Clinical Evaluation of the HBV-Infected Patient - 2 of 2

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Clinical Evaluation of the HBV-Infected Patient - 2 of 2

Phases of Chronic Hepatitis B Infection

In cases of adult-acquired chronic hepatitis B, the serum alanine

aminotransferase (ALT) level generally correlates well with the HBV DNA level

and the severity of disease activity. However, in young patients with

perinatally acquired hepatitis B, it is not uncommon to have a normal serum ALT

level yet a markedly elevated HBV DNA level.[22] This is described as the

immune-tolerant phase of the disease. Hepatic histologic damage tends to be

minimal if a biopsy is performed. Patients may remain in the immune-tolerant

phase for decades.

Patients with perinatally acquired HBV infection often transition from an

immune-tolerant phase to an immune clearance phase of the disease in the second

to third decade of life. In HBeAg-positive patients, seroconversion to anti-HBe

may occur during this phase, which may trigger a rise in serum aminotransferase

levels and HBV DNA level.[23] Although often asymptomatic, this transition can

provoke symptoms of acute hepatitis, occasionally resulting in hepatic

decompensation.[1,5]

Some patients who are HBsAg-positive have persistently low or undetectable HBV

DNA and no elevation in serum ALT. These patients, referred to as inactive

carriers, have little or no active viral replication. They are generally

HBeAg-negative and anti-HBe-positive. It should be recognized, however, that

chronic hepatitis B is a dynamic disease; conversion from an inactive to an

active, replicative state can occur in carriers, particularly if they are

immunocompromised. Although often mild or asymptomatic, such a reactivation can

be severe enough to cause fulminant hepatic

failure.[24]

Role of Liver Biopsy

Most experts agree that a liver biopsy is not necessary in every patient

diagnosed with chronic hepatitis B. However, a liver biopsy provides useful

information regarding HBV disease activity and, in some settings, is an

important factor in determining whether to initiate antiviral therapy. Serum ALT

and HBV DNA levels are, in general, good surrogate markers of disease activity;

however, in some cases marked inflammation may be present on liver biopsy in the

setting of a normal ALT and minimally elevated HBV DNA.[18] Similarly, the liver

may appear histologically normal despite a markedly elevated HBV DNA level.

Generally, a liver biopsy should be considered in patients with a normal serum

ALT yet an increased HBV DNA.[15] In such patients, the disease activity found

on liver biopsy will often influence the decision to begin antiviral therapy.

Counseling of the HBsAg-Positive Patient

Patients who screen positive for HBsAg should be advised on lifestyle

modifications to avoid additional insults to the liver and to minimize risk of

transmission of the virus. The patient should receive education on the potential

modes of transmission including sexual transmission, blood exposure, and

vertical transmission.[5] Close contacts should be tested for HBV and should be

vaccinated if not immune.[4,7] Additionally, patients with HBV infection should

be tested for other relevant hepatotropic viruses including hepatitis A and

hepatitis C viruses.[25] Hepatitis D virus should also be tested for, as

coinfection with HBV is seen on occasion. HIV testing should also be done given

that coinfection confers an increased risk of disease progression and may have

an impact on the choice of antiviral therapy.[26] Risk factors for the

acquisition of these other viruses should also be addressed. Those who are not

immune to hepatitis A should be offered

vaccination.[4] Abstinence from alcohol is recommended as there is no definitive

amount of alcohol that is safe.[5] Patients should be advised to avoid

hepatotoxic medications if possible, with specific attention to herbal

supplements and other over-the-counter agents.

Screening for HCC

Patients with chronic HBV infection have a 0.5% annual incidence of HCC, placing

them at 100-times-greater risk of developing HCC than individuals without HBV

infection.[2,3] In patients with chronic HBV infection, HCC can arise even in

the absence of cirrhosis.[2]

The American Association for the Study of Liver Diseases practice guidelines for

the management of HCC recommend screening for HCC in the following patients with

chronic hepatitis B: Asian men older than 40 years old, Asian women older than

50 years old, black patients over age 20 years, all patients with cirrhosis, and

all patients with a family history of HCC.[2] Asian hepatitis B carriers who

lose HBsAg-positivity should continue to undergo surveillance indefinitely.[17]

Until recently, the preferred method for HCC screening included both liver

ultrasound examination and measurement of serum alpha-fetoprotein (AFP).

