Fainted "Syncope"

By Thomas Sim, 17 Sept, 2008

"Syncope" is pronounced as "Syn-co-pi", not "Syn-cop". From Wikipedia, it is pronounced as "sɪŋkəpi" and carries the medical meaning of loss of consciousness, or blacking out caused by the Central Ischaemic Response. Central Ischaemic Response is a more scientific way of saying the same thing. Nevertheless, we should understand the science behind it and thus, will be explained later.

'Fainted' is a layman term to describe this sudden loss of consciousness or 'black out'. The common reason leading to that is lack of sufficient blood and oxygen in the brain. The initial symptoms a person feels before fainting are dizziness; a dimming of vision, or brownout; tinnitus; and feeling hot. Moments later, the person's vision turns black, and he or she drops to the floor (or slumps if seated in a chair).

In YouTube, you are bound to find a few celebrities and contestants (Miss World or Miss Universe) passing out in front of crowds on stage or during Q&A session of a reality show. Although joke provoking, it is still a life and death situation.

This is why we need to understand the term - Central Ischaemic Response. Ischaemia - which means "situation when cells are deprived of oxygen" is a dangerous phenomenon in stroke and heart disease. Ischaemia may occur in the brain or any tissue which is deprived of oxygen. If it occurs in the heart, it is ischaemic heart disease - which may be described as Chest Pain, or Myocardiac Infarction (MI)- heart attack! When ischaemia happens in the brain, brain cells die and permanent death of cell in the brain would lead to paralysis of neuromotor function. That is why people who had stroke cannot talk or move body parts.

During a stroke, blood vessel(s) in the brain burst and blood supply to the brain is compromised. Some part of the brain is thus deprived of oxygen. The area which is ischaemic will die and result in non-functioning of the brain cells, shutting down the alertness and motor function of the body.

When an episode of loss of consciousness occurs, it is an emergency! What next?

Call for help! We are not paramedics or doctors, so don't pretend to be one. Next, check if the sufferer is breathing by listening to his nostrils, or by observing his chest movement. If the sufferer is lying on the ground, clear any obstacles or dangerous objects nearby in case of subsequent dangers. Give him air (which is bigger space), and allow the blood flow to the brain by leaving him flat on the ground. If you are familiar with checking the pulse, do so.

If he is not breathing and you can't feel the pulse, or heart beat, he is in great danger! Do CPR - cardiopulmonary resuscitation. Clear the airway by tilting the head up a bit, blow into the mouth, and see the lung being inflated. Then, count 1, 2 ,3 as you press your palms on the chest rips to expel the air. Like what you see in the movies, repeat doing CPR until the rescue arrives or the sufferer starts breathing on his own. If their is no sign, and you don't want to do mouth-to-mouth, at least massage the chest to stimulate possible response of breathing function.

CPR is unlikely to restart the heart, if it is really the heart that has already failed, but rather its purpose is to maintain a flow of oxygenated blood to the brain and the heart, thereby delaying tissue death and extending the brief window of opportunity for a successful resuscitation without permanent brain damage.

If the sufferer does not wake up. Please do not try to feed him. This is because you don't want to choke him with fluid or food. On gaining consciousness, do raise him up against a gentle support and clear his throat. Now, some fluid would be beneficial as most people experienced syncope due to dehydration. Replenishing fluid and sugar would be helpful but to be done slowly. Clear the surrounding space for more fresh air or move him to a open space.

He may be sweating wet (which is a common scenario), so getting cold and losing heat. You may want to change his clothing or add cover to him to preserve warmth. Always remember to ask if he is feeling any pain when he first gains consciousness. As we all know, angina or MI (heart attack) do present with pain radiating from the arms or at the chest.

By this time, the paramedic should have arrived. Leave to the experts to do their job. You have done yours, and that could have already saved his life!

