Conquering the Silent Killer—Hepatitis B
One Family’s Story
In the apartment blocks where my family and I lived—this was in 1970s Beijing—there were many things that could make a family or a person stand out. My family featured an anti-communist grandfather in residence. Our next-door neighbors, a couple with a beautiful girl, had to send her away to her grandparents because her mother was a madwoman, unable to raise a child properly. On the second floor there was an old doctor, who had been a well-known pediatrician before retiring. Her suffering was discussed behind her back: she had been orphaned at a young age, widowed at middle age, and now, shortly after she turned seventy, she was about to lose one of her daughters to a brain tumor. Of course the doctor was not to be blamed, people said; although, come to think of it, how could a woman bring so many disasters into a family if not for her possessing some bad karma, or at least the tendency to attract tragedies?
But then there were other things that helped one blend in. For instance, we were equal under the ration system, and the paucity of meat and cooking oil and other luxury foods made all families alike in one sense: toward dinnertime most apartment doors were kept open, and what was being cooked was made known to passersby; some, like the family living across from us, cooked in the hallway on a paraffin stove: there was nothing to hide. To be just like others, to not to stand out—such was the lesson every child learned quickly in communal life.
One family, however, did not participate in the dinnertime openness, and this family included Tien, my only friend before I entered elementary school. Tien and I were born fifteen days apart, each the second daughter of the family; her sister and my sister went to the same school; her father worked in the same research institute as my father; her mother, a nurse, had exchanged tips about child-rearing with my mother. In many ways Tien and I could replace each other: the nursery school teachers even commented on how we looked alike with our heads too big, hair too short, eyes too inquisitively rude.
We shared that solid world of friendship between little girls who had found each other by chance, and our secret knowledge of life was unknown to the grownups. When we came back from nursery school, we spent our time in the building’s stairwell, constantly having to stand up to greet the grownups. They asked questions for which they either didn’t wait to hear the answers, or else provided answers themselves and then moved on. These interruptions were inconvenient, but Tien’s family hadn’t issued an invitation for me to go to her place, nor had my parents ever given me permission to bring her home. It didn’t occur to me that this was strange, even though in a communal life, most people were free to open a neighbor’s door for the smallest reason.
One day Tien asked me to go to her apartment—with or without her parents’ permission, I could not tell. Nothing disastrous happened. Her mother acted warmly when she saw me; her father, a nuclear physicist trained in Moscow, treated me with absentminded kindness. He was a well-respected scientist—this I’d learned from eavesdropping on conversations around me—because no one would question the authority of a Soviet training.
When it was dinnertime, they invited me to stay, and I readily agreed. To my disappointment, their meal was much too meager, even taking rations into consideration. My father, who cooked our meals, had all sorts of inventions to give a dinner a sumptuous feeling: twice-cooked pork evenly distributed on top of unsavory vegetables, one egg maneuvered into a pot of egg soup for five people, tofu fried in lard so it would be more alluring to my sister and me. Tien’s family, however, simply had millet porridge with some pickled cabbage on the side.
When I returned home, our dinner was already waiting. Where, my mother demanded, had I gone, and how did I account for the hour that my sister couldn’t find me in the stairwell?
I told her I had gone to Tien’s apartment, and that I had eaten with her family. This innocent fact sent my mother into a rage. “Did you,” she said, “invite yourself to their place, or did they? Did you invite yourself to dinner, or did they?”
As was always the case when my mother flew into inexplicable wrath, I started to waver: had I asked Tien to bring me to her place? Had I expressed my hunger so that her family felt obliged to offer me a plate at their table? If there was one family that was close enough to host me for dinner it was Tien’s. Did I eat their ration? But they didn’t even have any meat or egg or anything that required being cooked by oil at dinner.
My father explained then that Tien’s father was afflicted with liver disease. Hepatitis was not a term introduced into our conversations until much later, when I was in school. I was given two rules: to never visit Tien’s house without my parents’ permission again; to never eat anything Tien or her family offered me. To my parents’ credit, they also warned me not to broadcast my knowledge about his disease—certainly I had the habit of telling everyone everything—especially not to Tien. Their considerateness escaped my understanding; their seriousness made a strong impression on me. Having a father with liver disease was worse than having a madwoman in the house or an unlucky old doctor fated to suffer; it was worse than having an outspoken grandfather, whose uninhibited criticism of Chairman Mao often sent us rushing to close the windows and door, for fear of his being overheard. You could not really catch something from these bad lucks; but with liver disease, you had to be careful: you could easily become the next one.
