RESUMEN
BACKGROUND: HCV infection is frequently associated with liver steatosis. AIMS AND METHODS: We studied 126 frozen liver HCV positive specimens (genotype-3=27) without any features of metabolic syndrome, searching for a correlation between the number of HCV infected hepatocytes and the presence, amount and distribution of steatosis in relation to different genotypes. RESULTS: Mean steatosis score was higher in genotype-3 with respect to non-3 (1.11 vs 0.66, p=0.022). HCV-antigens were detected by an immunoperoxidase technique in 91/126 (72.2%) cases. A significant correlation between the number of HCV-antigen positive cells and the degree of liver steatosis was observed in genotype-3 (p=0.01) but not in non-3 patients, matched for sex and age. Steatotic cells usually outnumbered HCV-infected cells. Steatosis was observed both in HCV-antigen positive and negative hepatocytes, and HCV-antigens were detected in both hepatocytes with and without steatosis: while no lobular codistribution was found in genotype non-3, in genotype-3 steatosis and HCV-antigens were usually found in the same areas. CONCLUSION: Our data support the role of HCV-antigen liver expression in the pathogenesis of steatosis in genotype-3, however, since the presence of HCV-antigens is not directly related to steatosis within single hepatocytes, an indirect mechanism might be operative too.
Asunto(s)
Hígado Graso/genética , Antígenos de la Hepatitis C/genética , Hepatitis C Crónica/genética , Adulto , Comorbilidad , Hígado Graso/epidemiología , Hígado Graso/inmunología , Hígado Graso/metabolismo , Hígado Graso/virología , Femenino , Genotipo , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/inmunología , Hepatitis C Crónica/metabolismo , Hepatocitos/inmunología , Hepatocitos/virología , Humanos , Inmunohistoquímica , Hígado/inmunología , Hígado/virología , Masculino , Persona de Mediana EdadRESUMEN
Hepatitis C virus (HCV) infection is characterized by a number of autoreactive manifestations, such as autoantibody production, cryoglobulinemia and thyroid disorders. We will analyse critically the mechanisms invoked, and partially documented, to explain such manifestations arising in genetically predisposed individuals exposed to HCV. In particular we will examine the available evidence implicating the virus in lowering the B cell activation threshold, in directly infecting lymphocytes and in inducing self-reactivity through a mechanism of molecular mimicry. We will then move to the HCV related clinical immunopathological manifestations, with a specific attention to the effects of antiviral treatment.
Asunto(s)
Enfermedades Autoinmunes , Hepatitis C/inmunología , Autoanticuerpos/sangre , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/inmunología , Linfocitos B/inmunología , Predisposición Genética a la Enfermedad , Hepatitis C/sangre , Hepatitis C/genética , Antígenos de Histocompatibilidad/genética , Humanos , Linfocitos T/inmunologíaRESUMEN
BACKGROUND: Treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) is difficult with low response rates. AIM: To assess the safety and efficacy of pegylated-interferon (PEG-IFN) alfa-2b + ribavirin (RBV) in patients with post-LT recurrent genotype-1 HCV and to establish stopping rules according to response. METHODS: Fifty-three patients with post-LT HCV recurrence were enrolled. Patients received PEG-IFN alfa-2b 1.0 micro/kg/week plus RBV 8-10 mg/kg/day for 24 weeks. Those with 'early virological response at week 24' (EVR24) continued treatment for 24 weeks (group A). Patients without EVR24 were randomized to continue (group B) or to discontinue (group C). RESULTS: Overall sustained virological response (SVR) was 26% (14/53). Alanine aminotransferase, rapid virological response, EVR12, EVR24, undetectable serum HCV-RNA at weeks 12 (cEVR12) and 24 (cEVR24) were related to SVR. cEVR12 and cEVR24 (OR: 14.7; 95% CI: 2.02-106.4) were independent predictors of SVR. All patients with SVR, had cEVR12. No patient in groups B and C achieved end-of-treatment response. One patient in group B had SVR. CONCLUSIONS: Pegylated-interferon alfa-2b was effective in one of four of patients with HCV genotype 1 after LT. Treatment should be discontinued in patients with no virological response at week 12. Further studies are needed to evaluate whether a longer treatment period may be beneficial in patients with > or =2 log10 drop in HCV-RNA at week 24.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Trasplante de Hígado/patología , Ribavirina/uso terapéutico , Adulto , Anciano , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , Selección de Paciente , Polietilenglicoles , ARN Viral/genética , Proteínas Recombinantes , Prevención Secundaria , Resultado del TratamientoRESUMEN
