Management of hepatitis B in China : Chinese Medical Journal (original) (raw)
Hepatitis B virus (HBV) infection is a global public health problem. According to the data of World Health Organization (WHO), 2 billion people worldwide have been infected with HBV, and among them 350–400 million are chronic HBV carriers. Hepatitis B causes about 1 million deaths of HBV related liver failure, cirrhosis, and hepatocellular carcinoma annually.
In China, HBV infection is highly endemic. The seroepidemiological survey on HBV infection conducted in 2006 showed that HBsAg carrier rate was 7.18% in the overall population. Accordingly there were an estimated 93 million HBV carriers, and among them 30 million were patients with chronic hepatitis B.1
Chronic hepatitis B creates a great financial burden to patients, their families, and the whole country. A survey on disease burden carried out in Shanghai revealed that the annual direct and indirect medical costs for each patient with chronic hepatitis B were 3000 USD, while the costs for a patient with compensated or decompensated liver cirrhosis were 5100 USD and 5200 USD, respectively.2 Given these high costs, it is important to emphasize that hepatitis B is a preventable disease. Universal hepatitis B vaccination is the best, cost effective preventive strategy for hepatitis B control. Since 1992, the Ministry of Health of China has implemented a series of regulations on the management of hepatitis B vaccination. As a result, the routine infant HBV immunization was recommended from 1992, but until 2002, unlike other expended program of immunization (EPI) vaccines, families paid for HBV vaccine. In 2001, the central government of China decided to integrate HBV vaccination into the EPI, requiring local authorities of all levels to provide free HBV vaccine to all infants since 2002, but the families had to pay the service fee for the vaccination procedure. Finally, in 2005, the Chinese government adopted a completely free HBV vaccination program for all neonates.3 In the past 10 years, the incidence of acute HBV infection in children has decreased dramatically. The hepatitis B surface antigen (HBsAg) carrier rate decreased from 9.67% in 1992 to the current 0.96% in children 1 to 4 years old and to 2.42% in children 5 to 14 years old in 2006.1
In September 2005, the WHO Western Pacific Regional Office set a goal of reducing chronic HBV infection rate to less than 2% among children five years of age by 2012, as an interim milestone towards the final goal of less than 1%.4 As an active participant, China announced the control of hepatitis B infection, along with three other infectious diseases that were the country's highest priority. On February 13, 2006, China issued its own 2006–2010 hepatitis B control plan, with a goal to reduce HBsAg carrier rate to less than 1% in children younger than 5 years old, and to less than 7% in the overall population by 2010. In provinces with HBsAg carrier rate less than 7%, the goal was to reduce it by another 1%.5 To achieve this goal, the current national hepatitis B vaccine immunization strategy should be amended. (1) Consistently strengthen the general newborn hepatitis B vaccination. For the neonates born to HBsAg positive mothers, they should receive a combination immunization of hepatitis B vaccine (either 10 μg recombinant yeast vaccine or 20 μg Chinese hamster oocyte (CHO) and hepatitis B immunoglobulin (HBIG) (≥100 IU) within 24 hours after birth, although 12 hours after delivery is optional. By combining hepatitis B vaccine together with HBIG injection, a 95%-97% protective rate could be achieved in the neonates born to HBsAg positive mothers, while only 87.8% of the newborn infants could be protected if hepatitis B vaccine was inoculated alone. (2) Create a nation-wide program that provides “catch-up” immunization of HBV vaccine to children who were not vaccinated at birth. (3) Provide vaccines for high risk populations, and increase the vaccine dosage and number of shots for the immunocompromised patients or non-responders. For the non-responders who have completed 3 shots of HBV vaccine, another 3 doses should be given, or vaccines with different origins should be tried. (4) Provide immediate care to individuals exposed to HBV by accidents. To those with anti-HBs negative or status unknown, a combination of the hepatitis B vaccine and HBIG should be given immediately after exposure to the virus.
Accumulative 5-year liver cirrhosis incidence is 12%—15% in chronic hepatitis B patients.6 In addition, the accumulative 5-year liver cancer incidence is 6%—15% in patients with chronic liver cirrhosis.7 The 5-year mortality rate of patients with chronic hepatitis B, compensated, or decompensated liver cirrhosis is 0–2%, 14%-20% and 70%-86%, respectively.8 Problems are further exacerbated because without prompt diagnosis and standard antiviral treatment, chronic hepatitis B patients will develop liver cirrhosis and liver cancer. Fortunately, standardized antiviral treatment is becoming available which can delay or suspend the progress of the disease by long-term suppression of HBV replication, and attenuation of liver cell necrosis and fibrosis. This therapy also reduces or may even prevent complications of the disease, as well as improve the patients' quality of life and even extend their survival time. Therefore, there is an immediate need to promote antiviral treatments for chronic hepatitis B in China. According to a recent survey, only 19% of chronic hepatitis B patients have received antiviral treatments. Worse yet, only 55% of health care workers have knowledge of standard antiviral treatment for the chronic hepatitis B. Perhaps not surprisingly, 73% of physicians only use Chinese herbs and/or other hepatoprotective agents to treat chronic hepatitis B. In addition, the lack of a general education program for the whole population has led to serious discrimination against chronic hepatitis B patients. In fact, 38% chronic hepatitis B patients believe the fake drug advertisement.
