Do not look at the diameter of the hepatitis B virus is only 42 nanometers in size (1 nanometer is one millionth of a millimeter), but contains the “five internal organs”, divided into several “zones” (parts): the former S / S area, the former C / C area, P area and X area (see figure), really “The virus is small, but it has all the organs! The “five internal organs” of the hepatitis B virus are all subject to mutation. The purpose of their mutation is to escape from the immune system; the second is the occurrence of drug resistance, against the inhibitory effect of drugs. Look at the “five internal organs” (genome) of the hepatitis B virus. The pre-C region and the C region (the basic core promoter) are the key sites that determine how the e antigen “program” is written. When the body’s immune system attacks the virus, or under strong drug suppression, the hepatitis B virus may “yield”, the e antigen is suppressed, and the serum of the five indicators of hepatitis B “major triple-positive” will become The e antigen is suppressed and the “major triplet” of the five indicators in the serum becomes a “minor triplet”. But sometimes viruses are not “willing” to fail, they change their appearance in order to find ways to escape from the immune system, not to produce e antigen or produce less e antigen, so that they still look like “minor triplets”, but can still produce the viral gene –DNA, becoming a mutant virus. This mutant virus is often referred to as the pre-C/ C promoter variant (pre-C variant), and is also referred to as e antigen-negative chronic hepatitis B in our “Guidelines for the Prevention and Treatment of Chronic Hepatitis B”. Patients with this type of e antigen-negative chronic hepatitis B do not have as high a serum HBV DNA as those with “major triple-positive” infection, and their transaminases often fluctuate at low levels, but they are no less destructive to the liver, often leading to cirrhosis and hepatocellular carcinoma. Therefore, treatment with antiviral drugs is required. The pre-S/S region, which determines the “programming” of the hepatitis B surface antigen, also wants to evade the immune system by dropping the pre-S or S protein, the outermost layer of the virus, and producing a mutant virus without a “coat”. This hepatitis B virus is not detected in the serum of infected people with hepatitis B surface antigen, but there is still a small amount of viral DNA replication and anti-HBc positivity. This is what is referred to as occult chronic hepatitis B in our “Guidelines for the Prevention and Treatment of Chronic Hepatitis B”. However, this condition is extremely rare and one need not worry too much. The P-zone is where the hepatitis B virus DNA polymerase is located, and oral anti-hepatitis B virus drugs such as lamivudine and telbivudine are designed to inhibit hepatitis B virus replication by inhibiting the DNA polymerase in the P-zone. Therefore, after long-term treatment with these drugs, mutations occur at the site of drug action in the P region, and the mutated hepatitis B virus becomes resistant to the drugs (drug resistance). Patients who take nucleoside (acid) drugs are more likely to develop drug resistance if they frequently miss doses or interrupt treatment. Treatment becomes more difficult after drug resistance. To prevent the occurrence of drug resistance, we must do the following: do not treat blindly, take medication without interruption, do frequent tests, and follow medical advice. Hepatitis B virus is very cunning, don’t look at its small size, but it plays tricks with humans in different ways. We should not take it lightly!