Viral hepatitis series: The viral replication, and viral replication only, is the thing

Dr. Liang asked me to give a talk about viral hepatitis at Taiwanese Bible Study last Saturday.  It is a timely talk on account of the recent dramatic success of treating hepatitis C with the direct anti-viral drugs, as Dr. Dienstag (of MGH) claimed “hepatitis C is the only chronic viral infection that can be cured.”  The hepatitis B treatment over the past 10 years is less impressive but certainly not far behind; good news is not lacking.

Katy sent a dispatch to World Journal reporting my talk of viral hepatitis

And of course, the topic was chosen because of the high prevalence of hepatitis B in Taiwan for which Taiwan cannot claim as a “developed” country.  We should take pride in the great contribution of Taiwanese medical profession to the understanding of viral hepatitis and the success of its treatment.

I’ll write a series of articles to cover this complex topic, each with a theme.

Oscar Wilde said “The play, and play only, is the thing”, and I say “The viral replication, and viral replication only, is the thing.”  I cannot over emphasize the importance of viral replication and its implication.

How hepatitis B virus (HBV) or hepatitis C virus (HCV) replicates

All viruses are either DNA or RNA wrapped inside a protein coat.  Once getting into liver cell, the virus removes its protein coat and enters the nucleus, integrating into host DNA, it is a covalent bond—a stronger chemical bond.  No wonder Dr. Baruch Blumberg (who discovered Australia antigen, was later identified as HBsAg) said “We have met the enemy and he is us.” The virus then takes over the “manufacture machinery”, making their own stuff; repackaged and new virion is released from cell.

We can measure the total number of virus in blood by doing a quantitative HBV DNA by PCR (for hepatitis B) or HCV RNA by PCR (for hepatitis C).  High numbers of virus is a reliable marker of active viral replication.

I’ll devote one article to the serology of hepatitis B.  Once the hepatitis B virus invades us, the liver cells mount an immune response, a defense, so to speak.  The foreign invaders, virus, whose various components that can trigger an immune response are called antigens: hepatitis B surface antigen (HBsAg), core antigen (HBcAg) and e antigen (HBeAg).  Having e antigen in the blood signifies active viral replication.

Of all things about hepatitis B or C virus infection, viral replication is the one matters most, everything else is the consequence of it.  Let’s talk about a few things to make a point.

The consequence of active viral replication

Pregnant mother with positive e antigen, active viral replication that is, has 90-95% chance of passing along the virus to the infant, whereas only 30% of the infants infected with the virus if the mother has no HBeAg in the blood.

Chronic hepatitis B patients with positive HBeAg tend to have disease progression, leading to cirrhosis of liver and have higher risk for hepatocellular carcinoma (liver cancer).  Viral replication is the driver for liver injury.

Suppressing viral replication changes the natural history of the disease.  Active viral replication is the main indication of treatment and the goal of treatment is to achieve the sustained viral suppression; call it “cure” if you will.  So the loss of HBeAg or seroconversion (loss of HBeAg and appearance of Hepatitis B e antibody) is a wonderful thing and may be safe to discontinue therapy.

One may not fully recover from hepatitis B by having positive HBsAg (without HBs antibody) and positive HBc antibody, which indicates infection of HBV.  But one can be an inactive carrier, which is defined as no active or progressive liver disease, the liver function should be normal and hepatitis B e antigen should be negative with no active viral replication and hepatitis B e antibody positive.