A Chinese group claims to explain partially why males infected with hepatitis B virus have more serious clinical outcomes than females. They find in a mouse model of hepatitis B infection (mice with the HBV genome inserted into their genome) that different forms of apolipoprotein A-I are present in livers of males but not females, and they confirm this using serum from human patients who have chronic hepatitis B. The human data are in figures 5 and 6.

I remain unconvinced. In mice they said downregulation of isoform 2 and upregulation of isoform 3 was found. In human males, isoform 2 is down (p=.024) and 3 is up a little (p=.002). In females, 2 is down (p=.021) and 3 is insignificantly down (p=.057). But the expression of 3 is a lot less than 2 to begin with. Can you discern a pattern from this? I don't think the data supports the conclusion that in females, the Apo A-I isoform pattern is undisturbed. I don't think this study is conclusive by any means, so it doesn't really deserve the minor media hoopla. Science news tends to skew results all the time.

A few blog posts ago I mentioned how Dr. So told a group of APAMSA Hepatitis B conference participants that before one does any screening/outreach, you make sure there are institutions in the community that let the patients go on to the next step. In other words, if you educate them about the susceptibility and severity of hepatitis B, make sure there are places for people to get screens and vaccinations. Many people don't have primary care physicians or don't have health insurance, don't want to get registered in the health system, whatever. If you do a screening event, make sure that people have somewhere to get to get care.

Today that message was reiterated at a dinner discussion hosted by Team HBV at Harvard, featuring Dr. Daryl Lau, an associate professor of medicine at HMS and Director of Translational Liver Research at Beth Israel Deaconess Medical Center. She told us a story about the community outreach work she did in Houston some years back at an Asian health fair. She and a team of GI doctors and graduate students and research associates set up a station at the fair and administered hepatitis B screens to about 500 people.

While people waited for their turn with the phlebotomists, they filled out 15-ish-item educational surveys. To boost response rate, they wouldn't get their blood tube until they handed in a survey, and there were volunteers walking around offering to clarify questions and to essentially make sure they were doing the surveys. In the waiting area, people could also view a educational video about hepatitis B. They found some pretty analyzable things about the cohort there, such as frequency of misperceptions concerning transmission.

They were testing out a new quick HBsAg screening kit that would give results in just a few minutes, but they also checked with serological testing in Dr. Lau's lab. As expected with any Asian American population, there's a significant number who turn out to be chronically infected and they didn't know it. In this case, thirty-something people had chronic hepatitis B, who were then contacted and advised to see their PCP.

Tough thing is, many people didn't have PCPs or health insurace. So one would feel bad for doing these screens and scaring chronic carriers who did not have the means to seek care. So, while these people were not her patients (and I think might've not been able to register as her patient if they lacked insurance?), Dr. Lau met with them and gave them advice. I've from another physician that sometimes the most important job of being a doctor is just giving advice, being sympathetic to the patient's needs and listening carefully to their concerns.

Sometimes these patients would bring their families; finding out you have a disease is a big deal. In our outreach, we are cognizant of the major role that families play in Asian cultures. We mention that getting screened and vaccinated helps protect their family. We hope that our brochures can be left on the kitchen table and spark a discussion in the family. Some people in the ESL classes we visit seemed especially concerned about vertical transmission and how to prevent it; I surmise that they asked those questions because they are/know carriers who plan to have children.

Moral of the day is: if you're doing screenings in a community setting, partner with PCPs. Research how much people have access to health care in your area.

Luckily, in our outreach population, people can turn to Free Care and MassHealth. Data from the Boston Public Health Commission show that >96% of Asians in Boston have health care coverage (I suppose illegal immigrants are excluded), but only 71%, the lowest of all ethnic groups, have a primary care provider. I think people don't know they have all these resources at their disposal, or they see them as unnecessary (I feel healthy!).

As summed up by the NYT: "volunteers were vaccinated against the virus that causes hepatitis B; several months later, the happy volunteers showed a stronger response to the vaccine than the unhappy volunteers."

In scientific terms, the authors found "an association between dispositional positive affect and magnitude of secondary antibody response to hepatitis B vaccination."

The authors speculate about many mechanisms, including neuroendocrine, in which psychology and immunity can be related. They also address various confounding factors like social relationships and exercise. 

There are some important implications. Positive affect can help explain the "interindividual variability in the maintenance of protective immunity over time." In other words, psychology may have to do with why some people lose hep B protection over time and require booster shots.