However, recent guidelines question the utility of AFP monitoring in HCC

screening.[2] Using 20 ng/mL as a cutoff value for abnormal AFP levels, serum

AFP has a sensitivity of only 60%.[27] Liver ultrasound exam has a sensitivity

ranging between 65% and 80% and a specificity of more than 90% for the detection

of HCC.[28] In some patients, the utility of ultrasound examination may be

limited, such as in those with obesity. In this population, screening with a

more sensitive test such as magnetic resonance imaging with contrast or

triphasic computed tomography scan should be considered.[2] The preferred

interval for screening ultrasound is every 6 months. There are some data to

indicate that annual screening may be as effective as biannual screening;

however, there is no clear survival benefit to screening more frequently than

every 6 months.[29,30]

Conclusion

Hepatitis B infection is a major health problem worldwide and is associated with

life-threatening complications. Individuals who should be offered screening

include those from areas of the world where HBV infection has intermediate or

high prevalence and those who exhibit risk factors for acquiring HBV infection,

including high-risk sexual behavior and intravenous drug use. Testing for HBsAg

and anti-HBs is a reasonable approach to screening for HBV infection. If an

individual tests positive for HBsAg, additional serologic and virologic work-up,

including testing for HBeAg, anti-HBe, and HBV DNA, should be done to

characterize the status of the HBV infection. HBsAg-negative individuals who are

not yet immune should be offered vaccination. Not all individuals with chronic

hepatitis B require a liver biopsy, but in a subset of patients, the liver

histology will influence the decision of whether to begin antiviral therapy. The

role of HBV genotype has not yet been clearly defined, but it may assume a

pivotal role in the management of chronic HBV infection in the future. HBV

infection confers a greatly elevated risk of developing HCC, even in the absence

of cirrhosis. Screening for HCC with liver ultrasound exam every 6 months in

select HBV-infected populations is recommended.

This activity is supported by an independent educational grant from Gilead.

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Clinical Evaluation of the HBV-Infected Patient - 2 of 2

Phases of Chronic Hepatitis B Infection

In cases of adult-acquired chronic hepatitis B, the serum alanine

aminotransferase (ALT) level generally correlates well with the HBV DNA level

and the severity of disease activity. However, in young patients with

perinatally acquired hepatitis B, it is not uncommon to have a normal serum ALT

level yet a markedly elevated HBV DNA level.[22] This is described as the

immune-tolerant phase of the disease. Hepatic histologic damage tends to be

minimal if a biopsy is performed. Patients may remain in the immune-tolerant

phase for decades.

Patients with perinatally acquired HBV infection often transition from an

immune-tolerant phase to an immune clearance phase of the disease in the second

to third decade of life. In HBeAg-positive patients, seroconversion to anti-HBe

may occur during this phase, which may trigger a rise in serum aminotransferase

levels and HBV DNA level.[23] Although often asymptomatic, this transition can

provoke symptoms of acute hepatitis, occasionally resulting in hepatic

decompensation.[1,5]

Some patients who are HBsAg-positive have persistently low or undetectable HBV

DNA and no elevation in serum ALT. These patients, referred to as inactive

carriers, have little or no active viral replication. They are generally

HBeAg-negative and anti-HBe-positive. It should be recognized, however, that

chronic hepatitis B is a dynamic disease; conversion from an inactive to an

active, replicative state can occur in carriers, particularly if they are

immunocompromised. Although often mild or asymptomatic, such a reactivation can

be severe enough to cause fulminant hepatic

failure.[24]

Role of Liver Biopsy

Most experts agree that a liver biopsy is not necessary in every patient

diagnosed with chronic hepatitis B. However, a liver biopsy provides useful

information regarding HBV disease activity and, in some settings, is an

important factor in determining whether to initiate antiviral therapy. Serum ALT

and HBV DNA levels are, in general, good surrogate markers of disease activity;

however, in some cases marked inflammation may be present on liver biopsy in the

setting of a normal ALT and minimally elevated HBV DNA.[18] Similarly, the liver

may appear histologically normal despite a markedly elevated HBV DNA level.

