What is the clinical significance of a patient being Hepatitis B surface antigen (HBsAg) positive with a Hepatitis B virus (HBV) polymerase chain reaction (PCR) viral load of less than 10 IU/mL?

From the Guidelines

A patient with HBsAg positive and HBV DNA PCR less than 10 IU/mL is typically considered to be in an inactive HBV carrier state or have resolved HBV infection with persistent surface antigen, and no immediate antiviral treatment is usually necessary, but close monitoring is essential. This approach is based on the very low viral load, which suggests minimal risk of liver damage or disease progression, as indicated by the most recent guidelines 1.

Key Recommendations

• Monitor liver function tests every 6-12 months, HBV DNA levels annually, and consider abdominal ultrasound for hepatocellular carcinoma screening, especially in high-risk patients, as suggested by recent guidelines 1.
• Check HBeAg status if not already known, to determine the phase of the disease and guide management decisions.
• Educate the patient about preventing transmission to others, including safe sex practices and avoiding sharing personal items like razors or toothbrushes.
• Advise against donating blood or organs.
• If not already done, screen for hepatitis delta virus co-infection, particularly in endemic areas or high-risk individuals, as recommended by guidelines 1.
• Consider vaccination against hepatitis A if the patient is not immune, given the increased risk of severe disease in patients with chronic liver disease 1.

Rationale

The management of chronic hepatitis B is guided by the patient's HBV DNA level, HBeAg status, and liver disease severity, as outlined in recent guidelines 1. Patients with low HBV DNA levels (<2,000 IU/mL) and normal ALT levels are considered to be in the inactive carrier state, and treatment is not usually necessary. However, regular monitoring is crucial to detect any changes in viral activity or liver health that might necessitate treatment in the future. The persistent HBsAg indicates the virus is still present in liver cells, even if not actively replicating, hence the need for ongoing vigilance.

Additional Considerations

• The patient's HBeAg status and HBV DNA level should be monitored regularly to determine if treatment is necessary, as indicated by guidelines 1.
• The patient should be educated about the risks of transmission and the importance of prevention measures, such as safe sex practices and avoiding sharing personal items.
• The patient should be screened for other viral coinfections, such as hepatitis C and HIV, if they are at risk, as recommended by guidelines 1.

From the Research

Clinical Significance of HBsAg Positive with Low HBV PCR Viral Load

• A patient being Hepatitis B surface antigen (HBsAg) positive with a Hepatitis B virus (HBV) polymerase chain reaction (PCR) viral load of less than 10 IU/mL indicates a low level of viral replication 2.
• Low levels of HBsAg are associated with a lower risk for hepatocellular carcinoma (HCC) and inactive carrier state in HBeAg negative patients 3.
• The presence of HBsAg, even at low levels, suggests that the patient is still infected with HBV and may require ongoing monitoring and potentially treatment 4.
• HBV DNA levels, as measured by quantitative PCR, can provide early prediction of response to interferon treatment and allow for prompt modification of treatment 2.

Implications for Treatment and Management

• The goal of treatment for chronic HBV infection is to achieve a functional cure, defined as HBsAg loss and undetectable serum HBV DNA 4.
• Novel antiviral agents, such as small interfering RNA (siRNA) and core assembly modulators (CAMs), are being developed to achieve functional cure in a significant proportion of patients with chronic hepatitis B 4.
• Ongoing monitoring of HBsAg levels and HBV DNA levels is necessary to guide treatment decisions and predict the natural course of the disease 3, 5.

Diagnostic Considerations

• The measurement of HBV DNA by quantitative PCR is helpful in monitoring response to interferon treatment in chronic hepatitis B virus infection 2.
• HBsAg levels can be used as a surrogate marker for baseline and on-treatment decisions, and may be useful in predicting the risk of HCC and inactive carrier state 3, 5.
• Novel assays with improved sensitivity for detection of very low levels of HBsAg and to determine the source of HBsAg production will be required to measure efficacy of newer antiviral treatments for HBV cure 4.