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Hepatitis B Virus: Transmission, Prevention, Treatment and HIV Co-Infection

June/July 2001

A note from The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

Hepatitis B Virus (HBV) infection is very common with over 350 million chronically infected people worldwide including 1.25 million in the United States. The incidence of acute HBV infection in the U.S. has declined from 450,000 new infections per year in the 1980s to 80,000 in 1999. Vaccination against HBV, which has been available since 1982, is primarily responsible for this decline. Twenty to 80% of U.S. inmates have past or active HBV infection, and 0.8-1.4% of inmates acquire HBV while in prison.(1, 2, 3)

HBV Transmisson

High rates of HBV infection occur in people who have multiple sex partners, people who have percutaneous blood exposures (those who share injecting drug equipment and patients on hemodialysis) and health care or public safety workers who have frequent exposure to contaminated blood or other infectious fluids. In the correctional environment, tattooing with contaminated needles may be associated with HBV acquisition. Correctional officers may also be at increased risk of HBV infection because of exposure to inmates' blood and other body fluids during the course of their work. Household contacts of those with acute or chronic HBV infection and infants of mothers with chronic HBV infection are also at risk for acquiring HBV. In prisons, cellmates are analogous to household contacts. Transfusion as a cause of acute Hepatitis B (and Hepatitis C) has decreased dramatically in the past two decades since screening has become increasingly sensitive and more cost-effective. Since HIV and HBV have similar modes of transmission, coinfection is quite common.

Acute Hepatitis B Infection

The clinical, serologic, and immunologic responses following infection with HBV have been well-described. Only 25-50% of cases of acute HBV infection are symptomatic; the remainder are asymptomatic or are associated with inconsequential symptoms. Following an incubation period that varies from one week to six months, symptoms of the pre-icteric phase include malaise, weakness, anorexia, nausea, vomiting, and right upper quadrant pain. Oddly, these symptoms begin to abate during the icteric phase (jaundice) that persists for approximately three weeks. The hepatic transaminases peak, and then begin to decline during this time period. During the convalescent phase, which may last for up to six months, symptoms completely resolve.(4)

Following exposure to HBV, a well-defined immunologic response results in resolution of infection and protective immunity. The first serologic marker of HBV infection to appear is Hepatitis B surface antigen (HBsAg), a protein on the surface of the virus. This antigen usually persists in serum throughout the period of clinical illness, and is commonly used to diagnose acute HBV infection. During convalescence, the disappearance of HBsAg and the appearance of anti-HBsAg (HBsAb) mark resolution of the acute infection. In acute HBV infection, resolution occurs in six months or less. In addition, there are other serologic and immunologic markers of acute HBV infection. Hepatitis B core antibody (anti-HBc), an antibody directed against the nucleocapsid of HBV, generally appears at approximately the same time as HBsAb. HBc IgM develops initially and is eventually replaced by HBc IgG. In the minority of cases of acute HBV infection that come to clinical attention, HBsAb develops prior to the icteric phase. Since HBsAg disappears when HBsAb develops, HBsAg cannot be used to make the diagnosis of acute HBV infection in these rare instances. Instead, HBc IgM must be used to confirm the diagnosis. Another viral protein, Hepatitis B e antigen (HBeAg) and its corresponding antibody (HBeAb) follow a similar course to HBsAg and HBsAb, but these markers are rarely used for diagnosis of acute HBV infections. Seroconversion of HBeAg to HBeAb is associated with a decline in viral replication and disease severity.(4)Figure 1 summarizes the serologic and immunologic responses encountered in acute HBV infection.


Figure 1. Acute Hepatitis B Virus Infection with Recovery
Figure 1: Acute Hepatitis B Virus Infection with Recovery

Chronic HBV Infection

In approximately 10% of new infections, HBsAg persists in the serum for greater than six months, and chronic HBV infection is established. Individuals with persistent HBsAg are often called chronic carriers. Prior infection with HIV increases the likelihood that chronic HBV infection will occur.

The course of chronic HBV infection is characterized by the persistence of HbsAg in the serum and the failure to develop HBsAb, which provides protective immunity. In chronic HBV infection, the persistence of HBeAg (and failure to develop HBeAb) is associated with greater viral replication, higher HBV DNA in the serum, and more severe disease.

In the liver, chronic HBV infection causes inflammation, hepatic cell necrosis, and cirrhosis in approximately 50% of those infected. Hepatic failure and/or hepatocellular carcinoma occur in a significant number of patients. Chronic HBV infection is characterized by periods of disease activity and periods of disease quiescence. Serum transaminase levels increase with increased disease activity and may decrease to within normal limits during periods of disease quiescence. Serum quantitative HBV DNA levels also vary with disease activity. Clinically, symptoms may wax and wane with disease activity and may include fatigue, right upper quadrant discomfort, jaundice, and mild fever. Some patients are asymptomatic.(4)Figure 2 summarizes the serologic and immunologic course of chronic HBV infection.