I wonder, how did the researchers find so many graduate students at their institution who had not been vaccinated before. Surely this points to gaps in the system for universal vaccination.

For the original paper, see http://www.psy.cmu.edu/~scohen/Marsland_etal_BBI_May06.pdf

Dr. So told us he remade the world HBV prevalence map because some people are colorblind!

What a great idea. Turns out that roughly one in 20 Asian males are red-green color blind, meaning it's extremely difficult to distinguish between red and green.

The figure Dr. So showed had different shades of green (which translates into different shades/intensities of one color, I suppose).

In developing outreach materials, it's important to keep this in mind or else some people will not get your point.

This website has many suggestions for making figures friendly for the colorblind. Besides choosing more contrasting colors a, for example, one should implement "redundant coding" like bar graphs that are both colored and patterned, or line charts with different symbols and dashed lines. This idea also is important in delivering educational presentations: one should not refer to "this red line" but "this red line with round points."

1.  Be proactive.
   • Taking initiative and responsibility for our lives
   • Increasing our circle of influence
2. Beging with the end in mind
   • Imagine your own funeral
   • Develop a vision: "To live with integrity and to make a positive difference in the lives of others"
3. Put first things first
   • Doing the Right Thing >> Doing things right
4. Think win/win - seeking mutual benefit
5. Seek first to understand 
6. Synergize
7. Sharpen the Saw before you saw the tree down

First things first: "What is the one activity if you did well would have a signficant impact on your personal/professional life."

Everyone has 24 hours a day. Einstein and Edison had only 24 hours in a day. 

"If one cannot increase the supply of a resource, one must increase its yield." Peter Drucker. Innovation must start small and be focused. 

Margaret Mead - "Never doubt that a small group of thoughtful, committed, citizens can change the world. Indeed, it is the only thing that ever has."

Jane Hyun - Breaking the Bamboo Ceiling: Be politically astute. Use your bicultural and bilingual abilities.

Sindermann - Winning the games scientists play - akin to working your guanxi, relationships.

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Take-home points I get from Dr. Hu, organizers of this conference, and talking to Chinese students yesterday is that 1) Network and develop guanxi. 2) Don't doubt the power of grass-roots action. 3) Prioritize your time. 4) Embrace your cultural abilities.

Frank was telling me how at med school interviews you often only have time to talk in depth about one activity. So make it count. First things first. I realized recently that some activities on campus, including ones I've been involved with, are kind of self-serving and won't matter in your life in five years. Are you affecting the lives of others?

Members of Harvard Team HBV attended the Asian Pacific American Medical Student Association's annual Hepatitis B Conference on Halloween, which (on purpose) coincided with the annual meeting of the American Association for the Study of Liver Diseases right across the street in the Back Bay of Boston.

We heard talks by Anna Lok (UMich) on clinical aspects, Sam So (Stanford ALC) on outreach/advocacy aspects, and Corrina Dan (AAPCHO) on legislative/policy aspects of hepatitis B.

Some random tidbits I wrote down: Advise patients with chronic hepatitis B infection to not take herbal (e.g. TCM) medicines because they can add stress to the liver (in addition to alcohol and potentially obesity). Hepatitis B drug regimens cost $8-10k per year. 50% HBeAg seroconversion in 5 years of prescriptions (e.g. of entecavir and tenofovir). Half of the 1976 Nobel Prize in Physiology or Medicine went to Baruch Blumberg for discovering HBV and the vaccine for it ("new mechanisms for the origin and dissemination of infectious diseases"). The WHO has not succeeded in meeting its goals for getting universal newborn or childhood HBV vaccination programs. 10% 5 year survival rate for HCC in the US. Pay up front at first visit and Asian people will return to get their money's worth of the three-shot HBV vaccine series. 41 countries in east Asian and the south Pacific make up 76% of the global burden of hepatitis B.

At lunch we sat down at tables with hepatologists and chatted. I was at Sam So's table. Things I remember:

Before doing a screening/outreach campaign, make sure all the resources are in line. If you scare people about hep B, but they have no place to go to get tested or vaccinated, they will get ticked off. If they get screened but don't have a way to get treatment, they will get ticked off. Make sure there are institutions in your community already in place for these things.

The purpose of Team HBV Collegiate Chapters is primarily to activate and mobilize the campus on Asian issues.

Success requires building a coalition. Make all the key players sit down at the same table and talk about how to work together towards the same goals. The context here was referring to city-wide campaigns, like Hep B Free San Francisco and NYC.

