Hepatitis A to G
by Alan Berkman and Nicholas Bakalar
Excerpt from: Hepatitis A to G
On your right side, just above your intestines in front of your kidneys and under your rib cage beneath your lungs, lies the most complex organ in your body: your liver. In most adults, it weighs around three pounds, making it by a considerable margin your largest internal organ. Blood is constantly flowing through this organ-in fact, all the blood in your body flows through it to process useful nutrients and get rid of toxins.
Any irritation of the liver, anything that makes it in-flamed, is called hepatitis. But the term is most commonly used to describe a group of infectious diseases caused by a handful of different viruses that attack the liver. These viruses, and their effect on the liver, are the subject of this book. There are vaccines for some of these viruses, but not for all. Some of the diseases they cause are chronic, some come and go like a very bad case of the flu, and some are deadly. Six different kinds of hepatitis, A, B, C, D, E, and G, have now been discovered.
Each of these is caused by a different virus. Five of the types cause disease; one, hepatitis G, lives in the blood without causing any apparent illness.
Hepatitis is very common. One hundred and twenty-five thousand new cases of hepatitis A occur every year. In the U.S., five thousand people a year die from hepatitis B. Hepatitis C is the main reason for liver transplantation in the United States-more people get new livers because of hepatitis C infection than because of alcoholism-and more than 240 million people are infected worldwide. Hepatitis E is extremely rare in the United States, but is widespread in other parts of the world where inadequate sanitation allows it to flourish.
Hepatitis A is a nasty disease that can be prevented by a simple and nearly painless vaccination. Hepatitis B, too, can be prevented by a vaccine. But if you contract hepatitis B, you can get a chronic form of it that will be with you for the rest of your life. Hepatitis C is a chronic and sometimes deadly disease with no vaccine, no cure, and a treatment that is effective in only a limited number of cases. A coinfection of hepatitis D with hepatitis B can make the disease much worse. Travelers to endemic areas must be aware of the risks of hepatitis E. In other words, hepatitis is of immediate concern to your health and that of your family. This book is intended to equip you with the knowledge you need to diminish your risk.
The Liver: What It Does, How It Works
The liver does much more than purify the blood and process nutrients. Its healthy functioning is essential to other bodily systems-the blood, bile, lymph, and immune systems-and it also performs more than five hundred chemical functions that make your body work properly, including the following:
* Manufacturing proteins
* Regulating the transport of fat stores and controlling the production and excretion of cholesterol
* Regulating blood clotting
* Producing bile essential to the proper digestion of fats
* Purifying the blood by neutralizing and destroying poisonous substances
* Metabolizing alcohol and other drugs
* Maintaining hormone balance
* Forming blood before birth
* Protecting the body from infection by producing immune factors and removing bacteria from the bloodstream
* Regenerating its own damaged tissue
In short, if your liver is functioning poorly, so is almost everything else in your body. If the liver fails, other organs begin to fail as well. The kidneys, colon, bile duct, lungs, and mucous membranes become poisoned. Rashes, eczema, aches and pains, and organ failures may occur.
And finally, the risk of liver cancer increases. So any organism that attacks the liver can cause serious problems everywhere. And that is what, among other things, the hepatitis virus does.
Hepatitis: Inflammation of the Liver
The diagnosis of hepatitis-or at least the recognition of its symptoms-is almost as old as the history of medicine.
Hippocrates described epidemic jaundice in the fifth century b.c., and what he was seeing was almost certainly a form of the hepatitis virus (though perhaps not a form we know today). The first recorded cases of hepatitis B (which used to be called serum hepatitis) probably were those following the administration of a smallpox vaccine to German shipyard workers in 1883, and the disease was observed repeatedly during the early and middle parts of the twentieth century following the use of contaminated needles and syringes.
The effect of the various hepatitis viruses on the liver-like the effect of alcohol and other toxins-is to scar it. The initial inflammation caused by the virus induces the body's immune system to fight it with immune cells called lymphocytes. But the lymphocytes, while attacking the virus, also harm the liver. Eventually the liver becomes scarred-this is called fibrosis-and when the scarring is severe enough, it begins to hamper blood flow. This is called cirrhosis, and at this stage blood backs up into other organs and the essential functions the liver performs become more and more difficult, and finally impossible, to accomplish.
