insights in HBV

Screening of Hepatitis B

The presence of HBsAg establishes the diagnosis of

hepatitis B. Chronic versus acute infection is defined

by the presence of HBsAg for at least 6 months. The

prevalence of HBsAg varies greatly across countries,

with high prevalence of HBsAg-positive persons

defined as _8%, intermediate as 2% to 7%, and low as

<2%.(21,22) In developed countries, the prevalence is

higher among those who immigrated from high- or

intermediate-prevalence countries and in those with

high-risk behaviors.(22,23)

HBV is transmitted by perinatal, percutaneous, and

sexual exposure and by close person-to-person contact

(presumably by open cuts and sores, especially among

children in hyperendemic areas).(24,25) In most countries

where HBV is endemic, perinatal transmission

remains the most important cause of chronic infection.

Perinatal transmission also occurs in nonendemic countries

(including the United States), mostly in children of

HBV-infected mothers who do not receive appropriate

HBV immunoprophylaxis at birth. The majority of

children and adults with CHB in the United States are

immigrants, have immigrant parents, or became

exposed through other close household contacts.(26,27)

HBV can survive outside the body for prolonged periods.(

28) The risk of developing chronic HBV infection

after acute exposure ranges from 90% in newborns of

HBeAg-positivemothers to 25%-30% in infants and children

under 5 to less than 5% in adults.(29-33) In addition,

immunosuppressed persons are more likely to develop

chronicHBV infection after acute infection.(34)

Table 3 displays those at risk for CHB who should

be screened for HBV infection and immunized if seronegative.(

23,35,36) HBsAg and antibody to hepatitis B

surface antigen (anti-HBs) should be used for screening

(Table 4). Alternatively, antibody to hepatitis B core antigen (anti-HBc) can be utilized for screening

as long as those who test positive are further tested for

both HBsAg and anti-HBs to differentiate current

infection from previous HBV exposure. HBV vaccination

does not lead to anti-HBc positivity.

Some persons may test positive for anti-HBc, but

not HBsAg; they may or may not also have anti-HBs,

with the prevalence depending on local endemicity or

the risk group.(37,38) The finding of isolated anti-HBc

(anti-HBc positive but negative for HBsAg and anti-

HBs) can occur for a variety of reasons.

i. Among intermediate- to high-risk populations,

the most common reason is previous exposure to

HBV infection; the majority of these persons

recovered from acute HBV infection earlier in

life and anti-HBs titers have waned to undetectable

levels, but some had been chronically

infected with HBV for decades before clearing

HBsAg. In the former case, the risk of hepatocellular

carcinoma (HCC) or cirrhosis attributed to

HBV is minimal. In the latter, these persons are

still at risk of developing HCC, with an incidence

rate that appears to be similar to those

with inactive chronic HBV with undetectable

HBV-DNA levels.(39-41) These individuals usually

have low HBV-DNA levels (20-200 IU/mL,

more commonly if they are anti-HBs negative

than if they are anti-HBs positive) and are typically

born in regions with high prevalence of

HBV infection or have HIV or hepatitis C virus

(HCV) infection.(37,42-44)

ii. Much less commonly with new, more specific

anti-HBc tests, anti-HBc may be a false-positive

test result, particularly in persons from lowprevalence

areas with no risk factors for HBV

infection. Earlier anti-HBc enzyme immunoassay

and radioimmunoassay tests were less specific,

more frequently yielding false-positive results.(45)

iii. Anti-HBc may be the only marker of HBV

infection during the window phase of acute hepatitis

B; these persons should test positive for anti-

HBc immunoglobulin M.(37,38)

iv. Last, reports exist of HBsAg mutations leading

to false-negative HBsAg results.(37)

Because of the risk for HBV transmission, screening

for anti-HBc occurs routinely in blood donors and, if

feasible, in organ donors.(37) Since the original anti-

HBc studies, the specificity of anti-HBc tests has

improved to 99.88% in blood donors and 96.85% in

non-HBV medical conditions.(46,47) Individuals with

HIV infection or those about to undergo HCV or

immunosuppressive therapy are at risk for potential

reactivation if they have preexisting HBV and should

be screened for anti-HBc.(37,48)