I started to pay more attention to Tien and her family after that. Some details I hadn’t noticed before: Tien’s mother, a loud and happy woman, was friendly with all neighbors, but this friendliness only existed outside people’s apartments—she never went into anyone’s home; Tien’s sister, in second grade then, did not participate in the games in the courtyard, where a throng of girls, including my sister, gathered daily after school; Tien, too much like me in all ways, too familiar, was less interesting; Tien’s father, however, became a fixation of mine.
He was a tall man, slightly overweight, and his face and hands looked puffy. (How can a man with liver disease grow fat, I asked my sister, and she could not answer). He moved with a slow dignity seen only in older men. He rarely stopped and talked to anyone in the stairwell or outside the building but greeted people courteously, who responded with the same distant courtesy.
He played music. He was the first musician I had ever known. Every night between seven and eight, he played the two-string fiddle on their balcony. If there was any protest about that I never knew it. In fact, the only other means of entertainment would have been a radio, and even that was not a guaranteed possession for every family. (We had two, a big one that occupied the entire space on top of a chest of drawers, which required a couple minutes of warming up before transmitting anything—this was a forbidden machine for my sister and me; and a small one, made by my father, with wires and metal parts dangling around.) In any case, what did people do in those long evenings before television? I don’t remember well; what I do remember is the music from the upstairs balcony, where Tien’s father sat every evening, playing to no one.
If anyone says a child at five does not understand music in the most profound and mysterious way, this person’s judgment or memory should not be fully trusted: before words and before reading there is music. I’d never seen Tien’s father play; I doubt anyone had other than his family, but I was one of his most loyal audiences for years. Music from his strings spoke of things for which I could not find words. I often made a nest underneath our treadle sewing machine—a piece of fabric, covering the sewing machine, made a perfect curtain. It would be silly or even disastrous—depending on who looked under the curtain, though this never happened—to be found in tears; still, I couldn’t stop wiping tears off my face. So much pain, so much sadness, so much loneliness, so much helplessness from an illness—none of these words was in my possession then, the understanding beyond my age–but I felt the emptiness left by the music, which could not be filled afterwards and had to be erased by a night of sleep, only to be renewed the next night. This I could not share with anyone, not even the musician’s daughter. Was she listening too when he played?
Soon Tien and I entered elementary school, still in the same class, but my world of friendship expanded breathlessly. She was no longer my only companion, and her father’s music started to feel less urgent at night, when I would be doing my homework or fiddling with the small radio my father had made.
And liver disease—which by then was defined more accurately as hepatitis—was understood, and everything about Tien’s family made sense: their diet (people afflicted with liver problem were to avoid greasy food, or any food with fat); their isolation from the neighbors (once you have hepatitis, you never get free from it); and worse, the reason Tien’s sister did not participate in the girls’ games after school: it was for the same reason that Tien was no longer included in our games.
Did it agonize me to see her drift away? If it did, it was only skin-deep. I was too busy to notice her quietness, which was increasingly like her sister’s and her father’s. Once or twice she explained to me, as we walked to school together, that her father’s hepatitis was not contagious, using her mother, her sister and herself as examples—they were all healthy. That I accepted without questioning, though I could not change the fact that she was the daughter of her father.
One day I was stopped by her mother in the stairwell. She asked me if I could invite Tien to our games. I felt ashamed, caught perhaps, but then there was nothing I could do. Tien knew little about our games, the rules or the tricks; to be in a world required more than just being physically present in it. This, even though I could not voice to her mother, I understood by intuition, and no doubt Tien did, too.
