Hepatitis B

Hepatitis B is a viral infection of the liver caused by hepatitis B virus, a partially double stranded deoxyribonucleic acid hepadnavirus. It is transmitted through percutaneous or mucosal exposure to infected blood or body fluids, including sexual contact, perinatal transmission from mother to infant, and blood or needle exposure.

It can produce acute, self limiting infection or, in a proportion of cases, chronic infection. Risk of chronicity is strongly determined by age at acquisition. Chronic infection carries substantial long term risk of cirrhosis and hepatocellular carcinoma.

Pathophysiology and natural history

• Liver injury reflects predominantly host immune mediated destruction of infected hepatocytes rather than direct viral cytopathic effect.
• The outcome of infection (spontaneous clearance versus chronicity) is strongly determined by the maturity and vigour of this immune response at the time of exposure.
• Risk of chronic infection is inversely related to age at acquisition. Perinatal infection carries a very high risk (approaching ninety percent) of chronicity, given immature neonatal immune tolerance. Infection acquired as a healthy immunocompetent adult carries a risk of less than five percent.
• This is an important epidemiological principle underlying the emphasis on perinatal and early childhood vaccination and prevention strategies.
• Chronic infection progresses through recognised phases: immune tolerant, immune active, inactive carrier, and, in some patients, a further immune reactivation phase.
• Ongoing viral replication and immune mediated liver inflammation over years to decades drive progressive fibrosis and cirrhosis. Hepatocellular carcinoma risk is particularly high in those with cirrhosis or high viral replication.

• Acute infection ranges from asymptomatic (the majority) to a symptomatic illness resembling hepatitis A, with malaise, nausea, right upper quadrant discomfort and jaundice.
• Occasionally an associated serum sickness like prodrome (arthralgia, urticarial rash) occurs, reflecting immune complex formation.
• Fulminant acute hepatic failure occurs in a small minority of acute infections, presenting with coagulopathy and encephalopathy, and represents a medical emergency.
• Chronic infection is frequently entirely asymptomatic for years to decades. It is often identified through incidental screening (antenatal screening, blood donation, or targeted screening in at risk populations) rather than symptomatic presentation.
• Symptoms, when they eventually occur, typically reflect the development of advanced fibrosis, cirrhosis or hepatocellular carcinoma rather than the underlying viral infection itself.
• Extrahepatic manifestations of chronic infection, though uncommon, include polyarteritis nodosa and membranous glomerulonephritis, reflecting immune complex mediated pathology.

• Hepatitis B surface antigen indicates current infection (acute or chronic), with persistence beyond six months defining chronic infection.
• Hepatitis B surface antibody indicates immunity, either from prior resolved infection or successful vaccination.
• Hepatitis B core antibody (total, comprising both immunoglobulin M and immunoglobulin G) indicates current or past infection and is not induced by vaccination. It is an important marker for distinguishing natural infection derived immunity from vaccine derived immunity.
• Hepatitis B core immunoglobulin M specifically indicates recent acute infection.
• Hepatitis B e antigen and hepatitis B viral deoxyribonucleic acid quantification (viral load) assess replicative activity and infectivity. They are central to staging chronic infection, guiding treatment decisions, and monitoring treatment response.
• Liver function tests, together with assessment of liver fibrosis (using non invasive markers, transient elastography, or, where indicated, liver biopsy), guide the assessment of disease activity and the need for treatment in chronic infection.
• Screening for hepatocellular carcinoma with six monthly liver ultrasound (with or without alpha fetoprotein) is recommended for defined higher risk groups within the chronic hepatitis B population.
• These groups include those with cirrhosis, a family history of hepatocellular carcinoma, and specific demographic groups at elevated risk even in the absence of cirrhosis, according to established regional and international guidance.

• Acute hepatitis B infection is generally managed supportively, as for hepatitis A, given the high rate of spontaneous resolution in immunocompetent adults. Antiviral therapy is reserved for severe or fulminant acute disease under specialist hepatology guidance.
• Chronic hepatitis B treatment decisions are based on a combination of viral load, liver enzyme levels, hepatitis B e antigen status and the degree of liver fibrosis.
• Treatment is generally indicated for patients with significant viral replication and evidence of active liver inflammation or fibrosis. Those in the immune tolerant or inactive carrier phase without significant liver inflammation are typically monitored rather than treated immediately.
• First line oral antiviral agents are tenofovir disoproxil fumarate 245 mg once daily, tenofovir alafenamide 25 mg once daily, or entecavir 0.5 mg once daily. They are chosen for their high potency, favourable resistance profile and generally good tolerability.
• Tenofovir alafenamide is associated with a more favourable renal and bone safety profile, particularly relevant for long term use. Entecavir is increased to 1 mg once daily in patients with prior lamivudine exposure or resistance.
• Therapy is long term, often indefinite, given the low rate of functional cure with currently available agents.
• Pegylated interferon alfa 2a, given as a weekly subcutaneous injection (180 micrograms once weekly) for a finite course of forty eight weeks, is an alternative for selected patients. It suits particularly younger patients without cirrhosis seeking a finite treatment duration.
• It offers a chance of durable off treatment response including hepatitis B surface antigen loss in a minority, though its tolerability profile is less favourable than the oral nucleos(t)ide analogues.
• Regular monitoring, including liver function, viral load and hepatocellular carcinoma surveillance, continues throughout and beyond treatment. Current nucleos(t)ide analogue therapy is generally suppressive rather than curative, so lifelong follow up is typically required.
• Prevention of perinatal transmission is a critical public health priority. It is achieved through maternal antenatal hepatitis B surface antigen screening.
• Infants of hepatitis B surface antigen positive mothers receive both hepatitis B immunoglobulin and the first dose of hepatitis B vaccine within twelve to twenty four hours of birth, followed by completion of the standard infant vaccination schedule.
• Maternal antiviral therapy (typically tenofovir) is considered in the third trimester for mothers with high viral load, given evidence of further reduced transmission risk with this combined approach.
• Universal infant hepatitis B vaccination, given as part of the routine immunisation schedule (typically as a three or four dose series, often combined with other antigens in a combination vaccine), is the cornerstone of long term population level prevention.
• Post exposure prophylaxis following a significant percutaneous or mucosal exposure (needlestick injury, sexual exposure) in a non immune individual comprises hepatitis B immunoglobulin together with initiation of the vaccine series. Give it as promptly as possible, ideally within forty eight hours of exposure.
• Screening for and vaccination of household and sexual contacts of a newly identified chronic hepatitis B case is an important component of management. Add counselling regarding transmission risk reduction.
• Where relevant, screen for hepatitis D coinfection. Hepatitis D requires the presence of hepatitis B surface antigen for its own replication and is associated with more severe and rapidly progressive liver disease when present.

Continue next 5