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The blood supply in developed countries has been screened for HBV for many years and at present transmission by blood transfusion is extremely rare. Major routes of transmission among adults in Western countries are intravenous drug use and sexual contact. The risk of HBV infection is notably high in promiscuous homosexual men but it is also transmitted sexually from men to women and women to men. Transmission is probably prevented by correct use of condoms. Health care workers and patients receiving hemodialysis are also at increased risk of infection.
Effective vaccines are available for the prevention of HBV infection. All individuals at risk for infection should be vaccinated. Post-exposure prophylaxis with hepatitis B immune globulin is also effective for non-immune individuals after a known exposure (e. g. needle stick).
Acute hepatitis B can range from subclinical disease to fulminant hepatic failure in about 2% of cases. Many acutely infected individuals develop clinically apparent acute hepatitis with loss of appetite, nausea, vomiting, fever, abdominal pain and jaundice. In cases of fulminant hepatic failure from acute HBV infection, orthotopic liver transplantation can be life-saving. About 90% to 95% of acutely infected adults recover without sequelae. About 5% to 10% of acutely infected adults become chronically infected.
The natural history of chronic HBV infection can vary dramatically between individuals. Some will develop a condition commonly referred to as a chronic carrier state. These patients, who are still potentially infectious, have no symptoms and no abnormalities on laboratory testing. Nonetheless, some of these patients will have evidence of hepatitis on liver biopsy.
Some individuals with chronic hepatitis B will have clinically insignificant or minimal liver disease and never develop complications. Others will have clinically apparent chronic hepatitis. Some will go on to develop cirrhosis. Individuals with chronic hepatitis B, especially those with cirrhosis but even so-called chronic carriers, are at an increased risk of developing hepatocellular carcinoma (primary liver cancer). Although this type of cancer is relatively rare in the United States, it is the leading cause of cancer death in the world, primarily because HBV infection is endemic in the East.
Chronic infection with HBV can be either "replicative" or "non-replicative." In non-replicative infection, the rate of viral replication in the liver is low and serum HBV DNA concentration is generally low and hepatitis Be antigen (HBeAg) is not detected. HBeAg is an alternatively processed protein of the pre-core gene that is only synthesized under conditions of high viral replication. In "replicative" infection, the patient usually has a relatively high serum concentration of viral DNA and detectable HBeAg. Patients with chronic hepatitis B and "replicative" infection defined by the presence of detectable HBeAg have a generally worse prognosis and a greater chance of developing cirrhosis and/or hepatocellular carcinoma than those without HBeAg. In rare strains of HBV with mutations in the pre-core gene, "replicative" infection can occur in the absence of detectable serum HBeAg.
Acutely infected individuals who do not clear HBV continue to have serum HBsAg. In most cases, the chronic infection becomes "non-replicative" and the subjects lose serum HBeAg and develop antibodies against HBeAg. In some cases, "replicative" infection persists along with detectable serum HBeAg. In chronically infected individuals, infection can switch from "non-replicative" to "replicative" and vice-versa. One goal of treatment (see below) is to convert patients with chronic hepatitis B from a "replicative" (HBeAg positive) to "non-replicative" (HBeAg negative) state.
Diagnosis of hepatitis B is confirmed, and prognosis is assessed, by liver biopsy. Most people who are chronic carriers (no symptoms, HBsAg positive and normal serum aminotransferase activities) generally have little or no inflammation on biopsy. In such patients, you can often see "ground glass cells" on liver biopsy which are liver cells in which large amounts of HBsAg is being synthesized. Other individuals with chronic hepatitis B will have various degrees of liver inflammation on biopsy. Others will have fibrosis or cirrhosis. The amount of inflammation, and the presence of fibrosis or cirrhosis, correlate with a worse prognosis.
In individuals suspected of having chronic hepatitis B, the appropriate screening test is for serum HBsAg. Individuals who may have chronic hepatitis B who should be considered for testing include:
Patients treated with interferon-alpha should have evidence of infection with hepatitis B virus, documented by the presence of hepatitis B surface antigen in the blood, for six months. The patients should also have evidence of virus replication, documented by the presence of hepatitis B e antigen in the blood. Ongoing inflammation of the liver should also be present as documented by an elevation in serum aminotransferase activities. A liver biopsy should also be performed prior to treatment. Patients with severe, decompensated liver disease (eg. encephalopathy, ascites, very high serum bilirubin, prolonged prothrombin time, etc.) should not generally be treated with interferon alfa except in the setting of an approved clinical study.
The recommended dose of interferon alfa-2b for the treatment of chronic hepatitis B is 5,000,000 units daily, administered by subcutaneous or intramuscular injection, for a total of 16 weeks. The patient must be monitored carefully during the treatment period for side effects including flu-like symptoms, depression, rashes, other reactions and abnormal blood counts.
A meta-analysis of several randomized trials of interferon alfa-2b in the treatment of patients with chronic hepatitis B showed such treatment to be cost-effective (Wong et al. Annals Intern. Med. 1995;122:664-675). This analysis showed that treatment with interferon alfa-2b decreased viral replication, documented by loss of serum hepatitis B e antigen, in about 45% of patients compared to less than 10 % of untreated patients. About 8% of patients also lost hepatitis B virus surface antigen (cured) within one year of treatment compared to a rate of about 1% a year for untreated patients.
Other treatment options for chronic hepatitis B include nucleoside analogues. In December, 1998, the United States Food and Drug Administration approved lamivudine , also known as 3TC and is also effective against HIV, for the treatment of chronic hepatitis B (patients who are HBeAg positive). Lamivudine is taken orally at 100 mg/day for chronic hepatitis B. In studies where they were compared, lamivudine was equally effective to interferon-alpha in inducing a loss of serum HBeAg. It also has been shown to improve liver biopsy results in patients treated for one year. In September 2002, the United States Food and Drug Administration approved adevofir dipivoxil, another nucleoside analogue also effective against HIV, for the treatment of hepatitis B. The dose is 10 mg/day for chronic hepatitis B. At the present time, other nucleoside analogues are being studied in clinical trials. The combination of interferon-alpha and a nucleodide analogue, two nucleoside analogues together (such as lamivudine and adefovir) are also under investigation.
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