In retrospect, as a mother, I see what I missed when I was young. Tien’s mother, the least melancholy and most courageous person in the family, continues to haunt me. Her professional knowledge as a nurse might have eased her daughters’ worries about their own health, but it did little to change anything outside their apartment. Even more than the music from Tien’s father’s fiddle, I started to find it unbearable to face Tien’s mother’s smile: always so optimistic, never for a moment admitting defeat; yet both her daughters, by the time they were teenagers, had become reticent and withdrawn.
I received my first hepatitis B vaccine when I was in America—I worked in a medical research lab then. Three doses in six months—it’s that simple. Had Tien received the immunization, she would have had proof that she was safe to befriend. Perhaps she would have grown into a different person.
But even that wish, perhaps, is wishful thinking. When I talk to my friends back in China, or read people’s stories, it’s clear that the decades-old stigma associated with hepatitis B patients and carriers still has deep roots. Workplace and institutional discrimination remains unchallenged; lovers break up sometimes when one of them comes from a family with a carrier; even worse, marriages may dissolve if one party did not initially acknowledge being a carrier or being connected to a carrier—a deception thought worse than an extra-marital affair.
Where do these stories end? One hopes for effectiveness not only from vaccination but from education, and one hopes that after a generation or two, Tien’s family story will not be repeated.
When I came to the United States in 1996 to pursue a Ph.D. in immunology research, I told the first doctor I met in Iowa that I would like to focus my research on hepatitis B. Eventually I became a writer, though my interest in the disease and the vaccine has remained. Tien’s story is never just her story. Some basic background and knowledge of hepatitis B and its vaccine are outlined below: these have to do with thousands and millions of people; their stories could be Tien’s, too.
History of Hepatitis B
• Epidemic jaundice was described by Hippocrates in the 5th century BCE
• The first recorded cases of “serum hepatitis,” or hepatitis B (HBV), are thought to be those that followed the administration of the smallpox vaccine in Bremen, Germany in 1883
• In that instance, 1,289 shipyard employees were vaccinated with lymph from other people. After several weeks, and up to eight months later, 191 of the vaccinated workers became ill with jaundice and were diagnosed as suffering from serum hepatitis. Other employees who had been inoculated with different batches of lymph remained healthy. Dr. Lurman’s paper on the case, now regarded as a classic example of an epidemiological study, proved that contaminated lymph was the source of the outbreak
• Later, numerous similar outbreaks were reported following the introduction, in 1909, of hypodermic needles that were used repeatedly for administering Salvarsan for the treatment of syphilis
Hepatitis B Virus
• HBV is a small, double-shelled virus in the family Hepadnaviridae
• Humans are the only known host for HBV, although some nonhuman primates have been infected in laboratory conditions
• HBV is relatively resilient and, in some instances, has been shown to remain infectious on environmental surfaces for more than 7 days at room temperature
• An estimated 2 billion people worldwide have been infected with HBV, and more than 350 million people have chronic, lifelong infections
• HBV infection is an established cause of acute and chronic hepatitis and cirrhosis. It is the cause of up to 80% of hepatocellular carcinomas (liver cancer)
• The World Health Organization estimates that more than 780,000 people die every year worldwide from hepatitis B-associated acute and chronic liver disease
• Transmission of hepatitis B virus results from exposure to infectious blood or body fluids containing blood. Possible forms of transmission include sexual contact, blood transfusions and transfusion with other human blood products, re-use of contaminated needles and syringes, and vertical transmission from mother to child (MTCT) during childbirth
• Without intervention, a mother who is positive for HBsAg carries a 20% risk of passing the infection to her offspring at the time of birth. This risk is as high as 90% if the mother is also positive for HBeAg
• HBV can be transmitted between family members within households, possibly by contact of non-intact skin or mucous membrane with secretions or saliva containing HBV
• Other risk factors for developing HBV infection include working in a healthcare setting, transfusions, dialysis, sharing razors or toothbrushes with an infected person, travel in countries where it is common, and living in an institution
• Tattooing and acupuncture led to a significant number of cases in the 1980s; however, this has become less common with improved sterility
• The virus cannot be spread by holding hands, sharing eating utensils or drinking glasses, kissing, hugging, coughing, sneezing, or breastfeeding
• At least 30% of reported hepatitis B cases among adults cannot be associated with an identifiable risk factor
Signs and symptoms
• Illness begins with general ill health, loss of appetite, nausea, vomiting, body aches, mild fever, and dark urine, and then progresses to development of jaundice
• Itchy skin has been indicated as a possible symptom of all hepatitis virus types
• The illness lasts for a few weeks and then gradually improves in most affected people. A few people may have more severe liver disease (fulminant hepatic failure), and may die as a result. The infection may be entirely asymptomatic and may go unrecognized
