Routes of Infection and Natural History of Infection with HBV

HBV is transmitted by perinatal, parenteral, and venereal exposure. Close person-to-person contact can also be responsible for transmission of infection, especially within households and between young children. HBV is endemic in certain geographic regions, including Asia, the South Pacific region, the Middle East, and Sub-Saharan Africa, as well as in the indigenous population of Alaska and the Arctic. In Western countries, HBV is most common among immigrants from endemic areas, injection drug users, hemodialysis patients, men who have sex with men, and promiscuous heterosexuals. The risk of chronic infection relates largely to the age at exposure. Most adults and adolescents infected will experience an acute infection, which is generally symptomatic but may be subclinical.

Acute infection is characterized by presence of HBsAg in the blood. Recovery is heralded by the loss of HBsAg and generation of antibody to HBsAg (HBsAb). A small proportion of these individuals—probably less than 5%—will go on to establish chronic infections, defined as HBsAg persisting beyond 6 months. In newborns and infants infected by their mothers, infection is rarely diagnosed clinically, but over 90% will develop chronicity. Rates of chronicity in those infected as children are intermediate between these rates. Additionally, immunosuppressed individuals are at high risk for developing chronic HBV infection.

Chronic HBV infection has several different phases, characterized by different levels of viral replication and liver inflammation. Following acute infection, those patients in whom persistent infection is established will enter a relatively quiescent phase of immunotolerance. In this phase, liver enzymes are typically normal or modestly increased and the liver biopsy demonstrates minimal necroinflam-matory activity. HBV DNA levels tend to be high.

After a variable period of time—often decades in peri-natally infected individuals—the immune system becomes activated against the virus, triggering necrosis of infected hepatocytes. Serum aminotransferases are elevated and the liver biopsy reflects ongoing chronic hepatitis, which may be quite severe. HBV DNA levels begin to decrease. During this inflammatory phase, liver damage is most likely to occur.

If the immune system is successful in halting viral replication, the patient may enter an inactive phase where liver enzymes normalize and HBV DNA either becomes undetectable or is detectable only by sensitive polymerase chain reaction techniques. In this phase, HBeAg is lost, and antibody to HBeAg (HBeAb) develops. Although still at risk for development of HCC and progressive liver dysfunction, patients in the inactive phase of infection have a much improved prognosis (Niederau et al, 1996). Most commonly, patients who achieve the inactive phase of HBV infection remain in that phase, but sometimes, viral replication reactivates. As well, there are some patients who "flipflop" between active viral replication and inactivity. These patients appear to be at high risk for rapidly progressive liver fibrosis. Among patients who stably convert from HBeAg to HBeAb, some may eventually seroconvert from HBsAg to HBsAb, at an annual rate of approximately 5%.

In a variant form of chronic HBV infection, patients may have high levels of HBV DNA, elevated aminotransferases and necroinflammatory activity on liver biopsy despite the absence of HBeAg, and presence of HBeAb. In most cases, these patients are infected with an HBV strain with a genome that has mutated in the so-called "precore" region. This variant is responsible for many, if not most, chronic HBV infections in the Mediterranean region and Asia, and is being increasingly recognized in North America. Patients infected with precore mutant strains of HBV are more likely to have serum aminotransferases that fluctuate between normal and abnormal, and are less likely to experience a sustained viral response to antiviral therapy.

Constipation Prescription

Constipation Prescription

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