, SAM, ATG, aCL). The use of glucocorticoids or immuno-suppressant agents in HCV infected individuals, which are needed to treat autoimmune and rheumatic disorders, leads to a risk of worsening the clinical outcome of HCV. Under these conditions, the viral infection often needs to be treated with antiviral agents, mainly pegylated interferon combined with ribavirin. However, cyclosporine A seems to be safe and effective in patients with autoimmune disease (AD) and concomitant chronic HCV infection as is documented by the reduction in viremia and transaminases, particularly in patients with high baseline levels. Finally, HCV is the main trigger of mixed cryoglobulinemia. An attempt at viral eradication is therefore indicated in most patients, and is particularly effective in the case of mild or moderate manifestations. In severe cases, rituximab is an apparently safe and effective alternative to conventional immunosuppression and, specifically, it controls B-cell proliferation.

Galeazzi M, Bellisai F, Giannitti C, Manganelli S, Morozzi G, Sebastiani GD. · U.O.C. di Reumatologia, Policlinico Le Scotte, Viale Bracci 53100 Siena, Italy. · Ann N Y Acad Sci. · Pubmed #17911470 No free full text.

Abstract: Because of the relatively high prevalence of both hepatitis C virus (HCV) infection and autoimmune disorders (ADs), it is not rare to encounter in daily clinical practice patients with ADs also carrying HCV. Corticosteroids and/or immunosuppressant drugs are needed to treat ADs, but they place HCV-infected patients at risk of worsening the infection. So, rheumatologists have often refrained from using corticosteroids or immunosuppressants in AD when HCV-RNA is also present. Cyclosporin A (CsA) is an immunosuppressive agent used to treat a wide range of ADs, but there is a large evidences in the literature, both in vitro and in vivo, suggesting that CsA also exerts an inhibitory effect on HCV replication at standard therapeutic dose. Therefore, this evidence has opened new ways to improve the therapy and the prognosis in patients with HCV-related liver diseases, including those with transplants. Recent reports, although limited in number, also suggest the safety of CsA in the treatment of patients with AD and concomitant HCV infection. In this review we also report our personal experience on the combination treatment with CsA and anti-TNF-alpha agents in rheumatoid arthritis.

Galeazzi M, Bellisai F, Manganelli S, Morozzi G, Sebastiani GD. · U.O.C. di Reumatologia, Policlinico Le Scotte-Viale Bracci 53100 Siena, Italy. · Autoimmun Rev. · Pubmed #16920576 No free full text.

Abstract: Due to the relatively high prevalence of both HCV infection and autoimmune disorders (AD), it is not rare to encounter patients with AD also carrying HCV. Considering that the use in HCV infected individuals of corticosteroids or immunosuppressant drugs, that are indeed needed to treat AD, is considered a risk for worsening the clinical outcome of HCV infection, rheumatologist have often refrained from using these drugs in AD when HCV-RNA is also present. Cyclosporine (CsA) is an immunosuppressive agent used to treat a wide range of autoimmune disorders but there is in literature a large body of evidence suggesting that CsA also exerts an inhibitory effect on HCV replication at standard therapeutic dose. The anti-HCV effect of CsA has been demonstrated both in vitro and in vivo. Therefore, these evidences have opened new ways to improve the therapy and the prognosis in patients with HCV-related liver diseases including transplanted ones. Recent reports, although limited in number, also suggest the safety of CsA, in the treatment of patients with AD and concomitant HCV infection. Good results have also been obtained in the treatment in rheumatoid arthritis patients even in association with anti-TNF agents.

Giannitti C, Benucci M, Caporali R, Manganelli S, Bellisai F, Sebastiani GD, Galeazzi M. · No affiliation provided · Int J Immunopathol Pharmacol. · Pubmed #19505408 No free full text.

Abstract: This study further expands our previous observation demonstrating the usefulness of combination therapy of anti-TNF-alpha and cyclosporine A in the treatment of rheumatoid arthritis and concurrent hepatitis C virus infection, as well its efficacy and safety in controlling HCV viremia and liver toxicity. Seven patients were included in the study; transaminase levels remained unchanged, HCV RNA serum levels decreased significantly and DAS 28 significantly improved after twelve month follow-up. No side effects were registered.

Giannitti C, Morozzi G, D'Alfonso S, Bellisai F, Galeazzi M. · Sezione di Reumatologia, Dipartimento Medicina Clinica e Scienze Immunologiche, Università di Siena, Siena. · Reumatismo. · Pubmed #18854880 links to  free full text

Abstract: OBJECTIVE: To test whether an association between HCV genotype, HLA class II alleles distribution and extra-hepatic manifestations (EHM ) can be demonstrated in a group of Italian patients with chronic HCV infection . METHODS: Sixty patients affected by HCV infection with EHM were consecutively enrolled. 163 HCV patients without EHM were tested as controls for the prevalence of HCV genotypes, while we referred to literature as to the controls for HLA distribution. HCV-RNA was quantified by a RT-PCR. HLA class II alleles typing was performed using a standard microlymphocytotoxicity assay. We used chi-square or Fisher test (p<0.05 significant). Odds Ratio (OR) was performed by 2X2 contingency table. RESULTS: HCV 2c genotype was found in 63.46% of patients compared to 19.63% of controls (p<0.0001; OR=7.11). Furthermore, it correlated with carpal tunnel syndrome (p=0.03; OR=4.5) and autoimmune thyroiditis (p=0.02; OR=9.2). On the contrary, 1b genotype protected from EHM in toto (p=0.0004; OR=0.21) and particularly from carpal tunnel syndrome (p=0.0014; OR=0.07). Moreover, 3a genotype prevented HCV people from having cryoglobulinemia (p=0.05; OR=0.11). As to HLA, DR6 seemed to facilitate EHM in HCV patients (p=0.041; OR=1.61), while DQ2 (p=0.03; OR=0.5) and DQ3 (p=0.002; OR= 0.5) may play a protective role. In addition, HLA DR3 was associated with cryoglobulinemia (p=0.02; OR=9.5). CONCLUSIONS: According to our findings, 2c genotype can be considered as a major risk factor for developing HCVrelated EHM, while 1b genotype seems to prevent their onset; there are also evidences suggesting that HLA might play a role in chronic HCV infected patients.

