Role of viral factors in the natural course and therapy of chronic hepatitis B

Abstract

Hepatitis B virus (HBV) infection is a global health problem that causes a wide spectrum of liver disease, including acute or fulminant hepatitis, inactive carrier state, chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). The pathogenesis of hepatocyte damage associated with HBV is mainly through immune-mediated mechanisms. On the basis of the virus and host interactions, the natural history of HBV carriers who are infected in early life can be divided into four dynamic phases. The frequency, extent, and severity of hepatitis flares or acute exacerbation in the second immune clearance and/or fourth reactivation phase predict liver disease progression in HBV carriers. In the past decade, hepatitis B viral factors including serum HBV DNA level, genotype, and naturally occurring mutants predictive of clinical outcomes have been identified. The higher the serum HBV DNA level after the immune clearance phase, the higher the incidence of adverse outcomes over time. In addition, high viral load, genotype C, basal core promoter mutation, and pre-S deletion correlate with increased risk of cirrhosis and HCC development. As to the treatment of chronic hepatitis B, patients with high HBV DNA level and genotype C or D infection are shown to have a worse response to interferon therapy. In conclusion, serum HBV DNA level, genotype, and naturally occurring mutants are identified to influence liver disease progression and therapy of chronic hepatitis B. More investigations are needed to clarify the molecular mechanisms of the viral factors involved in the pathogenesis of each stage of liver disease and the response to antiviral treatments.

Hepatitis B virus and hepatitis C virus infection in healthcare workers

“…HBV genotypes show a peculiar geographical distribution [12] . Genotype A predominates in Northern Europe and North America, genotypes B and C in central Asia, genotype D in Mediterranean countries, genotype E in sub-Saharan Africa and in Madagascar, genotype F in South and Central America, genotypes G and H in Mexico and some countries in Central America [13,14] and genotypes I and J in Eastern Asia [15] . The age at the time of infection modulates the progression to chronicity of HBV infection, which occurs in around 90% of babies born to hepatitis B e antigen (HBeAg)-positive mothers, a rate that progressively decreases with the increase in age up to 2%-5% in the adult population [16] .…”

“…These categories reflect the predominant patterns of transmission and outcomes of HBV infection. In geographical areas with a high HBV endemicity, such as some countries in Eastern Asia or in sub-Saharan Africa, the majority of HBsAgpositive individuals acquired HBV infection at birth or in early childhood, when the risk of progression to chronicity is very high [7,15] . In geographical areas with an intermediate HBV endemicity, such as countries in Northern Africa, the Middle East and Southern Asia, and Eastern Europe, the majority of HBsAg-positive subjects acquired HBV infection in childhood or early adulthood, and family transmission plays an important role in the spread of HBV infection.…”

A mathematical model of the intracellular replication and within host evolution of hepatitis type B virus: Understanding the long time course of chronic hepatitis

“…Chronic hepatitis is a major risk factor of liver cirrhosis and hepatocellular carcinoma. The chronic hepatitis is frequently developed when the patient is infected HBV in the perinatal period or early childhood (Kao, 2007). Over 350 million people are chronically infected with HBV.…”

“…The manifestation of hepatitis often changes during the long time course of chronic hepatitis, for example, from chronic to flare (Hunt et al, 2000;Kao, 2007;Kusumoto et al, 2008;Ikegami et al, 2008;Cui et al, 2010). Such alteration of the clinical course of hepatitis may cause within host evolution of HBV.…”

Genetic Diversity of HBV Genotypes/ Subgenotypes and Their Correlation with Disease Progression

“…226 Lamivudine resistance mutations are more frequent in HBV genotype A than D. 178 As to the treatment of chronic hepatitis B, patients with high HBV DNA level and genotype C or D infection are shown to have a worse response to interferon therapy. 95 In a study from China, the response to IFN alpha in patients with genotype B is markedly better than in those with genotypes C and D, and the complete response to IFN alpha is only observed in genotype B. 122 In a study from Japan, genotype C is considered more refractory to antiviral therapies than genotypes A and B.…”