BACKGROUND: Primary biliary cirrhosis (PBC) may be associated with various rheumatological disorders. AIM: To investigate the frequency and significance of 'rheumatological' antinuclear antibodies in the field of autoimmune chronic liver disease, with special regard to PBC. METHODS: We studied 105 patients with PBC, 162 autoimmune liver disease controls (type 1 and 2 autoimmune hepatitis, primary sclerosing cholangitis), 30 systemic lupus erythematosus and 50 blood donors. Sera were tested for the presence of antibodies to extractable nuclear antigens (anti-ENA) by counterimmunoelectrophoresis, enzyme-linked and immunoblot (IB) assay, and for the presence of anti-centromere antibodies (ACA) by indirect immunofluorescence on HEp-2 cells and IB. RESULTS: The overall prevalence of IB-detected anti-ENA in PBC (30%) was higher than in type 1 autoimmune hepatitis (2.5%, P < 0.0001), type 2 autoimmune hepatitis (0%, P < 0.0001) and primary sclerosing cholangitis (11.5%, P = 0.006) and lower than in systemic lupus erythematosus (53%, P = 0.03). The most frequent anti-ENA reactivity in PBC was anti-SSA/Ro-52kD (28%). ACA were detected by IB in 21% PBC patients and never in the other subjects (P < 0.0001). Anti-SS-A/Ro/52kD positive PBC patients had at the time of diagnosis a more advanced histological stage (P = 0.01) and higher serum levels of bilirubin (P = 0.01) and IgM (P = 0.03) compared with negative ones. CONCLUSIONS: In the autoimmune liver disease setting, anti-SS-A/Ro-52kD and ACA have a high specificity for PBC and can thus be of diagnostic relevance in anti-mitochondrial antibodies negative cases. If confirmed in further studies with adequate follow-up, anti-SS-A/Ro-52kD antibodies might identify PBC patients with a more advanced and active disease.
Asunto(s)
Anticuerpos Antinucleares/sangre , Enfermedades Autoinmunes/diagnóstico , Cirrosis Hepática Biliar/etiología , Hepatopatías/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Autoinmunes/inmunología , Enfermedad Crónica , Femenino , Técnica del Anticuerpo Fluorescente/métodos , Humanos , Hepatopatías/complicaciones , Hepatopatías/inmunología , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
BACKGROUND: Antibodies directed against citrullinated proteins (eg anti-cyclic citrullinated peptide (CCP)) have excellent diagnostic and good prognostic potential for rheumatoid arthritis. Type 1 autoimmune hepatitis (AIH-1) is a chronic liver disease characterised by a variety of serum autoantibodies. Recently, in a large group of patients with AIH-1 without clear rheumatoid arthritis overlap, a relatively high percentage (9%) of anti-CCP2 positivity was scored. OBJECTIVES: To characterise the citrulline-dependence of the observed anti-CCP2 positivity in AIH-1 sera as well as in other groups of patients without rheumatoid arthritis (mainly rheumatic diseases). METHODS: Serum samples of 57 patients with AIH-1 and 66 patients without rheumatoid arthritis, most of them reported as anti-CCP positive, were tested for citrulline-specific reactivity with a second generation anti-CCP kit, with the citrullinated and the corresponding non-citrullinated (arginine-containing) antigen. A subset of AIH-1 sera was also tested with a CCP1 ELISA (and arginine control). RESULTS: The anti-CCP2 reactivity of most non-rheumatoid arthritis rheumatic diseases samples (87-93%) was citrulline-specific, whereas a relatively high percentage of AIH-1 samples (42-50%) turned out to be reactive in a citrulline-independent manner. The use of citrullinated and non-citrullinated CCP1 peptides confirmed a high occurrence of citrulline-independent reactivity in AIH-1 samples. CONCLUSIONS: In rheumatoid arthritis and most non-rheumatoid arthritis rheumatologic disease sera, anti-CCP positivity is citrulline-dependent. However in some patients, particularly patients with AIH-1, citrulline-independent reactivity in the anti-CCP2 test can occur. A positive CCP test in a non-rheumatic disease (eg liver disease) should therefore be interpreted with care, and preferably followed by a control ELISA with a non-citrullinated antigen.