Chronic Hepatitis B Inactive Carrier

By Thomas Sim, 10 June, 2008


-->

There is long been confusion among patients regarding who is actually a Chronic Hepatitis B Carrier. It can be understood by layman that sero-converted surface antigen HBsAg to presence of HBsAb in the blood is taken as the ultimate ‘cure’ from the infection. However, is that so? Let us look at some recent publications.

Before I go on, let me briefly explain the meaning of Chronic Inactive Hepatitis B. 'Chronic' here signifies that the person is still under infection, whether persistently with viral replication or minimal residual viral activity. If the viral replication is active, i.e. with viral DNA measurable in the blood and significantly high, this patient is having Chronic ACTIVE disease. However, if there is undetectable or low DNA in the blood stream, this patient is having Chronic INACTIVE disease and therefore with minimal risk of liver damage or infection to others. With this fundamental information in mind, we take a step forward to see what is clinically encountered in practice.

I once attended a meeting by haematologists during which treatment of lymphoma in HBV and HCV patients was one of the topics for discussion. One of the participants said that he had patients who were supposed to have gained immunity to HBV (presence of antibody), unfortunately after having received chemotherapy, their HBV came back. So, the question of ‘cure’ in this spontaneous seroclearance of HBsAg patients may not confer total eradication of the Hepatitis B Virus in the real sense.

My previous article also touched on the Italian Study that the spontaneous sero-conversion is around 1% per year. This is again supported by a recent Taiwanese Study by Chu et al entitled: HBsAg seroclearance in asymptomatic carriers of high endemic areas: appreciably high rates during a long-term follow-up. Hepatology 2007; 45: 1187-1192.

The expert commentary mentioned that if such question by patient is asked: ‘Will I ever be cured of my hepatitis B infection?’ Chu et al allows us to answer, with some confidence, that is possible, but is an uncommon event, occurring at a rate of approximately 1% per year.

Another confirmation to the scenario above, it may still be possible for hepatocellular carcinoma to develop particularly in those with cirrhosis, and second, even though serologic evidence of HBV infection is gone, HBV DNA still persists and can be reactivated during periods of severe immunosuppression. An earlier Japanese study did find the presence of HBV DNA in such patients after 9 years of follow-up.

So, who is actually ‘cured’ of HBV infection? At this moment, I guess nobody really knows. However, if there is no liver cirrhosis and the status is asymptomatic inactive, such patient, even though still considered chronic carrier, would have good chance of ‘reasonably long life’ and a potential to experience seroclearance of HBsAg. The highest rate of conversion happens after age 50 at annual rate of 1.83%.

From Chu et al, the annual conversion rate ranges from 0.77% to 1.83% from age groups of <30>50 years with the average at 1.15% per year.

Virology and Immunology

By Thomas Sim, 14 April 2004

Virology is the study of viruses. Immunology is the study of our immune system. Immune system is the primary defense against foreign invader in our body. This article is about the common myths and misunderstanding of these subjects.

Viruses are once classified as organisms like bacteria but now it is vastly recognized as non-living things which only become 'active living' in a host organism. If you say a bacterium is like an orange, then viruses are the size of beans. Some viruses live in bacteria as their host. Therefore, for the sack of comparison, viruses can live in our body cells, just like they live in a bacterium (which is a single cell).

Immunity is our defense against foreign organism. We can acquire this immunity by recognising the invader (be a bacterium or a virus). If we develop some form of immunity (defense) against this organism, generally we refer to have some antibody against it.

Therefore, we develop vaccine to prevent certain infection from virus or bacteria. There are many diseases and infections that we can get vaccinated against. In simple languages, we teach our body to defense against a particular invader by giving mock attack to our immune system. This is largely carried out by government in all strata of population in a national vaccination programme. For example, new borns are vaccinated against Hepatitis B virus in a 3 doses vaccination programme.

However, the interesting part of the viro-immunology is that antibody to the virus does not indicate defense. In many instances, it is taken as indication of infection and thus does not render a person protected against the virus. This is the most misunderstood part of the science by any lay person.

