INTRODUCTION

Hepatitis B virus (HBV) is a partially double stranded DNA virus, which is a significant cause of acute and chronic viral hepatitis in all parts of the world.  There are an estimated 300,000 cases of the infection in the U.S. per annum; ten percent of which develop chronic hepatitis.  Hepatocellular carcinoma is a sequella of hepatitis B virus infection. 

Clinically, HBV infection is distinguished from other viral hepatitides by the time from exposure to symptoms (28 to 180 days) and the presence of specific serological markers.  Newly developed hybridization assays afford additional tests useful in diagnosing and monitoring the disease.

RISK FACTORS

Persons at risk for HBV include persons living in endemic regions of the world.  In South East Asia, transmission is predominantly vertical (mother to infant); while in Africa, the disease is mostly spread horizontally (child to child).  Persons with HBV infection in the U.S. also come from well-defined groups including individuals from endemic regions of the world, parenteral exposure (developmentally disabled and institutionalized, intravenous drug abuse, health-care workers, renal dialysis patients), and sexual exposure.  In infected persons, viral antigens are found in high concentrations in serum and plasma, and are easily recoverable in semen, and saliva.  Thirty percent of persons with HBV infections do not have defined risk factors.

HBV INFECTION

The severity of disease is a function of T-cell mediated response to the hepatitis B core antigen (HbcAg) expressed on the membrane of infected hepatocytes; persons with a sluggish response clear the infection slowly (chronic carrier state) while those with a particularly vigorous response often present with fulminant hepatitis.   

Symptoms are indistinguishable from those of other viral hepatitis, and include jaundice, fatigue, myalgia, nausea, vomiting, diarrhea, and low-grade fever.  Up to 40 percent of infections are asymptomatic.

CHRONIC INFECTION

Six to 10 percent of cases of HBV remain positive for the HbsAg six months or more after the onset of symptoms.  HbeAg and HbcAb (IgM) may or may not be present.  By contrast, HbsAb are invariably absent.  Persons who are chronically infected may be asymptomatic and healthy but are infectious.  Chronic hepatitis B infections can progress to chronic persistent hepatitis, chronic active hepatitis, and cirrhosis.  All chronic carriers are at increased risk for heptaocellular carcinoma. 

HbsAg is an envelop protein.  The viral envelop is produced in excess.  Excess envelop protein can be “commandeered” by the delta agent, a “defective virus”, to produce a delta hepatitis superinfection or coinfection. 

Development of the chronic carrier state is more frequent in persons who acquire their infection perinatally, and in early childhood.

DISEASE MONITORING

Recent studies suggest that alpha interferon is useful in treating individuals with chronic hepatitis due to hepatitis B virus.  Furthermore, therapeutic responses may be predicted by measuring the quantity of circulating virus; those with the greatest serum viral loads are less likely to respond.  Viral quantitation is also useful in monitoring the effectiveness of treatment; alpha interferon responders show a rapid fall in viral concentration. 

Viral load is most reliably measured by newly developed, quantitative DNA hybridization assays.  These procedures can also be useful in detecting HBV mutants such as the Mediterranean variant, a strain of hepatitis B, which does not express the “e” antigen.  This test is routinely performed by the Molecular Diagnostic Reference Laboratory of Central Blood Bank.

VACCINATION

In the U.S., recombinant HBV vaccines have replaced the plasma-derived vaccines.  These vaccines are safe and effective; over 85 percent of individuals who receive the three dose series (administered at 0, 1, and 6 months) show protective levels of HbsAb. 

Protective immunity is indicated by an HbsAb titer greater than 10 mlU/ml.  Of the nonresponders, a significant proportion can achieve immunity with one or two additional boosters.  There are neither defined guidelines as to the duration of immunity nor the need for revaccination, but it is known that up to 35 percent of health-care workers who responded to an initial vaccine series do not have protective antibody titers five years later.  By OSHA standards, all health-care workers who are at occupational risk for hepatitis must be offered the vaccine series.  There is a growing trend in the United States to vaccinate newborns. 

Copies of the Transfusion Medicine Update can be obtained by contacting Deborah Small at (412) 209-7320 or
by e-mail:  dsmall@itxm.org.