Asunto(s)
Artritis/inmunología , Autoanticuerpos/sangre , Citrulina/inmunología , Hepatitis Autoinmune/inmunología , Péptidos Cíclicos/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Artritis/diagnóstico , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/inmunología , Autoantígenos/inmunología , Biomarcadores/sangre , Niño , Ensayo de Inmunoadsorción Enzimática/métodos , Epítopos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Juego de Reactivos para Diagnóstico , Enfermedades Reumáticas/inmunologíaRESUMEN
Hepatitis C Virus is associated with a wide series of extrahepatic manifestations. Based on available data the link between the virus and some of these extrahepatic diseases is only suggested and needs further confirmation. Hepatitis C Virus-related lymphoproliferative disorders, whose prototype is mixed cryoglobulinaemia, represent the most closely related extrahepatic manifestations of Hepatitis C Virus. Other Hepatitis C Virus-associated disorders include nephropathies, thyreopathies, sicca syndrome, idiopathic pulmonary fibrosis, porphyria cutanea tarda, lichen planus, diabetes, chronic polyarthritis, cardiopathy and atherosclerosis. A pathogenetic link between Hepatitis C Virus and some extrahepatic manifestations was confirmed by their responsiveness to antiviral therapy, which is now deemed the first therapeutic option to consider. By contrast, there are diseases where treatment with interferon was ineffective or dangerous. The aim of the present paper is to outline the most recent evidence concerning extrahepatic disorders that are possibly associated with Hepatitis C Virus infection. Special emphasis will be given to discussion of the most appropriate clinical approaches to be adopted in order to diagnose, treat (possibly prevent) and follow-up extrahepathic diseases in patients with Hepatitis C Virus infection.
Asunto(s)
Hepatitis C/complicaciones , Enfermedades Autoinmunes/etiología , Enfermedades Autoinmunes/inmunología , Crioglobulinemia/etiología , Crioglobulinemia/inmunología , Hepatitis C/inmunología , Humanos , Liquen Plano/etiología , Liquen Plano/inmunología , Linfoma de Células B/etiología , Linfoma de Células B/inmunología , Trastornos Linfoproliferativos/epidemiología , Trastornos Linfoproliferativos/etiología , Paraproteinemias/etiología , Paraproteinemias/inmunología , Porfiria Cutánea Tardía/etiología , Porfiria Cutánea Tardía/inmunologíaRESUMEN
We report the case of a 35-year-old woman with a diagnosis of coeliac disease at the age of 32 due to a severe malabsorption and flat mucosa without endomysial and tissue transglutaminase antibodies. The lack of clinical and histological improvement after 1 year of a gluten-free diet led to a diagnosis of refractory sprue. She had a good clinical response to steroids that were stopped after 3 months when she became pregnant. After delivery, she again started to complain of malabsorption with arthritis. Positivity for enterocyte autoantibodies together with a flat mucosa persistence allowed to identify a condition of autoimmune enteropathy; moreover, a rheumatological assessment gave evidence of an associated rheumatoid arthritis. Treatment by steroids and methotrexate brought to the remission of intestinal and articular symptoms together with an improvement of duodenal histology. This is the first description of an autoimmune enteropathy associated with rheumatoid arthritis. Autoimmune enteropathy should be always ruled out in patients with a villous atrophy unresponsive to a gluten-free diet, autoimmune manifestations and negativity of coeliac disease markers.
