Pathogenesis of hepatitis C: HCV consensus 2007

Abstract

The chronic hepatitis C virus (HCV) infects approximately 130 million people worldwide [1]. It is estimated that approximately 15% of HCV-infected individuals eliminate the virus spontaneously, that 25% develop a mild form of the disease, and that 60% develop the chronic progressive form [2]. The elimination or persistence of HCV infection depends on the balance between the effectiveness, specificity and rapidity of the innate and adaptive immune responses, as well as on the HCV replication rate [3]. Persistence of HCV can also be caused by infection at privileged (extrahepatic) sites, viral inhibition of antigen presentation, selective immune suppression, negative regulation of HCV gene expression, viral mutations, immune exhaustion of T cells and the incomplete differentiation of memory T cells [4,5].Fibrosis is the principal complication of chronic hepatitis C, and it is estimated that 20% of patients develop cirrhosis over a period of 10, 20 or 30 years [2,6]. The progression of fibrosis increases morbidity and mortality in chronic hepatitis C [7], since it can lead to death due to complications caused by cirrhosis or hepatocarcinoma [2].Various studies have associated the progression of fibrosis in hepatitis C with diverse factors such as: the kinetics and pathogenicity of HCV; host-HCV interaction; intrinsic host factors such as demographic profile, body mass index and diabetes mellitus; host exposure to external factors; and the form of HCV acquisition. Life Cycle and Pathogenicity of HCVBelonging to the Flaviviridae family, HCV is a small enveloped virus [8]. Its genome consists of one RNA molecule that is composed of two terminal regions, 5'-and 3'-untranslated regions, and between these there is a single open reading frame that encodes a polyprotein with approximately 3000 amino acids. This polyprotein cleaves at the N-terminal side of three structural proteins, the nucleocapsid (core), envelope 1 (E1) and envelope 2 (E2), all of which are involved in the architectural organization of HCV. At the carboxylterminal side, the polyprotein cleaves to six nonstructural proteins, NS2, NS3, NS4 (NS4A and NS4B), NS5 (NS5A and NS5B) and NS6, which are responsible for the life cycle of the virus [9].After entering a susceptible host, HCV invades, infects and replicates within the blood stream, repeating the process in various tissues, as well as in peripheral B and T lymphocytes, as it proceeds to the liver by tropism, passing through various tissues such as those of the pancreas, thyroid, adrenal glands, spleen and bone marrow [10][11][12]. Since HCV can also directly infect the lymphatic tissue, its stimulation can lead to the development of B-cell lymphomas [13]. It is known that the liver is the principal site of HCV replication, and various studies have shown that this virus infects approximately 10% of hepatic cells [5]. Infection with HCV at extrahepatic sites can promote the appearance of HCV variants [14,15], thereby decreasing the chance that the immune system will recognize the virus.To enter the host ...

Genotype Base Prevalence of Hepatitis C

“…It is reported that 20 % of infected individuals produced cirrhosis over a span of 10-30 years. The progression of fibrosis can lead to increases morbidity and mortality in chronic HVC patients due to complications caused by cirrhosis or hepatic-cellular-carcinoma of HCV which can even lead to death 5 . HCV showed worldwide great genetic heterogeneity to increase in multiple strains.…”

Evaluation of Thyroid Hormones in Chronic Hepatitis C Patients on Oral Antiviral Therapy

“…HCV related death enormously increased between 1990 to 2013 2 . The progression of fibrosis can lead to increase the probability of morbidity and mortality in CHC patients because of complications caused by cirrhosis or hepatic-cellular-carcinoma of HCV which can even lead to death 3 .…”

Esteato-hepatite não alcoólica e esteatose em hepatite crônica pelo vírus C: prevalência e relações entre dados demográficos e clínico-laboratoriais com parâmetros histopatológicos

“…Com relação à história natural da infecção pelo VHC, estima-se que 15% dos pacientes infectados obtêm resposta imunossuficiente para eliminar o vírus, enquanto a infecção crônica desenvolve-se em torno de 55 a 85% dos indivíduos (EASL, 1999;Hoofnagle, 2002). A evolução para doença hepática crônica ou eliminação do vírus depende da resposta inata, com ativação de citocinas e potencial inibição da replicação viral, da resposta adaptativa ao vírus, com neutralização das partículas virais e destruição de células infectadas (Thimme et al, 2006), assim como da resposta imunomediada, com participação de linfócitos T citotóxicos, LTCD8+ ou LTCD4+ e secreção de citocinas mediadoras da inflamação (Viso, 2007).…”