Find a champion for your cause.

ALC is about education first. You (APAMSA chapters) don't need to screen people to make a difference.

Politicians need to be educated too. They're like grade school students. Simplify the message and tell them the important facts; they will care.

From the aging farmer to the young man in his 20s, people seem to have some idea of what HBV, 乙肝, basically is, but it is unclear the extent of their knowledge and possible misperceptions. I asked some questions of an uncle, who is a ranking official in a city public health bureau, an office similar to a city-level CDC, FDA, and multi-hospital administration. He says that people still worry about transmitting it through food, and that there is indeed discrimination from employers regarding HBV (though illegal). Hiring is competitive. At the hospital, some of the med students told me that there is a lot of pressure in college, and they talk of a few suicides in the past. I thought Chinese universities were less stressful than high school, considering the gao kao, so I asked why was there still so much pressure in college. They said there's competition for employment after graduation, so you need good grades. According to my uncle, it's common that if a typical employer has a pool of applicants to choose from, it's going to make the choice a bit easier by cutting out people who have HBV, if they can find that out somehow. That's especially true if they find out that you test positive for all three big indicators - I assume DNA, surface, and e antigen - of an active, transmittable infection that indicates greater risk for liver disease.

I remember one time in our health education presentations when we were giving out surveys and one woman remarked to us (was it Ang? and me), 'oh we've all been checked, and if we had hepB, we wouldn't have been able to get out of China.' I asked my uncle about this too. He said that if you have hepB, you'll probably have trouble getting out of China. (I'm not sure if the problem is with getting out of China or getting into the US). But the key is whether you declare it on forms. Just like on the health declaration forms we filled out coming into China, of course we're not going to check the boxes for coughing, sneezing, whatever. And of course people wanting to immigrate to America are not going to say that they're members of the Communist Party of China, as many are. Then I asked, don't they do a health check though? The answer: yes, but it's very simple to find a way not do them. You can easily get it stamped off, or get 阳 (positive) changed to 阴 (negative). Like someone at their office just takes everyone's forms and gets them approved for them, even though they technically require people to be somewhere in person and maybe take some exam or other. As the woman from the Fairbank Center for Chinese Studies who gave the pre-departure presentation for Harvard studying abroad put it, corruption is a way of business in China.

In other news, HBV vaccine has been free for newborns nationwide since 2002. Announced this week, HBV vaccine is free for everyone under 15 who hasn't been vaccinated. 

I scrubbed in on two partial hepatectomies and a splenectomy. One hepatectomy case did not involve HBV and the nurse sounded surprised when she found that out. But those (liver cancer without HBV) happen from time to time. The other hepatectomy case did involve HBV and one surgeon stuck himself with a scalpel. At that point he took off his gloves, squeezed blood out of his wound for a few minutes, rescrubbed. Typical procedure after that is you report it and get some shot(s). I don't know for what, but I imagine it's for HBIG and/or HBV vaccine booster. Another surgeon commented that he stuck himself once and forgot about reporting it because he was busy and because the process is tedious. I don't know what the underlying condition was for the splenectomy, but apparently hypersplenectomy is a common condition that occurs with HCC and requires a splenectomy, so I presume that's why a liver surgeon was doing it.

The surgical facilities and equipment at this hospital are pretty modern, but I didn't see that they had much laparoscopic surgery going on. Staff adhere strictly to sterilization standards in surgery, but alcohol gels are on the doors of some inpatient wards (hematology) and not others (general surgery). Nurses count and double count sponges and instruments before and after the surgery. 