Asunto(s)
Artritis Reumatoide/complicaciones , Artritis Reumatoide/diagnóstico , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/diagnóstico , Enfermedades Intestinales/inmunología , Adulto , Autoanticuerpos/análisis , Enfermedades Autoinmunes/patología , Enterocitos/inmunología , Femenino , Humanos , Enfermedades Intestinales/diagnóstico , Enfermedades Intestinales/patologíaRESUMEN
AIMS: To evaluate the diagnostic significance of anti-filamentous actin antibodies (A-FAA) assessed with a commercial ELISA in comparison with immunofluorescence reactivity and patterns of anti-smooth muscle antibodies (SMA); and to correlate A-FAA positivity with clinical, immunogenetic, laboratory, and histological features in patients with autoimmune hepatitis type 1 (AIH-1). METHODS: We studied 78 consecutive untreated AIH-1 patients and 160 controls: 22 with autoimmune hepatitis type 2 (AIH-2), 51 with hepatitis C, 17 with coeliac disease (CD), 20 with primary biliary cirrhosis (PBC) and 50 blood donors. SMA was evaluated by indirect immunofluorescence (IIF) on frozen sections of rat tissues, and A-FAA with a modified commercial ELISA. RESULTS: SMA was detected by IIF in 61 (78%) of 78 AIH-1 patients, of whom 47 (60%) had the SMA-T/G and 14 (18%) the SMA-V pattern. Of the pathological controls, 32 (20%) had the SMA-V pattern (25 with hepatitis C, 2 with AIH-2, 2 with PBC, 3 with CD). A-FAA were present in 55 AIH-1 patients (70.5%; 46 with SMA-T/G, 7 with SMA-V, and 2 SMA-negative), and in 10 controls (6%), of whom five had hepatitis C, two AIH-2, two PBC and one CD. The association between A-FAA and the SMA-T/G pattern was statistically significant (p<0.0001). A-FAA levels were higher in SMA-T/G positive than SMA-V positive AIH-1 patients and controls (p<0.0001). A-FAA positivity was significantly associated with higher gamma-globulin and IgG levels, but did not correlate with other considered parameters. CONCLUSION: The modified A-FAA ELISA strictly correlates with the SMA-T/G pattern and is a reliable and operator independent assay for AIH-1. Detection of A-FAA, even if devoid of prognostic relevance, may be useful when interpretative doubts of standard IIF arise.
Asunto(s)
Actinas/inmunología , Autoanticuerpos/análisis , Hepatitis Autoinmune/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Azatioprina/uso terapéutico , Biomarcadores/análisis , Estudios de Casos y Controles , Niño , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Estudios de Seguimiento , Glucocorticoides/uso terapéutico , Hepatitis Autoinmune/tratamiento farmacológico , Humanos , Inmunohistoquímica/métodos , Masculino , Persona de Mediana Edad , Músculo Liso/inmunología , Prednisona/uso terapéutico , Sensibilidad y Especificidad , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
BACKGROUND: Anti-ganglioside antibodies have been described in sera of coeliac patients with peripheral neuropathy and cerebellar ataxia. AIMS: To investigate the correlation between anti-ganglioside antibodies and neurological involvement in coeliac disease before and after gluten-free diet. PATIENTS AND METHODS: Twenty-two untreated coeliac patients with neurological dysfunction and 30 untreated coeliacs without neurological dysfunction, 20 patients with neurological disorders, 50 autoimmune disease and 20 blood donors were tested for anti-GM1, anti-GD1b and anti-GQ1b IgG and IgM antibodies by enzyme-linked immunosorbent assay. RESULTS: IgG antibodies to at least one of the three antigens tested were positive in 64% of coeliac patients with neurological symptoms compared to 30% of coeliacs without neurological dysfunction (P=0.02), 50% of patients with neurological disorders (P=ns), 20% with autoimmune diseases (P=0.003) and none of blood donors (P=0.0001). A strict gluten-free diet determined anti-ganglioside antibody disappearance in about half of coeliacs. CONCLUSIONS: A significant correlation between anti-ganglioside antibodies and neurological disorders in patients with an underlying coeliac disease has been found. Anti-ganglioside antibodies may represent a new immunological marker to identify neurological impairment in patients with coeliac disease.
