National Scale

Symposium (VII)

TAIWAN CAN HELP – COMBAT AGAINST DIGESTIVE DISEASES ON A NATIONAL SCALE

UNIVERSAL VACCINATION TOWARD ELIMINATING HBV: A 35YEAR JOURNEY OF TAIWAN

Yen-Hsuan Ni Department of Pediatrics, College of Medicine and Children’s Hospital, National Taiwan University, Taipei, Taiwan

The world’s first nationwide HBV universal vaccination program for infants was launched in Taiwan in July, 1984. Though different countries provide different schedules, most programs consist of 3 doses of recombinant HBV vaccines and hepatitis B immunoglobulin (HBIG). The first dose and the HBIG should be administered within 24 hours after birth. The program now consists of prenatal maternal screening and antiviral therapy if indicated, birth dose of HBIG and a timely 3-dose vaccination, and post-vaccination monitoring. The prevalence of hepatitis B surface antigen (HBsAg) carriers declined from 9.8% to 0.5% in children in Taipei City after 35 years of universal vaccination when we did not start the high viremic maternal antiviral therapy. Can we further reduce the chronic carrier rate to 0%? We have studied that the higher the mother’s viral load, the more likely the newborn could acquire chronic HBV infection. The answer may be that mother-to-infant transmission cannot be over-emphasized and should be intervened if we attempt to eradicate HBV. To completely eliminate hepatitis B virus (HBV) infection worldwide, we need to achieve the following three tasks: (1) to eradicate all of the infectious sources, (2) to interrupt every transmission route, (3) to immunize every susceptible individual. We need to develop effective antiviral therapy to control all the infectious sources; we need to screen the blood bank and all the other possible transmission routes; surely the implementation of universal vaccination program is the most fundamental part to prevent against HBV. We are now at the point to do all these work and hopefully we can achieve this aforementioned goal in this decade.

Symposium (VII)

TAIWAN CAN HELP – COMBAT AGAINST DIGESTIVE DISEASES ON A NATIONAL SCALE

TOWARD ELIMINATION OF HCV IN 2025: THE ROAD AHEAD

Chien-Jen Chen National Hepatitis C Program Office, Ministry of Health and Welfare, Taiwan

In 1990, the seroprevalence of antibody against hepatitis C virus (anti-HCV) in Taiwan was first documented to be 0.95% in volunteer blood donors, 90% in hemophiliacs, and 81% in parenteral drug abusers. The anti-HCV seroprevalence was 17% in HBsAg-positive and 63% in HBsAgnegative patients with hepatocellular carcinoma (HCC). The risk factors for HCV infection in Taiwan include iatrogenic transmission (medical injection, hemodialysis, acupuncture, and blood transfusion), tattooing, and sexual transmission. The long-term risk of hepatic and non-hepatic diseases has been reported by REVEL-HCV study. Prediction models for HCV-related hepatocellular carcinoma have also been developed and validated. A national program of antiviral therapy for chronic viral hepatitis was lauched in Taiwan in 2003. Mortality rates of end-stage liver diseases decreased continuously from 2000-2003 to 2008-2011 in all age and gender groups. Elimination of HCV is an ambitious task that requires integrated national and international efforts as indicated by World Health Organization (WHO). When the World Health Assembly adopted the Global Health Sector Strategy on Viral Hepatitis in 2016, it immediately caught the attention of the people and government in Taiwan. National program to eliminate hepatitis C was very carefully evaluated. It became a consensus to reach the WHO’s goals in 2025, five years earlier than the 2030 deadline set by WHO. Taiwan Hepatitis C Policy Guideline 2018-2025 was approved and published at the beginning of 2019. According to the most recent estimation, there are around 400,000 hepatitis C cases in Taiwan with nearly 7,000 new infections per year. Three strategies for the national HCV elimination program include prevention, screening and therapy. The coverage of HCV screening and treatment has been increasing significantly since 2017, and the budget to cover the cost of new drugs increased from US$101 million in 2017 to US$219 million in 2019. A total of US$1.7 billion will be provided from 2017 to 2025 for the elimination of HCV. The number of chronic hepatitis C (CHC) patients receiving new drug therapy increased from 9,538 in 2017, 19,549 in 2018, to 45,807 in 2019. However, the COVID-19 pandemic decreased the number of treated CHC patients to 36,159 in 2020 and 10,648 in the first-half of 2021. The cure rate based on SVR12 was 96.8% in 2017, 97.4% in 2018, 98.7% in 2019, 99.0% in 2020 and 99.1% in 2021. Both screening and treatment programs will be accelerated to achieve WHO targets of treating 80% eligible HCV patients by 2025. A total of 121,701 CHC patients have been treated with DAA by June 30, 2021. Over 80,000 CHC patients have been successfully treated with peginterferon and ribavirin before 2021. Taiwan is on track to eliminate HCV by 2025 because of strong commitment by the Ministry of Health and Welfare to finance this national program. Other measures including awareness and active screening program and funding for linkage to care programs are also reinforced. Based on the triple focus of the Taiwan Hepatitis C Policy Guideline (therapy spearheads prevention, screening supports therapy, and prevention secures outcome), it is expected that Taiwan will achieve WHO’s HCV elimination goal by 2025.

