Hepatitis: Borgia G

Gentile I, Viola C, Borgia F, Castaldo G, Borgia G. · Dipartimento di Medicina Pubblica e Sicurezza Sociale - Sezione di Malattie Infettive, Universită di Napoli "Federico II", Italy. · Curr Med Chem. · Pubmed #19275615 No free full text.

Abstract: Chronic hepatitis C affects 130,000,000 people worldwide. Hepatitis C virus (HCV) is a single-strand RNA virus responsible for most cases of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC) in the Western world. The gold standard for the treatment of chronic hepatitis C (combination of pegylated-interferon alpha and ribavirin) results in a sustained virological response (namely, clearance of serum HCV RNA 6 months after therapy withdrawal) in only about half treated patients. Therefore, there is a race to develop new drugs for the treatment of HCV infection. One of the most promising approaches is to use protease inhibitors, i.e. drugs inhibiting NS3/NS4A HCV protease, which plays a crucial role in the viral life cycle. Telaprevir (VX-950) is the protease inhibitor in the most advanced phase of clinical testing. Telaprevir is orally available and when used in monotherapy it induced a median decline of 4 logs of HCV RNA after two weeks of therapy. However, mutants with a lower sensitivity to telaprevir have been demonstrated in a high proportion of patients within 14 days of monotherapy. The drug has been used in clinical trials in combination with pegylated-interferon and ribavirin. This triple combination resulted in a higher rate of SVR but also in a higher rate of side effects (rash, gastrointestinal disorders, and anemia) than standard treatment. This review focuses on the mechanism of action, pharmacokinetics, clinical efficacy, and tolerability of telaprevir, and on possible use of this drug in combination with other drugs for the treatment of HCV infection.

Borgia G, Gentile I. · Department of Public Medicine and Social Security, Section of Infectious Diseases, Center for Basic and Clinical Immunology Research, CISI, University of Naples Federico II, via S. Pansini, 5, I-80131 Naples, Italy. · Curr Med Chem. · Pubmed #17073632 No free full text.

Abstract: Three hundred and fifty million people worldwide are estimated to be chronically infected with hepatitis B virus. 15-40% of these subjects will develop cirrhosis, liver failure or hepatocellular carcinoma during their life. The treatment of chronic hepatitis B has improved dramatically over the last decade thanks to the advent of nucleoside/nucleotide analogues and the use of pegylated interferons. However, these agents have increased the complexity of the management of hepatitis B. Five drugs have been approved for chronic hepatitis B treatment: standard interferon-alpha 2b, pegylated interferon-alpha 2a, lamivudine, adefovir dipivoxil, and entecavir. A definite course of standard or pegylated interferon is administered to induce hepatitis B virus clearance. Unfortunately, these agents are not effective in all patients and are associated with not negligible side effects. Nucleoside or nucleotide analogues that inhibit hepatitis B virus polymerase induce on-treatment suppression of viral replication but patients tend to relapse after cessation of treatment. Consequently, these analogues, which are well tolerated, should be used for prolonged periods, even indefinitely. However, prolonged treatment is associated with a high rate of resistance. The following anti-hepatitis B virus drugs are currently undergoing clinical testing: telbivudine, emtricitabine, tenofovir disoproxil fumarate, clevudine and thymosin-+/-1. Here we will examine the mechanism of action, efficacy, safety, tolerability and emergence of resistance of agents used to treat chronic hepatitis B. We shall also examine the potential of drugs now being tested and of combination treatment.

Varriale M, Salvio A, Giannattasio F, d'Errico T, Montone L, Borgia F, Gentile I, Reynaud L, Borgia G, Rossiello R, Visconti M. · Unit of Hepatology D.H., Department of Internal Medicine Ospedale degli Incurabili, ASL NA 1, Naples, Italy. · Minerva Gastroenterol Dietol. · Pubmed #15788990 No free full text.