Figure 2. Progression to Chronic Hepatitis B Virus Infection
Figure 2: Progression to Chronic Hepatitis B Virus Infection

Treatment of HBV Infection

There is no specific therapy for acute viral hepatitis. Supportive therapy including intravenous fluids, antiemetics, mild analgesia, and antipyretics may be necessary in some cases. It is prudent to stop potentially hepatotoxic medications, including antiretroviral drugs, until transaminase levels approach normal values. Acute fulminant hepatitis and death occur in 0.5-1% of cases of acute HBV infection.

Treatment and monitoring of patients with chronic HBV infection should be carried out by providers who are experienced in managing chronic HBV. Prior to treatment, liver biopsy is generally performed. Patients with decompensated liver failure or severe cirrhosis should not be treated for chronic HBV infection because treatment in these cases may actually lead to hepatic failure. Side effects are commonly encountered during treatment.

Interferon alpha 2b was the first drug approved by the United States Food and Drug Administration (U.S.F.D.A.) for the treatment of chronic HBV infection. The recommended treatment course is 5 million units injected subcutaneously daily or 10 million units injected subcutaneously three times per week for 16 weeks. Approximately 40% of those receiving this treatment will have a successful outcome, which is defined as seroconversion of HBeAg (i.e., loss of e antigen and acquisition of HBeAb). It appears that treatment with interferon reduces the occurrence of cirrhosis, hepatic failure, and hepatocellular carcinoma. Co-infection with HIV is a predictor of poor response to interferon treatment.

Lamivudine (Epivir-HBV tablets or oral solution) has also been approved by the U.S.F.D.A. for the treatment of chronic HBV infection. The recommended dosage is 100mg qd. The optimal duration of treatment is unclear, although most studies have involved one year of treatment. Approximately 15% of patients treated with lamivudine have seroconversion of HBeAg. HBV DNA disappears during treatment, but usually becomes detectable again when treatment is stopped. ALT also decreases during treatment, but may rebound to two or three times the baseline value after treatment is stopped. Lamivudine-resistant HBV have emerged during treatment with lamivudine. It is unclear whether patients have a decrease in clinical endpoints such as cirrhosis, liver failure, and hepatocellular carcinoma following treatment with lamivudine.

Hepatic transplantation is an option for patients with end-stage liver disease secondary to chronic HBV infection.

Preventing HBV Infection

Avoiding contact with contaminated blood by using universal precautions is the only way to be 100% protected against HBV infection. However, it has been shown that immunization with recombinant HBV vaccine is an effective means of preventing infection. The Immunization Practices Advisory Committee (ACIP) of the Centers for Disease Control and Prevention recommends that all newborns, children, and adolescents be immunized to help eliminate HBV in the United States. Adults in high risk groups should be vaccinated but vaccination of all adults is not recommended at this time. In addition, older adults are at lower risk. One hundred and ten other countries have a similar policy.

When vaccination is required, Recombivax HB and Engerix-B are two preparations that are available in the United States. The most common vaccination schedule is three intramuscular injections with the second and third doses being administered one and six months after the first; Engerix-B has also been licensed for a series of four injections given at 0, 1, 2, and 12 months.(2)

When an exposure to HBV occurs in a susceptible individual, post-exposure prophylaxis with Hepatitis B Immune Globulin (HBIG) and/or vaccination is recommended in most cases. Table 1 is a guide to post-exposure prophylaxis.(2) Available Hepatitis vaccines are presented in Table 2.

Table 1: Guide to Post-Exposure Immunoprophylaxis with HBIG and HBV Vaccine
Type of ExposurePost-Exposure Prophylaxis
PerinatalVaccination + HBIG
Sexual -- acute infectionHBIG +/- vaccination
Sexual -- chronic carrierVaccination
Household contact -- chronic carrierVaccination
Household contact -- acute caseNone unless known exposure
Household contact -- acute case, known exposureHBIG +/- vaccine
Infant (<12 months) -- acute case in primary caregiverHBIG + vaccination
Inadvertent percutaneous/permucosalVaccination +/- HBIG

Table 2: Hepatitis Vaccines
Hepatitis A (HAV) VaccinesHepatitis B (HBV) Vaccines
  • Two HAV vaccines available perform equally well; both are based on an inactivated virus

  • Two doses are recommended, the second dose given 6-12 months after the first

  • Havrix: manufactured by Glaxo Smith Kline

  • VAQTA: manufactured by Merck, there is a pediatric version available for use up to 18 years of age

  • Twinrix: a combination HAV and HBV vaccine consisting of inactivated HAV and genetically derived HBsAg is currently undergoing trials
  • There are three HBV vaccines available; all are recombinant (genetically engineered) HBsAg vaccines

  • The vaccine schedule involves three intramuscular injections at 0, 1, and 6 months.

