[medical enjoyment] information: the antiviral drug Vemlidy (tenofovir alafenamide, TAF, 25mg) developed by the US pharmaceutical giant Gilead is approved by the US FDA for the treatment of chronic hepatitis B patients.
The European Commission (EC) has also authorized gilding's drug Vemlidy to enter the European market. This marks the first batch of hepatitis B virus (HBV) treatment approved by the European Union in the past ten years.
Recently, Vemlidy has also heard good news in Asia's regulation. The Ministry of health and labor and welfare of Japan (MHLW) has approved Vemlidy for chronic hepatitis B patients. It is specific for people who have hepatitis B virus replication and abnormal liver function.
What is hepatitis B?
Hepatitis in the vast majority of cases comes from the virus infection. According to the disease prototype, viral hepatitis can be divided into five kinds of hepatitis viruses: HAV, HBV, HCV, HDV and HEV, respectively. The common and different types of hepatitis symptoms are fatigue, fatigue, insomnia, anorexia, nausea, abdominal distension, jaundice, liver pain etc.. Among them, hepatitis B is the largest type of infection.
Hepatitis B, also known as serological hepatitis and viral hepatitis B, is a disease caused by hepatitis B virus (HBV) infection.
Hepatitis B virus (HBV) is a kind of Hepatovirus, which mainly exists in hepatocytes and damages liver cells, causing inflammation, necrosis and fibrosis of liver cells. The clinical manifestations of hepatitis B are varied, and it is easy to develop into chronic hepatitis, liver fibrosis and liver cirrhosis, and a few patients can be transformed into primary liver cancer.
Current status of hepatitis B: China is a big country of hepatitis B
It is estimated that as many as 3.5-4 billion of hepatitis B patients worldwide, the disease can lead to cirrhosis and is a direct cause of the 80% primary liver cancer in the world.
Because of the high incidence of the disease and the large population base, Asia has become a severe area of hepatitis B virus infection. China is a big country of hepatitis B. According to conservative estimates, there are nearly 100 million chronic hepatitis B virus (HBV) carriers in 1 billion 300 million of the country, accounting for about 1/3 of the world's hepatitis B carriers. According to the statistics of the 2015 Health Planning Commission, the number of hepatitis B patients in 2015 was 930 thousand, and the number of deaths was 352.
In recent years, with the implementation of the comprehensive prevention and control of hepatitis B China vaccination strategy to give priority to, including ensuring high vaccination rate of hepatitis B serum screening for pregnant women, to strengthen the monitoring and comprehensive intervention, has significant effect on the prevention of hepatitis B, the incidence rate decreased year by year.
Why is hepatitis B virus strong?
[mode of communication]
HBV is transmitted by the blood and body fluid and has a chronic state of carrying, which is 50-100 times the capacity of HIV (HIV). The main ways of infection are as follows:
(1) repeated use of unclean syringes;
(2) vertical transmission of mother and baby, HBsAg positive mothers have 20% chances to infect infants during childbirth, and if the mother is HBeAg positive, the rate of infection is up to 90%;
(3) there is no protection in the family, which can be transmitted through the secretion or saliva containing HBV.
(4) sexual communication
[genetic characteristics]
Hepatitis B genetic material is incomplete cyclic DNA, part of which is single strand of DNA, and several other hepatitis viruses are RNA virus.
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Due to the lack of correction domain for HBV replication, the mutation rate of HBV genome at each locus is as high as 1.4 X 10-5-3.2 X 10-5 during replication. The high mutation rate of genome leads to the emergence of more subtypes of hepatitis B virus and the rapid enrichment of drug-resistant genotype. Even in patients with good prognosis, the hepatitis B virus will revive. The genetic characteristics of the hepatitis B virus have led to an increase in the difficulty of treatment.
Treatment of hepatitis B
At present, chronic hepatitis B has not been found completely cured drugs. It is the main purpose of the treatment of hepatitis B to clear the virus, prevent the liver complications and improve the quality of life of the patients. The treatment of hepatitis B mainly includes antiviral therapy, immunomodulatory therapy, anti-inflammatory therapy and anti fibrosis treatment, in which antiviral therapy is the key.
There are 2 major categories of common therapeutic drugs. Immunomodulators and nucleoside analogues.
[immunomodulator]
The immunomodulator was injected with interferon (IFN), thymosin -&alpha, 1, and cytokine. They are a class of small molecule activity biologics that can resist HBV infection by enhancing immune response (e.g., enhancing T cells to differentiate and mature). The advantage of immunomodulator is that it does not produce virus resistance, high serum conversion rate and long lasting response, and has dual functions of regulating immunity and anti-virus. The disadvantage is subcutaneous injection, expensive and side effects.