Just to give two examples: HIV and HBV

A patient is diagnosed of HIV (Human Immunodeficiency Virus) by antibody screening. In fact, by checking whether a person develops antibody to the HIV becomes the means to determine whether a person is infected by the virus. In conventional thinking, a person who develop antibody to virus is considered immune to the virus. Just compare the distinction of the difference! By misunderstanding the antibody, a person separates himself from heaven and hell! Hence, when a doctor tests for HIV antibody, in fact it is not a great news. If found positive, it is sentencing a patient to HIV positive! This means the patient is infected by HIV and going to need HIV treatment.

Next it is Hepatitis B Virus (HBV). In recent years, advances in immunology and in particular, Polymerase Chain Reaction (PCR) technology have revolutionalised the thinking of monitoring HBV viral load. A patient who has acquired antibody to the surface antigen (HBsAg ) - Anti-HBs, doesn't necessarily render the patient free from the harm of the virus. There is still trace of the virus DNA in the blood for as long as 7 years after patient had seroconverted from HBsAg+ve to Anti-HBs+ve. There is still question for blood product on this group of donors as no conclusive data is available to rule out danger of virus transmission from blood of the recovered HBV patient.

Updates on Hepatitis B, 2007

By Thomas Sim, 14 August 2007

In this article I would try to summarize the recent information about Hepatitis B virus - HBV, after the annual scientific meeting of American Association for the Study of Liver Diseases (AASLD), the Asian Pacific Association for the Study of Liver Diseases (APASLD), and the European Association for the Study of the Liver (EASL) this year - 2007.

It is an intriguing virus when one comes face to face with HBV. It is a difficult virus to really appreciate too because although it is the most contagious transmissible DNA virus, it is not much treated due to its cohabitation with human especially in the South East Asian Countries. This is mainly due to early infection in childhood and lateral transmission of the infection from mother to newly born babies. Such prevalence in Asia and S.E.Asia makes it less emphasized by western countries because rather than Hep B virus, Hep C virus (HCV) is more common in the West.

One comes to the understanding that viruses have been living with the human race from many centuries. In most instances, we human has already tolerated the viruses as part of us - something like transposon in the study of bacteriology in the first few chapters of biological science and microbiology in undergraduate studies.

There are some new treatment changes in this year's meeting. Nevertheless, the overall strategy to treat HBV infection stays the same. With the availability of more anti-virals and understanding of their resistance pattern, there seems to be a more aggressive approach to treatment of previously E-antigen negative patients, i.e. HBeAg negative patients. Although this basis is built on HBV DNA level more than 2,000 IU/ml - which corresponds to about >11,200 copies of DNA/ml (conversion ratio 1 IU:5.6 copies), the essence of the treatment is to pick up Pre-CORE mutants and treat this group of patients more aggressively with the new anti-virals, especially adefovir and entacavir.

This piece of information must not be confused with Chronic (inactive) carriers state because largely, this group of patient still do not require any treatment. In short, this more aggressive threshold is to further scrutinize the chronic carriers who had HBeAg seroconversion to identify those with high DNA replication (thus suffering liver damage) so that treatment could be extended to this patient group.

However, there is less documentation - almost none - regarding the other aspects of the Hepatitis B disease. The common complaints that the patients first present to the doctors especially among the chronic (inactive) carrier state are not been discussed. Let me further explain the underlying reason for these complaints.

HBV is a clever virus. It is clever because it hides in the host cell - hepatic cells, as part of host DNA. This co-habiting DNA will be replicated as our cells multiply or undergo cellular activities, generates proteins like HBsAg and others into the blood stream. This proteins act as 'markers' or 'flags' as they settle down at different parts of the body. These 'markers' and 'flags' initiate immunological response (if infected in adulthood, this responses will be more intense) by host immunity to attack these 'labelled' organs and tissues.

