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      Extrahepatic manifestations associated with Chronic Hepatitis C Virus Infection Translated title: Manifestaciones extrahepáticas asociadas a la infección crónica por el virus de la hepatitis C

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          Summary

          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.

          Resumen

          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.

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          Most cited references42

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          Relationship between steatosis, inflammation, and fibrosis in chronic hepatitis C: a meta-analysis of individual patient data.

          Steatosis is a frequent histologic finding in chronic hepatitis C (CHC), but it is unclear whether steatosis is an independent predictor for liver fibrosis. We evaluated the association between steatosis and fibrosis and their common correlates in persons with CHC and in subgroup analyses according to hepatitis C virus (HCV) genotype and body mass index. We conducted a meta-analysis on individual data from 3068 patients with histologically confirmed CHC recruited from 10 clinical centers in Italy, Switzerland, France, Australia, and the United States. Steatosis was present in 1561 patients (50.9%) and fibrosis in 2688 (87.6%). HCV genotype was 1 in 1694 cases (55.2%), 2 in 563 (18.4%), 3 in 669 (21.8%), and 4 in 142 (4.6%). By stepwise logistic regression, steatosis was associated independently with genotype 3, the presence of fibrosis, diabetes, hepatic inflammation, ongoing alcohol abuse, higher body mass index, and older age. Fibrosis was associated independently with inflammatory activity, steatosis, male sex, and older age, whereas HCV genotype 2 was associated with reduced fibrosis. In the subgroup analyses, the association between steatosis and fibrosis invariably was dependent on a simultaneous association between steatosis and hepatic inflammation. In this large and geographically different group of CHC patients, steatosis is confirmed as significantly and independently associated with fibrosis in CHC. Hepatic inflammation may mediate fibrogenesis in patients with liver steatosis. Control of metabolic factors (such as overweight, via lifestyle adjustments) appears important in the management of CHC.
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            Mixed cryoglobulinemia: demographic, clinical, and serologic features and survival in 231 patients.

            Mixed cryoglobulinemia (MC) is a systemic vasculitis secondary to circulating immune complex deposition in the small vessels. In the overwhelming majority of patients, hepatitis C virus (HCV) infection represents the triggering factor of the disease. MC is characterized by multiple organ involvement, mainly skin, liver, renal, peripheral nerves, and less frequently by widespread vasculitis and cancer. To investigate the demographic, clinical, serologic features, and survival in a large series of MC patients. The study included 231 MC patients recruited between 1972 and 2001 at the Rheumatology Unit of the University of Pisa. All patients underwent wide clinicoserologic and virologic assessment. Cumulative survival rates were computed by the Kaplan-Meier method; moreover, the prognostic relevance of the main variables was investigated by Cox model analysis. In 92% of cases, the presence of HCV infection was demonstrated (anti-HCV antibody, 92%; HCV RNA, 90%), whereas hepatitis B virus (HBV) represented the possible causative agent in only 1.8% of patients (HBV DNA). Clinically, the MC syndrome followed a relatively benign clinical course in over 50% of cases, whereas a moderate-severe clinical course was observed in one third of patients whose prognosis was severely affected by renal and/or liver failure. In a limited, but significant, percentage (15%) of individuals, the disease was complicated by a malignancy, ie, B-cell lymphoma, and less frequently by hepatocellular carcinoma, or thyroid cancer. The survival study by the Kaplan-Meier method revealed a significantly lower cumulative 10th-year survival, calculated from time of diagnosis, in MC patients compared with expected death in the age- and sex-matched general population. Moreover, significantly lower survival rates were observed in males and in subjects with renal involvement. The multivariate analysis by the Cox proportional hazard regression model further supported the above findings: an increased mortality risk of 98% was observed for male gender (male/female hazard ratio, 1.978) and of 197% in patients with, compared with those without, renal involvement (hazard ratio, 2.967). At the end of the follow-up, 97 patients were deceased, and in 79 of 97 patients, the causes of death were ascertained: nephropathy (33%), malignancies (23%), liver involvement (13%), and diffuse vasculitis (13%) were the most frequent causes of death. Careful patient monitoring is recommended for a timely diagnosis of life-threatening MC complications, mainly nephropathy, widespread vasculitis, and B-cell lymphoma or other malignancies.
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              The cryoglobulinaemias.

