RESUMEN
BACKGROUND & AIMS: Untreated patients with autoimmune hepatitis (AIH) who present with aspartate aminotransferase (AST) levels that are more than 5-fold greater than the upper limit of normal (UPLN) have a mortality rate of up to 80%. This study evaluated whether serum AST levels of patients, determined at presentation, are associated with disease course or outcome. METHODS: The records of 235 patients (median age, 46 y; range, 5-80 y) who presented with AIH, based on International AIH Group score (median, 22; range, 16-28), between 1970 and 2005, were examined. AST levels at presentation were available for 213 patients, who were assigned to 3 groups: group 1, AST less than 2x the UPLN, n = 26 (median, 62 IU; range, 23-97 IU); group 2, AST 2 to 10x the UPLN, n = 71 (median, 241 IU; range, 107-500 IU); and group 3, AST greater than 10x the UPLN, n = 116 (median, 1073 IU; range, 563-4603 IU). RESULTS: Patients in groups 1 and 2 had a significantly worse outcome (risk of liver transplantation or death) compared with those in group 3 (60% survival vs 82%; P = .01; odds ratio, 2.1). These patients were more likely to present with ascites (P < .001), hematemesis (P = .009), and cirrhosis or advanced fibrosis based on an index biopsy (P < .001). Patients in groups 1 and 2 also had lower bilirubin levels at presentation (P < .001) and were less likely to be symptomatic (P < .001). CONCLUSIONS: In patients with AIH, AST levels greater than 10x the UPLN at presentation were associated with a lower risk of cirrhosis and a better long-term outcome than those with AST levels that were less than 10x the UPLN.
Asunto(s)
Aspartato Aminotransferasas/sangre , Hepatitis Autoinmune/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bilirrubina/sangre , Niño , Preescolar , Femenino , Humanos , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND/AIMS: Autoimmune hepatitis (AIH) predominantly affects women. Reasons for this are unclear and few series have assessed long-term outcomes of men with AIH. METHODS: To evaluate the clinical course and outcomes of 51 men from a total of 238 consecutive patients with definite AIH at a single centre from 1971 to 2005. The primary outcome measure was death or liver transplantation. RESULTS: Median age at diagnosis was 39 y in men and 49 y in women (p = 0.0589). HLA A1, B8 and DR3 allotypes and the HLA A1-B8-DR3 haplotype were more frequently expressed in men (63% vs. 45%, p = 0.049; 74% vs. 38%, p < 0.001; 62% vs. 44%, p = 0.058; and 50% vs. 23%, p = 0.003; respectively). There were no significant differences in clinical manifestations at presentation. Over 96% of patients demonstrated a complete initial response to treatment. A greater number of men experienced at least one relapse (71% vs. 55%, p = 0.0591). However, women were significantly more likely to die or require liver transplantation (Log rank test p = 0.024). CONCLUSIONS: Men with AIH appear to have a higher relapse rate and younger age of disease onset which may relate to increased prevalence of HLA A1-B8-DR3. Despite this, men have significantly better long-term survival and outcomes than women.
Asunto(s)
Hepatitis Autoinmune/epidemiología , Hepatitis Autoinmune/terapia , Adulto , Edad de Inicio , Análisis de Varianza , Antiinflamatorios/uso terapéutico , Autoanticuerpos/análisis , Autoanticuerpos/inmunología , Azatioprina/uso terapéutico , Europa (Continente)/epidemiología , Femenino , Hepatitis Autoinmune/patología , Humanos , Inmunosupresores/uso terapéutico , Leucocitos/inmunología , Hígado/patología , Pruebas de Función Hepática , Cuidados a Largo Plazo , Masculino , Prednisolona/uso terapéutico , Recurrencia , Caracteres Sexuales , Razón de Masculinidad , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Twin and family studies suggest there is a significant genetic component to primary biliary cirrhosis (PBC). However, the inability to replicate reported associations has been a recurring problem, with the only consistently reported genetic association that between PBC and HLA-DRB1*0801. However, recently even this has been questioned, and a number of novel associations have also been reported. We reinvestigated HLA class II DRB1, DQA1, and DQB1 alleles and haplotypes in a total of 492 well-characterized PBC patients, 412 from the United Kingdom and an additional 80 patients from northern Italy. There was a clear and significant association with HLA-DRB1*0801 in both groups of patients compared to population-specific healthy controls (12% versus 4% in the UK patients, P=.00087, OR=3.05; and 18% versus 6% in the Italian patients, P=.021, OR=3.15). There were also significant protective associations with DRB1*11 in the Italian patients (28% versus 47%, P=.0071, OR=0.42), but not in the UK patients (8% versus 8%) and a protective association with DRB1*13 in both series (14% versus 20%, P=.042, OR=0.65 in the UK patients; and 10% versus 31%, P=.00092, OR=0.25 in the Italian patients). In conclusion, a complex relationship exists between HLA and PBC, and some genetic associations may be population specific.
Asunto(s)
Alelos , Aminoácidos/metabolismo , ADN/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Cirrosis Hepática Biliar/genética , Progresión de la Enfermedad , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Cadenas alfa de HLA-DQ , Cadenas beta de HLA-DQ , Cadenas HLA-DRB1 , Haplotipos , Humanos , Italia/epidemiología , Cirrosis Hepática Biliar/epidemiología , Cirrosis Hepática Biliar/metabolismo , Masculino , Reacción en Cadena de la Polimerasa , Prevalencia , Pronóstico , Reino Unido/epidemiologíaRESUMEN
Polymorphism amongst the human leucocyte antigen (HLA) class II genes could influence antigen presentation and the ability to control human immunodeficiency virus (HIV)-1 by modulating the virus specific CD4 immune response. To examine the effect of such polymorphisms on disease progression, we studied a cohort of 46 HIV-1 infected long-term non-progressors (LTNPs), 87 intermediate progressors (IPs) and 26 rapid progressors. Kaplan-Meier survival analysis of all patients in the cohort on time to a CD4 count less than 350 cells/ micro l, showed a trend for a slower rate of CD4 decline in patients with, compared to those without, the DRB1*15-DQB1*06 haplotype (hazard ratio (HR) 0.69, 95% CI 0.46-1.01, P = 0.06). A similar effect was not observed with the DRB1*13-DQB1*06 haplotype (HR 1.18, 95% CI 0.75-1.88, P = 0.46), but was observed when DQB1*06 alleles were considered irrespective of their DR association (HR 0.74, 95% CI 0.52-1.05, P = 0.06). Major HLA-DQ6 alleles encode aspartate (Asp) at position 57 on the DQbeta chain, a phenotype associated with protection from other immune disorders. We therefore examined the frequency of all DQbeta57 Asp+ alleles, but could not detect a significant effect on the rate of CD4 decline. To examine whether the genotype associated with slower CD4 decline was over-represented in patients with a slow rate of disease progression, we conducted a categorical analysis of a subset of patients with an extended follow-up of 14+years. We found a higher proportion of LTNPs at 14+ years possessed the DRB1*15-DQB1*06 haplotype compared to IPs at 14+ years (38.46 versus 18.18%), though this difference did not reach statistical significance. When DQB1*06 alleles irrespective of their DR association were considered, the protective effect was greater (76.9% LTNPs versus 18.18% IPs, P = 0.04). Our results highlight the potential protective effect of HLA DQB1*06 alleles on the course of HIV disease.