Down through the generations?
Further analysis showed that over half of those infected with hepatitis B in Taiwan acquired it in their early childhood. Among those people, half got it via "vertical transmission" from the mother at birth and the other half were directly infected by the age of two. Back then in Taiwan, 15% to 20% of expectant mothers were hepatitis B carriers. If this route of infection were not cut off, the disease would continue to be passed from generation to generation.
"If a person can recover from hepatitis B naturally and produce antibodies, the complications will not be severe, so the main focus of prevention is aimed at the chronic carrier. And the age of infection is a principal factor determining whether a person will become a chronic carrier," says Chen, pointing out that the earlier the age of hepatitis B infection, the fewer the symptoms, but also the greater the likelihood of becoming a carrier. The carrier will gradually show hepatitis symptoms in his twenties or thirties, which could become life-threatening cirrhosis or liver cancer in his forties or fifties. As many as 60% of carriers contract liver cancer, so of a total of 3 million carriers nationwide, perhaps 1.8 million will come down with it. The impact on society and the healthcare system is obvious.
But because the effects of a hepatitis B infection are not as readily visible as symptoms of, say, polio, people remain relatively impassionate, even doubtful, about the threats that loom in the next 20 or 30 years. Therefore health organizations must remind people time and again about the importance of hepatitis prevention and treatment.
Massive hepatitis B vaccinations were carried out under the banner of clinical trials. It might be considered the first such case in Taiwan's public health history. At that time laws and regulations regarding clinical trials were few and far between, so even the consent forms had to be translated by Chen himself. But though the vaccinations weren't mandatory, public acceptance of the program was considerable. And the vaccination rate has since then risen from 90% to 95% (98% in Taipei). Not counting premature births and people with congenital disease who are not suited for such vaccination, the number who actually refuse vaccination are few indeed.
"Cooperation among government and public health employees, doctors and the general public is very good, almost flawless," says Chen, giving Taiwan's hepatitis B prevention program a 100% thumbs up. But he doesn't mince words: if this program had been initiated today, it would not have been as effective due to considerations of human rights and medical risk.
Battling a public enemy
After 20 years of steadfast combat, Taiwan has achieved significant results in hepatitis B prevention.
It is estimated that the number of hepatitis B carriers in Taiwan has dropped from 3 million to 2.5 million in the last two decades, a drop of 500,000.
In addition, serum epidemiology studies conducted every five years by the pediatrics division at NTU show that the carrier rate for children under 18 in Taiwan has dropped sharply: as of 2004 it was under 0.6%, and the incidence of juvenile liver cancer has fallen by more than 75%. It is estimated that the number of chronic hepatitis B sufferers in this new generation will be reduced by 85% between 2004 and 2014.
"We expect that the hepatitis B carrier rate among those born after 1984 will be lower than 0.1%. Taiwan will gradually escape the grip of hepatitis B," says Chen.
Taiwan's experience has become a paradigm for global hepatitis B prevention. According to UN figures for 2002, 128 countries have followed Taiwan's lead, having initiated full-scale hepatitis B vaccinations.
Still a national disease
Although Taiwan has been successful in hepatitis B prevention, its fight against the "national disease" is not over. Now, liver disease still remains among the top ten causes of death among Taiwan's citizens.
Because HBV is so stubborn, once a person is infected, treatment options are limited. Numerous drugs have been developed, such as interferon a and various nucleoside analogs, but the former has many side effects and drug resistance easily develops with the latter. The efficacy of treatment is not great.
"The average age of onset for liver cancer patients in Taiwan is 54, but usually they were already infected with hepatitis B in their infancy. It has become an important issue among medical circles to identify the 60% of these carriers who are at high risk for liver cancer.
Celebrities like singer Simon Hsueh, International Community Radio Taipei DJ David Wang and chef Fu Pei-mei died of liver cancer at the peaks of their careers, while hepatitis B carriers like former Mainland Affairs Council chairman Su Chi and legislator Kao Chin Su-mei have gradually recovered after liver cancer surgery.
Why different fates for carriers of the same virus?
According to Chen, research has shown that the occurrence of liver cancer is higher among those with high virus counts (over 10,000 HBV per milliliter of blood).
Aside from virus count, the genetic makeup of the host is also an important factor. "The genetic interactions between virus and host differ from person to person. We know that liver cells that have been more seriously harmed by the virus are more likely to become cancerous. As to why some people's cells are more easily damaged and why some can be lifelong carriers without ever becoming sick, we still await the answers."
Targeting the number two killer
Of chronic hepatitis, cirrhosis and liver cancer cases in Taiwan, over 80% stem from hepatitis B while 15% are cased by hepatitis C. But there are also those who suffer from both diseases.
Following the great headway that has been made with hepatitis B, sights are now being increasingly set on the number-two killer, hepatitis C. At present there are about 400,000 to 500,000 hepatitis C carriers in Taiwan.
Vaccine development for hepatitis C is difficult because of the virus's propensity to mutate quickly, so we have to start by cutting off routes of infection. Fortunately, hepatitis C is not as infectious as hepatitis B: its principal vector is direct infection through needles and blood transfusions, so it's relatively easy to block.
Chen, in cooperation with the central government's Development Center for Biotechnology, came up with a locally developed hepatitis C screening reagent. Beginning in 1992, blood donation centers throughout Taiwan have been screening the blood of donors for hepatitis C. Estimating from the former 15-20% infection rate of blood transfusion recipients, each year some 5000 fewer people have contracted hepatitis C from transfusions.
In addition, the results of hepatitis C treatment are more effective. Of six genotypes, four can be treated with interferon in combination with the antiviral drug ribavirin, boasting a cure rate of 90%. In 1991, NTU Hospital was the first to develop this combined treatment, which has become a standard model for hepatitis C treatment worldwide.
Building a research base
Taiwan's first group of babies inoculated with the hepatitis B vaccine in 1984 are now 23 years old. No antibodies have been detected in their bodies, and therefore some people worry whether the vaccine's protective power continues to exist.
"We are closely monitoring the situation," says Chen. Not being able to detect antibodies does not necessarily mean that there is no resistance. The proof of the pudding is in the eating, and as of now the Department of Health's examinations have not found an increase in hepatitis prevalence.
Chen has shown great success in the battle against hepatitis B. Nevertheless, the war is not yet over, and he continues to fight against the crafty, mercurial virus and its enigmatic pathological mechanisms.
Why is it that the younger one is when infected with hepatitis B, the greater the chance for chronic infection? Why is it the opposite for hepatitis C? How does chronic infection lead to fibrosis and cirrhosis? Why does cirrhosis easily lead to liver cancer? Why does the post-treatment relapse rate for liver cancer remain so high? Unsolved riddles abound.
"In addition to the proteins, virus antigens and antibodies of the past, now we can add genetic makeup to the mix when looking at these problems," says Chen, aiming to gain further understanding of how to block the disease process. He is confident that he will see results in his lifetime.
Chen Ding-shinn, who has devoted the best years of his life to hepatitis B prevention, is like an old tree firmly rooted in its native soil. He will continu to reach new heights as he keeps on researching hepatitis, guiding and fostering new students, and defending the people of Taiwan.
Chen Ding-shinn :Born 1943
Education School of Medicine NTU College of Medicine
Occupation Professor at NTU's Hepatitis Research Center
Academic honors
Outstanding Scientist Award, Executive Yuan (1984)
Nineteenth Class of Academicians, Academia Sinica (1992)
US National Academy of Sciences, Overseas Academician (2005)
Caring Physician of the World award, World Medical Association (2005)
Trieste Science Prize, Academy of Sciences for the Developing World (2006)