HBV infection is globally distributed, with a high prevalence in developing countries such as Asia and Africa. About 400 million people are infected with HBV worldwide. Since 1992, China has included hepatitis B vaccination for newborns in the national immunization program, and the HBsAg positivity rate has dropped from 9.75% in 1992 to 7.18% in 2006, which is a significant reduction. However, there are still 20-30 million chronic hepatitis B patients, which is extremely harmful to people’s health and promote economic construction, and is a national priority disease.
Chronic hepatitis B is a progressive, difficult-to-treat disease. Without long-term effective antiviral treatment, it can progress to cirrhosis, liver failure and hepatocellular carcinoma (HCC).
According to the “Guidelines for the Management of Chronic Hepatitis B” developed by domestic and foreign hepatology societies, it is unanimously pointed out that “the quality of life and survival time can be improved by continuously suppressing HBV, reducing the lesions, reducing and preventing their progression to cirrhosis, decompensated cirrhosis, liver failure and HCC. “. The European Annual Meeting of the Liver (EASL) further proposed “Endpoints for the treatment of chronic hepatitis B”. Treatment endpoints for HBeAg(+) chronic hepatitis B.
①Desired treatment endpoint: sustained HBsAg conversion or seroconversion
②M Intended therapeutic endpoint: sustained HBeAg seroconversion;
③Essential treatment endpoint: sustained serum HBV DNA undetectable.
Treatment endpoints for HBeAg(-) hepatitis B.
①Desirable treatment endpoint: sustained HBsAg conversion or seroconversion;
(iii) Sustained serum HBV DNA undetectable.
Therefore, the strategy to achieve the goals and endpoints of antiviral therapy for chronic hepatitis B should be sustained maximal suppression of HBV and achievement of immune control.
Obtaining sustained maximal suppression of HBV requires optimization and individualization of therapy and resistance management. Immunocontrol should be achieved by the disappearance or seroconversion of HBeAg and HBsAg, which is a marker for the emergence and improvement of HBV immune function, especially specific immune function; sustained disease remission (no detectable HBV DNA; ALT normalization; histologic improvement); satisfactory treatment endpoints, with a limited course of therapy; and the possibility of achieving HBsAg disappearance or seroconversion. The treatment endpoints of HBsAg disappearance or seroconversion are ideal); reduce or prevent the occurrence of cirrhosis and H CC; improve quality of life and increase survival.
The disappearance of HBsAg and seroconversion suggest the enhancement and restoration of specific immune response to HBV; it is the “ideal treatment endpoint”, close to the outcome of cure; significantly improve the hepatic histological lesions and prevent disease progression; significantly reduce the level of HBVcccDNA in the liver; reduce the incidence of cirrhosis and hepatocellular carcinoma, significantly improve the quality of life and prolong survival. The incidence of cirrhosis and hepatocellular carcinoma is reduced, and the quality of life and survival are significantly improved.
Chronic hepatitis B antiviral therapy on the one hand is to be rapid, potent and continuous suppression of the virus in addition to the induction of immune control. Since the emergence of HBeAg seroconversion and HBsAg disappearance/seroconversion is slow and difficult, how to predict the emergence of HBeAg seroconversion and HBsAg disappearance/seroconversion due to HBeAg seroconversion? In recent years, a new experimental assay technique, HBeAg and HBsAg quantitative assay, can predict HBeAg seroconversion and HBsAg disappearance/seroconversion.
Fried et al. applied peg-IFNa-2a to treat 814 patients with HBeAg(+) chronic hepatitis B. S machine was divided into three groups: pegIFNa-2a 180 mg/w, pegIFNa-2a 180 mg/w + lamivudine 100 mg qd and lamivudine 100 mg qd, treated for 48 weeks and discontinued S visit for 24 weeks, for a total of 72 weeks. HBeAg quantification was performed at 24 weeks of treatment in 263 patients treated with pegIFNa-2a alone, and HBeAg levels were £10 PEIU/mL in 137 patients (52%), and HBeAg seroconversion was 71/137 (52%) at S-visit to 72 weeks, while HBeAg levels
>Lau et al. used the same design scheme with HBsAg quantification, and at 24 weeks of treatment, HBsAg levels <1500 IU/mL The HBeAg blood [conversion rate was 66/129 (51%) at 1 year of drug discontinuation, where the HBsAg disappearance rate was 20%, and the HBeAg blood [conversion rate was 32% and 19% at 1 year of drug discontinuation when HBsAg was 1500-<20,000 IU/mL and 20,000 IU/mL, respectively.
Moucari et al. reported that 49 patients with HBeAg(-) chronic hepatitis B were treated with Peg-IFNa-2a for 48 weeks with an S visit of 24 weeks, and HBsAg levels decreased > 0.5 log10 IU/mL at 12 weeks from baseline with SVR (S visit after 48 weeks of treatment). 24 weeks of treatment, HBVDNA < 70copies/mL) positive predictive value and negative predictive value were 89% and 90%, respectively, and the baseline reduction of HBsAg level > 1 log10 IU/mL at 24 weeks of treatment SVR positive predictive value and negative predictive value were 92% and 97%, respectively. This suggests that early HBsAg levels can predict SVR.
Dynamic changes in HBsAg levels can predict response, relapse and no response.
How to improve HBeAg seroconversion rate and HBsAg or seroconversion rate?
Treatment regimen can be decided based on the amount and dynamics of early HBeAg and HBsAg decline. Combination therapy or longer treatment courses are possible. Takkenberg et al. treated with peg-IFNa-2a 180mg/w + ADV10mg/d for 48 weeks, S-visit for 24 weeks and S-visit for 2 years for long-term S-visit. The rates of HBsAg disappearance and HBsAg serological conversion at the end of treatment, at the end of S-visit and at the end of long-term S-visit were 9/60 (15%) and 8/60 (13%; 8/55 (15%) and 8/55 (15%); 11/55 (20%) and 11/55 (20%), respectively.
HBeAg and HBsAg quantitative assay, pegylated interferon was used to treat patients with HBeAg (+) and (-) chronic hepatitis B. The level of HBeAg and HBsAg decrease at 24 weeks of treatment was used to determine the next step to optimize the individualized treatment regimen and improve the efficacy according to the RGT strategy.