Abstract: Ranitidine may cause liver injuries ranging from transient, subclinical serum transaminases increase every 100-1,000 treated patients to cholestatic hepatitis in less than 1/100,000. Other H2-receptor antagonists are more dangerous: 11 toxic hepatitis cases have been reported as adverse effect after 1 year of marketed ebrotidine. A 75-year-old male with ischemic cardiopathy history was started on an 8 days treatment of oral ranitidine due to pirosis, without any other changes of therapy; 48 h after drug withdrawal, light-coloured stools, dark urine and icteric scleras developed. On hospital admission, 10 days later, physical examination showed slight hepatomegaly and severe jaundice with skin excoriations followed by serum mixed bilirubin further increase and aminotransferases activities mild rise. Total bilirubin peaked at 381.33 mmol/l (5.1-17.1) and progressively returned to normal, after discharge home, in 3 months and now, 1 year later, there is no sign of liver disease. Ultrasonographic biliary anomalies and the most frequent causes of liver damage were excluded. Liver biopsy confirmed ranitidine as the most likely cause of liver toxicity since histological and ultramicroscopical study revealed a drug-induced picture. We report a rare case of intrahepatic cholestasis jaundice related to ranitidine, a widely used drug. Diagnosis would need an ethically unacceptable rechallange test.

Borgia G. · Department of Public Medicine and Social Security, Institute for Infectious Diseases-Ed 18, University of Naples Federico II, via Pansini 5, I-80131, Naples, Italy. · IDrugs. · Pubmed #15197662 No free full text.

Abstract: Evidence has suggested that the hepatitis C virus (HCV) does not elicit neutralizing antibodies, and hence that the presence of anti-HCV antibodies is only a marker of infection. Subsequently, HCV neutralizing antibodies have been identified and methods for their detection were devised. HCV neutralizing antibodies are present in anti-HCV-positive blood units but there is no correlation between the anti-HCV antibody titer and the HCV neutralizing antibody titer. There are two patented methods for the production of polyclonal HCV immunoglobulin: (i) from anti-HCV-positive blood units containing high titers of anti-HCV antibodies (EP-00447984); and (ii) from a large number of anti-HCV-positive blood units that contain high titers of HCV-neutralizing antibodies against the different HCV strains (US-06372216 and EP-00896545). Several monoclonal antibodies have been patented for clinical use in HCV-infected patients; however, only one has undergone a clinical trial. This review examines the use of specific immunoglobulin against HCV, which, similarly to specific immunoglobulin against hepatitis B virus, contains high titers of antibodies that neutralize the different HCV strains, and could thus be efficacious in the same settings (e.g., re-infection of transplanted liver, post-exposure prophylaxis, sexual transmission and patients undergoing hemodialysis).

Borgia G, Reynaud L, Gentile I, Piazza M. · Dept. of Public Medicine and Social Security, Institute for Infectious Diseases-Ed 18, Federico II University of Naples, via Pansini 5, I-80131 Naples, Italy. · Infection. · Pubmed #14562947 No free full text.

Abstract: Hepatitis C virus (HCV) infection occurs in about one-third of HIV-seropositive patients and in about 90% of HIV-positive drug abusers. After the introduction of highly active antiretroviral therapy (HAART) and the subsequent reduction in mortality from opportunistic infections, HCV-related liver failure has become a frequent cause of death in HIV-positive patients. In HIV-seropositive patients, the course of HCV infection is accelerated and there is evidence that HCV is an important factor for HIV progression. Consequently, it is important to establish the appropriate treatment for HCV infection in HIV-seropositive patients. This review examines the epidemiology, physiopathology, diagnostics and treatment of HIV/HCV coinfection with particular regard to the impact of HAART.

Reynaud L, Carleo MA, Talamo M, Borgia G. · Department of Public Medicine and Social Security - Section of Infectious Disease University of Naples "Federico II", Italy. · Ther Clin Risk Manag. · Pubmed #19436619 links to  free full text

Abstract: Recent literature is reviewed about treatment of chronic hepatitis B virus (CHB), focusing on tenofovir disoproxil fumarate (TDF; Viread((R))), among the nucleotide and nucleoside analogs. TDF pharmacokinetics and pharmacodynamics, activity in respect of hepatitis B virus (HBV) multi-drug-resistant mutations, efficacy in treatment-naïve and treatment-experienced patients, and side effects are described. The most predictive response factors to TDF therapy are discussed and all available combination therapies to optimize clinical outcome in the various patient profiles are analyzed, such as compensated and/or decompensated cirrhotic patients. The use of TDF in pregnancy, and prophylaxis after exposure to HBV and post-liver transplantation are also evaluated.

