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13. What are the phases of chronic hepatitis B?

Here’s the other thing that is confusing to our physician colleagues, which is the so-called phases of chronic hepatitis B. This was institutionalized by the NIH at a consensus conference about 5 or 6 years ago in a publication in our literature. They made the suggestion that we should try to characterize our patients who have hepatitis B virus infection into being either in the immunotolerant phase, the immunoactive phase that in our lingo we call ‘chronic hepatitis B’, or who are inactive carriers. Now how do we tell the difference? Well, sometimes it takes more than one series of tests, but immunotolerant phase are e-Positive, so they have the wild type, their DNA is high, sometimes so high that it’s very frightening to the patient and to the doctor, but the ALT is normal. So the concept here is that these are people infected at birth or early in life, when their body’s immune system was immature, and the virus was not seen as foreign. They were born with it, so the immune system doesn’t see it as some sort of foreign protein in the body, so there’s no immune reaction against the virus. For reasons that are unclear, some time in early adult life, something triggers and the immune system begins to see the virus as foreign, and that’s when the liver enzymes go up. This is the immunoactive phase, when there’s immune activity against the virus. From all of our studies with interferon, lamivudine and adefovir, our drugs are most effective when given in this phase because there’s two things going on: the body’s immune system is trying to get rid of the virus, and then we prescribe an anti-viral agent, so it’s sort of like a double hit, an active immune system and an anti-viral agent. Therapy in the immunotolerant phase has not been particularly effective in getting a sustained clearance of the virus. And it’s OK, because although this is frightening to doctors and patients sometimes, there’s really very little going on in the liver. If you do liver biopsies, which we don’t routinely do, the biopsies are normal or there’s just very minimal inflammation in the liver. Now in the phase that we call chronic hepatitis B, the e-antigen may be positive if it’s wild type, or negative if it’s one of the two mutants, DNA is high, sometimes on average a little less higher, the ALTs are elevated and patient may or may not have symptoms. Most often there’s no symptoms, but there may be some vague right upper quadrant aching that’s quite nonspecific in nature. Now if all goes well, in the wild type, in the immunoactive phase with the e-Positive, will go down to this phase and will become an inactive HBsAg carrier. Now the old lingo we used to use was “healthy carrier”, the NIH said that’s a misnomer, because these people have infection, they’re still at risk for liver cancer, and to use the word healthy is inaccurate. So the lingo now is inactive HBsAg carrier, these are e-Negative, DNA becomes low now and is typically less than 10 to the fourth so you still may have detectable DNA, but the ALT tends to be normal. These are the people that occasionally, in the Chinese and Taiwanese study, may actually lose surface antigen and have a clearance.