• HBV infection cannot be differentiated on the basis of clinical symptoms alone, and definitive diagnosis depends on the results of serologic (blood) testing
• Most acute HBV infections in adults result in complete recovery
• Approximately 5% of all acute HBV infections progress to chronic infection, with the risk of chronic infection decreasing with age
• As many as 90% of infants who acquire HBV infection from their mothers at birth become chronically infected
• Of children who become infected with HBV between 1 year and 5 years of age, 30% to 50% become chronically infected
• By adulthood, the risk of acquiring chronic HBV infection is approximately 5%
• People with chronic infection are often asymptomatic and may not be aware that they are infected; however, they are capable of infecting others and have been referred to as carriers
• Chronic infection is responsible for most HBV-related morbidity and mortality, including chronic hepatitis, cirrhosis, liver failure, and hepatocellular carcinoma
• Approximately 25% of persons with chronic HBV infection die prematurely from cirrhosis or liver cancer
• Chronic active hepatitis develops in more than 25% of carriers and often results in cirrhosis
• Persons with chronic HBV infection are at a 12 to 300 times higher risk of hepatocellular carcinoma than noncarriers
• The frequency of infection and patterns of transmission vary in different parts of the world
• 45% of the global population live in areas with a high prevalence of chronic HBV infection (8% or more of the population is HBsAg positive)
• 43% live in areas with a moderate prevalence (2% to 7% of the population is HBsAg positive)
• 12% live in areas with a low prevalence (less than 2% of the population is HBsAg positive)
• In China, Southeast Asia, most of Africa, most Pacific Islands, parts of the Middle East, and the Amazon Basin, 8% to l5% of the population carry the virus
• In these areas, because most infections are asymptomatic, very little acute disease related to HBV occurs, but rates of chronic liver disease and liver cancer among adults are very high.
• In the 1940s, F. O. MacCallum, a British doctor specializing in liver disease, was concerned with the deadly yellow fever transmitted by mosquitoes, which was killing soldiers in Africa and South America. He developed a vaccine, but noticed that a sizable proportion of soldiers who received it developed hepatitis a few months later
• MacCallum coined the terms hepatitis A for the form of the disease that is spread primarily through food and water contaminated with minute quantities of fecal material, and hepatitis B for the form that is transmitted mainly by exposure to contaminated blood
• For two decades, scientists tried and failed to isolate the infectious agents responsible for hepatitis. In the early 1960s, a breakthrough occurred
• HBsAg is the surface antigen of the hepatitis B virus (HBV). It indicates current hepatitis B infection
• The so-called ‘Australia Antigen’ was first isolated in 1963 by the American research physician and Nobel Prize winner Baruch S. Blumberg
• HBsAg was discovered to be part of the virus that caused serum hepatitis by virologist Alfred Prince in 1968
• Prince’s assertion was confirmed over the next two years by numerous scientists around the world, including Kazuo Okochi of the University of Tokyo, Alberto Vierrucci of the University of Sienna, D.S. Dane of Middlesex Hospital and K.E. Anderson in New York
• In 1972, laws were passed in the USA to prevent carriers of HBsAg from donating blood. The antigen could be detected using a blood screening technique called radioimmunoassay
• Working with Irving Millman at the Fox Chase Cancer Center, Blumberg proposed that a vaccine could be made from HBsAg particles obtained from the blood of hepatitis B carriers
• This would be the first vaccine ever made from human blood using parts or ‘sub-units’ of human virus
• It was Maurice Hilleman and colleagues at the Merck Institute for Therapeutic Research who, throughout the 1970s, developed a sub-unit hepatitis B vaccine from HBsAg purified from blood
• Hilleman collected blood from gay men and intravenous drug users—groups known to be at risk for HBV infections. At this time, HIV was unknown to medicine. In addition to the sought-after hepatitis B surface proteins, the blood samples likely contained HIV. Hilleman devised a multistep process to purify this blood so that only the hepatitis B surface proteins remained
• Trials were also conducted at the New York Blood Center by Wolf Szmuness, a Polish immigrant who became interested in the virus when his wife was nearly killed by liver disease caused by it
• Szmuness and Hilleman have both been accused of starting the HIV epidemic among homosexual males through these trials. However, this theory has never been proven and is widely disregarded
• In 1980 the vaccine was shown to provide up to 90% protection against hepatitis C, with no adverse side effects
• In 1981 this blood-derived vaccine, called Heptavax, was made available for general use
• At this time, work had already begun to develop a vaccine made from recombinant HBsAg grown in yeast
• This work was conducted by, among others, William Rutter (UCSF) and Benjamin Hall (University of Washington)
• In 1981 Rutter founded Chiron Corporation with Pablo DT Valenzuela and Edward Penhoet
• In partnership with the Merck Institute, Chiron Corporation eventually developed the recombinant vaccine (an achievement attributed to or claimed by various individuals!)