Borgia G, Gentile I, Fortunato G, Borrelli F, Borelli S, de Caterina M, Di Taranto MD, Simone M, Borgia F, Viola C, Reynaud L, Cerini R, Sacchetti L. · Dipartimento di Medicina Pubblica e Sicurezza Sociale - Sezione di Malattie Infettive, Università di Napoli Federico II, Napoli, Italy. · Liver Int. · Pubmed #18662278 No free full text.

Abstract: BACKGROUND: Chronic hepatitis C affects about 3% of the world's population. Pegylated interferon (IFN) alpha plus ribavirin is the gold standard treatment. Methylenetetrahydrofolate reductase(MTHFR) is a key enzyme in the metabolism of homocysteine. MTHFR gene polymorphisms and high levels of homocysteine are associated with a high degree of steatosis and fibrosis, conditions associated with a low sustained virological response (SVR) rate. AIMS: To evaluate whether MTHFR polymorphisms and homocysteine levels are predictors of the outcome of treatment in 102 prospectively enrolled patients with chronic hepatitis C naive to treatment. METHODS: Patients were treated with pegylated interferon alpha-2b plus ribavirin. All patients underwent blood tests, assessment of homocysteine, vitamin B(12), folate, hepatitis C virus (HCV)-RNA levels, screening for MTHFR gene polymorphisms and liver ultrasound examination. RESULTS: Homocysteine levels were deranged (>16 micromol/L) in 10.5% of MTHFR wild-type patients vs 40.3% of non-wild-type patients (P=0.015). Homocysteine levels were 14.4 micromol/L in SVR patients and 15.5 micromol/L in non-SVR patients (P=0.049). The SVR rate was 40.0% in MTHFR wild-type patients, 52.0% in heterozygote mutants and 39.3% in homozygote mutants (P=0.467). At logistic regression analysis, genotypes 2 and 3 (odds ratio: 12.328, 95% confidence interval: 3.390-44.837, P=0.0001), homocysteine <16 micromol/L (odds ratio: 3.397, 95% confidence interval: 1.033-11.177, P=0.044) and aspartate aminotransferase (AST) levels <48 U/L (odds ratio: 3.262, 95% confidence interval: 1.125-9.458, P=0.029) were independent predictors of SVR. CONCLUSIONS: In patients with chronic hepatitis C, homocysteine levels are associated with the outcome of pegylated-IFNalpha plus ribavirin treatment, while polymorphisms of MTHFR are not.

Fortunato G, Calcagno G, Bresciamorra V, Salvatore E, Filla A, Capone S, Liguori R, Borelli S, Gentile I, Borrelli F, Borgia G, Sacchetti L. · Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy. · J Interferon Cytokine Res. · Pubmed #18338947 No free full text.

Abstract: We have studied 35 single nucleotide polymorphisms (SNPs) in the interferon (IFN) pathway to determine their contribution to multiple sclerosis (MS) and hepatitis C virus (HCV) infection. A total of 182 patients with MS, 103 patients with chronic hepatitis C, and 118 control subjects were enrolled in the study. Of the 35 SNPs studied, 3 were in IFN-alpha receptor (IFNAR-1), 10 in IFN-alpha/beta receptor (IFNAR-2), 9 in Stat1, 5 in Stat2, and 8 in IFN regulatory factor-1 (IRF-1). Compared to controls, Stat1 gene polymorphisms were significantly more frequent in MS patients (rs# 2066802 OR = 7.46, 95% CI = 2.22-25.10; rs# 1547550 OR = 1.69, 95% CI = 1.01-2.81) and in HCV patients (rs# 2066802 OR = 5.95, 95% CI = 1.55-22.81; rs# 1547550 OR = 2.30, 95% CI = 1.24-4.24). Also one IRF-1 gene SNP was associated with MS (rs# 2070721 OR = 2.05, 95% CI = 1.03-4.09), and four IRF-1 gene SNPs were associated with HCV infection (rs# 2070721 OR = 2.59, 95% CI = 1.23-5.43; rs# 2070723 OR = 4.8, 95% CI = 1.26-18.20; rs# 2070728 OR = 9.81, 95% CI = 1.21-79.4; rs# 2070729 OR = 3.6, 95% CI = 1.23-10.48; rs# 839 OR = 4.67, 95%CI = 1.29-16.87). Characteristic nucleotide combinations on single chromosomes (haplotype) generated block structures, including SNPs, that differed between patients and controls. Using a permutation test to detect differences in haplotype distribution between groups, the CCATTGA and the CCGAA haplotypes in the IRF-1 gene were more frequent in MS (p = 0.03) and in HCV patients (p = 0.001) than in controls. In conclusion, our data show that genetic variants in the IRF-1 and Stat1 genes of the IFN pathway are associated with MS and HCV infection.

