Extrahepatic manifestations associated with Chronic Hepatitis C Virus Infection.

Chronic hepatitis C virus (HCV) infection has been associated with both organ-specific and systemic autoimmune diseases, with cryoglobulinemia being the most frequent associated disease. Experimental, virologic, and clinical evidence have demon-strated a close association between HCV infection and some systemic autoimmune diseases, especially Sjögren's syndrome, but also rheumatoid arthritis and lupus. A higher prevalence of hematological processes has also been described in patients with HCV infection, including cytopenias and lymphoproliferative disorders (B-cell lymphoma). In addition, patients with chronic HCV infection have a higher frequency of other extrahepatic manifestations including endocrine, metabolic and cardiovascular disorders that may worse the prognosis of patients, along with neuropsychiatric manifestations and general symptoms that have a significant influence on the quality of life of the patient. Direct-acting antiviral therapies (DAAs) that have recently begun to be used are providing the opportunity to effectively cure chronic HCV infection and reduce the burden of both hepatic and extrahepatic complications.

The -174G/C Interleukin-6 Gene Promoter Polymorphism as a Genetic Marker of Differences in Therapeutic Response to Methotrexate and Leflunomide in Rheumatoid Arthritis.

Objective. To evaluate the association of -174G/C IL-6 polymorphism with failure in therapeutic response to methotrexate (MTX) or leflunomide (LEF). This prospective, observational cohort included 96 Mexican-Mestizo patients with moderate or severe rheumatoid arthritis (RA), initiating MTX or LEF, genotyped for IL-6 -174G/C polymorphism by PCR-RFLP. Therapeutic response was strictly defined: only if patients achieved remission or low disease activity (DAS-28 < 3.2). Results. Patients with MTX or LEF had significant decrement in DAS-28 (p < 0.001); nevertheless, only 14% and 12.5% achieved DAS-28 < 3.2 at 3 and 6 months. After 6 months with any of these drugs the -174G/G genotype carriers (56%) had higher risk of therapeutic failure compared with GC (RR: 1.19, 95% CI: 1.07-1.56). By analyzing each drug separately, after 6 months with LEF, GG genotype confers higher risk of therapeutic failure than GC (RR = 1.56; 95% CI = 1.05-2.3; p = 0.003), or CC (RR = 1.83; 95% CI = 1.07-3.14; p = 0.001). This risk was also observed in the dominant model (RR = 1.33; 95% CI = 1.03-1.72; p = 0.02). Instead, in patients receiving MTX no genotype was predictor of therapeutic failure. We concluded that IL-6 -174G/G genotype confers higher risk of failure in therapeutic response to LEF in Mexicans and if confirmed in other populations this can be used as promissory genetic marker to differentiate risk of therapeutic failure to LEF.

Manifestaciones extrahepáticas asociadas a la infección crónica por el virus de la hepatitis C / Extrahepatic manifestations associated with chronic hepatitis C virus infection

La infección crónica por el virus de la hepatitis C (VHC) se ha asociado tanto a enfermedades autoinmunes específicas de órganos como a enfermedades autoinmunes sistémicas, siendo la más frecuente la crioglobulinemia. Las evidencias experimentales, virológicas y clínicas han demostrado una estrecha asociación entre la infección por el VHC con algunas enfermedades autoinmunes sistémicas, especialmente el síndrome de Sjögren, junto con la artritis reumatoide y el lupus. Se ha descrito una mayor prevalencia de procesos hematológicos en pacientes con infección por VHC, incluyendo citopenias y trastornos linfoproliferativos como el linfoma B. Además, los pacientes con infección crónica por el VHC presentan una mayor frecuencia de otras manifestaciones extrahepáticas que incluyen alteraciones endocrinas, metabólicas y cardiovasculares que pueden afectar seriamente el pronóstico de los pacientes, junto con manifestaciones neuropsiquiátricas y de afectación del estado general que influyen notablemente en la calidad de vida del paciente. Las terapias antivirales de acción directa (DAA) que han empezado a utilizarse recientemente están proporcionando la oportunidad de curar eficazmente la infección crónica por VHC y reducir la carga causada por las complicaciones hepáticas y extrahepáticas (AU)

Chronic hepatitis C virus (HCV) infection has been associated with both organ-specific and systemic autoimmune diseases, with cryoglobulinemia being the most frequent associated disease. Experimental, virological, and clinical evidence have demonstrated a close association between HCV infection and some systemic autoimmune diseases, especially Sjögren’s syndrome, but also rheumatoid arthritis and lupus. A higher prevalence of hematological processes has also been described in patients with HCV infection, including cytopenias and lymphoproliferative disorders (B-cell lymphoma). In addition, patients with chronic HCV infection have a higher frequency of other extrahepatic manifestations including endocrine, metabolic and cardiovascular disorders that may worse the prognosis of patients, along with neuropsychiatric manifestations and general symptoms that have a significant influence on the quality of life of the patient. Direct-acting antiviral therapies (DAAs) that have recently begun to be used are providing the opportunity to effectively cure chronic HCV infection and reduce the burden of both hepatic and extrahepatic complications (AU)