Host Factors Associated with the Persistence and Progression of Hepatitis C

nullIn HCV infection, the genetic constitution and immune ‘status’ of the host are important factors in the persistence and progression of the virus (Chitturi and George, 2000 and Gremion and Cerny, 2005), since they influence antigen recognition and presentation, as well as the type of Th response (Thursz et al., 1997).
Some MHC class II alleles, such as DR5, have been associated with a lower incidence of cirrhosis in individuals chronically infected with HCV (Thursz et al., 1997). Rehermann et al., 1996 identified CTLs restricted by histocompatibility leukocyte antigen A2 in 97% of chronic hepatitis C patients, compared with 2% of anti-HCV-negative controls. It is speculated that the MHC class II molecule presentation of antigens is deficient in HCV-infected cells, since some viral proteins inhibit the presentation of the antigen through IFN-induced negative immunoregulation (Taylor et al., 2000).
Some pro-inflammatory cytokines appear to be associated with the viral infection response as well as with the expression of specific haplotypes (Thursz et al., 1997), such as IL-10 haplotypes, which can be predictors of spontaneous elimination of HCV (Mangia et al., 2004). However, there is disagreement in the literature, since other authors did not find evidence for polymorphism in the studied genes being considered as a relevant factor in the elimination of HCV or in the response to treatment (Bozkaya et al., 2000; Constantini et al., 2002 and Minton et al., 2005).
The influence of demographic data such as age, gender (Poynard et al., 1997 and Bellentani et al., 1999) and ‘race’ (Reddy et al., 1999 and Lepe et al., 2006) in the progression of hepatitis C can be due to genetic variations existent among those. Some studies report that HCV positivity increases with age (Bellentani et al., 1999 and Lepe et al., 2006), thereby leading to a greater chance of progression of the disease (Poynard et al., 1997 and Bellentani et al., 1999). The male gender is more prevalent in most studies on hepatitis C (Poynard et al., 1997 and Lepe et al., 2006) and, in addition, it was associated with the progression of the disease to cirrhosis (Poynard et al., 1997 and Bellentani et al., 1999). Some studies suggest that Afro-Americans, due to a greater propensity to chronicity, resistance to treatment (higher percentage of genotype 1) and development of hepatocarcinoma, present a worse evolution of hepatitis C than do Caucasian-Americans (Reddy et al., 1999 and El-Serag, 2001). Analyzing 99 chronic HCV-infected individuals and 31 individuals who had spontaneously eliminated HCV, Sugimoto et al., 2003 found evidence that the CD4+ T-cell response was less vigorous in Afro Americans than in Caucasian-Americans, with a predominance of the Th2 response and maintenance of the infection. The evolution of hepatitis C in different ethnicities could be due to genetic factors, such as the presence of HLAclass II alleles, which could define the spontaneous elimination of HCV (Azocar et al., 2003).
There are various extrinsic host factors that are related to the progression of chronic hepatitis C: alcohol abuse; smoking (Poynard et al., 1997; Bellentani et al., 1999; Pessione et al., 2001; Campollo, 2002; Vento and Cainelli, 2002; Monto et al., 2004 and El-Zayadi et al., 2006) the endovenous acquisition of HCV; and coinfection with other viruses such as HIV, HBV and human T-cell lymphotropic virus (Poynard et al., 1997; Kishihara et al., 2001 and Einav and Koziel, 2002).
The prevalence of HCV infection is higher among individuals who consume alcohol (Campollo, 2002 and Sanchez, 2002). Studies suggest that alcohol increases the ability of HCV to enter and persist within the organism (Campollo, 2002). Other studies argue that alcohol intake affects some components of the immune response (Campollo, 2002) and can alter the inflammatory response of cytokines, thereby increasing viremia, which can be an important cofactor in the development of hepatocarcinoma (Schiff, 1999). In addition, alcohol intake in HCV-infected individuals increases hepatic steatosis and induces apoptosis (Campollo, 2002; Vento and Cainelli, 2002 and Bhattacharya and Shuhart, 2003).
Smoking, in addition to increasing inflammatory activity and hepatic fibroses (El-Zayadi et al., 2006), can induce direct injury to the liver, as well as causing indirect damage (toxic effect), and can have immunological effects (production of IL-1, IL-6 and TNF-a, which cause liver damage).