Tosone G, Borgia G, Gentile I, Cerini R, Conte MC, Orlando R, Piazza M. · Department of Public Medicine and Social Security Section of Infectious Diseases, University of Naples Federico II, Via Sergio Pansini 5, I-80131, Naples, Italy. · Acta Diabetol. · Pubmed #17721757 No free full text.

Abstract: We report the case of a 42-year-old woman with chronic hepatitis C (genotype 1), who in June 2004 started therapy with pegylated interferon alpha (PEG-IFNalpha) plus ribavirin. Two months later, she discontinued treatment because of polydipsia, polyuria and vomiting leading to a marked dehydration. Biochemical data showed type 1 diabetes mellitus with ketoacidosis, and insulin therapy was started. The patient, who before starting PEG-IFN alpha plus ribavirin therapy tested negative for glutamic acid decarboxylase antibodies (GADAb) and islet cell (ICAb) antibodies, became strongly positive for both autoimmune markers. This case confirms that patients with chronic hepatitis C who do not have baseline markers of pancreatic autoimmunity may develop severe ketoacidosis during treatment with PEG-IFNalpha, as well as with standard IFNalpha. In order to avoid this complication, as no guidelines are available and the pancreatic autoimmunity markers are not routinely analysed, we suggest frequent monitoring (e.g., every one to two weeks) of glycaemic values: e.g., every one to two weeks during the first 3 months (when this complication occurs most frequently) and monthly thereafter so as to identify diabetes at an early stage and before the onset of the appearance of severe ketoacidosis, which is life-threatening.

Perrella A, Borgia G, Guida GM, Graf M, Gnarini RM, Viola C, Atripaldi L, Sbreglia C, Perrella O. · No affiliation provided · J Gastroenterol Hepatol. · Pubmed #16048590 No free full text.

This publication has no abstract.

Gentile I, Viola C, Reynaud L, Borrelli F, Cerini R, Ciampi R, Piazza M, Borgia G. · Department of Public Medicine and Social Security, Institute of Infectious Diseases( Ed. 18), University of Naples Federico II, Naples, Italy. · J Interferon Cytokine Res. · Pubmed #15871666 No free full text.

Abstract: A 53-year-old woman admitted to our department for histologically proven chronic hepatitis C had previously been treated with pegylated interferon-alpha2b (PEG-IFN) plus ribavirin. Combination therapy had been withdrawn after 5 weeks because of severe anemia (hemoglobin 8.2 g/dl) despite a reduction in ribavirin dose. A second liver biopsy showed moderate chronic hepatitis with portoportal and portocentral bridges (Ishak score: grading 14/18, staging 4-5/6). Consequently, the patient was retreated with 1.5 microg/kg body weight weekly PEG-IFN and 1000 mg/day ribavirin. Ribavirin was withdrawn about 3 months later because of anemia. After 1 month of PEG-IFN alone, hemoglobin had decreased further to reach 7.9 g/dl; consequently IFN was stopped. An elevated reticulocyte count, indirect bilirubin concentration, and lactic dehydrogenase (LDH) concentration, and a positive direct Coombs test (IgG3, C3d also for panagglutinant irregular antibodies on eluate) led us to diagnose autoimmune hemolytic anemia (AHA). The patient received 1 mg/kg body weight/day prednisone, and all parameters normalized within 20 days. This is the first case of IFN-related AHA during PEG-IFN plus ribavirin therapy. Physicians should be aware that PEG-IFN can be the cause of AHA during a ribavirin-containing regimen for chronic hepatitis C.

