INFECT DIS TROP MED 2017; 3 (3): E412 Current epidemiology, prevention and treatment of Hepatitis B in China M. Yue, H. Mingshou Department of Infectious Diseases, Guangzhou Panyu Central Hospital, Guangzhou, China ABSTRACT: — Hepatitis B is still the main cause of chronic liver disease in China, causing a huge burden on people’s health and economic development. During the past two decades, great efforts in the prevention and treatment of hepatitis B have been made, with a lot of achievements. However, antiviral therapy for hepatitis B virus (HBV) infection and disease eradication remain a major challenge. This paper focuses on the prevalence of HBV in- fection and its prevention and treatment in China. — Keywords: Hepatitis B virus, Epidemiology, Prevention, Treatment. INTRODUCTION the aging of the infected HBV population, coupled with the widespread use of antiviral drugs cause an elevated Worldwide, there are about 240 million people with proportion of patients with HBeAg-negative CHB5. HBV infection, with a high rate of infection in China1. In 2006, the National Hepatitis B serum epidemio- In the past two decades, hepatitis B transmission has logical survey showed that the proportion of HBV car- been significantly controlled in China due to the im- riers was 7.18% in the 1 to 59 years old population6,7. provement in understanding HBV natural history, strict According to the data, there are about 93 million peo- screening of blood or blood products, the successful ple with chronic HBV infection, of which 20 million development of new antiviral drugs and especially the cases are CHB patients. There are areas of high, me- nationwide implementation of Hepatitis B vaccination. dium, and low endemicity based on a prevalence of Although the prevention and treatment of hepatitis B HBsAg positivity of ≥8, 2-7, and <2%, respectively8,9. infection is still very difficult to achieve, it is no longer China is a country with a high endemicity, where 90% impossible to control the spread of hepatitis B. of new infections occurred among infants and young children due to perinatal or household transmission. As a result of the strict implementation of screening for The epidemiology of Hepatitis B virus in China HBsAg and HBV DNA, transfusions cause rare trans- mission of HBV. However, there are still other trans- According to the World Health Organization, about 2 missions, such as unprotected sexual contacts, tattoos, billion people have been infected with HBV, of which and intravenous drug use. Thanks to the introduction 240 million people are chronically infected. Every of the HBV vaccination and the wide availability of an- year, about 650,000 people die of liver failure, liver tiviral drugs to treat the primary infection in infected cirrhosis and hepatocellular carcinoma (HCC) caused subjects, HBV prevalence has decreased a lot. In 2014, by HBV infection. Globally, the proportion of liver the Chinese Center for Disease Control and Prevention cirrhosis and HCC caused by HBV infection are 30% (CDC) conducted a survey on hepatitis B sero-preva- and 45%2,3, respectively, while the proportion in China lence on 1 to 29 years of age group. The results showed is 60% and 80%4, respectively. Due to the universal that the prevalence rates of HBsAg positive subjects implementation of Hepatitis B vaccination, acute HBV were 0.32%, 0.94% and 4.38% from 1 to 4, 5 to 14, and infection has been significantly reduced. Meanwhile, 15 to 29 years of age, respectively10. CORRESPONDING AUTHOR: HUANG MINGSHOU, MD; E-MAIL: [email protected] 1 INFECT DIS TROP MED antiviral drugs approved in China are lamivudine, ade- The prevention of Hepatitis B in China fovirdipivoxil, entecavir, telbivudine, tenofovir diso- proxil fumarate, conventional interferon-alfa (IFN), Most of Chinese patients develop chronic infection due and pegylated interferona2a (Peg-IFN-2a)17. The goal to perinatal or household transmission. Efforts to control of therapy for chronic HBV infection is to improve the transmission should, therefore, be focused on prevent- quality of life and survival of the infected person by ing infection of newborns. Hepatitis B vaccination is the preventing progression of the disease and prevention most effective way to prevent virus transmission. Every of transmission of HBV to others18. This goal can be newborn in the whole country receives Hepatitis B vac- achieved if HBV replication can be suppressed in the cine10. Each pregnant woman who goes to hospital for majority of people and for a long period. The indica- prenatal care undergoes screening for Hepatitis B. The tions for treatment are generally based mainly on the infants born from HBsAg-positive mothers receive vac- combination of three criteria: serum HBV DNA lev- cine plus hepatitis B immune globulin (HBIG). With the els, serum ALT levels and severity of liver disease availability of both hepatitis B immune globulin (HBIG) (assessed by clinical evaluation, liver biopsy or non- and hepatitis B vaccine (at first plasma-derived, later re- invasive methods). Indications for treatment should combinant), there was a marked reduction