The China Hepatitis Prevention and Control Foundation, the Chinese Medical Association, the Chinese Society of Hepatology and the Society of Infectious Diseases co-hosted a press conference on the 2015 edition of the Chinese Guidelines for the Prevention and Treatment of Chronic Hepatitis B and C in Beijing, where the Chinese Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2015 edition) and the Guidelines for the Prevention and Treatment of Hepatitis C (2015 updated edition) were released. 2015 updated version).
The 2015 edition of the Hepatitis B Guidelines points out that the Chinese Medical Association’s Hepatology and Infectious Diseases Sections organized domestic experts to develop the Guidelines for the Prevention and Treatment of Chronic Hepatitis B (first edition) in 2005 and revised them for the first time in 2010. The new Guidelines are intended to help clinicians make rational decisions in the diagnosis, prevention and antiviral treatment of chronic hepatitis B, but are not mandatory standards and cannot include or solve all problems in the diagnosis and treatment of chronic hepatitis B. Jie Shenghua, Department of Infection, Wuhan Union Medical College Hospital
The Hepatitis B Guidelines emphasize that when a clinician is faced with a particular patient, he or she should develop a comprehensive and reasonable treatment plan based on his or her professional knowledge, clinical experience and available medical resources, with full knowledge of the best clinical evidence about the disease and careful consideration of the patient’s specific condition and his or her wishes.
What is included in the new Hepatitis B Guidelines?
So, what does this new Hepatitis B Guideline include?
Part I: Explanation of 22 terms, including chronic HBV infection, chronic hepatitis B, HBeAg-positive chronic hepatitis B, HBeAg-negative chronic hepatitis B, inactive HBsAg carriers, hepatitis B recovery, acute exacerbation of chronic hepatitis B, hepatitis B reactivation, HBeAg-negative, and HBeAg serologic conversion.
Part II: Epidemiology and prevention (about 20 million cases of chronic hepatitis B in China)
According to the World Health Organization, about 2 billion people worldwide have been infected with HBV, of which 240 million are chronic HBV infected, and about 650,000 people die each year from liver failure, cirrhosis and hepatocellular carcinoma (HCC) caused by HBV infection. Globally, the proportion of patients with cirrhosis and HCC caused by HBV infection is 30% and 45%, respectively. Among patients with cirrhosis and HCC in China, the proportions caused by HBV infection are 60% and 80%, respectively.
In 2006, the national hepatitis B seroepidemiological survey showed that the HBsAg carriage rate of the general population aged 1-59 in China was 7.18%. According to this projection, there are about 93 million people with chronic HBV infection in China, including about 20 million cases of chronic hepatitis B. The results of the 2014 national hepatitis B seroepidemiological survey of people aged 1~29 years showed that the prevalence of HBsAg in people aged 1~4 years, 5~14 years and 15~29 years were 0.32%, 0.94% and 4.38%, respectively (China CDC).
HBV is mainly transmitted via blood (e.g. unsafe injection, etc.), mother-to-child and sexual contact. Mother-to-child transmission occurs mainly in the perinatal period, mostly from exposure to blood and body fluids of HBV-positive mothers during delivery. HBV is not transmitted through the respiratory and digestive tracts, and epidemiological and experimental studies have not found that HBV can be transmitted by blood-sucking insects (mosquitoes, bedbugs, etc.).
In this part, the new version of the Guidelines points out that hepatitis B vaccination is the most effective way to prevent HBV infection; the Guidelines also propose the treatment of accidental post-exposure prophylaxis, management measures for patients and carriers, and strategies to cut off the transmission route.
Parts III-IX of the Guidelines
Parts III to IX of the Guideline introduce the pathogenesis, natural history and pathogenesis, laboratory tests, non-invasive diagnosis of liver fibrosis, diagnostic imaging, pathological diagnosis of liver tissue, and clinical diagnosis related contents. The following are some excerpts.
1. laboratory tests: including HBV serological tests, HBVDNA, genotype and variant tests, and biochemical tests.
2. imaging diagnosis: the main purpose of imaging examination is to monitor the clinical progress of CHB, understand the presence or absence of cirrhosis, detect occupying lesions and identify their nature, especially to monitor and diagnose HCC. ultrasound, CT and magnetic resonance imaging (MRI) can be performed on the liver, gallbladder and spleen.
3. Clinical diagnosis: Based on serology, virology, biochemical tests and other clinical and ancillary findings in HBV-infected patients, chronic HBV infection can be classified as: chronic HBV carriers, HBeAg-positive chronic hepatitis B, HBeAg-negative chronic hepatitis B, inactive HBsAg carriers, occult chronic hepatitis B, and hepatitis B cirrhosis.