Perrella A, Borgia G, Borrelli F, Di Sirio S, Gnarini M, Grattacaso S, Graf M, Guida M, Viola C, Guarnaccia M, Perrella O. · Department of Public Medicine and Social Security, Institute for Infectious Diseases, Federico II Medical School University of Naples, Italy. · Int J Immunopathol Pharmacol. · Pubmed #15698524 No free full text.

This publication has no abstract.

Borgia G. · Department of Public Medicine and Social Security, Institute for Infectious Diseases-Ed 18, University of Naples Federico II, via S Pansini 5, 80131 Naples, Italy. · Curr Opin Investig Drugs. · Pubmed #15600247 No free full text.

Abstract: XTL Biopharmaceuticals is developing HepeX-C, a combination of two antibodies (HCV-AB68 and HCV-AB65) as a potential therapy for hepatitis C virus infection. By September 2003, phase II trials of HCV-AB68 alone had been conducted and XTL Biopharmaceuticals announced that it planned to conduct a phase I study of the antibody combination.

Genovese A, Borgia G, Bouvet JP, Detoraki A, de Paulis A, Piazza M, Marone G. · Division of Clinical Immunology and Allergy, University of Naples Federico II, Naples, Italy. · Int Arch Allergy Immunol. · Pubmed #14707465 No free full text.

Abstract: Protein Fv, an endogenous protein produced in the liver, is released in biological fluids during viral hepatitis. Acute and chronic viral hepatitis can be associated with cardiovascular derangements. Protein Fv induced the release of histamine, tryptase and the de novo synthesis of prostaglandin D(2) and cysteinyl leukotriene C(4) from mast cells isolated from human heart tissue (HHMC). Protein Fv absorbed with protein A-Sepharose coated with polyclonal IgG did not induce histamine secretion. The maximal percent histamine secretion induced by protein Fv correlated (r(s) = 0.60; p < 0.05) with that induced by anti-IgE, whereas there was no correlation between the release caused by proteins Fv and C5a. Preincubation of HHMC with protein Fv or anti-IgE caused complete cross-desensitization to subsequent challenge with heterologous stimulus. HHMC from which IgE had been dissociated no longer released histamine in response to anti-IgE and protein Fv. A human monoclonal IgE blocked both anti-IgE- and protein Fv-induced release. Three human monoclonal IgM V(H)3(+) inhibited protein-Fv-induced secretion of histamine from HHMC, whereas monoclonal IgM V(H)6(+) did not inhibit the release induced by protein Fv. Protein Fv acts as an endogenous immunoglobulin superantigen by interacting with the V(H)3 domain of IgE to induce the release of mediators from HHMC.

Borgia G, Reynaud L, Gentile I, Borrelli F, Cerini R, Ciampi R, Piazza M. · Department of Public Medicine and Social Security, Institute of Infectious Diseases (Ed. 18), University of Naples Federico II, Naples, Italy. · J Interferon Cytokine Res. · Pubmed #12639294 No free full text.

Abstract: Some latent diseases, such as immune disorders, can appear during interferon-alpha (IFN-alpha) therapy. These disorders are difficult to predict because of their low prevalence in the general population. We describe a case of pernicious anemia (PA) in a patient affected by chronic hepatitis C and macrocytosis during IFN-alpha therapy. Hemoglobin (Hb) concentration reached 7.3 g/dl. Anti-intrinsic factor (IF) antibodies were present, but not antiparietal cell antibodies (APCA). Suspension of IFN-alpha and administration of vitamin B(12) resulted in normal Hb concentrations. This case is the first instance of early PA (at the second month of IFN therapy) in a patient affected by chronic hepatitis C. The only other case of PA in a patient affected by hepatitis C virus (HCV) infection occurred during the second year of maintenance IFN therapy. We recommend that particular attention be paid to such clinical and laboratory conditions as macrocytosis in administering IFN-alpha therapy for chronic hepatitis C.