in the infant also take into account age, health status, family history infection rate. There is still failure occurring in infants of HCC or cirrhosis and extra hepatic manifestations. born form HBeAg-positive mothers with pre-delivery Lamivudine (LAM) is the first drug approved in China HBV DNA ≥6 log10 copies/ml11,12. Therefore, short- in 1999, leading to a decrease of mortality in patients term maternal NAs starting from 28-32 weeks of ges- with chronic hepatitis B. At present, the recommend- tation are advisable for mothers with HBV DNA levels ed first-line agents include pegylated interferon and above 6 log10 IU/ml13,14. Besides, it was suggested that 2 nucleotide analogues, entecavir and tenofovir diso- personnel regarded as high risk, such as medical staff, proxil fumarate, which have potent HBV-DNA sup- workers contacting with blood, staff working in child pression activity and high genetic barrier to resistance. care institution, organ recipient, family members of HB- Although prolonged lamivudine (LAM) therapy is sAg-positive carriers, man having sex with men, should associated with the emergence of LAM-resistant mu- also receive hepatitis B vaccine. tations, it is still a commonly used therapy in China The statement above is crucial to protect those in- because of its low cost and long-term safety. Immuno- dividuals who are at risk. The other important way modulatory agents including conventional interferon-a of prophylaxis is cutting off transmission. It has been (IFN) and pegylated interferon (Peg-IFN) have been concluded that contaminated needles can spread HBV, approved in China for more than 10 years19. These including intravenous drug users, acupuncture, tattoos, agents have dual actions: enhancing host immunity ear piercing and needle prick injuries in hospital set- to mount a defense against HBV and modest antiviral tings15. Hence, China national medical ministry pays action. Over the past two decades, IFN-based thera- much attention to the disposal of sharp instruments and py has been an important treatment for CHB patients. public health education. Nowadays, disposable needles For HBeAg-positive patients receiving Peg-IFN-based are used for acupuncture and ear piercing. Besides, treatment, the following baseline predictors are relat- education and surveillance concerning the disposal of ed to a higher sustained response rate, such as HBV sharps, the banning of recapping needles, and needle DNA <2×10 8 IU / ml, high ALT levels, genotype A or disassembly are also enforced in China. B, low HBsAg levels at baseline, liver inflammation The management of HBsAg-positive carriers or pa- necrosis of G2 or more20. However, there are no base- tients was also emphasized by the government. Those line and on-treatment predictors of response to IFN for who have been identified as HBsAg positive, should the HBeAg-negative petients21. The patients who are be referred to the Local Disease Prevention and Con- young (including adolescent patients), or wish to have trol Center. The family members of the HBsAg-posi- babies, or want to complete a short-term therapy and tive personnel are recommended to check HBV serum those who receive antiretroviral therapy for the first markers and those anti-HBs negative members should time, may be recommended IFN therapy. Frequent side receive HBV vaccine. Moreover, it was advisable that effects and subcutaneous injection are the main disad- the HBsAg-positive members are followed up by an in- vantages of IFN treatment. IFN is contraindicated in fectious disease doctor every 3-6 months10. patients with decompensated HBV-related cirrhosis or Although great achievements have been reached, autoimmune disease, in patients with uncontrolled se- China still faces the lack of vaccine programs and use vere depression, and in pregnant women22. in the undeveloped regions. Limits of current antiviral treatment THE TREATMENT OF HEPATITIS B IN CHINA The antiretroviral therapy controls the replication Antiviral therapy of HBV effectively, being shown to decrease he- patic fibrosis or reverse cirrhosis, and to reduce the Antiviral therapy is the main strategy for patients with development of hepatocellular carcinoma (HCC). 2 chronic hepatitis B in China, and in the world16. The However, it is difficult to eradicate the virus. HB- CURRENT EPIDEMIOLOGY, PREVENTION AND TREATMENT OF HEPATITIS B IN CHINA sAg seroclearance, although the ideal endpoint, is understood. The knowledge about human HBV infec- only achievable in 10-12% of patients by multicenter tion and its related disease is constantly accumulating. trials usually studying relatively young patients23. Chinese scientists made a major breakthrough in HBV A research showed that it would take 52.2 years to receptor research. In 2012, the team of Prof. Li Wenhui clear serum HBsAg completely, indicating a treat- from Peking Institute of Life Sciences found that sodi- ment of decades or even the whole life if choric hep- um taurocholate cotransporting polypeptide was a func- atitis B patients receive current nucleoside (acid) tional receptor for human hepatitis B and D virus28.