China is a highly endemic area of HBV whose surface antigen carrying rate accounts for about 7.18% of the total population. From this calculation, about 93 million people in the country carry HBV, of which about 20 million are chronic HBV patients. The World Health Organization's "2017 Global Hepatitis Report" shows that the number of chronic HBV carriers in China has reached 120 million, 30 million patients have chronic HBV and 2 million have been treated, which is less than 10% of the total. However, during past several years, the path for many Chinese patients with HBV to see a doctor was bumpy. The book "China's First Disease" said: "To treat the disease, they listened to the so-called expert guidance and propaganda in the advertisement so that they took countless medicines and spent money. Various liver medicines took away the villagers` money but the condition has not improved, more and more patients are like snowballs..."
So, why is the treatment process for HBV so rough and difficult? First of all, HBV is a highly mutated virus. Due to the lack of correction functions of RNA polymerase and reverse transcriptase, under the dual pressure of host immunity and antiviral drugs, its nucleic acid is mutated at some sites. Conventional drugs have no effect on the HBV after gene mutations-that is HBV drug-resistance. The ability of the originally effective drugs to inhibit the virus replication will be greatly reduced, leading to repeated illnesses and disease progression. Once drug resistance occurs, the antiviral efficacy will be reduced to one ten thousandth of the original. HBV can mutate naturally in the course of chronic persistent infection and it can also mutate due to antiviral drug treatment, which are able to lead to a decrease in the sensitivity of antiviral drugs. All about this has caused great difficulty in the choice of drugs, the treatment process is extremely troublesome and the cure is also very difficult.
Assuming that the mutation site of HBV resistance gene can be accurately detected, the DNA sequence of the drug-resistant virus can be obtained and the targeted drugs can be used for precise strike like the elimination of cancer cells, then the complicated and long problem of treating HBV will be solved. In fact, this method is the gold detection magic weapon for precision medicine in the 21st century, also known as the "gold standard"-Sanger sequencing. The dynamic treatment of precision medication is divided into three stages: 1. Judging whether pre-existing drug resistance occurs before antiviral treatment can help doctors choose appropriate initial treatment drugs. 2. Early detection of primary drug-resistant mutations during treatment, and detection every six months to find drug-insensitive sites in time to help doctors switch from non-first choice to reasonable first choice. Predict the occurrence, prognosis and postoperative survival of patients with HCC. 3. When the antiviral treatment is poor, the pathological breakthrough or the load remains high, the genotype mutation can be accurately detected and the treatment plan can be adjusted in time.
The Sanger Sequencing Method is the gold standard in the detection of HBV drug resistance. The detection sites are comprehensive which can detect HBV genotype plus drug resistance sites. The 6 nucleotide analogues have reported 10 sites in the guide and more than 20 sites reported in the literature, compared with the traditional probe method, the detectable target sequence of which is more comprehensive. At present, the detection sensitivity can be as low as 100IU/ml. Therefore, the Sanger sequencing method is the best method for HBV resistance detection, which greatly reduces the difficulty and complexity of the treatment process.