Asunto(s)
Autoanticuerpos/sangre , Biomarcadores/sangre , Enfermedad Celíaca/inmunología , Ataxia Cerebelosa/complicaciones , Gangliósidos/inmunología , Enfermedades del Sistema Nervioso Periférico/complicaciones , Adulto , Enfermedades Autoinmunes/inmunología , Enfermedad Celíaca/complicaciones , Enfermedad Celíaca/dietoterapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/inmunologíaRESUMEN
Hepatitis C virus (HCV) plays a major role in the induction of type II mixed cryoglobulinaemia (MCII). The role of HCV proteins and virus-host interaction in the pathogenesis of MC remains to be defined. To address this issue, we have characterized, in detail, the monoclonal IgM and the viral component of circulating immune complexes in eight patients with HCV-associated MCII. The proportion of HCV-RNA compartmentalized in the cryoprecipitate (CP) varied greatly (10-80% of total HCV-RNA). The complementary determining region (CDR)3 sequences of monoclonal immunoglobulin M (IgM) VH and VK genes were highly homologous to rheumatoid factor and to antibodies against HCV-E2. Furthermore, the CDR3 sequences in some of our MCII patients were highly similar to those described in HCV-positive patients with non-Hodgkin's lymphoma (NHL). From these results, it appears that, as in the case of NHL, the IgM-rheumatoid factor (RF) production in MCII patients is antigen driven, namely by E2. However, the limited number of mutations in VH and VK genes with respect to the germline and their distribution showed that the B-cell response in these cases was prevented from undergoing affinity maturation. Furthermore, in patients with monoclonal IgM and definite compartmentalization of HCV in either CP or supernatant, a highly homogeneous E2-hypervariable region (HVR)1 sequence distribution was found (90-100% identical clones), a feature of the quasispecies frequently associated with an impaired humoral immune response to HCV. These findings suggest that in patients with HCV-associated MCII, maturation of monoclonal B lymphocytes may be blocked in a primitive stage preventing serious damaging effects because of the auto-reactivity of their secreted immunoglobulins.
Asunto(s)
Complejo Antígeno-Anticuerpo/inmunología , Crioglobulinemia/inmunología , Hepatitis C/inmunología , Inmunoglobulina M/inmunología , Proteínas del Envoltorio Viral/inmunología , Anciano , Secuencia de Aminoácidos , Regiones Determinantes de Complementariedad/genética , Crioglobulinemia/complicaciones , Femenino , Hepatitis C/complicaciones , Humanos , Inmunoglobulina M/genética , Región Variable de Inmunoglobulina/genética , Masculino , Persona de Mediana Edad , Mutación , ARN Viral/análisis , Alineación de SecuenciaRESUMEN
BACKGROUND: Serum antinuclear antibodies giving the 'multiple nuclear dots' or the 'rim-like/membranous' patterns are frequently detected by indirect immunofluorescence on HEp-2 cells in patients with primary biliary cirrhosis. AIM: To assess the accuracy of multiple nuclear dot and rim-like/membranous antinuclear antibodies for the diagnosis of primary biliary cirrhosis. METHODS: Sera from 4371 consecutive patients referred to our laboratory were analysed under code for antinuclear antibodies testing by indirect immunofluorescence on HEp-2 cells. RESULTS: Review of the clinical records of the 4371 patients allowed identification of 101 patients with antimitochondrial antibody-positive primary biliary cirrhosis and 22 with antimitochondrial antibody-negative variant. Multiple nuclear dot and/or rim-like/membranous patterns were found in 59 (1.3%) of the 4371 patients: 31 antimitochondrial antibody-positive primary biliary cirrhosis, 17 antimitochondrial antibody-negative primary biliary cirrhosis and 11 non-primary biliary cirrhosis. The specificity for primary biliary cirrhosis of both the antinuclear antibodies pattern was 99%. Positive predictive value and likelihood ratio for a positive test were 86% (95% CI: 72.7-94) and 221 (95% CI: 91.7-544) for multiple nuclear dot, 79% (95% CI: 62.2-90.1) and 132 (95% CI: 56.8-312.7) for rim-like/membranous, respectively. CONCLUSIONS: Multiple nuclear dot and rim-like/membranous antinuclear antibodies are rare findings. Their positivity strongly suggests the diagnosis of primary biliary cirrhosis, irrespective of antimitochondrial antibody status. The high specificity for primary biliary cirrhosis makes them a useful diagnostic tool especially in antimitochondrial antibody-negative patients.
