Hepatitis B (HBV) is the ninth leading cause of death worldwide. Globally, an estimated 300 million people are currently infected, and approximately 1 million people die annually. In the United States, over 200,000 new cases of HBV occur each year.1 HBV is usually self-limiting after acute infection but can progress into a chronic state, as well. Due to similar modes of transmission, there are a large number of patients co-infected with HBV and human immunodeficiency virus (HIV).
Co-infected individuals are at greater risk for the development of chronic HBV. Comorbid HIV disease also increases the viral burden of HBV and worsens its course. Co-infected individuals have a propensity for a more rapid progression of liver disease and are more likely to develop cirrhosis and/or hepatocellular carcinoma (HCC). In the past decade, significant progress has been made toward understanding the molecular biology and pathogenesis of HBV and in the initial exploration of treatment options.
HBV was identified in 1968 as the first virus of the hapadnevirus group. Several different genotypes of HBV have now been identified, and they vary geographically. Genotypes A and D are more prevalent in Western countries; genotypes and B and C are found more commonly in Asia and Japan.2
There are three primary routes of transmission. Direct inoculation can occur via needle-stick injuries, dialysis, or the sharing of needles in injection drug use. HBV is also a sexually transmitted infection and is found in body fluids such as semen and vaginal secretions. It can also be transmitted from mother to fetus (vertical transmission) during pregnancy. Transmission from blood transfusions has been all but eradicated in the United States due to careful donor screening.
Needle-stick injuries are a much more efficient means of HBV transmission than of HIV. Transmission rates for HBV are 10%-30% compared to less than 1% in HIV disease.3 There is a higher than average incidence of HBV among men who have sex with men (MSM) and among injection drug users (IDUs), although many new cases in the United States are the result of heterosexual transmission.4 Vertical transmission is the most common cause of HBV infection in the pediatric population, and all pregnant women should be screened for the disease.
HBV has an incubation period ranging from 6 weeks to 6 months. When following the clinical course of acute HBV infection, it's important to note that the great majority of pediatric cases and up to 50% of adult cases are subclinical or asymptomatic.1 For those with symptomatic infection, the course of acute HBV consists of a predictable series of events. Each stage may have a variable duration for a given individual.
The Prodromal Phase can manifest with symptoms that include general malaise, arthralgias, myalgias, rhinitis, pharyngitis, lymphadenopathy, anorexia, nausea/vomiting, diarrhea or constipation, and the most common complaint, fatigue. Fever, if present, is rarely greater than 39.5¡C, and dark urine, right upper quadrant pain, hepatosplenomegaly, and aversion to cigarette smoking may also be present. The second stage is the Icteric Phase. As the name implies, the patient becomes jaundiced. Liver enzyme levels peak, and the signs and symptoms of the Prodromal Phase worsen. Following the Icteric Phase, the patient usually has a prolonged Convalescent Phase with resolution of illness.
Clinical and laboratory recovery occurs at around 16 weeks. At this point, the patient may be feeling better and liver enzymes will probably have begun to normalize. The Recovery Phase indicates loss of infectivity. Normally, this phase occurs at around 6 months following infection. The determination as to whether a patient is still infectious must be made through assessment of a series of laboratory markers over the span of the illness.
Patients are said to have chronic HBV if they remain positive for hepatitis B surface antigen (HBsAg) on two occasions 6 months or more apart. Although chronic HBV is relatively rare in the United States, groups that have an increased risk for developing chronic disease include Asian Americans, persons who have had multiple transfusions, IDUs, MSMs, patients who are institutionalized, and patients who have immune deficiencies. Chronicity is inversely proportional to age. Infection at birth results in up to a 90% risk of developing chronic disease. Risk of chronic HBV decrease to between 25% and 50% by age five; adult infection produces a much lower rate of chronicityÑaround 10%. It is felt that many people in the United States who have chronic HBV may actually have immigrated from a country with a higher prevalence rate, and that they became infected vertically or in early childhood. There is a high degree of variability in the clinical presentation of the chronically infected patient.
There are over 20 drugs in development for the treatment of chronic HBV. Only two have actually been FDA-approved: alpha interferon and lamivudine (Epivir¨).5 Alfa interferon has been found to be less effective for the treatment of chronic HBV due to the large dose required (5-10 million U tiw SC) and the drug's side effects. Lamivudine is highly effective against HBV and HIV.6 It is often retained as part of highly active antiretroviral therapy (HAART) for HIV disease or "tacked on" to a HAART regimen for this beneficial effect.
As with HIV, lamivudine resistance to HBV can develop. In the presence of lamivudine resistance, HBV appears to remain sensitive to adefovir and tenofovir. Adefovir is being used experimentally at lower doses for the treatment of HBV.7 Since the dose of adefovir used to treat HBV does not have activity against HIV, the use of tenofovir may be a more attractive option.
Recent data from the 10th International Symposium on Viral Hepatitis and Liver Disease suggest that those co-infected with HIV/HBV may not present with the classic laboratory markers.8 This means that significant numbers of co-infected patients could be falsely presumed to be HBV-negative. Diagnosis of these individuals is still a research endeavor, because HBV DNA testing has not yet received FDA approval for routine clinical use. Moreover, because it is uncertain whether these patients will ultimately develop liver disease, the significance of these findings are not clear.
There is a highly effective vaccine for HBV, and the goal in the United States and other developed countries has been universal immunization. It is important to note that some individuals, such as those with chronic renal insufficiency or chronic liver disease, or those with severe immune suppression, may not mount an adequate response to the vaccine.9 Since the vaccine is not a live vaccine, there is no risk associated with vaccinating people with chronic illnesses, individuals with immune deficiency diseases, or pregnant women.
HBV vaccine is given as series of three injections for adults. A two-dose regimen for adolescents aged 11-15 has been approved recently. All infants, children, and adults who do not show laboratory evidence of immunity to HBV may be immunized. It is vital to immunize all susceptible persons with comorbid HIV disease.
Negative outcomes have not been observed from inadvertently immunizing patients with a history of HBV infection. Individuals without immunity who are exposed to HBV should receive hepatitis B immune globulin (HBIG) as well as initiation of the HBV immunization series.10
Patients with hepatitis B should be counseled to notify their provider before taking any prescription or over-the-counter medications. Simultaneous use of alcohol and acetaminophen (Tylenol¨) is contraindicated in those with chronic hepatitis because of the risk of fulminant hepatitis.
Because of escalating morbidity and mortality rates, hepatitis B continues to be an important disease worldwide. Those with acute and/or chronic infection as well as those who may benefit from immunization must be identified. It is vital to screen every person infected with HIV for HBV because of the likely accelerated progression to chronic disease, cirrhosis, and hepatocellular carcinoma.
Michael Goins, MSN, FNP is Nursing Director of HIV Clinical Services, Yonkers General Hospital, and co-founder and co-president of Key-Med, LLC. Hema Santhanam MSN, FNP, ACRN is co-founder/co-president of Key-Med, LLC .
References
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10. Keeffe EB, Benner KG. Hepatitis A through E: distinguishing the etiologic agents. Modern Medicine. 1993;(61):42-62.