As we said above, there are now six different species of hepatitis virus known to infect the blood (and some others that might). These are not really strains of the same virus-they're all different organisms that happen to attack the liver and cause similar symptoms. We include much more detail about their natural histories and effect on humans later in this book, but here's a quick review of the facts about them.
In March 1997 hepatitis A (also known as HAV) made the news when 153 cases were reported in Calhoun County, Michigan, and the outbreak was traced to crates of frozen strawberries imported from Mexico. But while foodborne outbreaks like this are serious and must be controlled, they are relatively uncommon. Usually hepatitis A is transmitted by oral contact with the feces of infected people. This can happen in various ways-for example, in nursery schools and day care centers, through contact with infected water in swimming pools, or by eating shellfish that grew in water contaminated with sewage. Hepatitis A can also be transmitted by infected blood, but this is very rare.
Often people who contract hepatitis A have no symptoms at all, and the only way you can tell if they have (or at one time had) the disease is by testing their blood for antibodies to the virus. When there are symptoms, older people usually suffer more than younger people: fever, loss of appetite, nausea, stomachaches, dark urine, and jaundice (yellow skin and eyes) are common. Of course, you can have symptoms very much like these without having hepatitis A-the only way to tell if you have it is with a blood test. The unpleasant symptoms usually last less than two months, but they can persist for as long as six months. The incubation period for the virus is about one month-that is, you can be infected with the virus for about a month, and only then begin to have symptoms.
HAV is not spread by casual contact in the office, school, or factory. But it is spread by contact within families and by sexual contact. In the great majority of cases, people recover from hepatitis A infection, and, since infection confers immunity, never have to worry about it again. In some cases, however, known as ëëfulminant hepatitis,'' the case-fatality rate can be as high as 50 percent despite modern medical interventions such as liver transplantation. About a hundred people a year die from this kind of HAV, usually older people, and often with a preexisting chronic liver disease. If a person is infected with chronic hepatitis C, then hepatitis A infection is a very serious disease with a high fatality rate.
Hepatitis A epidemics are cyclic, occurring about once every ten to fifteen years. The last big epidemic was in 1989. But there is always a large number of people infected-an estimated 125,000 new cases per year.
People most at risk for getting HAV in the United States are children in day care centers and nursery schools and household members of infected people. In the U.S., HAV is largely a pediatric disease-more than 30 percent of reported cases occur in children under fifteen years old, and since most children infected before age five do not have symptoms and are therefore not reported, the actual percentage of cases in children is probably much higher.
There is no cure for hepatitis A, but there is a vaccine, and there is a substance-immune globulin-that can be given after infection to prevent, or at least ameliorate, symptoms. Certain groups of people should routinely get the vaccine. And there are important warnings for travelers that must be heeded: intermediate and high rates of HAV cover most of the globe, and travelers to these areas should be vaccinated. Children under two years old cannot be vaccinated. Chapter 2 gives the details. Interestingly, certain people you might think ought to be vaccinated-sewage workers, food service workers,.health care workers, and day care attendees-should in fact not be routinely vaccinated.
Hepatitis B (HBV) can be a more serious disease than HAV. Unlike HAV, it has both an acute and a chronic form. The incubation period for HBV is between 45 and 180 days-that's how long you can have the infection before you see any symptoms-and the onset of acute disease develops gradually. Doctors call this an ëë insidious'' onset. Not all people who are infected with the virus develop symptoms, and most who do get sick will recover and have immunity from then on. But a large number continue to have chronic infection. Every year in the United States there are about 200,000 new cases of HBV. Eleven thousand of these people get so sick they have to be hospitalized, and 20,000 remain chronically infected. There are now approximately 1.25 million Americans with chronic HBV, and about 5,000 people die each year from the liver disease and liver cancer caused by HBV.
This is a disease of young adults-people between twenty and thirty-nine years of age have the highest rates of infection. Children's rates are relatively low in the United States (and often concentrated in communities of immigrants from countries where rates are high), although rates among kids are higher than the number of reported cases might suggest because asymptomatic cases are common and not noticed. But the disease in young children is very dangerous because 80 to 90 percent of infants infected during the first year of life, and about half of children infected between the ages of one and four, develop chronic HBV infection. HBV can be passed on by infected mothers to their children during childbirth-about a quarter of all chronic HBV infections are acquired in this way.