Asunto(s)
Autoanticuerpos/sangre , Técnica del Anticuerpo Fluorescente Indirecta/métodos , Cirrosis Hepática Biliar/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Técnica del Anticuerpo Fluorescente Indirecta/normas , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: There is increasing evidence that hepatic steatosis contributes to the progression of liver fibrosis, whereas its impact on the efficacy of anti-viral treatment is still under investigation. AIM: To evaluate the effect of steatosis on the outcome of combined anti-viral treatment. METHODS: We studied 102 consecutive naive patients with chronic hepatitis C receiving combined anti-viral therapy (peg-interferon alpha-2b and ribavirin). RESULTS: Fifty (49%) of 102 patients had evidence of hepatic steatosis (29 grade 1, 16 grade 2 and 5 grade 3). Sustained virological response was similar in patients with and without steatosis (58% vs. 56%); moreover, the grade of steatosis did not affect the rate of sustained virological response (grade 1: 58%, grade 2: 56% and grade 3: 60%). Patients with steatosis had significantly higher serum levels of aspartate transaminase, alanine transaminase and gamma-glutamyltransferase (P = 0.007, 0.004 and 0.03, respectively), higher histological activity (P = 0.03), more advanced stage of fibrosis (P = 0.0394) and more often hepatitis C virus genotype 3 (P = 0.04). CONCLUSIONS: Our findings suggest that hepatic steatosis in chronic hepatitis C, irrespective of its grade, is not a negative prognostic factor of response to combined anti-viral therapy, even when the histological and biochemical profile of the disease is more aggressive.
Asunto(s)
Antivirales/uso terapéutico , Hígado Graso/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Quimioterapia Combinada , Femenino , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , Polietilenglicoles , Proteínas RecombinantesRESUMEN
BACKGROUND: Besides the autoantibodies included in the diagnostic criteria of type 1 autoimmune hepatitis, many other autoantibodies have been described in this condition. Recently, antibodies against cyclic citrullinated peptide have been validated as specific diagnostic and prognostic markers of rheumatoid arthritis. AIM: To assess whether these antibodies are part of the autoantibody repertoire of type 1 autoimmune hepatitis and correlate with rheumatological manifestations. METHODS: Antibodies against cyclic citrullinated peptide were tested by a commercially available enzyme-linked immunosorbent assay. RESULTS: The antibodies were found in 12 of 133 (9%) type 1 autoimmune hepatitis, two of 49 (4%) with primary biliary cirrhosis, one of 80 (1%) with hepatitis C virus-related chronic liver disease and 53 of 89 (60%) with rheumatoid arthritis serum samples. High titres were found only in rheumatoid arthritis and type 1 autoimmune hepatitis. No clinical (in particular rheumatological manifestations), biochemical or immunoserological differences were detectable between antibodies against cyclic citrullinated peptide positive and negative type 1 autoimmune hepatitis sera, with the exception of rheumatoid factor, always negative in the positive ones. CONCLUSIONS: Antibodies against cyclic citrullinated peptide can be detected in a subgroup of patients with type 1 autoimmune hepatitis. They might be part of the wide range of autoantibody production characteristic of this condition and/or, less probably, be predictive of future rheumatoid arthritis development.
