HBx protein, which is required for virus replication and which may act as a transcriptional transactivator for viral genes and a wide variety of host genes. It has been implicated in the pathogenesis of HBV-associated liver cancer.
The course of the disease can be followed clinically by monitoring certain serum markers (
Fig. 16.10
HBsAg appears before the onset of symptoms, peaks during symptomatic disease, and then usually declines to undetectable levels in 12 weeks (though it may occasionally persist as long as 24 weeks).
http://ebooksmedicine.net 4–12 weeks Months to Years
Fig. 16.10 TemporalchangesinserologicmarkersforhepatitisBviralinfection.(A)Acuteinfectionwithresolution.(B)progressiontochronicinfection.NoteinsomecasesofchronicHBVinfection,serumtransaminasesmaybecomenormal.
Anti-HBs antibody appears after the acute disease is over and usually is not detected until a few weeks to several months after HBsAg disappears. Anti-HBs may persist for life and confers protection, which is the rationale for current vaccines containing HBsAg.
HBeAg and HBV DNA appear in serum soon after HBsAg and signify ongoing viral replication. Persistence of HBeAg is an indicator of progression to chronic hepatitis. The appearance of anti-HBe antibodies implies that an acute infection has peaked and is on the wane.
IgM anti-HBc becomes detectable in serum shortly before the onset of symptoms, concurrent with the onset of elevated serum aminotransferase levels (indicative of hepatocyte destruction). Over a period of months, the IgM anti-HBc antibody is replaced by IgG anti-HBc. As in the case of anti-HAV, there is no direct assay for IgG anti-HBc; its presence is inferred from decline of IgM anti-HBc in the face of rising total anti-HBc.
Occasionally, mutated strains of HBV emerge that do not produce HBeAg but are replication competent and express HBcAg. In such patients, the HBeAg may be low or undetectable despite the presence of serum HBV DNA. A second ominous development is the appearance of HBV mutants in vaccinated individuals that replicate in the presence of normally protective anti-HBs antibodies.
The host immune response is the main determinant of the outcome of the infection. Innate immune mechanisms protect the host during initial phases of the infection, and a strong response by virus-specific CD4+ and CD8+ interferon γ–producing cells is associated with the resolution of acute infection. HBV generally is not directly hepatotoxic, and most hepatocyte injury is caused by CD8+ cytotoxic T cells attacking infected cells.
Patient age at the time of infection is the best predictor of chronicity. In general, the younger the age at the time of HBV infection, the higher the chance of chronic infection. Treatment of chronic hepatitis B with viral polymerase inhibitors and interferon can slow disease progression, reduce liver damage, and prevent liver cirrhosis or liver cancer but does not eliminate the infection. As a result, treatment sometimes fails due to emergence of viruses bearing mutations that lead to drug resistance.
HCV is a major cause of liver disease, with approximately 170 million individuals affected worldwide. Approximately 4.1 million Americans (1.6% of the population) have chronic HCV infection. Notably, there has been a decrease in the annual incidence of infection from a mid-1980s peak of over 230,000 new infections per year to 30,000 new infections per year currently, due primarily to a reduction in transfusion-associated cases as a result of effective screening procedures. Until recently, the number of patients with chronic infection appeared likely to continue to increase, but new therapies (discussed later) are changing the outlook for the better.