Elimination of viral hepatitis-Progress in China

Zhongping Duan

Beijing Youan Hospital Capital Medical University

Viral Hepatitis • Viral hepatitis is classified as Class B infectious disease

according to the Law of the Prevention/Treatment of Infectious Diseases in China.

• Medical institute should report patient’ personal information to CDC while providing medical service.

• In 2016, the total viral hepatitis incidence was 89.108/100,000.The annual reported cases was 1,221,479.

2016 China CDC data

Viral Hepatitis Distribution

WHO: Global Health Sector Strategy on Viral Hepatitis 2016-2021 Towards Ending Viral Hepatitis

Hepatitis A

• 1991: incidence rate was 55.69/100,000

• 2016: incidence rate was 1.55/100,000, the lowest ever in the history

• In 2015: total 23, 000 hepatitis A reported patients in China.

Challenge:

• The outbreak risk of Hepatitis A is still existed, medical professionals' education is necessary.

2016 China CDC data

Hepatitis B

In 1992: hepatitis B vaccination for newborns and

infants

In 2002: hepatitis B vaccine was integrated into

national expanded program on immunization

From 2009 to 2011, a catch-up campaign was launched

for children younger than 15 years, which succeeded in

vaccinating nearly 68 million children

China has achieved remarkable results in controlling hepatitis,

http://www.nhfpc.gov.cn/jkj/s3582/201307/518216575e544109b2ca ca07fca3b430.shtml

Hepatitis B

According to the national survey, the prevalence of

HBsAg for aged 1–59 yrs declined from 9.8% to 7.2%

during 1992- 2006.

HBsAg prevalence in aged 1–29 yrs declined during

1992–2006, from 10.1% to 5.5% and during 2006–2014

it declined from 5.5% to 2.6%.

At present, there are estimated about 70 million

HBsAg carriers (5–6% prevalence).

Liu J, et al. Lancet Infect Dis. 2016 Jan;16(1):80–6

Polaris Observatory Lancet Gastroenterol Hepatol. 2018 06;3(6):383–403

Third-dose coverage for infants has increased from 30.0% to 99.5% during 1992 -2015. Timely birth-dose coverage has increased from 22.2% to 95.6% during 1992 – 2015.

Target and actual hepatitis B virus vaccination coverage and hospital delivery rate in China, 1992-2015

Liu et al. Bull world health organ 2019;97:230-238

Hepatitis B

• HBsAg prevalence in aged 1-5 yrs declined to 0.32% in 2014.

• First demonstrated that the presence of HBV DNA in cord blood could predict failure of passive-active immunization.

• Oral antiviral drugs in the third trimester of pregnancy can further reduce mother-to-infant transmission, with good safety which was referenced in AASLD and EASL guidelines.

Zuo H, et al. J Viral Hepat, 2012;Feb;19(2):e18-25

Pan et al. NEJM 2016,374(24):2324-2334

TDF reduces mother-to-child transmission of hepatitis B

Hepatitis B Therapy

• Chronic HBV prevention and treatment guidelines (Chinese version will updated soon)

• Recommendations:

• 6. Patients with HBV DNA positive and consistent ALT >UNL and excluded other causes, antiviral therapy should be prescribed (B1)

• 7. Compensated chronic hepatitis patients with cirrhosis and HBV DNA positive, HBsAg positive decompensated chronic hepatitis B patient are recommended antiviral therapy(A1).

• 8. Serum HBV DNA positive, ALT normal, having one of the following condition are recommended antiviral therapy:(1) Liver biopsies indicate inflammation/fibrosis( G ≥2 and/ S≥2)(A1);（2）have hepatitis B cirrhosis or hepatitis B related liver cancer family history and older than 30 years old (B1); (3) consistent ALT normal, ＞30 years old, are recommended to have non-invasive liver fibrosis test or liver histology examination, have obvious liver inflammation or fibrosis(A1); (4) having Extrahepatic manifestations associated with HBV (HBV associated glomerulonephritis)

Available Antiviral Therapies

• Treatment naïve patients should first use potent low drug resistance NAs (ETV, TDF, TAF).

