What is the importance of hepatitis B virus mutation? Hepatitis B virus (HBV) is composed of viral antigen wrapped in viral nucleic acid (DNA). HBV nucleic acid (HBV DNA) forms the genes of hepatitis B virus, which are composed of tandem nucleic acid codons. The hepatitis B virus gene determines the replication activity of the virus, and a variation in one codon at a key site may reduce or enhance the replication activity of the virus. If viral replication is enhanced it can aggravate liver lesions and contribute to the progression to severe chronic liver disease. It is as if the number of destructive molecules has increased and the damage caused is naturally more serious. The hepatitis B virus antigen is synthesized by its viral gene code. The mutation of 1 key codon will change the nature and function of the viral antigen, thus allowing the hepatitis B virus to escape the body’s immune clearance. It is as if the sabotaging molecule undergoes a makeover and is not easily detected, but also adapts to an environment that would otherwise be unfavorable to it and replicates even more. How does hepatitis B virus mutation occur? Your child looks like you because he or she is a “copy” of your genetic template; but there is always something different, which can be described as “mutation”. The hepatitis B virus has a high replication rate and undergoes an uncountable number of replication generations in the human body during infection, with the possibility of nucleotide incorporation errors that can cause transmission distortion. The mutation rate of hepatitis B virus is tens of thousands of times higher than that of other DNA viruses, with hundreds of thousands of mutations per nucleotide codon per year, but the vast majority are not in critical positions, and this natural variation has little biological significance. However, mutations promoted by human immunity or antiviral drugs are different, and may occur at the site of viral antigen attacked by immunity or at the target site of viral antigen acted upon by drugs. After mutation, the virus can still replicate, or even replicate more actively, and can evade immune clearance (immune evasion) or can evade drug suppression (drug-resistant mutation). What are the risks of hepatitis B virus mutations? The two types of hepatitis B virus mutations mentioned above can have serious effects on chronic hepatitis B. The most important ones are two: one is the mutation of the pre-C region or C promoter of the hepatitis B virus, which is not easily recognized by the body’s immune system and is more difficult to clear, making it very easy for chronic hepatitis B to recur in “small triplets”. Therefore, patients with chronic hepatitis B with HBeAg(C) should not take it lightly. The other is resistance mutation to nucleoside analogues, where the virus is no longer sensitive to the drug used and can have cross-resistance to other nucleoside analogues, or, although the same resistance mutation does not occur with other nucleoside analogues, the sensitivity of the virus to the new drug can be reduced to varying degrees; this can even lead to early resistance mutation of the new drug. The topic of resistance mutation of nucleoside analogues is a very important one, and I will introduce it to the network later.