For ease of explanation, when the 'markers' settle in the kidney, the immunity attacks the kidney, and thus, the patient could suffer from proteinuria (protein leaks out of blood into urine). Interestingly, and cleverly, the virus doesn't kill its host immediately. May be this is a way to continue living in the host like what parasites do. Thus, the proteinuria or damage to the kidney is minimal but chronic.

Some patients of HBV chronic (inactive) carrier may also suffer from episodes of stomach discomfort and intestinal complaints. This is also part of the whole immunity response of the patient to these 'markers' labeling the organs. Thus, continuous monitoring of the health status of carriers is still the only strategy to manage chronic HBV infection and its future complications, if any.

Although Hepatitis Chronic (inactive) carriers are vague in interpretation, it is now recognized that if an infected patient is not treated, the patient may undergo 5 stages of natural course of the disease. They are:

Firstly, the patients are completely cured by the seroconversion of HBsAg to HBsAb during the acute infection period. They are the lucky ones and hence considered having acquired immunity to the infection for life. Very few patients actually die of the acute infection.

Secondly, the patients could become chronic active carrier with persistent HBsAg and HBeAg, high HBV DNA copies in the blood and persistent damage to the liver shown by elevated ALT and other liver enzymes.

Thirdly, the same active patients managed to overcome the disease and develop HBeAb, with disappearance of HBeAg, and HBV DNA becomes undetectable by commercially available testing (<2000iu/ml).

Main Findings

Significantly more cirrhosis and liver-related deaths in untreated patients with HBeAg persistence over long term

HCC, hepatocellular carcinoma.

1. 18 patients cleared HBsAg without any treatment

2. Cumulative probability of HBeAg seroconversion in untreated patients high at 25-year follow-up

• 5 years: 67%
• 10 years: 93%
• 25 years: 97%

3. 9 patients remained HBeAg positive throughout trial

8 patients developed cirrhosis

• Successful interferon treatment: n = 1
• Nonliver-related deaths: n = 2
• Deaths due to liver failure: n = 4
• Death due to HCC: n = 1
  

1 patient living absent of cirrhosis

4. Majority of 40 inactive carriers did not develop cirrhosis

Cirrhosis: n = 7

• Liver-related deaths from HCC: 2
• Non-liver-related deaths: 3

No cirrhosis: n = 33

5. Mixed outcomes in 21 patients with active hepatitis

1. HBeAg reversion: n = 1
2. HBeAg negative: n = 9
2a. Cirrhosis: n = 4
Liver-related deaths: n = 3
OLT: n = 1
2b. No cirrhosis: n = 5
3.HCV or HDV coinfection: n = 8
3a. Cirrhosis: n = 5
3b. No cirrhosis: n = 3
4. Non alcoholic fatty liver disease: n = 3

Cumulative survival probabilities (Kaplan-Meier method) at 25 years statistically higher for inactive carriers when compared with either of the other 2 groups

• Inactive carriers: 95%
• HBeAg persistent: 40%
• HBeAg negative but detectable HBV DNA or HBeAg reversion: 50%

Male sex, cirrhosis at entry, and lack of sustained remission all significant factors affecting risk of liver-related death

At the end of story, one must appreciate the fact that HBV is a smart virus. It wouldn't normally kill its host with one blow. If all course of the disease is to 'parasite' the host, it is to maintain its hidden position and slowly replicate and transmit to new patients without being known to the host.

The common route of HBV transmission is by sexual intercourse or sharing of blood and body fluids. If there is a cut in the mouth, the virus could be found in the saliva of a HBV chronic active patient. If the patient's saliva comes into contact with an open wound, it could then transmit the virus. Unlike hepatitis A, HBV transmission is not via oral-faecal route which is a common misconception. Therefore, eating seafood like clams or taking food with flies would not make one infected with HBV.

So, to those who are chronic (inactive) carriers, monitoring is the only surveillance you have. To those who are chronic (active) carriers, please seek treatment. It is already known that the more senior of age, male gender and presence of cirrhosis are adverse factors affecting survival.