Medications currently available for the treatment of hepatitis B virus (HBV) infection are highly effective but not curative. The current paradigm is to recognize patients who require long-term treatment (with its inconveniences) among the majority of healthy carriers who do not need treatment. International guidelines have been established to identify patients requiring treatment but differences concerning the cut-off levels for viral load and transaminases, or need for liver biopsy, compromise their interpretation.

Patients with strictly defined typical forms (HBeAg-positive, normal transaminases level, very high viral load HBV-DNA more than 2×10⁶ IU) have very limited liver injury and do not require treatment. Patients with atypical forms (low viral load HBV-DNA less than 2×10⁶ IU) have a potential risk of more severe histological lesions, but the need for liver biopsy and treatment remains a matter of debate. Immune tolerant patients aged over 40 years should be treated because of the higher risk of hepatocellular carcinoma, even without cirrhosis.

Typical forms with elevated viral load and transaminases level should be treated. Mild hepatitis with moderately elevated transaminases levels (1–2 times upper limit of normal) can cause variable degrees of liver damage, and liver biopsy is necessary. HBeAg-positive hepatitis with very high transaminases levels have a very high rate of spontaneous HBe seroconversion. Hepatitis with high transaminases levels but low viral (HBV-DNA less than 2000 UI) is possible in HBe-negative patients but unusual in HBe-positive patients. Another cause of liver disease could be involved (hepatitis D, steatosis, alcohol).

In the typical form, patients have a normal transaminases level and HBV-DNA less than 2000 IU; histological lesions are in general minimal. Treatment is not indicated. Atypical forms with normal transaminases levels but elevated HBV-DNA more than 2000 IU remain problematic. Forms with high-normal transaminases levels have a higher risk of complications. In the event of inactive cirrhosis, treatment is indicated if replication persists, even at a low level.