• In 1986 this vaccine was approved by the FDA, and it is this kind of vaccine that remains in use today
• Hilleman and his colleagues at Merck also went on to develop a vaccine for hepatitis A
• More than 1 billion doses have been given around the world
• It is administered intramuscularly
• A course of 2 or 3 shots is given, the second one month after the first, the third six months after the second
• After the vaccination, the body’s immune system establishes an antibody to HBsAg in the bloodstream. This antibody is named anti-HBs and provides immunity to the virus
• Thanks to the body’s immunological memory, the vaccine is believed to provide lifelong protection.
• The vaccine appears on the World Health Organization’s List of Essential Medicines
• The WHO recommends a pentavalent vaccine, combining vaccines against diphtheria, tetanus, pertussis and Haemophilus influenzae type B with the vaccine against hepatitis B
• Examples include Twinrix (for hep A and B) and Comvax (for hep B and flu)
Administering the vaccine
• Babies born to mothers with hepatitis B are vaccinated at birth and injected with Hepatitis B immunoglobulin (HBIG)
• Many countries now routinely administer the vaccine to infants
• Many countries require health workers and laboratory staff to be vaccinated
• It is also recommended for international travelers to regions with high or intermediate levels (HBsAg prevalence of 2% or higher) of endemic HBV infection, and persons with HIV infection
• Following the primary course of vaccinations, a blood test taken after 1–4 months can establish if there has been an adequate response
• Such a response, which occurs in 85–90% of individuals, is defined as an anti-Hbs antibody level above 100 mIU/ml
• An anti-HBs level between 10 and 100 mIU/ml is considered a poor response. These patients should receive a single booster vaccination at this time, but do not need further retesting
• People who fail to respond (anti-Hbs antibody level below 10 mIU/ml) should be tested to exclude current or past hepatitis B infection, and given a repeat course of 3 vaccinations, followed by further retesting
• Those who still do not respond to a second course of vaccination may respond to intradermal administration, or to a high-dose vaccine, or to a double dose of a combined hepatitis A and B vaccine. Those who still fail to respond will require hepatitis B immunoglobulin (HBIG) if later exposed to the hepatitis B virus
• Poor responses are mostly associated with age (40+), obesity, smoking, and alcoholism, especially if combined with advanced liver disease
• Patients who are immunosuppressed or on renal dialysis may respond less well and require larger or more frequent doses of vaccine. At least one study suggests that hepatitis B vaccination is less effective in patients with HIV
• More than 60% of liver cancers worldwide have been linked to hepatitis B. One study has shown that chronic carriers of the hepatitis virus are about 100 times more likely than non-carriers to die of liver cancer. The hepatitis B vaccine thus holds promise for substantially preventing deaths from liver cancer, and is considered the first anti-cancer vaccine
Precautions, Contraindications, Concerns
• A severe allergic reaction (anaphylaxis) to a vaccine component or following a prior dose of hepatitis B vaccine is a contraindication to further doses. Such allergic reactions are rare
• Persons with moderate or severe acute illness should not be vaccinated until their condition improves. However, a minor illness, such as an upper respiratory infection, is not a contraindication to vaccination
• Specific studies of the safety of hepatitis B vaccine in pregnant women have not been performed. However, more than 20 years of experience with inadvertent administration to pregnant women have not identified vaccine safety issues for either the woman or the fetus. In contrast, if a pregnant woman acquires HBV infection, it may cause severe disease in the mother and chronic infection in the newborn baby
• Hepatitis B vaccine does not contain live virus, so it may be used in persons with immunodeficiency. However, response to vaccination in such persons may be suboptimal.
