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[Chronic viral hepatitis C. Part 1. General considerations]
1Departamento de Gastroenterologia da Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP.
Insights
Hepatitis C virus (HCV) infection is primarily transmitted through blood and drug use. While screening has reduced post-transfusion cases, understanding HCV genotypes and their impact on disease severity is crucial for developing effective vaccines.
Area of Science:
- Hepatology and Virology: Focus on Hepatitis C Virus (HCV) and novel DNA virus (TTV).
- Immunology: Exploring immune responses to HCV envelope E2 protein and vaccine development.
- Epidemiology: Analyzing HCV genotype distribution and transmission routes.
Context:
- Hepatitis C virus (HCV) identified in 1989 as the main cause of non-A, non-B hepatitis.
- High prevalence linked to blood transfusions and intravenous drug abuse.
- Advancements in screening have reduced post-transfusion hepatitis incidence.
Purpose:
- To review the natural history, epidemiology, and clinical significance of Hepatitis C virus infection.
- To explore the association between HCV genotypes and disease severity.
- To discuss potential vaccine development strategies and the role of novel viruses like TTV.
Summary:
- HCV genotype distribution varies geographically, with subtypes 1a, 3a, and 1b being most prevalent.
- Subtype 1b is associated with a more severe disease course, mitochondrial dysfunction, and impaired oxidative phosphorylation.
- Intrahepatic HCV levels are not determined by host or viral factors, and negative serum RT-PCR does not rule out liver infection.
Impact:
- Understanding genotype-specific disease progression aids in targeted treatment and management.
- Research into immune modulation and novel vaccine strategies offers hope for controlling highly mutable HCV.
- Further investigation is needed to clarify the pathogenic role of TTV and its association with disease.
Abstract:
Hepatitis C virus was identified in 1989 as the main causative agent of non-A, non-B and was followed by the recognition of a high prevalence of hepatitis C virus infection after transfusion of infected blood or blood products and in association with intravenous drug abuse. The availability of sensitive and reliable techniques to screen blood for hepatitis C virus has reduced the incidence of post-transfusion hepatitis. True healthy carriers of hepatitis C virus did not exist. Approximately 95% of hepatitis C virus infected individuals can be identified by third generation anti-hepatitis C virus testing. Retrospective studies of iatrogenic hepatitis C virus infection are the main source of the natural history of the disease. The distribution of different hepatitis C virus genotypes varies according to the geographic region. In South America, Europe, The United States and Japan hepatitis C virus genotypes 1, 2 and 3 account for the majority of the infections, being (sub)type 1b the most prevalent. Epidemiological parameters (age, risk factors and duration of infection) may be associated with hepatitis C virus genotypes (intravenous drug abuse with types 1-a and 3-a and 1-b with post-transfusion hepatitic C). Subtype 1-b, lead to a more severe course of viral infection, with ultrastructural alterations of the mitochondria, and greater impairment of the process of oxidative phosphorylation. No increased production of free radicals may influence the evolution of the liver disease by an enhancement of the cytopathic effect of hepatitis C virus. The clinical significance of intrahepatic hepatitis C virus level in patients with chronic hepatitis C virus infection is not determined by host factors (age of patient, mode or duration of infection) or by virus factors (hepatitis C virus genotypes) and, repeatedly negative RT-PCR for hepatitis C virus RNA in serum does not indicate absence of hepatitis C virus from the liver. The association between autoimmunity and hepatitis C virus is questioned. Markers of its does occur with high frequency in these patients. Modulation of immune responses to hepatitis C virus envelope E2 protein following injection of plasmid DNA, has been used for induction of specific response to hepatitis C virus. The spectrum of such responses could likely be broadened by combining plasmids, delivery routes, and other forms of encoded immunogens (peptide vaccines). These may be important to the development of a vaccine against the high mutable hepatitis C virus. The pathogenic role of novel DNA virus (TTV) is under spotlight. As with hepatitis G, however, the association of TTV with disease is far from clear.