Part X: Treatment Goals
The treatment goals identified in the Guidelines are to maximize long-term suppression of HBV replication, reduce inflammatory necrosis of hepatocytes and liver fibrosis, and achieve delay and reduction of liver failure, cirrhotic decompensation, HCC and other complications, thereby improving quality of life and prolonging survival time. In the course of treatment, clinical cure of chronic hepatitis B, i.e., sustained virological response after cessation of therapy, disappearance of HBsAg with ALT reversion and improvement of liver histology, should be pursued as much as possible for some suitable patients.
In addition, the Guidelines set three major treatment endpoints, as follows.
1. desirable endpoint: HBeAg-positive and HBeAg-negative patients who obtain durable HBsAg disappearance with or without HBsAg serologic conversion after discontinuation of the drug.
2. Satisfactory endpoints: HBeAg-positive patients, obtaining sustained virological response and ALT normalization with HBeAg serological conversion after drug discontinuation; HBeAg-negative patients, obtaining sustained virological response and ALT normalization after drug discontinuation.
3. Essential endpoints: long-term maintenance of virologic response (undetectable HBVDNA) during antiviral therapy if sustained response after drug discontinuation cannot be obtained.
Part XI to XV: Treatment regimen related
Parts XI-XV of the Guideline focus on treatment regimen-related content, including indications for antiviral therapy, interferon alpha therapy, NAs therapy and monitoring, antiviral therapy recommendations and follow-up management, and antiviral therapy recommendations for special populations. The following are some excerpts.
1. China has approved regular interferon (IFN-α) and pegylated interferon (PegIFN-α) for the treatment of chronic hepatitis B.
2. The Guide describes the efficacy of five NAs drugs, including entecavir, tenofovir disoproxil fumarate, telbivudine, adefovir, and lamivudine.
Part XVI: Top Ten Issues to be Addressed
The last part of the Guideline presents the top 10 issues to be addressed, as follows: 1. the status and role of biological markers in the natural history, treatment indication, efficacy prediction and prognosis determination of hepatitis B; 2. the status and role of noninvasive diagnostic tools for liver fibrosis in treatment indication, efficacy determination and long-term follow-up; 3. efficacy confirmation and cost effectiveness analysis of combination/sequential regimens for NAs and IFNs; and 4. search for clinical criteria and biological markers to predict NA discontinuation; 5. impact of long-term NA therapy on cirrhosis reversal and HCC incidence; 6. safety of long-term NA therapy and impact of NA therapy during pregnancy on long-term safety of mother and child; 7. clinical efficacy studies based on long-term follow-up cohorts and large databases; 8. explore the establishment of a new chronic disease management model of doctor-patient interaction to improve patient adherence. 9. conduct health economics studies, explore effective ways to reduce drug prices and improve treatment accessibility; 10. explore new therapies for HBsAg clearance and long-term clinical regression after HBsAg clearance.
Hepatitis B treatment: clear recommendation of potent, low drug resistance drugs as first-line drugs
The new version of the Guidelines was revised by a total of 19 experts and scholars, including Academician Zhuang Hui, Professor Jia Jidong and Professor Hou Jinlin. Academician Zhuang Hui, Professor of Peking University School of Medicine, pointed out that the updated version of the Hepatitis B Guidelines clearly recommends strong and low drug-resistant drugs as first-line drugs based on 15 years of clinical experience in the antiviral treatment of hepatitis B in China.
Although the guidelines of various countries for hepatitis B make it clear that strong and low drug-resistant drugs should be the first choice of hepatitis B treatment, in China, 60% to 70% of hepatitis B patients still use highly drug-resistant drugs such as lamivudine, adefovir and telbivudine, especially in second- and third-tier cities and rural areas. It is reported that this updated guideline clearly points out that tenofovir disoproxil and entecavir, the representative drugs of strong and low resistance, are the first choice for oral use in patients with chronic hepatitis B primary treatment, while highly resistant drugs are not recommended.
In March, WHO issued its first hepatitis B treatment guidelines with five main recommendations
In addition to the importance China attaches to hepatitis B prevention and control; in March this year, WHO released its first-ever guidance on the treatment of chronic hepatitis B. This guidance document covers all elements of treatment, from determining who needs to be treated, to which drugs to use and how to monitor infected individuals over time. The five main recommendations made are as follows.
1. the use of several simple, non-invasive tests to assess the staging of liver disease to assist in determining who needs to be treated
2. prioritizing the treatment of patients with cirrhosis – the most advanced stage of liver disease.
3. administering treatment for chronic hepatitis B using tenofovir or entecavir, two safe and highly effective drugs
4. regular monitoring using a simple test for early detection of liver cancer to assess whether the treatment given is effective and whether it needs to be stopped.
5. the specialized needs of specific populations, such as HIV co-infected persons, children and adolescents, and pregnant women, are also taken into account.