• ADV and LAM are not recommended for Hepatitis B patients.

• Peg-IFN-α, interferon-α

Challenges- Reducing mortality

The mortality rate of HBV-related liver

cancer increased from 12.88 per 100,000 in

1990 to 16.42 in 2016.

Global health data results tool. Seattle: Institute for Health Metrics and Evaluation; 2018

Challenges- Increasing coverage

• Only 16.1 million (19%) of CHB patients are diagnosed ( versus 90% in the 2030 target).

• Only 2.8 million(10-11%) of CHB patients are receiving antiviral therapy( versus 80% in 2030 targets).

Wang FS, et al The global burden of liver disease: the major impact of China. Hepatology, 2014 Dec;60(6):20099-108

Hepatitis C

The prevalence of anti-HCV was 0.43% in 2006 national serum survey.

The annual reported number of hepatitis C patients increased from 21,000 to 207,000 during 2003 to 2016.

The cumulated reported number of hepatitis patients is about 1.8M in 2016.

Zhuang H., et al A report on the status of hepatitis C infection in China and its prevention and control strategies.

People’s Medical Publishing House 2017

Seroepidemiological study of hepatitis C in China, Chin J Epidemiol 2011,32(9):888-891; Shen T, et al. PLoS ONE 2011;

6(8):e23550; Zhuang H., et al A report on the status of hepatitis C infection in China and its prevention and control strateg ies.

People’s Medical Publishing House 2017;Dai S, et al. J Med Virol, 2012, 84(1):1-5; Su Y，et al. J Med Virol, 2013, 85(3):425-

432;

Population Anti-HCV (%) Estimated Hepatitis C Pts

General population (1.3 B) 0.43 5.60M

HIV patients(0.7 M) 60-90 0.4-0.6M

Hemodialysis patients(0.6M) 20-50 0.1-0.3M

MSM( 5-10M) 4 0.2-0.4M

Commercial sex worker (6M)

6 0.36M

IVDUs(1.16M)

70-90 0.8-1M

STD population(6M) 15-20 0.9-1.2M

Blood donor (10M) 1 0.1M

Organ transplant population(15M) 5-13 7500-19500

Other high risk population(10M) ～30 3M

Total ～10M

The Types of Hepatitis C

Three DAA drugs have just been

incorporated into the national health

insurance

Phar NS3/4A NS5A NS5B

BMS Asunaprevir Daclatasvir

Gilead Ledipasvir;

Velpatasvir

sofosbuvir

Abbive Paritaprevir;

Glecaprevir

Ombitasvir;

Pibrentasvir

Dasabuvir

MSD Grazoprevir Elbasvir

Ascletis Danoprevir

Oral anti-HCV screen Three DAA drugs have just been

incorporated into the national health insurance

Yang et al PLoS ONE 2019; 14(2): e0211795

Hepatitis E

•The accumulative reported Hepatitis

E patient number was 329,519 from

2004 to 2017 in China.

• Only very small percentage of HEV identified in China

Sun et al. Chin J Prev Med, April 2019,vol 53,No.4

Hepatitis E

• Hepatitis E vaccine, the first made in China vaccine,

was developed and marketed in 2012.

• It is classified as class B vaccine, which means people

may get vaccination and pay by themselves.

• Currently the epidemic of Hepatitis E is stabile in China.

Zhu FC et al. Lancet, 2010;

Zhang et al. NEJM, 2015

SUMMARY

• To work together with WHO, Chinese government launch national viral hepatitis prevention and control plan in 2017.

• Though China have made tremendously progress in control viral hepatitis, but we still face lot of challenges.

• We have strong confidence that there will be more achievements in the future.

National viral hepatitis prevention and control plan (2017–2020)

National Health Commission of the People’s Republic of China. China Union Medical University Press; 2017.