Symposium (VII)

TAIWAN CAN HELP – COMBAT AGAINST DIGESTIVE DISEASES ON A NATIONAL SCALE

ERADICATING THE BUG AND SAVE THE STOMACH

Yi-Chia Lee Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Gastric cancer is the third most common cause of death worldwide, accounting for more than 800,000 deaths each year. What may come as a surprise is that most gastric cancer is the result of Helicobacter pylori infection. H. pylori is a bacterium that can survive in the stomach’s acidic environment, leading to chronic stomach inflammation that increases the risk of stomach cancer. Eradicating Helicobacter pylori bacteria can heal the inflammation and stop the progression of mucosal and genetic damage. However, this strategy has never been adopted on a policy level due to the lack of evidence concerning long-term benefits and risks.[1] Before designing a screening program, we have considered the differences in the baseline risk, living environment, and socioeconomic status of the target populations. In this presentation, I will demonstrate three approaches to implement this strategy on the population level. First, starting 2004, we have launched a stomach cancer prevention program, which was called the “mass eradication method”, on the northernmost islands of Taiwan, the Matsu Islands, where the prevalence rate of H. pylori infection and incidence rate of stomach cancer are high. [2] Residents in four townships there were invited to receive an H. pylori breath test, and those who tested positive were treated with one to two courses of antibiotics.After 6 rounds of the program, the prevalence rate of H. pylori infection was reduced from 64.2% to 15.7%, with a reinfection rate of less than 1% per person-year. The decline in H. pylori infection was accompanied by a 53% drop in the occurrence of stomach cancer. The trend shows that by 2023, fewer than 6 people per 100,000 will be diagnosed with stomach cancer in the study area. By 2025, the stomach cancer mortality rate will be cut by a significant 39%.[3] Over the 15-year period, our research team has demonstrated that mass screening and eradication of H. pylori could effectively reduce the incidence of gastric cancer and make this cancer a rare affliction. Long-term follow-ups of the participants’ condition revealed zero increase in the incidence of other digestive tract cancers, such as esophageal and colorectal cancers, the sites most vulnerable to the dysbiosis associated with the antibiotic treatment. Second, starting 2014, we carried out a community-based, randomized trial by inviting a population who faced burden associated with both gastric and colorectal cancers. Mass screening of colorectal cancer using fecal immunochemical testing (FIT) has been ongoing for more than a decade since 2004. The existing FIT screening offered an opportunity to deliver H. pylori stool antigen (HPSA) testing concurrently with FIT, to offer a two-in-one screening strategy, which was called “the combination method”. The goal of this program was to reduce the incidence of gastric given the presence of competing diseases for the limited resources, such as the colorectal cancers. [4] Targeting an intermediate-risk population for stomach cancer, we have found that under the framework of a mass screening program for colorectal cancer, the additional HPSA testing was applicable and of benefit when performed together with FIT for simultaneous prevention of gastric

and colorectal cancers. We have demonstrated that in a general population, the willingness to get antibiotics and compliance to treatment are high. Given the higher participation rate, the detection of colorectal neoplasia has been increased. Considering the high eradication rate, participants are likely to benefit from treatment for peptic ulcers and premalignant lesions, and chemoprevention for gastric cancer. Both of these benefits support the population-wide implementation of this strategy. Third, in Taiwan, there were some subpopulations with high stomach cancer risk, particular in the residents living in the Indigenous communities, most of which located in the rural, remote, and high mountain areas. As a matter of fact, the number of Taiwanese Indigenous peoples has grown; however, their life expectancy remains 8.3 years lower than that of the non-Indigenous population. Cancer is the most prevalent cause of death for Indigenous peoples, who face a 1.3fold greater risk than non-Indigenous peoples and a disproportionate prevalence of certain kinds of cancer. These observations provide us with an opportunity to establish a plan of action. Targeting the gastric cancer, starting 2018, we have developed a strategy called “the index case method”, through which we invited the family members of the test positives and provided eradication treatment with the family as the unit.[5] This policy has been gradually expended to 33/50 Indigenous Counties in Taiwan. Overall, in this presentation, I will emphasize the step-by-step for implementing the screenand-treat program of H. pylori infection for gastric cancer prevention. Within any population, there are subpopulations that vary in risk such that a “one size fits all” approach is unlikely to be ideal. In policy making, it will be required to identify if the programs can be utilized by the heterogeneous populations and will likely require adjustments to accommodate the needs of subpopulations.