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Autoanticuerpos/sangre , Enfermedades Autoinmunes/inmunología , Anticuerpos Antihepatitis/sangre , Hepatitis/inmunología , Péptidos Cíclicos/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND: Hepatitis C virus (HCV) infection is associated with the appearance of liver steatosis. AIM: To search for a correlation between the number of HCV infected hepatocytes and the presence, amount and distribution of steatosis. METHODS: A total of 124 frozen liver biopsies from HCV patients (genotype 3 = 21) were studied. HCV-antigens were detected on frozen liver sections using a four steps immunoperoxidase technique. Steatosis was graded by haematoxilin-eosin counterstaining on a serial section. RESULTS: Steatosis was detected in 82 of 124 (66.1%) patients without differences between different genotypes. Uric acid, body mass index, gammaGT levels significantly correlated with steatosis in non-3 (P < 0.01, P < 0.05, P < 0.01, respectively) but not in genotype 3 patients. HCV-antigens were detected in 95 of 124 (76.6%) cases. A positive correlation between steatosis and the number of infected hepatocytes was observed only in genotype 3 patients (P = 0.06). In most cases the number of cells with steatosis greatly outnumbered that of HCV infected cells. CONCLUSION: We confirm a possible role of the virus in the genesis of steatosis in HCV genotype 3 infected patients; however, as steatosis do not appear to be directly related to the presence of HCV-antigens within single hepatocytes, an indirect, possibly cytokine mediated, mechanism might be operative.
Asunto(s)
Hígado Graso/virología , Hepatitis C/complicaciones , Adolescente , Adulto , Anciano , Antígenos Virales/análisis , Recuento de Células , Hígado Graso/inmunología , Hígado Graso/patología , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C/sangre , Hepatitis C/genética , Hepatocitos/patología , Hepatocitos/virología , Humanos , Técnicas para Inmunoenzimas/métodos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: The usual onset of type 1 autoimmune hepatitis occurs at puberty or around menopause, whereas disease presentation in the advanced age is less often reported. AIM: To assess the clinical, immunological and histological features of Type 1 autoimmune hepatitis in elderly Italian patients. METHODS: We assessed, at diagnosis, the clinical and immunological features of 76 consecutive Italian patients with type 1 autoimmune hepatitis, focusing particularly on a subgroup of 20 patients presenting at > or = 65 years (females 95%, median age 72 years, range 65-82). RESULTS: In comparison with the younger group, at the time of autoimmune hepatitis diagnosis, elderly Italian patients are more often asymptomatic (25% vs. 7%; P = 0.04), are more frequently positive for antinuclear autoantibodies (95% vs. 52%; P = 0.0004) and HLA-DR4 (45% vs. 18%; P = 0.03); among the extra-hepatic manifestations, autoimmune thyroid disorders are prevalent in the elderly group (25% vs. 5%; P = 0.02). However, no difference was observed in the histological/biochemical expression of the liver disease and response to immunosuppression. CONCLUSIONS: In elderly Italian patients, autoimmune hepatitis has typical serological and genetic characteristics, is more frequently asymptomatic, although prognosis and response to therapy is similar to that of younger patients. As a concomitant autoimmune thyroid disorder is common, autoimmune hepatitis should be suspected and investigated in elderly patients with autoimmune thyroid disorder and abnormal liver function tests.