The symptoms of acute HBV infection are very unpleasant: loss of appetite, tiredness, pain in muscles and joints, stomachaches, diarrhea and vomiting, jaundice. The chronic disease is even worse: it damages the liver in ways that can cause liver cancer and death.
A blood test can determine whether a person has the acute or chronic form of the disease. Recovery from the acute disease generally confers immunity. Sometimes the acute disease becomes chronic-this, too, can be determined
by testing the blood.
HBV is a bloodborne and sexually transmitted disease. The virus is present in the highest concentrations in blood and blood fluids, and in lesser concentrations in semen, vaginal fluid, and saliva. Blood exposure and sexual contact are quite efficient modes of transmission. Although it doesn't happen often, tattooing, ear piercing, acupuncture, and accidental needlesticks can be routes of bloodborne transmission. The cause of perinatal transmission is most often contact of the infant's mucous membranes with maternal blood during delivery. The Centers for Disease Control in Atlanta has concluded that about 50 percent of cases have a sexual risk factor. Men who have sex with men are at particular risk. In fact, the
original hepatitis B vaccine trials were carried out among gay men at high risk. Fifteen percent of cases have a drug use risk factor, 4 percent have other risk factors (household contact, health care employment), and 31 percent have no identifiable risk factor.
There is a highly effective and very safe vaccine for HBV, and the current standard is that everyone under eighteen, and those in certain risk groups over eighteen, should be vaccinated (see chapter 3 for the details). The aim of this vaccination policy is the total elimination of HBV virus transmission in the United States, and this is now within reach.
This is the nastiest hepatitis variety of all. About 85 percent of people who are infected by this virus never get rid of it. Chronic liver disease afflicts about 70 percent of people who are infected with hepatitis C (HCV), and this can lead to liver cancer and death. Some studies suggest that 40 percent of all liver disease in the United States can be attributed to HCV infection, making it as important a contributor as alcohol abuse. Between 8,000 and 10,000 people a year die from the effects of HCV infection. We can put it this way: of 100 people who get infected with HCV, about 85 will be chronically infected, about 70 will develop chronic liver disease, about 15 will develop cirrhosis over a period of twenty to thirty years, and about 5 will die of cirrhosis or liver cancer. A small percentage of people infected develop ëëextrahepatic'' conditions-that is, conditions that afflict other parts of the body besides the liver.
There are several blood tests, some available only in research projects, that will determine if you have HCV, and chapter 4 explains what the tests involve and what.10 Hepatitis A to G they reveal. A person can be infected for five to six weeks before the currently licensed test reveals antibodies to HCV-though the person may still have no symptoms. Although a small number of HCV cases turn out not to be chronic, there is no test to distinguish acute from chronic disease as there is for HBV.
If symptoms of HCV do appear, they usually take about six to seven weeks after the initial infection, but only about 30 to 40 percent of people infected develop any acute symptoms at all. About a quarter of those who develop symptoms have jaundice. The real problems come later, during the period of chronic infection, when liver disease can develop. Until recently it was believed that most people infected with HCV went on to develop liver disease, but this was probably a mistaken impression left by the fact that only people with symptoms are likely to be diagnosed and treated. In fact, people can be infected for many years without symptoms of any kind.
While there is no vaccine for HCV, there is a treatment: antiviral drugs such as interferon are approved for the treatment of chronic HCV. But unfortunately, interferon usually doesn't work: only 15 to 20 percent of people get better on it. When you combine interferon with ribavirin, another antiviral drug, the cure rate goes up to between 30 and 50 percent. Ribavirin used alone is not effective at all. Interferon therapy has many unpleasant, and some dangerous, side effects. Most people who take the drug get flulike symptoms (fever, chills, a fast heart rate, and muscle and joint aching). In time, other side effects may include tiredness, hair loss, low blood count, moodiness, confusion, and depression. Severe side effects (if you don't consider these severe enough) occur in about 2 percent of people on interferon: thyroid disease, depression with suicidal thoughts, seizures, acute heart or kidney failure, eye and lung problems, hearing loss, and blood infection. About 15 percent of people who start interferon treatment can't continue because of these problems. Adding ribavirin makes the treatment more effective, but risks causing serious anemia. Pregnant women cannot use interferon.
