The hepatitis B-positive patient

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Chapter 36 THE HEPATITIS B-POSITIVE PATIENT

KEY POINTS

• Chronic hepatitis B virus (HBV) infection is common, affecting approximately 3.5 million people worldwide.
• There are three antigens and each has corresponding antibodies:

– Surface antigen (HBsAg) indicates current infection, and surface antibody (HBsAb) indicates immunity
– E antigen (HBeAg) indicates active viral replication and high infectivity. E antibody (HBeAb) indicates clearance of HBe antigen
– Core antigen is never found in the serum. HBV core antibody (HBcAb IgM) generally indicates infection within the previous 10 months. HBcAb IgG indicates past infection.

• HBV-DNA is the best test for viral replication.
• There are two main settings for HBV transmission:

– Transmission in early life in a highly endemic area (mother to baby or infection by other members of the extended family within the first year of life)
– Transmission in adolescence or adult life by injecting drug use and sexual contact.

• The natural history of chronic HBV can be divided into three phases:

– Immunotolerant replicative phase. High viral replication but transaminases and histology virtually normal
– E antigen clearance phase. May be rapid with development of e antibody and minimal hepatitis or prolonged with cycles of regeneration and repair. Mutations in the precore or the basal core promoter regions may develop
– Residual integrative phase. Regard people in this phase as potentially having cirrhosis.

• Three common scenarios:

– The ‘healthy’ or asymptomatic chronic carrier
– The chronic carrier with liver disease
– Acute hepatitis B.

• Antiviral treatment. A number of drugs have been approved for treatment of chronic HBV infection, including interferon alfa-2b, lamivudine, adefovir dipivoxil, entecavir, peginterferon alfa-2a and telbivudine.
• Transplantation may be appropriate in highly selected patients.
• Screening for hepatocellular carcinoma (HCC). The most common program is ultrasound and alpha-fetoprotein at 6-monthly intervals.

INTRODUCTION

At least 350 million people worldwide are chronically infected with hepatitis B virus (HBV).

Acute hepatitis B is subclinical in young children, and only 50% of adults are likely to be symptomatic. Acutely infected adults have a 90% chance of clearing the surface antigen within 6 months, whereas young babies and children have a <10% chance of clearing HBV.

This chapter focuses mainly on the chronic carrier.

THE ANTIGENS AND THEIR ANTIBODIES

Table 36.1 and Figure 36.1 summarise the tests available for HBV and their clinical relevance. There are three antigens, and each has corresponding antibodies:

• Surface antigen (HBsAg) indicates current infection, and surface antibody (HBsAb) indicates immunity (either from vaccination, or from past infection)
• E antigen (HBeAg) indicates active viral replication and high infectivity. HBeAg is highly immunogenic, and much of the host immune response is directed against this antigen rather than against HBsAg. E antibody (HBeAb) has no protective role—its presence simply indicates clearance of HBeAg
• Core antigen is never found in serum. However core antibodies are detectable as a marker of past infection. As a general rule, HBcAb IgM indicates infection within the previous 10 months, and so can be used as a marker of recent infection (occasionally it can also re-appear in the serum of chronic carriers during a severe flare). HBcAb IgG indicates past infection, duration undefined
• HBV DNA is the best test for active viral replication. It is always positive if HBeAg is present, and may be positive when HBeAb is positive, in the case of precore mutant infection.

TABLE 36.1 Clinical investigations in chronic hepatitis B

image

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FIGURE 36.1 Indications for biopsy and treatment.

ALT = alanine aminotransferase; HBeAg = hepatitis B e antigen; HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus.

TRANSMISSION OF HBV

HBV is highly infectious in someone who has replicating virus—the virus will be present in all body fluids at high concentration. There are two main settings for HBV transmission. The most common global setting is transmission in early life in a highly endemic area (i.e. most parts of the world except the highly Westernised countries of Western Europe, USA, Canada and Australia). Transmission can occur from mother to baby (95% likelihood in mother with replicating HBV). Babies who do not acquire it from their mothers in these areas have a high chance of being infected by other members of the extended family within the first year of life. Such young children do not develop symptoms, but remain subclinical for the first few decades of life (Figures 36.2 and 36.3). Most people in these endemic regions are either carriers or immune by adult life. Such transmission is responsible for most of the world’s burden of HBV-related disease.

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FIGURE 36.2 The outcome of HBV depends upon age of acquisition.

HBV = hepatitis B virus; HCC = hepatocellular carcinoma.

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FIGURE 36.3 The natural history of hepatitis B virus acquired at birth, showing: phase 1—the immunotolerant replicative phase; phase 2—the e antigen clearance phase; phase 3—the residual integrative phase.

From Digestive Health Foundation 2000, with permission.

ALT = alanine aminotransferase; HBeAg = hepatitis B e antigen; HBV = hepatitis B virus; HCC = hepatocellular carcinoma.

The second setting is transmission in adolescence or adult life by more ‘Western’ practices, such as injecting drug use, and sexual contact. Other risk factors are listed in Table 36.2.

TABLE 36.2 Some risk factors for acquisition of hepatitis B virus

• Perinatal
• Sexual contact (especially male–male)
• Close family/domestic contact
• Injecting drug use
• Blood transfusion
• Non-sterile medical injections
• Tattoos

• Living or working in crowded condition (e.g. prisons)
• Living or working in institutions for the intellectually disabled
• Contact with renal dialysis
• Folk/cultural practices involving skin penetration

NATURAL HISTORY OF HEPATITIS B

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