Generally, a liver biopsy should be considered in patients with a normal serum

ALT yet an increased HBV DNA.[15] In such patients, the disease activity found

on liver biopsy will often influence the decision to begin antiviral therapy.

Counseling of the HBsAg-Positive Patient

Patients who screen positive for HBsAg should be advised on lifestyle

modifications to avoid additional insults to the liver and to minimize risk of

transmission of the virus. The patient should receive education on the potential

modes of transmission including sexual transmission, blood exposure, and

vertical transmission.[5] Close contacts should be tested for HBV and should be

vaccinated if not immune.[4,7] Additionally, patients with HBV infection should

be tested for other relevant hepatotropic viruses including hepatitis A and

hepatitis C viruses.[25] Hepatitis D virus should also be tested for, as

coinfection with HBV is seen on occasion. HIV testing should also be done given

that coinfection confers an increased risk of disease progression and may have

an impact on the choice of antiviral therapy.[26] Risk factors for the

acquisition of these other viruses should also be addressed. Those who are not

immune to hepatitis A should be offered

vaccination.[4] Abstinence from alcohol is recommended as there is no definitive

amount of alcohol that is safe.[5] Patients should be advised to avoid

hepatotoxic medications if possible, with specific attention to herbal

supplements and other over-the-counter agents.

Screening for HCC

Patients with chronic HBV infection have a 0.5% annual incidence of HCC, placing

them at 100-times-greater risk of developing HCC than individuals without HBV

infection.[2,3] In patients with chronic HBV infection, HCC can arise even in

the absence of cirrhosis.[2]

The American Association for the Study of Liver Diseases practice guidelines for

the management of HCC recommend screening for HCC in the following patients with

chronic hepatitis B: Asian men older than 40 years old, Asian women older than

50 years old, black patients over age 20 years, all patients with cirrhosis, and

all patients with a family history of HCC.[2] Asian hepatitis B carriers who

lose HBsAg-positivity should continue to undergo surveillance indefinitely.[17]

Until recently, the preferred method for HCC screening included both liver

ultrasound examination and measurement of serum alpha-fetoprotein (AFP).

However, recent guidelines question the utility of AFP monitoring in HCC

screening.[2] Using 20 ng/mL as a cutoff value for abnormal AFP levels, serum

AFP has a sensitivity of only 60%.[27] Liver ultrasound exam has a sensitivity

ranging between 65% and 80% and a specificity of more than 90% for the detection

of HCC.[28] In some patients, the utility of ultrasound examination may be

limited, such as in those with obesity. In this population, screening with a

more sensitive test such as magnetic resonance imaging with contrast or

triphasic computed tomography scan should be considered.[2] The preferred

interval for screening ultrasound is every 6 months. There are some data to

indicate that annual screening may be as effective as biannual screening;

however, there is no clear survival benefit to screening more frequently than

every 6 months.[29,30]

Conclusion

Hepatitis B infection is a major health problem worldwide and is associated with

life-threatening complications. Individuals who should be offered screening

include those from areas of the world where HBV infection has intermediate or

high prevalence and those who exhibit risk factors for acquiring HBV infection,

including high-risk sexual behavior and intravenous drug use. Testing for HBsAg

and anti-HBs is a reasonable approach to screening for HBV infection. If an

individual tests positive for HBsAg, additional serologic and virologic work-up,

including testing for HBeAg, anti-HBe, and HBV DNA, should be done to

characterize the status of the HBV infection. HBsAg-negative individuals who are

not yet immune should be offered vaccination. Not all individuals with chronic

hepatitis B require a liver biopsy, but in a subset of patients, the liver

histology will influence the decision of whether to begin antiviral therapy. The

role of HBV genotype has not yet been clearly defined, but it may assume a

pivotal role in the management of chronic HBV infection in the future. HBV

infection confers a greatly elevated risk of developing HCC, even in the absence

of cirrhosis. Screening for HCC with liver ultrasound exam every 6 months in

select HBV-infected populations is recommended.

This activity is supported by an independent educational grant from Gilead.

_________________________________________________________________

Helping your favorite cause is as easy as instant messaging. You IM, we give.

http://im.live.com/Messenger/IM/Home/?source=text_hotmail_join