Hepatitis B biomarkers: Clinical significance of the old and the new

Chronic hepatitis B is a dynamic disease with a very variable outcome ranging from mild, asymptomatic, nonprogressive disease to end-stage liver disease and/or hepatocellular carcinoma. Clinically significant endpoints take years or decades to develop and thus various biomarkers-ranging from clinical data to sophisticated virologic diagnostics-are used as surrogates for disease progression. Liver biopsy remains a robust indicator of disease severity; however, noninvasive markers may offer a useful alternative with some advantages. Clinical decisions are often made using alanine transaminase; however, it lacks adequate specificity to be used in isolation. Serologic markers (hepatitis B early antigen and hepatitis B surface antigen) provide information about the degree of immune control of viral replication, and thus remain important therapeutic indices. Sensitive measurement of serum hepatitis B virus DNA level is an indispensable biomarker. Its suppression is important, but only because it represents a bridge to more permanent stages of disease resolution. Newer assays, including hepatitis B surface antigen titers and hepatitis B genotyping, have therapeutic implications and are becoming more widely available. Clinicians caring for patients with chronic hepatitis B must be aware of the utility and limitations of available surrogate biomarkers.