There are somewhere between 30 and 60 ORs, and there are more surgeons working at the same time than lockers for their clothes available. Yet surgeons have pretty much a 40 hour work week; the professor I followed had on average less than one surgery a day. Meanwhile one student tells me there's a doctor shortage in China. I saw doctors having very relaxed hours, even on top of the traditional 2-3 hour noon break, in internal medicine more so than in surgery. I saw a predominance of males in surgery, taller than average. I saw an obscene level of crowding in the outpatient building during business hours and a shortage of inpatient beds in liver surgery. One family waited in line at the clinic from 3am to be first in line (register - 挂号) to see the professor at 2:30pm. I saw that same family try to bribe (with 200 yuan) the professor in order to get a bed the same day, but he said even if they gave him 10000 yuan, he couldn't make an extra bed appear. After a patient who the professor seemed familiar with showed up at the clinic looking to be admitted, he made a call to a colleague to ask her to save some beds for him when she discharges anyone the next day or two. For a few days earlier in the week, one guy who was waiting for a bed to open up hung around the surgery floor, asking the doctors every day if they have a discharge. I guess he got past the bouncers at the doors of the surgical building somehow. Others, such as one farmer and his dad who has a complicated liver tumor, are less eager to get in the hospital because of the financial burden of surgery and the uncertainty of its success. The surgery and 2-3 week hospital stay costs upwards of 30k yuan. In addition, patients/families traditionally give the surgeon a 红包 (red envelope of money). If the family is unsuccessful at getting the money to the surgeon (maybe it's refused, maybe a middleman is needed, maybe you need to slip it in discreetly), it could be upsetting for the family, who will worry the surgery will not go as well as hoped. There's a lot of interesting culture and sociology behind this practice of informal payments. But, my Chinese classmate tells me, this practice is gradually phasing out with the younger generations.

Families and patients seem to carry some degree of initiative when it comes to their treatment. If they complain, for example, of cold symptoms, and ask for some simple prescription, the doctor will write it for them pretty readily to get the persistent family/patient off their back. If there's a problem with overprescription of diagnostics or drugs, I suspect that blame lies on hypochondriac families more than profit-seeking doctors. In the outpatient clinic, one anxious-looking man who had acute HBV infection in 1990 came in complaining of urine that was too yellow. His HBV test results in 2004 suggested that he had cleared the infection pretty well (as the vast majority of HBV infections are), but he's still worried that it could come back. The doc asks, do you drink much water usually? Patient answers, well, no, not really. The doc then orders another round of HBV and HCV blood tests, and recommends that if the tests are negative and the patient is still worried after that and wants more tests, he should ask a psychiatrist. =O 

Similarly, I saw the issue of TCM come up a few times, and the discussion was always initiated by the patient/family. It seems many in the mainstream believes in TCM. One doctor in the hematology division opined that yes, TCM is probably effective for some problems. Yet another told a family member straight out, no, TCM isn't going to be effective against your family member's leukemia. There is one division/floor in the internal medicine building dedicated to the integration of Eastern and Western medicine. On the whole, however, doctors at this major teaching hospital are trained in the mindset of Western medicine. In non-TCM medical school, students take at most a one semester survey of Eastern medicine. One patient's medical history had a list of traditional Chinese medicines, and a few doctors had to work together to pool their knowledge and decipher what it said. 

They were also aided by the computer system. Computers are used frequently to look up medicines or disease specifics, order tests, print results, but not for keeping patient histories. Walking around the hospital you see families/patients carrying around large flat pink bags that contain their CT/MRI/X-ray images. Once again, the patients have some degree of responsibility for these. If you've been scanned and visit the outpatient clinic, you're expected to bring the scan images. There's no centralized system to call them up.

I went to China this summer and one goal of mine was to find out more about hepatitis B from the experts. The following are segments of an email I sent to my group over the summer, but this has not otherwise been put on the web elsewhere. I've broken the long email into chunks that are roughly thematically grouped. This one is just an intro and about treatments I saw being used in a big city hospital.

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I'm in my ancestral home of Wuhan for 10 days seeing relatives and I decided to shadow some doctors for kicks. In the past week I've been at a major medical school in Wuhan. For part of that time I shadowed a professor in the hepatic surgery department. The following are my observations and various people's answers to my questions about hepatitis and healthcare in general in China.

Liver resection is considered the most effective treatment for hepatocellular carcinoma (HCC). Chemo- and radiotherapy are considered supplements. Even then, some families ask whether they should pursue treatment in traditional Chinese medicine. The answer given is that TCM is considered as pretty much a third-line treatment, i.e. something to pursue if surgery and chemo/radiation fail.

In complicated cases of HCC, where surgery is not optimally effective, a few treatments (in addition to or in place of surgery) are common at this hospital. The most common is called bǐrù, transcatheter arterial chemoembolization (TACE). An arterial catheter is used to deliver something that blocks the hepatic artery; the catheter can also be used to deliver localized chemotherapy. I didn't get to see TACE, but I did see weībō, microwave ablation, which is the second most common non-surgical treatment. A probe is inserted into a tiny hole cut in the skin and guided towards the tumor with the help of ultrasound, and six minutes of microwave pulses ablates the tumor. The last treatment that's common, percutaneous ethanol injection, I am not familiar with.