[nucleoside drugs]
Nucleoside drugs are the most important class of antiviral drugs, and are classified as competitive inhibitors in pharmacy. The principle of competitive inhibitors is to design a drug similar to the substrate structure, making it “ deception ” virus enzyme, instead of substrate and enzyme binding, so that the virus enzyme can not bind to substrate, the virus will not be able to replicate. The structurally modified nucleoside selectively inhibits the virus's polymerase to prevent the replication of the virus.
The nucleoside drugs, which are widely used at present, are:
• pyrimidine analogues, lamivudine, telbivudine (He Puding) (- downs);
• guanosine nucleoside analogues [entecate Cave (Bo Luding)];
• purine nucleoside prodrug [adefovir (He Weili)];
&bull ring; adenosine analogues (tenofovir, TDF)
The advantages of nucleoside drugs are effective, convenient and safe. But there are also some shortcomings, such as unfixed course of treatment, easy to occur virus resistant mutation, and relapse after drug withdrawal.
The best antiviral drug of HBV - a new nucleoside reverse transcriptase inhibitor
As everyone knows, for Knoff Vee (TDF) 2015 "chronic hepatitis B prevention guide" recommended treatment of hepatitis B drug of choice for one of the strongest anti viral effect, in a trial for 8 years, for Knoff Vee (TDF) was detected in related drug resistance, is effective for the poor treatment effect of lamivudine or other antiviral drug resistance patients. So it's also known as “ high - and low - resistant ” antiviral drugs.
The FDA approved Vemlidy (TAF tenofovir, alafenamide fumarate, Ella Phenolamine tenofovir fumarate) is a new type of nucleoside reverse transcriptase inhibitors (NRTI), the drug is Gilead has listed drug Viread (tenofovir, TDF) upgrade. In clinical trials, TAF has been proved to have a very high antiviral efficacy at a dose less than Viread 1/10, and has better safety, which can improve renal function and bone safety parameters.
2 III phase studies of hepatitis B: Study 108 and Study 110
The 2 studies were randomized, double-blind, and 96 week III phase clinical trial. They were carried out in 1298 adult patients with hepatitis B (HBV) who had not received treatment before treatment. The primary end point was the proportion of patients with plasma HBV DNA level < 29 IU/mL. Key secondary endpoints included changes in the bone mineral density of the hip and spine from baseline at 48 weeks, and the changes in serum creatinine from baseline at 48 weeks. Other secondary endpoints included the normalization of ALT at 48 weeks and changes in the eGFR from the baseline.
[main end point]
(1) in Study 108, 425 cases of hepatitis B e antigen (HBeAg) negative hepatitis B patients were randomly assigned to TAF (n=285) or Viread (n=140) for the proportion of 2:1. Data showed that in the forty-eighth week of the study, the proportion of patients achieving HBV DNA level < 29 IU/mL in the TAF treatment group was 94% (n=268/285), and the Viread treatment group data was 92.9% (n=130/140), reaching the non inferiority main point (CI -3.6% +7.2%, p=0.47).
(2) in Study 110, 873 cases of hepatitis B e antigen (HBeAg) positive hepatitis B patients were randomly assigned to TAF (n=581) or Viread (n=292) for the proportion of 2:1. Data showed that in the forty-eighth week of the study, the proportion of patients achieving HBV DNA level < 29 IU/mL in the TAF treatment group was 63.9% (n=371/581), and the Viread treatment group data was 66.8% (n=195/292), reaching the non inferiority main point (CI -9.8% +2.6%, p=0.25).
[changes in renal function and bone parameters]
The TAF scheme is superior to the Viread scheme. In the 2 study, at forty-eighth weeks, compared with the Viread treatment group, the bone mineral density of the hip and spine in the TAF treatment group decreased significantly from the baseline (P < 0.001). In the Study 110 study, a small increase in serum creatinine (p=0.02) was observed in the TAF treatment group. In addition, the estimated glomerular filtration rate (eGFR) from baseline to 48 weeks in the 2 study was beneficial to the TAF group (P < 0.01).
[ALT normalization]
In the study, 2 criteria were used to evaluate the normalization of serum ALT levels: the cut-off value of the central laboratory and the American Association for the study of liver diseases (AASLD). Data show that when evaluated using AASLD criteria, the 2 studies, compared with Viread treatment group, TAF treatment group in ALT normalization showed statistical significance is significantly improved; when the value of cut-off (defined by central laboratory normalization at a high level of ALT) evaluation, the 2 treatment groups ALT no statistically significant difference in normal.
At present, TAF has not yet been listed on the mainland of China. If patients want to get the drug, they can only buy from the United States or Hongkong through overseas channels. Hangzhou Health Management Consulting Co., Ltd. provides an overseas medical direct train to help patients travel to cost-effective medical institutions.
In addition, the Lao Ministry of health at the beginning of this year approved special Raphine (tenofovir alafenamide, TAF), for patients with decompensated liver disease in adult patients with chronic hepatitis B virus infection.
Hangzhou Health Management Consultancy Co., Ltd. provides a one-stop international medical consultation service to allow more patients to enjoy the latest international medical results.