Asunto(s)
Hepatitis Autoinmune/diagnóstico , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Anticuerpos Antinucleares/sangre , Enfermedades Autoinmunes/complicaciones , Azatioprina/uso terapéutico , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Antígeno HLA-DR4/sangre , Hepatitis Autoinmune/tratamiento farmacológico , Hepatitis Autoinmune/inmunología , Humanos , Inmunosupresores/uso terapéutico , Masculino , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Pronóstico , Enfermedades de la Tiroides/complicacionesRESUMEN
BACKGROUND: Anti-Saccharomyces cerevisiae and perinuclear anti-neutrophil cytoplasmic autoantibodies are markers of Crohn's disease and ulcerative colitis respectively. AIM: To determine the prevalence of anti-S. cerevisiae and perinuclear anti-neutrophil cytoplasmic autoantibodies in a large series of coeliac disease patients before and after gluten free diet, and to correlate anti-S. cerevisiae-positivity with intestinal mucosal damage. METHODS: One hundred and five consecutive coeliac disease patients and 141 controls (22 ulcerative colitis, 24 Crohn's disease, 30 primary sclerosing cholangitis, 15 postenteritis syndrome, 50 blood donors) were tested for anti-S. cerevisiae by enzyme-linked immunosorbent assay and for perinuclear anti-neutrophil cytoplasmic autoantibodies by indirect immunofluorescence. RESULTS: In coeliac disease anti-S. cerevisiae (immunoglobulin G and/or immunoglobulin A) were slightly less frequent (59%) than in Crohn's disease (75%, P = 0.16) and significantly more frequent than in ulcerative colitis (27%), primary sclerosing cholangitis (30%), postenteritis syndrome (26%) and blood donors (4%) (P = 0.009, P = 0.0002, P = 0.025, P < 0.0001). No correlation was found between anti-S. cerevisiae and degree of mucosal damage. Perinuclear anti-neutrophil cytoplasmic autoantibodies were detected only in one coeliac. After gluten free diet the disappearance of anti-S. cerevisiae-immunoglobulin A (93%) was more frequent than that of immunoglobulin G (17%, P = 0.0001); perinuclear anti-neutrophil cytoplasmic autoantibodies disappeared in the only coeliac positive at diagnosis. CONCLUSION: More than half of untreated coeliacs are anti-S. cerevisiae-positive irrespective of the severity of mucosal damage. Differently from immunoglobulin A, anti-S. cerevisiae-immunoglobulin G persisted in more than 80% after gluten free diet. The high prevalence of anti-S. cerevisiae in coeliac disease suggests that they may be the effect of a non-specific immune response in course of chronic small bowel disease.
Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/sangre , Anticuerpos Antifúngicos/sangre , Enfermedad Celíaca/inmunología , Saccharomyces cerevisiae/inmunología , Adolescente , Adulto , Anciano , Enfermedad Celíaca/dietoterapia , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Técnica del Anticuerpo Fluorescente Directa/métodos , Estudios de Seguimiento , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Masculino , Persona de Mediana EdadRESUMEN
Anti-mitochondrial antibodies are the serological markers of primary biliary cirrhosis. We analysed the detailed anti-mitochondrial antibodies patterns to see whether the immunological specificities detected at the time of the diagnosis correlate with the histological, clinical and immunological expression of the disease. One hundred and thirty primary biliary cirrhosis patients were studied at the time of presentation/diagnosis. Anti-mitochondrial antibodies reactivity was dissected and evaluated by Western immunoblotting with bovine heart submitochondrial particles as antigenic source. Six different Western immunoblotting patterns have been identified with the following hierarchy: pattern A (anti-PDC-E2+anti-E3BP, 38.5%), pattern B (anti-PDC-E2+anti-E3BP+anti-OGDC-E2, 20.8%), pattern C (anti-PDC-E2+anti-E3BP+anti-BCOADC-E2+anti-OGDC-E2, 13.1%), pattern D (anti-PDC-E2+anti-E3BP+anti-BCOADC-E2, 6.9%), pattern E (anti-BCOADC-E, 6.1%) and pattern F (anti-mitochondrial antibodies negative primary biliary cirrhosis, 14.6%). The different patterns were neither associated with peculiar clinical, biochemical, histological and immunological features nor with the Mayo Risk Score. The anti-mitochondrial antibodies pattern at presentation is independent of the stage of the liver disease; therefore, the Western immunoblotting characterisation of anti-mitochondrial antibodies does not seem to be helpful in identifying the clinical, biochemical or histological expression of primary biliary cirrhosis at the time of the diagnosis.