There is a further important risk to consider for women of childbearing age: ribavirin can cause severe birth defects. You must use two forms of contraception if you are taking ribavirin.
If there is any good news about HCV, it is that it isn't easy to get. It is almost exclusively transmitted in infected blood. You can't get it by breast-feeding, sneezing, hugging, coughing, from sharing eating utensils, from food or water, or by casual contact with an infected person.
Still, that leaves quite a few ways in which you can contract it. You can get it by injecting drugs-even if you injected only once years ago. You can get it if you were treated with a blood product made before 1987 (clotting factor, for example), or from an infected blood transfusion or a transplanted organ from an infected person. You can get it if you have been on long-term kidney dialysis, from accidental needlesticks if you are a health care worker, from your mother if she had it when you were born, or from sharing items, such as razor blades and toothbrushes, that have infected blood on them. In contrast to HIV and HBV, you are very unlikely to get HCV from sexual contact. But it is possible, most commonly through anal sex. Still, there are many HCV-positive people who do not appear to belong to any of these risk groups.
Although it may be surprising considering all the talk about HCV, there has actually been a decline in infection rates in recent years. This is probably due to some of the behavioral changes that have followed from the HIV epidemic: injection drug users observe safer practices, blood is screened more efficiently, changes in organ donor selection practices have been put into effect, and, since the early 1990s, all donated blood has been screened for HCV. Transmission by sexual, household, and occupational exposure, on the other hand, has remained
about the same over time.
Hepatitis D (HDV) is sometimes called the delta virus. It can't replicate, or reproduce, without the presence of HBV, which it needs to make the envelope of protein that encapsulates the HDV genome. It coexists with HBV in two ways: as a coinfection (occurring at the same time), or as a superinfection (occurring after hepatitis B infection is already established). A person with an HBV-HDV coinfection may have more severe acute disease and a higher risk of fulminant hepatitis compared with those infected with HBV alone. Yet chronic infection appears to occur less frequently in those with HBV-HDV than in those with HBV alone. People with HBV who then acquire HDV as a superinfection usually become chronically infected-70 to 80 percent of those with HDV superinfection develop chronic liver diseases, compared with 15 to 30 percent of those with HBV infection alone.
The symptoms and transmission of HDV are the same as for HBV-it is carried in infected blood and other bodily fluids, and can be transmitted by sexual contact. Sexual transmission is less efficient than for HBV, and perinatal transmission of HDV is rare.
Since HDV can only exist in the presence of HBV, the same preventive measures that apply to HBV also apply to HDV. The vaccine prevents both infections, and both can be treated prophylactically with immune globulin after infection. However, there is no way to prevent an HDV superinfection of a person already afflicted with chronic HBV infection.
Hepatitis E (HEV) is the enterically transmitted (that is, it is transmitted, like hepatitis A, by oral-fecal contact) non-A, non-B virus. HEV has an incubation period that ranges from two weeks to two months. The signs and symptoms are similar to other kinds of hepatitis: abdominal pain, jaundice, fever, nausea, vomiting, and so on. Diarrhea and various rashes are less common symptoms. The disease is transmitted by contact with the fecal matter of infected people, and is most common in regions with poor sanitation facilities. It is possible that there is a nonhuman carrier of the disease that serves as a reservoir between outbreaks in endemic areas. Unlike HAV, hepatitis E is rarely transmitted person-to-person. Instead, infected drinking water is the usual route. There have been no documented outbreaks of HEV in the United States, but nevertheless there is a small number of healthy people with antibodies to the disease in their blood. Where this infection comes from, no one knows. There is no vaccine or prophylactic treatment for HEV infection.
This is the most recently discovered hepatitis virus, first isolated in a blood sample of a Chicago surgeon. It looks a lot like HCV-that is, it shares about 85 percent of its genetic sequence with that virus. But so far, it doesn't seem to be infectious or to cause illness. In fact, the Chicago surgeon in question is still operating. There are between 900 and 2,000 cases of hepatitis G infection each year in the United States. Chronic infection develops in most infected people, but chronic disease is rare or may not occur at all. Hepatitis G is bloodborne, but there have been no infections found in transfusion recipients since 1991. It can occur as a coinfection with hepatitis.
(c) 2000 by Alan Berkman, M.D. and Nicholas Bakalar"
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