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Acute and Chronic Viral Hepatitis

We're going to talk about hepatitis A, B, C, D, E and G. There was thought to be a hepatitis F, but this has proved not to be the case. There are a lot of other viruses that cause hepatitis, but I am only going to talk about a couple of these hepatitis C, hepatitis B, hepatitis G, hepatitis E. The cytomegalovirus and the Epstein-Barr virus are the two viruses that normally cause infectious mononucleosis. Mononucleosis is a disease in which there is a tremendous infiltration of the liver of mononuclear cells and very little necrosis, so the transaminase levels are very low in mononucleosis and it is rare that somebody becomes jaundiced with mononucleosis. However, alkaline phosphatases may be high and it is a pretty benign disease except in people who are immunocompromised, at which point these viruses can cause a great deal of liver damage. The Epstein-Barr virus is the one that gives you heterophile-positive mononucleosis.

Let's start our alphabet soup by talking about hepatitis A. All of the viruses I am going to talk about now, except for hepatitis B, are RNA viruses. Hepatitis B is a DNA virus. Hepatitis A is spread fecal-orally and has an incubation period of sometime between four and eight weeks. Surveys have shown that some seventy percent of health care workers will have had hepatitis A sometime in the past, but in the general population, about fifty percent will have had hepatitis A.

If you ask for a show of hands of how many people have had any form of hepatitis, you usually get maybe one or two people. What that means is that hepatitis A is a disease usually acquired when you are a child. When you are a child, it usually does not cause you to become jaundiced.

The typical course of any of these hepatitis types - and there are a lot of exceptions to that - is that first thing that would happen if you were there to measure it, would be that the transaminase would start going up. Then the patient would start to develop symptoms and then after the symptoms, the bilirubin would start to rise if indeed the patient became jaundiced. The symptoms are very nonspecific symptoms.

In the typical case of viral hepatitis, whether it be A or B, the bilirubin increases for about two weeks and then it falls over a four-week period. If the bilirubin keeps rising for a longer than two-week period, you have to worry that some complication may be developing. What we are talking about is that in the symptomatic person, this is an eight-week illness. There are two weeks of anicteric dysfunction, two weeks of increasing jaundice and then four weeks of decreasing jaundice. Ninety-nine plus percent of patients recover.

Let me define fulminant hepatitis. When we use that term, we are talking about somebody who develops a disease that gets worse and worse and worse and that usually ends in death within a three-month period of the onset of disease.

How can we make the diagnosis? We can study the antibody level and in the acute phase of the disease there is an IgM antibody that develops and in the stage of immunity the patient has an IgG antibody that develops. If you have somebody who comes in with acute viral hepatitis or what you think is acute viral hepatitis as an adult and you want to test for acute hepatitis A, you get the IgM antibody level on the patient.

I have already indicated why just a pooled gamma globulin is going to have enough antibodies to be helpful in preventing the disease. We don't know how long a shot of gamma globulin works. In Peace Corps volunteers, what was the habit was to give these people 0.2 milligram per kilogram of pooled gamma globulin.

In summary, hepatitis A is a very common childhood disease apparently; the big problem has to do with epidemics, especially in the armed forces, when you get people who haven't been exposed coming to a barracks or coming to a college and they are adult, they can make them sick for a period of time, so they are out of action for four to eight weeks. It is not a problem as far as going on to chronic liver disease.

Hepatitis B is still a problem in the United States. It is not a problem from blood transfusions anymore, because blood is very, very carefully screened. It is still a problem in IV drug abusers and cocaine snorters, et cetera, but in a lot of patients we just don't know exactly how it is transmitted. I presume that one way it could be transmitted is the following: I happen to have a hangnail.

Trying to decide who gets the vaccination at birth is absolutely fascinating. If you give one shot of the vaccine, you are going to get an antibody response in maybe twenty percent of people. If you give two shots, may get a sixty percent response. It is only three shots that gives you up to that ninety five plus percent response. If you give that shot at zero time to a newborn, that baby is likely to develop perinatal hepatitis, because only a small fraction will have developed antibodies to that first shot. Luckily with this disease, if you give hyperimmune gamma globulin, it does not interfere with the vaccination at all, so the hyperimmune gamma globulin prevents that hepatitis until that time when the vaccine takes over. Let's talk about the term hyperimmume gamma globulin. Remember, when we were talking about hepatitis A, we were just talking about an ordinary pool gamma globulin. If I take just from three people, the likelihood is that one and one-half will have antibodies to hepatitis A. But less than one percent of the population are carriers of the antibody to hepatitis B. So we have to take a large pool from only patients who have antibodies to hepatitis B. That is called hyperimmune gamma globulin. If we give hyperimmune gamma globulin along with the beginning of the vaccination for hepatitis B, we will prevent perinatal hepatitis and then by the time the child is six months.

Hepatitis C is another bad actor. Fewer new cases per year are occurring, but we are detecting them mainly by a screening test that we get on people when we find a high transaminase. Most patients with hepatitis C, if they have symptoms, have such nonspecific symptoms that it doesn't lead you to the liver necessarily. It can lead you to almost anything. At least half of the cases we see we don't know any risk factors; they aren't tattooed, they aren't bisexual and they don't have any of these other things that look at as risk factors.

Unlike hepatitis B, where around three to five percent become carriers, eighty to ninety percent of patients with hepatitis C are going to become carriers. We get about ten thousand deaths a year in the United States and today, in the United States, hepatitis C is the number one reason that we do liver transplants. A long-term study was done in Japan and whether or not it holds in the United States I cannot be certain, but it will give you a bit of a framework for your thinking. If you have hepatitis C and if you go on to cirrhosis, it takes on the average about twenty years. If you go on to a hepatoma formation, it takes ten more years, so it takes thirty years from becoming infected. Now notice that I said if, because a recent study by Leonard Seif was done in which he was able to find blood from 45 years, found just a very small percentage of these people.

Hepatitis E - the E stands for epidemic or enteric - has been responsible for many epidemics that we used to think were due to hepatitis A. But when serologic tests for hepatitis A became available, we found that they were negative and now we have found this E virus. The most common epidemics have occurred in India and South America. There was one small epidemic in Mexico, so it is getting close to North America. The problem with this virus is that it acts exactly like hepatitis A with one exception.

The G virus does exist and is a relative of the C virus. It often occurs with other viruses, B and C, and is probably of trivial importance, other than to make you know that there is another virus out there. By itself, it probably causes very little problems. This doesn't answer the question about antibodies, except indirectly, but it does go to a little about frequency of various infections in society.