  • Engerix-B: manufactured by Glaxo Smith Kline

  • Recombivax-HB: manufactured by Merck

  • Comvax: manufactured by Merck, combination Haemophilus B conjugate and HBV vaccine

HBV and HIV Co-Infection

HIV and HBV interact when they occur in the same host, as previously noted.(5, 6) Like any other infection that occurs in HIV positive individuals, HBV infection activates the immune system leading to proliferation of CD4 cells which enhances HIV replication and increased plasma HIV RNA (viral load). In addition to this indirect effect on HIV replication, HBV proteins directly stimulate HIV replication. Theoretically, this results in more rapid HIV disease progression if the increase in HIV replication is sustained for a significant length of time. However, the literature does not consistently support the presumption that HIV progression is accelerated by concomitant HBV infection. It does appear however that HIV infection may accelerate the progression to hepatic failure and hepatic failure-related deaths in patients with chronic HBV infection.(6)

In coinfected patients, most published reports indicate that serum HBV DNA is higher, serum alanine aminotransferase levels (ALT) are lower, and liver inflammation and cirrhosis are less than in patients with HBV alone. This is not an unexpected finding since cell-mediated-immunity (CMI), the primary factor in eliminating HBV from infected hepatocytes, is impaired by HIV infection. In studies that demonstrated the efficacy of interferon-alpha 2b for chronic HBV infection, HIV negative participants with high serum HBV levels, low serum ALT levels, and mild histopathologic scores on liver biopsy were less likely to respond to interferon treatment for chronic HBV infection than participants who had lower HBV DNA levels, higher ALT levels, and more severe inflammation on liver biopsy. Given this fact, it is not surprising that patients with chronic HBV and HIV coinfection are less likely to respond to interferon treatment for chronic HBV infection. Patients with chronic HBV and HIV are more likely to have clinically significant hepatotoxicity when placed on antiretroviral agents in general and may have increased incidence and severity of indinavir-associated hyperbilirubinemia.(7)

When lamivudine is included in an antiretroviral regimen in patients with HIV and HBV coinfection, HBV viral replication is often reduced to nondetectable for the duration of lamivudine treatment. Whether this finding is associated with a more favorable hepatic outcome is unclear at the present time.

Correctional Hepatitis

The Centers for Disease Control (CDC), convened a meeting this Spring on Hepatitis in correctional settings that was attended by more than 100 federal and state correctional healthcare professionals. Representatives of correctional organizations (ACA, NCCHC) and representatives from federal agencies such as the OSHA and NIOSH also attended the meeting. CDC speakers discussed the need to expand HBV and HCV interventions, including screening, education, vaccination, and treatment of chronic Hepatitis in correctional settings. Guidelines for HCV and HBV management will be issued by the CDC as a supplement to the MMWR in the fall. While sources of funding for increased Hepatitis interventions in corrections were not specifically addressed, participants discussed promoting correctional settings as outposts for public health activities which may ultimately lead to increased financial support from federal and state sources for correctional treatment initiatives.

* Speaker's Bureau: Roche Pharmaceuticals.


  1. Sylvan S. WHO spearheads global initiative to eradicate hepatitis B. Lakartidningen 2000 August 30;97(35):3738-40.

  2. Hepatitis B Virus: A Comprehensive Strategy for Eliminating Transmission in the United States Through Universal Childhood Vaccination: Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR November 1991;40(RR-13); 1-19.

  3. Bader, T.F. Hepatitis B in prisons. Biomed Pharmacother 1986;40(7):248-51.

  4. Hoofnagle Jay H., M.D., and Schafer, Daniel F., M.D. Serologic Markers for Hepatitis B Virus Infection. Seminars in Liver Disease Vol. 6 No. 1, 1998.

  5. Hadler S.C., Judson F.N., O'Malley P.M., et al. Outcome of hepatitis B virus infection in homosexual men and its relation to prior human immunodeficiency virus infection. J Infect Dis 163:454-459, 1991.

  6. A.N.B. McNair, M.A., M.R.C.P.k, Janice Main, M.D., and H.C. Thomas, M.D., Ph.D. Interactions of the Human Immunodeficiency Virus and the Hepatotropic Viruses. Seminars in Liver Disease Vol. 12, No. 2, 1992.

  7. Gisolf E.H., Dreezen D., Danner S.A., Weel J.L., Weverling G.J.; Prometheus Study Group. Risk factor for hepatotoxicity in HIV-1infected patients receiving ritonavir and saquinavir with or without stavudine. Clin Infect Dis 2000 Nov;31(5):1234-9.

Back to the HEPP News June/July 2001 contents page.

A note from The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

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This article was provided by Brown Medical School. It is a part of the publication HEPP News.
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