Rendina D, Vigorita E, Bonavolta R, D'Onofrio M, Iura A, Pietronigro MT, Laccetti R, Bonadies G, Liuzzi G, Borgia G, Formisano P, Laccetti P, Portella G. · Dipartimento Assistenziale di Patologia Clinica, Facoltà di Medicina e Chirurgia Università di Napoli Federico II, Italy. · Eur J Epidemiol. · Pubmed #12081097 No free full text.

Abstract: Flaviviridae-hepatitis C virus (HCV) and GB virus C/hepatitis G virus (GBV-C/HGV)--and human immunodeficiency virus (HIV) frequently show similar modes of transmission. HCV and GBV-C/HGV infection was assessed in 134 consecutive patients with evidence of HIV infection, living in Campania, Italy. Data obtained from this cohort were compared with those obtained from 252 age- and sex-matched HCV infected patients without evidence of HIV infection (HCV control group). Following enzymatic immunoassays, samples were tested for the presence of HCV-RNA by RT-PCR. The HCV-RNA positive sera were genotyped by LiPA procedure. The prevalence of HCV infection in HIV patients was 19.40% and the largest group of HIV-HCV co-infected patients (84.62%) was represented by intravenous drug users (IVDU). The distribution of HCV genotypes in HIV-HCV patients was different, compared to that observed in HCV control group. HCV genotypes la (50%) and 3a (23.08%) were more frequently detected in HIV HCV patients, compared to HCV control group (5.16 and 5.56% for la and 3a, respectively). Conversely, HCV genotypes lb (55.70%) and 2a/2c (30.26%) were more represented in HCV control group, compared to HIV-HCV patients (15.38 and 0% for lb and 2a/2c, respectively). GBV-C/HGV seroprevalence was 41.04% in HIV patients and 6.54% in healthy control individuals. Differently from HCV, GBV-C/HGV infection did not correlate to a preferential risk behaviour in the HIV cohort. Comparative analysis of HCV and GBV-C/HGV infection indicates that the use of injecting drugs might play a key role in the epidemiology of HCV and, in particular, of la and 3a HCV genotypes, in HIV patients.

Fortunato G, Castaldo G, Oriani G, Cerini R, Intrieri M, Molinaro E, Gentile I, Borgia G, Piazza M, Salvatore F, Sacchetti L. · Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, via S. Pansini 5, I-80131 Naples, Italy. · Clin Chem. · Pubmed #11514405 links to  free full text

Abstract: BACKGROUND: Serologic markers have been proposed for monitoring hepatic fibrosis in chronic active liver disease. Because none of these markers, when used singly, is totally satisfactory, we developed and evaluated a multivariate approach. METHODS: We studied two cohorts of chronic hepatitis (54 patients) and cirrhosis patients (49 patients) to identify a panel of biochemical markers that discriminates between the two diseases. Using multivariate discriminant analysis, we selected a function, based on the concentrations of six biochemical markers (fibronectin, prothrombin, pseudocholinesterase, alanine aminotransferase, manganese superoxide dismutase, and N-acetyl-beta-glucosaminidase). We then prospectively validated this function on a second temporal cohort of patients. RESULTS: Multivariate discriminant analysis correctly classified 93.7% of patients (94.3% of chronic hepatitis and 92.9% of cirrhosis patients) in the first cohort and 85% of patients (89.5% of chronic hepatitis patients and 81% of cirrhosis patients) in the second cohort. CONCLUSIONS: Discriminant analysis of results of six inexpensive biochemical markers provides a high predictive value for differentiation between liver cirrhosis and chronic hepatitis. Consequently, these biochemical markers condensed into a multivariate discriminant analysis value for each patient provide information that can be contributory for subsequent options during the evolution of the natural history of chronic hepatitis.