Reference:

1. Gut and Liver. 2016;10:12-26. 2. Gut. 2013;62:676-82. 3. Gut. 2021;70:243-50. 4. Gastroenterology. 2021;160:2159-61. 5. Journal of Gastroenterology and Hepatology. 2020;35:609-16.

Symposium (VII)

TAIWAN CAN HELP – COMBAT AGAINST DIGESTIVE DISEASES ON A NATIONAL SCALE

CHEAP TEST BUT BIG EFFECT – 15-YEAR STORY OF CRC SCREENING PROGRAM

Han-Mo Chiu Department of Internal Medicine, National Taiwan University Hospital for the Taiwan Colorectal Cancer Screening Program

Globally, colorectal cancer (CRC) ranks third (1,849,518 new cases, 10.2% of total) as the most commonly diagnosed cancer after lung and breast, with it being second in women and third in men in 2018. It is also the second oncological cause of death worldwide, although with some global geographic differences in both incidence and mortality rates, with Asia contributing the highest, 957,896 (51.8%) of incident cases and 461,422 (52.4%) of deaths (all genders and ages) per 100,000 population in the world. Fecal immunochemical test (FIT) is a stool test that detect human hemoglobin in the stool, which is specific to detect lower gastrointestinal bleeding. Its user-friendly platform with resultant higher screening uptake, higher sensitivity for earlystage CRC, and the high-throughput features make FIT as the most popular test in population CRC screening worldwide. In 2004, Taiwanese government launched a nationwide screening program after a successful pilot program and FIT is offered biennially to individuals aged 50 to 69 (extended to 75 in 2013). The screening (coverage) rate of this screening was 21.4% and repeat screening rate was 28.3% in the inaugural 5 years (2004-2009) but improved to 56.6% and 52.3% in 2014. A recent analysis from the program have demonstrated that CRC mortality and incidence of advanced stage CRC has reduced by 35% and 29%, respectively, when comparing those who did and did not participate in FIT screening. Nevertheless, there were some challenges and obstacles that needed to overcome. First, the interval cancers have more unfavorable clinical outcomes and their occurrence largely affect the effectiveness of screening. Second, participation in the program is still satisfactory. Both the government and professional societies should elaborate on increasing the awareness toward CRC by the public. Third, some individuals are not compliant with colonoscopy after a positive FIT, which largely affect the effectiveness of the screening. Fourth, there is still discrepancy in the quality of colonoscopy among different units. Continuous effort in improving colonoscopy quality and clinical audit is indispensable. Finally, long-lasting financial support for this program is necessary for its sustainable development and success. All of these problems need to be remedied via collaboration between the screening organizer, screening distributor, and professional societies.

Reference:

1. GLOBOCAN. Estimated number of Colorectal cancer new cases in 2018, worldwide, both sexes, all ages Lyon, France: IARC; 2018. 2. Chiu HM, Jen GH, Wang YW, Fann JC, Hsu CY, Jeng YC, Yen AM, Chiu SY, Chen SL, Hsu WF, Lee YC, Wu MS, Wu CY, Jou YY, Chen TH. Long-term effectiveness of faecal immunochemical test screening for proximal

and distal colorectal cancers. Gut. 2021 Jan 25 (ePub):gutjnl-2020-322545. doi: 10.1136/ gutjnl-2020-322545. 3. Wang YW et al. Current status and future challenge of population-based organized colorectal cancer screening: Lesson from the first decade of Taiwanese program. J Formos Med Assoc. 2018;117:358-364. 4. Lee YC et al. Effects of screening and universal healthcare on long-term colorectal cancer mortality. Int J Epidemiol. 2018 ;48:538-548. 5. Chiang TH et al. Difference in performance of fecal immunochemical tests with the same hemoglobin cutoff concentration in a nationwide colorectal cancer screening program. Gastroenterology. 2014;147:131726. 6. Chiu SY et al. Faecal haemoglobin concentration influences risk prediction of interval cancers resulting from inadequate colonoscopy quality: analysis of the Taiwanese Nationwide Colorectal Cancer Screening

Program. Gut. 2017;66:293-300. 7. Lee YC et al. Association Between Colorectal

Cancer Mortality and Gradient Fecal Hemoglobin Concentration in Colonoscopy Noncompliers. J Nat Cancer Inst. 2017;109. 8. Cheng SY et al. Factors affecting compliance with confirmatory colonoscopy after a positive fecal immunochemical test in a national colorectal screening program. Cancer. 2018;124:907-915. 9. Peng SM et al. Faecal immunochemical test after negative colonoscopy may reduce the risk of incident colorectal cancer in a population-based screening programme. Gut. 2021;70:1318-1324. 10. Chiu HM et al. Effectiveness of fecal immunochemical testing in reducing colorectal cancer mortality from the One Million

Taiwanese Screening Program. Cancer. 2015;121:3221-9.