              Cryoglobulins are immunoglobulins that precipitate in vitro at temperatures less than 37°C and produce organ damage through two main pathways: vascular sludging (hyperviscosity syndrome, mainly in type I cryoglobulinaemia) and immune-mediated mechanisms (principally vasculitis, in mixed cryoglobulinaemia). Cryoglobulinaemia is associated with many illnesses, which can be broadly grouped into infections, autoimmune disorders, and malignancies; the most common cause is infection with hepatitis C virus. Mixed cryoglobulinaemic syndrome is diagnosed when a patient has typical organ involvement (mainly skin, kidney, or peripheral nerve) and circulating cryoglobulins. Cutaneous purpura is the most common manifestation of cryoglobulinaemic vasculitis. The most frequently affected internal organs are the peripheral nerves, kidneys, and joints. The course varies widely and prognosis is influenced by both cryoglobulinaemic damage to vital organs and by comorbidities associated with underlying diseases. More than 90% of cases of cryoglobulinaemia have a known underlying cause; therefore treatment is focused on the cause of the disorder rather than merely symptomatic relief. Studies suggest that both combined or sequential antiviral therapies and targeted biological treatments might be more effective than monotherapy. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Rev Esp Sanid Penit
                Rev Esp Sanid Penit
                sanipe
                Revista Española de Sanidad Penitenciaria
                Sociedad Española de Sanidad Penitenciaria
                1575-0620
                2013-6463
                2017
                2017
                : 19
                : 3
                : 87-97
                Affiliations
                [1 ] Laboratory of Autoimmune Diseases Josep Font, IDIBAPS-CELLEX, Department of Autoimmune Diseases, ICMiD, Hospital Clínic, Barcelona, Spain.
                [2 ] Department of Biomedical Research 02, Clinical Epidemiology Research Unit, Centro Médico Nacional de Occidente (CMNO), Instituto Mexicano del Seguro Social (IMSS), Hospital de Especialidades, Guadalajara, Mexico.
                [3 ] Programa de Doctorado en Ciencias Médicas, Centro Universitario de Investigaciones Biomédicas (CUIB), Universidad de Colima, Colima, Mexico.
                [4 ] Department of Hepatology, Hospital del Mar, IMIM (Instituto Hospital del Mar de Investigaciones Médicas), Univesity Autónoma de Barcelona, Barcelona.
                [5 ] Department of Hepatology, Hospital Clinic, IDIBAPS y CIBEREHD, University of Barcelona, Barcelona
                [7]Universitat de Barcelona, University of Barcelona, IDIBAPS, Barcelona, Spain
                [6 ] Department of Medicine, University of Barcelona, Barcelona, Spain
                Author notes
                [Correspondence: ] Dr. Manuel Ramos-Casals. Servei de Malalties Autoimmunes IDIBAPS/CELLEX, University of Barcelona Hospital Clínic- Email: mramos@ 123456clinic.cat
                [*]

                Alejandra Flores-Chavez holds a scholarship grant from the Mexican “Consejo Nacional de Ciencia y Tecnología (CONACyT)”.

                Article
                00004
                10.4321/S1575-06202017000300004
                6241927
                29364334
                027ea545-6ba3-4546-9975-d9e6f84e1249

                This is an open-access article distributed under the terms of the Creative Commons Attribution License

                History
                : 04 October 2017
                : 10 October 2017
                Page count
                Figures: 1, Tables: 5, Equations: 0, References: 39, Pages: 11
                Categories
                Revision

                prisons,hepacivirus,hepatitis c,antiviral agents,autoinmune diseases,lymphoma,spain,diabetes mellitus,prisiones,antivirales,enfermedades autoinmunes,linfoma,españa

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