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.