The majority of individuals positive for anti-HBc

alone do not have detectable HBV DNA,(37) especially

with older, less specific assays. For anti-HBc–positive

individuals, additional tests to detect past or current

infection include immunoglobulin M anti-HBc, antibody

to hepatitis B e antigen (anti-HBe), and HBV

DNA with a sensitive assay. Detectable HBV DNA

documents infectivity, but a negative HBV DNA result

does not rule out low levels of HBV DNA. Additionally

repeat anti-HBc testing can be performed over

time, particularly in blood donors in whom subsequent

anti-HBc negativity suggests an initial false-positive

result.(37,48) Although reports vary depending on the

sensitivity and specificity of the anti-HBc test used and

HBV prevalence in the study population, the minority

of patients have an anamnestic response to HBV vaccination,

with the majority having a primary antibody

response to hepatitis B vaccination similar to persons

without any HBV seromarkers.(23,49) Thus, vaccination

could be considered reasonable for all screening indications

in Table 3. Anti-HBc–positive HIV-infected

individuals should receive HBV vaccination (ideally

when CD4 counts exceed 200/lL) because most have

primary responses to HBV vaccination, with _60% to

80% developing anti-HBs levels _10 mIU/mL after

3 or 4 vaccinations.(50,51) Thus, limited data suggest

that vaccination may be considered.(48,52,53) When considering

the benefit of using an anti-HBc–positive

donor organ with possible occult HBV infection, the

harm of hepatitis B transmission must be weighed

against the clinical condition of the recipient patient.

While persons who are positive for anti-HBc, but

negative for HBsAg, are at very low risk of HBV reactivation,

the risk can be substantial when chemotherapeutic

or immunosuppressive drugs are administered singly or in combination (see Screening, Counseling,

and Prevention of Hepatitis B, section 6D). Thus, all

persons who are positive for anti-HBc (with or without

anti-HBs) should be considered potentially at risk for

HBV reactivation in this setting.

Diagnosis and Serology

HBV infection leads to a wide spectrum of liver disease

Ranging from acute hepatitis (including fulminant hepatic failure)

To chronic hepatitis, cirrhosis, and hepatocellular

Carcinoma (HCC). The diagnosis of HBV infection and

Its associated disease is based on a constellation of clinical,

biochemical, histological, and serologic findings. A number

of viral antigens and their respective antibodies can be

detected in serum after infection with HBV, and proper

interpretation of the results is essential for the correct

diagnosis of the various clinical forms of HBV infection

HBV DNA followed shortly afterward by HBsAg and

HBeAg are the first viral markers detected in serum.

HBsAg may be detected as early as 1-2 weeks or as late as

11-12 weeks after exposure, and its persistence is a marker

of chronicity

HBeAg correlates with the presence of high

levels of HBV replication and infectivity .Within a few

weeks of appearance of viral markers, serum alanine and

Aspartate aminotransferase (ALT, AST) levels begin to rise

and jaundice may appear. HBeAg is usually cleared early,

at the peak of clinical illness, whereas HBsAg and HBV

DNA usually persist in the serum for the duration of

clinical symptoms and are cleared with recovery. Anti-

bodies to the HBV proteins arise in different patterns

during acute hepatitis B.

Antibody to HBcAg (anti-HBc)

generally appears shortly before onset of clinical illness,

The initial antibody being mostly immunoglobulin M.

(IgM) class, which then declines in titer as levels of IgG

anti-HBc arise.

Antibody to HBeAg (anti-HBe) usually

appears shortly after clearance of HBeAg, often at the

peak of clinical illness. Thus, loss of HBeAg and appearance

of anti-HBe is a favorable serological marker during

acute hepatitis B, indicating the initiation of recovery.

Antibody to HBsAg arises late during infection, usually

during recovery or convalescence after clearance of HBsAg.

. Anti-HBs persists after recovery, being the antibody

associated with immunity against HBV. However, be-

Tween 10% and 15% of patients who recover from

Hepatitis B does not develop detectable anti-HBs and have anti- HBc

alone as a marker of previous infection

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