A substantial proportion of patients with chronic hepatitis B (CHB) do not fall into any of the defined phases and are considered to be in the "gray zone" or "indeterminate phase." Most of the current clinical practice guidelines have no recommendations for antiviral treatment for them. However, the gray zone CHB patients with significant hepatitis B virus levels (>2000 IU/mL) and persistently normal alanine aminotransferase (ALT) levels have a significantly high risk of hepatic inflammation, fibrosis, and hepatocellular carcinoma. The molecular, clinical, and economic data that we have reviewed collectively in this article provide support for simplification of treatment initiation strategies that incorporate broader treatment of adult patients with CHB in the gray zone (hepatitis B virus [HBV] DNA ≥2000 IU/mL), regardless of ALT levels.
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