The outcome of HBV infection varies widely, from (1) acute hepatitis with recovery and clearance of the virus; (2) nonprogressive chronic hepatitis; (3) progressive chronic disease ending in cirrhosis; (4) fulminant hepatitis with massive liver necrosis; and (5) an asymptomatic http://ebooksmedicine.net “healthy” carrier state. HBV-induced chronic liver disease is also an important precursor for the development of HCC. The approximate frequencies of various clinical outcomes of HBV infection are depicted in
Fig. 16.9
Liver disease due to HBV infection is an enormous global health problem. One-third of the world’s population (2 billion individuals) has been infected with HBV, and 400 million individuals have chronic infections. Seventy-five percent of chronic carriers live in Asia and the Western Pacific rim. The global prevalence of chronic hepatitis B infection varies from greater than 8% in parts of Africa to less than 2% in Western Europe, North America, and Australia.
The mode of transmission of HBV also varies with the geographic locale. In high-prevalence regions of the world, perinatal transmission during childbirth accounts for 90% of cases. In areas with intermediate prevalence, horizontal transmission, especially in early childhood, dominates. Spread among children usually occurs through minor breaks in the skin or mucous membranes following physical contact with infected individuals. In low-prevalence areas, unprotected sex and intravenous drug abuse (sharing of needles and syringes) are the chief modes of spread. Transfusion-related spread has been reduced greatly by screening of donated blood for HBsAg and by cessation of the practice of paying blood donors. Vaccination induces a protective antibody response in 95% of infants, children, and adolescents. Universal vaccination has had notable success in Taiwan and Gambia, but has yet to be adopted worldwide.
HBV has a prolonged incubation period (2–26 weeks). Unlike HAV, HBV remains in the blood during active episodes of acute and chronic hepatitis. Approximately 70% of adults with newly acquired HBV have mild or no symptoms and do not develop jaundice. The remaining 30% have nonspecific constitutional symptoms such as anorexia, fever, jaundice, and right upper-quadrant pain. In most cases, the infection is self-limited and resolves without treatment, but chronic disease develops in 10% of infected individuals. Fulminant hepatitis is rare, occurring in approximately 0.1% to 0.5% of acutely infected individuals.
HBV is a member of Hepadnaviridae, a family of DNA viruses that cause hepatitis in multiple animal species. The HBVgenomeisapartiallydouble-stranded,3200-nucleotide, circular DNA with four open reading frames, which encode the following proteins:
Nucleocapsid “core” protein (HBcAg, hepatitis B core antigen) and a longer polypeptide with a precore and core region, designated HBeAg (hepatitis B e antigen). The precore region directs the secretion of the HBeAg polypeptide into blood, whereas HBcAg remains in hepatocytes, where it participates in the assembly of virions.
Envelope glycoproteins (HBsAg, hepatitis B surface antigen). Infected hepatocytes synthesize and secrete massive quantities of noninfective envelope glycoproteins (mainly small HBsAg).
polymerase (Pol) with both DNA polymerase activity and reverse transcriptase activity, which enables genomic replication to occur through a unique DNA → RNA → DNA cycle via an intermediate RNA template. This unusual polymerase is the target of drugs used to treat hepatitis B infection (described later).