Under acceptable expense, chronic hepatitis B patients should receive timely standardized antiviral treatment. With proper medical care, HBV DNA load can be reduced, HBeAg seroconversion may occur, alanine aminotransferase (ALT) returns to normal, and liver histology improves. Even favorable clinical cure has been observed in a few patients after receiving a long-term antiviral treatment, and which was verified by HBsAg seroconversion and undetectable cccDNA in serum (by PCR). Standard antiviral treatment is strongly advocated for patients with persistent HBV infection in the immune clearance phase. Anti-fibrosis treatment should also be based on an effective antiviral treatment, only so liver fibrosis and cirrhosis status could be improved. If such proper and timely antiviral treatment is not provided, 15%—25% of chronic hepatitis B patients will eventually develop liver cirrhosis and hepatocellular carcinoma.9
Currently a contradicting phenomenon exists in China regarding chronic hepatitis B treatment. Though the majority of patients has not received antiviral treatment, over treatment exists, indeed. For example, two different antiviral medications were used simultaneously or antiviral treatment for the chronic HBV carriers in immunotolerant phase with consistent normal ALT and non apparent liver histology abnormality, or inactive HBsAg carriers (serum HBV DNA negative) with normal ALT. Simultaneously administering multiple anti-inflammatory and hepatoprotective medications wastes limited medical resources and increases the higher financial burden to patients.
It is never to excessive to emphasize that anti-inflammatory and hepatoprotective agent treatments are only part of the comprehensive therapy for chronic hepatitis B, and are not substitutes for antiviral treatment. For the patients with elevated serum ALT or apparently live histological necrosis, based on antiviral treatment, appropriate administration of anti-inflammatory and/or hepatoprotective medication are acceptable, but too many kinds of medications may compromise liver function and cause adverse reactions.8
In recent years, new anti-HBV drugs have become available for clinical use, which brings more hope to hepatitis B patients. However, if a standardized antiviral treatment is not implemented forcefully, such new options could adversely affect patients and bring them a great financial burden. Clinical practitioners should fully understand the features of these new antiviral medicines and follow an established treatment strategy, as well as improve their treatment and diagnosis skills. Only so will all chronic hepatitis B patients benefit from the standardized antiviral treatment.
REFERENCES
1. Data on 2006 seroepidemiological survey on HBV infection in China. (Accessed April 21, 2008 at http://www.moh.gov.cn)
2. Chen BX, Chen HF, Lacey L, Saal GB, Mulligan AT. Economic benefit of lamivudine in treatment of chronic hepatitis B virus infection. Chin Hepatol (Chin) 2002; 7: 79–81.
3. Zhuang H. Hepatitis B vaccination in China. Basic Med Sci Clin (Chin) 2004; 24: 136–140.
4. WHO regional EPI targets: eliminate measles and control hepatitis B by 2012. Fifty-sixth Session of the WHO Regional Committee for the Western Pacific, Noumea, New Caledonia, 2005. (Accessed at http://www.wpro.who.int/media_centre/press_releases/pr_20050922+RCM.htm)
5. Zhuang H. Challenge of chronic hepatitis B in China. Chin J Infect Dis (Chin) 2005; 23 Suppl: 2–5.
6. de Franchis R, Hadengue A, Lau G, Lavanchy D, Lok A, McIntyre N, et al. EASL International Consensus Conference on Hepatitis B. 13-14 September, 2002 Geneva, Switzerland. Consensus statement (long version). J Hepatol 2003; 39 Suppl 1: s3–s25.
7. Fattovich G, Bortoltti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol 2008; 48: 335–352.
8. Liaw YF, Leung N, Kao JH, Lau GKK, Merican I, McCaughan G, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol Int Liver Int 2005; 25: 472–489.
9. Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association. Guideline on prevention and treatment of chronic hepatitis B in China (2005). Chin Med J 2007; 120: 2159–2173.
© 2009 Chinese Medical Association