Ferri C, Ferraccioli G, Ferrari D, Galeazzi M, Lapadula G, Montecucco C, Triolo G, Valentini G, Valesini G, Anonymous00027. · Rheumatic Disease Unit, University of Modena and Reggio Emilia, Modena/Reggio Emilia, Modena, Italy. · J Rheumatol. · Pubmed #18688917 No free full text.

Abstract: OBJECTIVE: The prevalence of concurrent rheumatoid arthritis (RA) and hepatitis C virus (HCV) infection is probably underestimated because of the increasing spread of this virus worldwide, especially in developing countries. In these patients, anti-tumor necrosis factor-alpha (anti-TNF-alpha) therapy may aggravate hepatitis and increase viremia. We evaluated the safety of these treatments, which remain controversial. METHODS: Thirty-one HCV-positive patients (23 women, 8 men, mean age 59+/-13 yrs, mean disease duration 13+/-11.5 SD yrs) with active RA [Disease Activity Score 28 (DAS28)>3.2] unresponsive to conventional therapies were treated with TNF-alpha blockers (infliximab 11, etanercept 17, adalimumab 3) at standard dosages. Safety and efficacy were evaluated at the third month of treatment and at the patient's last observation. RESULTS: A significant clinical-serological improvement was recorded at the 3-month reevaluation. Mean values of patients assessment of general health on visual analog scale (range 0.100) decreased from 69+/-29 (SD) to 35+/-27 (p<0.0001), Ritchie index from 21.6+/-13.9 to 10.1+/-3.7 (p<0.0001), erythrocyte sedimentation rate from 36+/-25 to 28+/-22 mm/h (p=0.04), and DAS28 from 5.2+/-1.6 to 2.78+/-1.3 (p<0.0001); a DAS28<2.6 was recorded in 15/31 (48%) patients. At the last observation 19 patients (61%) continued TNF-alpha blockers, and the observed benefits persisted after 22+/-11 months of followup. Mean values of transaminases (ALT) and HCV viral load showed no significant variations; TNF-alpha blockers were discontinued in only one patient because of persistently elevated ALT not correlated to the variations of HCV viremia; this latter increased significantly (>or=2 log10) in 4 cases. CONCLUSION: Previous observations had suggested the safety of TNF-alpha blockers for treatment of RA in patients with concurrent HCV infection. Given the clinical-therapeutic implications, our results support the safety of TNF-alpha blockers in patients with HCV, provided there is close monitoring of clinical and virological data (mainly ALT and HCV viremia).

Bellisai F, Giannitti C, Donvito A, Galeazzi M. · Dipartimento Medicina Clinica e Scienze Immunologiche, Policlinico Le Scotte, U.O.C. Reumatologia, Viale Bracci, 53100 Siena, Italy. · Clin Rheumatol. · Pubmed #17143590 No free full text.

Abstract: We describe two cases of rheumatoid arthritis (RA) patients and concomitant hepatitis C virus infection (HCV), treated with cyclosporine A (CsA) and anti-TNF-alpha agents. SGOT/SGPT and HCV-RNA serum levels remained unchanged longer than 1 year of treatment. No side effects were registered. We suggest that combination therapy with CsA and TNF-alpha blockers should be considered safe and well-tolerated in the treatment of HCV-positive RA patients.

Sebastiani GD, Bellisai F, Caudai C, Rottoli P, Valensin PE, Pippi L, Morozzi G, Porciello G, Donvito A, Bilenchi R, Giannini F, Galeazzi M. · UOC of Rheumatology, S. Camillo-Forlanini Hospital, Roma, Italy. · J Biol Regul Homeost Agents. · Pubmed #16180280 No free full text.

Abstract: It has been postulated that host factors, such as the human leucocyte antigen (HLA) system, may play a predominant role in the pathogenesis of HCV-related extra-hepatic manifestations. This study was performed to investigate the role of HLA- DR and DQ alleles in a group of Italian patients, with HCV infection and associated extrahepatic manifestations and to test whether an association between HCV genotype, HLA locus and clinical or serological manifestations can be demonstrated. Thirty unrelated patients affected by HCV infection with extra-hepatic manifestations were consecutively included in the study. One hundred and sixty-three HCV patients without extrahepatic manifestations were tested as controls for the prevalence of HCV genotypes, and 283 healthy donors were used as controls for HLA class II alleles distribution. HCV-RNA was quantified by an reverse transcription-PCR. HLA class II alleles typing was performed using a standard microlymphocytotoxicity assay on B lymphocyte purified. HCV 2c genotype was found in 53.3% compared to 18.4% of controls (p=0.00001; OR=5.1). Cryoglobulins were detected in 72.7% DR6+ patients and in 31.6% DR6- patients (p=0.05; OR=3.21). Rheumatoid factor was found in 90.9% of DR6+ patients and in 42.1% DR6- patients (p=0.018; OR 13.7). Only two DR5+ patients (20%) had cryoglobulinemia, while 6 patients (30%) in the DR5- group had cryoglobulinemia (p=0.02; OR=0.07). Associations were found between DR7 and ANA (OR=1.74) and between DQ2 and ANA (OR=1.97). According to our findings HLA-DR6 might play an important role in developing extra-hepatic manifestations and genotype 2c could be considered as a risk factor for their onset.