Hepatitis B Update

By Danny Chu, M.D.

(printed in the July 2005 issue of CAMS Newsletter)

 As physicians treating the Chinese community with recent influx of new immigrants, we are faced with many patients with chronic hepatitis B (HBV).  It is still the 9^th leading cause of death worldwide with 300 million HBV carriers.  It affects 15 % of the Chinese population and is a known cause of liver cancer and cirrhosis.  Recently the U. S. Department of Health and Human Services added HBV to the list of cancer causing agents. 

 In the past tens years with the discovery of safer, more efficacious viral suppression for chronic hepatitis B, there are more research and data available about the disease.  HBV is now known to have 7 genotypes. The geographic distributions are as follow:  genotype A in North America and Western Europe, genotype B and C in Asia, genotype D in Southern Europe and India, genotype E and G are unclear and genotype H in Central America.  At this point the HBV genotyping has not come into clinical use.

 There are also many different variants of HBV. The most common is the wild type with the presence of HBV E antigen (HBeAg) but there exist strains that cause active liver disease without the presence of HBeAg.  In 27% of the patients, there are viruses with precore mutation that does not produce any HBeAg and in 44% of the patients, there are viruses with core promoter mutation, which has a down-regulated HBeAg production.  Other variant strains have emerged due to drug resistance.  In Lamivudine (Epivir) treated patients YMDD mutant occurs at a rate of 20% per year and in Adefovir (Hepsera) treated patients, N236T, A181V mutants occurs at a rate of 1.7% in two years.

 The disease states of HBV are now described in three phases.  Non-replicative phase defines the patients that use to be known as inactive carriers. They usually have negative HBeAg, low to undetectable HBV DNA and normal ALT.  These patients do not require treatment but should be screened for liver cancer.  Immune tolerant phase describes the patient with positive or negative HBeAg, elevated HBV DNA but a normal ALT.  Initiating treatment on these patients is controversial since the normal ALT suggests possible lack of liver inflammation.  Liver biopsy is usually recommended to assist in determining if therapy should be started.  Immunoactive phase describes the patient with positive or negative HBeAg, elevated HBV DNA and elevated ALT.  This group of patients should be treated with Interferon, Lamivudine, Adefovir or Entecavir (the current FDA approved therapies)

 In 2/03 a U.S. physician roundtable developed a HBV treatment algorithm.  Once the patient has a positive HBSAg, the HBeAg status, HBV DNA level (PCR) and the ALT are the key information needed to guide the treatment. 

 In compensated disease with positive HBeAg, treatment is required for HBV DNA greater than 100,000 copies/ml with elevated ALT.  Liver biopsy is recommended for normal ALT patients despite elevated HBV DNA.  With negative HBeAg patients, treatment is required for HBV DNA greater than 10,000 copies/ml with elevated ALT.   As before, liver biopsy is also recommended in this case for normal ALT patients with high DNA level.  The end point of treatment in HBeAg positive patient is the loss of e-antigen which indicates diminished viral activity.  While the end point of treatment for HBeAg negative patient is unclear. 

 In patients with compensated cirrhosis, treatment should be started if HBV DNA is greater than 10,000 copies/ml regardless of  the HBeAg status or the ALT level.  

 In all cases, laboratory monitoring is very important during and post treatment.  After therapy is initiated, labs for ALT, DNA and HBeAg (in eAg+ patients) should be obtained every three months.  Lab monitoring is also important once therapy is stopped since a flare of HBV can develop.

The algorithms are meant as a guideline and many patients cannot be classified into a phase or a graph.  Individualized treatment plans will be needed in cases such as HBV carriers who are starting chemotherapy or  infected healthcare workers who are at risk of transmitting HBV.  Currently there are clinical trials for treating pregnant patients during the third trimester with a hope of lowering vertical transmission and for treating patients with high viral load and a normal ALT to see if there are any clinical benefits.  With ongoing research and better therapy, hopefully the number of patients developing long term complications such as cancer and cirrhosis will be reduced.

 (Dr. Chu is Clinical Instructor at the Albert Einstein School of Medicine A noted gastroenterologist, Dr. Chu has contributed two previous articles on the treatment of hepatitis and this is the latest update.)