Informed Patient Conference 2006
June 10-11, 2006, Stanford California
Hepatitis B Treatment Today
Mindie Nguyen, MD, MAS, Assistant Professor of Medicine, Gastroenterology & Hepatology, Stanford University Medical Center
The key questions when talking about HBV treatment is: Who to treat? What to treat with? These are difficult to answer and many of the experts themselves don’t agree.
25-30% of chronic HBV patients can develop liver cancer without cirrhosis. This is different than with HCV patients who first develop cirrhosis and then liver cancer.
A large study in Taiwan (90,000 people screened for HBV with 24,000 enrolled) revealed that HBV DNA levels 104- 105 significantly increased the risk of liver cancer.
Genotype B is associated with less liver cancer than genotype C.
HBV Blood Tests (“serological markers”)
- HBsAg (surface antigen) marker of HBV infection; if positive > 6 months, then chronic HBV
- HBsAb (surface antibody) marker of recovery from infection and/or immunity from vaccination
- Anti-HBc (core antibody) marker of infection or immunity
- HBeAg (e-antigen) marker of active viral reproduction or pre-core mutant
- HBeAb (e-antibody) marker of inactive virus
- Chronic HBV high ALT, e-antigen positive or negative, high DNA (>104- 105)
- Inactive HBsAg carrier normal ALT, e-antigen negative, low DNA (<104- 105)
- Resolved HBV recovery from HBV infection with loss of HBsAg (surface antigen loss) and appearance of HBsAb (surface antibody production)
- Exacerbation or “Flare” high ALT (>10x upper normal limits or > 2x baseline); need to monitor for this especially when patients are on treatment; people with cirrhosis or less able to tolerate flares.
- Reactivation reappearance of necro-inflammatory disease in patients with known inactive or resolved HBV.
Phases of chronic HBV
- Immuno-Tolerant e-antigen positive (eAg+), high DNA (105- 1010), normal ALT; minimal inflammation (liver damage is caused by the immune response to the virus, not the virus itself).
- Immuno-Active e-antigen positive (wild-type virus) or e-antigen negative (mutant virus)
Screening for liver cancer
All people with chronic HBV should be screened for liver cancer, especially men who are at greatest risk. The AFP (alpha feto protein) blood test should be included every 6 months. For those who have cirrhosis or a family of liver cancer, then an ultrasound should be added every 6 months, too.
Although the official recommendation is to order an ultrasound for anyone over 35 years, physicians are now using ultrasound to screen for liver cancer at an earlier age since even children can get liver cancer!
Goals of treatment
The primary goal is to prevent the long-term consequences of chronic HBV – cirrhosis, liver cancer and liver failure.
The key “clinical endpoints” for treatment are:
- Decrease DNA viral load
- Normalize ALT
- Seroconversion (e-antigen)
In e-antigen positive patients, the critical endpoint is for e-antigen seroconversion (loss of e-antigen) and with treatment, there is about an 80% durable response after a drug is stopped.
In e-antigen negative patients, the critical endpoint is decreased DNA viral load and with treatment, there is a high relapse rate after a drug is stopped.
There are so many treatment guidelines! Some are conservative, others are more practical: AASLD (Lok & McMahon), NIH (Hoofnagle & LOK), EASL (deFranchis), APASL (Liaw), and Treatment Algorithm (Keeffe).
Although resistance is a serious concern with the orally available drugs, combination therapy may be an option and new promising drugs are in the research pipeline.