Borgia G, Reynaud L, Gentile I, Cerini R, Ciampi R, Dello Russo M, Piazza M. · Department of Public Medicine and Social Security, University of Naples "Federico II," 80131 Naples, Italy. · J Interferon Cytokine Res. · Pubmed #11506739 No free full text.

Abstract: We describe the case of a 56-year-old man who had high aminotransferase levels and anti-hepatitis C virus (HCV) antibodies. He underwent liver biopsy and biochemical screening to evaluate whether he would benefit from interferon (IFN) treatment. The patient was discharged with a diagnosis of HCV-related active chronic hepatitis, skin porphyria, and type 2 diabetes. On December 5, 1995, he began therapy with recombinant IFN-alpha at a dose of 3 MIU three times a week. He stopped this therapy in February 1996 because of asthenia, diplopia, headache, and anxiety. During IFN therapy, he had normal aminotransferase levels and no detectable HCV RNA, a condition that persists to the present. Between March and May 1996, the patient was admitted several times to a neurology clinic, where myasthenia gravis was diagnosed and treatment with pyridostigmine and cyclosporine was initiated. This case and others indicate that caution should be exercised in administering IFN because low doses can be correlated with myasthenia gravis in patients without malignancies.

Migliaresi S, Bresciani A, Ambrosone L, Spera M, Barbarulo D, Lombari V, Pirozzi G, Borgia G, Lombardi ML, Tirri G, Manzo C. · Istituto di Clinica Medica, Reumatologia, Seconda Università degli Studi, Napoli, Italy. · Ann Rheum Dis. · Pubmed #10627422 links to  free full text

Abstract: OBJECTIVE: To investigate whether quantitative alterations of both beta(2)microglobulin (beta(2)micro) associated HLA class I heavy chains (sHLA-I) and beta(2) micro free class I heavy chains (sHLA-FHC) in sera of patients with hepatitis C virus (HCV) infection occur and whether they distinguish patients with mixed cryoglobulinaemia (MC). METHODS: 83 HCV infected patients were studied and divided into three groups: (A) without cryoglobulinaemia (n=21), (B) with polyclonal MC (n=20), (C) with monoclonal MC (n=42). Serum sHLA-I and sHLA-FHC were measured by double determinant radioimmunoassay using monoclonal antibodies: TP25.99 as catching antibody, and NAMB-1 and HC-10 as revealing antibodies. Western blot identified HLA-I isoforms. RESULTS: The serum concentrations of sHLA-I and of sHLA-FHC in HCV infected patients versus controls were respectively 1.3(0.5) microg/ml (mean (SD)) versus 0.8 (0.3) (p<0. 001) and 13.9 (7.1) ng/ml versus 9.2 (5) (p<0.001). sHLA-I were 1.01 (0.4) microg/ml in group A, 1.04 (0.4) microg/ml in group B, and 1. 47 (0.4) microg/ml in group C (p=0.001). Statistical analysis showed a significant difference versus controls for groups B (p<0.02) and C (p<0.001). sHLA-FHC were 12.8 (8.3) ng/ml in group A, 17.2 (7.1) ng/ml in group B, and 12.9 (6.2) ng/ml in group C (p<0.02). A significant difference versus controls for each group was found (p<0. 02, p<0.001, and p<0.02, respectively). Different patterns of sHLA-I isoforms were observed. CONCLUSIONS: Increased serum concentrations of sHLA-I and sHLA-FHC characterise HCV infected patients. The highest sHLA-I concentrations seem to distinguish patients with monoclonal MC. In this last condition sHLA could play a part in the HCV escape and in B cell proliferation. The significance of sHLA-FHC is still undefined.

Perrella A, Atripaldi L, Sbreglia C, Borgia G, Sorrentino P, Tarantino G, Perrella O. · No affiliation provided · Clin Infect Dis. · Pubmed #15889382 No free full text.

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Perrella A, Borgia G, Perrella O. · No affiliation provided · Hepatology. · Pubmed #15486981 No free full text.

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Perrella A, Borgia G, Reynaud L, Borrelli F, Di Sirio S, Grattacaso S, Perrella O. · No affiliation provided · Gastroenterology. · Pubmed #15481022 No free full text.

This publication has no abstract.