• The hepatitis B vaccine is considered one of the safest and most effective vaccines ever made.
Hepatitis B in CHINA
• China has the greatest burden of hepatitis B virus and liver cancer in the world
• One third of the world’s chronic HBV sufferers live in China
• 130 million Chinese (1 in 10) have chronic HBV infection
• China accounts for 55% of the 600,000 worldwide deaths from liver cancer each year
• HBV takes a life in China every 60 seconds
• Every year, 300,000 Chinese die from HBV-related diseases
• In Guangdong and Fujian provinces, incidence of chronic HBV infection is over 15%
Vaccination and treatment
• By 2006, China claimed to have successfully immunized 11.1 million children living in the country’s poorest provinces against hepatitis B
• A private-public partnership in Qinghai (2006-2008) resulted in a unique two-part school-based immunization program to educate and provide free vaccination for all children in kindergarten and grade school within the region
• The success of this large-scale province-wide demonstration program led the Chinese government to announce the adoption of a new policy beginning in 2009 to provide free catch-up hepatitis B vaccination for all children in China under the age of 15 who have not been vaccinated
• Between 2008 and 2012, both timely birth dose and three-dose coverage of Hepatitis B showed steady improvement: timely dose increased from 90% to 95%
• By 2012, China has achieved the regional goal of reducing chronic hepatitis B infection rate to <1% among children at least five years of age.
• The Chinese spend $110 billion on treatments each year, attempting to prevent lasting liver damage by curing the illness. These treatments achieve limited rates of success
• Despite a 2010 law banning hepatitis B tests in job and school admission applications, 61% of state-run companies continue to use the test as a part of their pre-employment screening process
• Companies collaborate with hospitals to test applicants in secret during the hiring process, and employees are fired if they test positive during annual physical checkups
• Institutional discrimination started in the 1990s. First, the government forbade carriers from working as civil servants, and soon the practice was adopted by both state-owned and private companies. Even foreign-owned companies who do not test candidates for hepatitis B in their own countries adopted the practice in China
• Hospitals profit greatly from providing blood tests to would-be job applicants
• The medical market for hepatitis B is chaotic, filled with fake medicine and misleading commercials. Carriers are forced to seek medication on the black market
• 66% of carriers choose to stay silent, and many hire people to take the blood test under their names
List of Sources:
For global information:
CDC’s Hepatitis B information: http://www.cdc.gov/vaccines/pubs/pinkbook/hepb.html
WHO’s Hepatitis B information: http://www.who.int/immunization/diseases/hepatitisB
For information on China:
GAVI, the Vaccine Alliance, China immunises millions of children in historic collaboration between government and GAVI Alliance, 25 July 2006.
Information from the Asia and Pacific Alliance to Eliminate Viral Hepatitis: http://apavh.org/our-work/country-projects/china/
Information from the WHO Western Pacific Regional Office: http://www.wpro.who.int
Jia JD, Zhuang H., The overview of the seminar on chronic hepatitis B,
Zhonghua Gan Zang Bing Za Zhi, 2004 November, 12(11):698-9. In Chinese.
Liu, Shako, China’s Struggle with Hepatitis B Discrimination, The Atlantic, 3 December 2013.
So, Samuel, Director of the Asian Liver Center and Liver Cancer program at Stanford University, How Serious is Hepatitis B?, presentation, 2006.
Zhuang, H (2005). “The challenge of hepatitis B infection in China”, Chinese Journal of Infectious Disease, 2005, (23): 2–6. In Chinese.