September 13, 2011

The word hepatitis is derived from the Greek word for liver and is defined as inflammation of the substance of the liver. Although hepatitis is usually thought of as caused by a viral infection, it might be a result of any number of injuries, including medications, alcohol, genetic diseases, or many other causes in addition to infectious diseases.

A large number of infections can involve the liver, causing hepatitis as part of their systemic effects, but there are five major viruses that specifically attack the liver. These are referred to as hepatitis A through E. Other hepatitis viruses have been described—including hepatitis G, for example—but their clinical importance is somewhat unclear. In the United states, the most important viruses are hepatitis A, B, and C.


Hepatitis A infection usually results from the consumption of food contaminated with virus-laden feces of infected individuals. Foods that may be contaminated include shellfish, with many reports of outbreaks in people who eat raw clams or oysters; this is also because the virus is very hardy and requires cooking temperatures to be inactivated in foods or drinks infected by food handlers with poor hygiene. shellfish are a notorious potential source of infection since, as filter feeders in shallow waters (and therefore, possibly exposed to water contaminated with sewage), they can concentrate a large amount of hepatitis virus. Because of its means of transmission, it frequently causes many people to become infected simultaneously. For example, an outbreak may result from a common source or from poor hygiene practices in an institutionalized setting (e.g., daycare centers or facilities housing the mentally retarded) leading to transmission from one infected person to another. Less commonly, people have acquired hepatitis A via infected blood transfusions, intravenous drug use, or sexually.

Hepatitis A is found worldwide. In developed countries, the rate of hepatitis A infection tends to slowly rise throughout childhood and early adulthood. In contrast, among developing countries, with crowded living conditions, inadequate sanitation, and contaminated drinking water, there is a very high rate of infection in the first few years of life. In the United States, it is estimated that 33% of the population has been infected with hepatitis A.

In children, hepatitis A often causes an illness with mild or even no symptoms. Because infected children often are not recognized as being ill, and because children may excrete virus for longer periods than adults, they play a major role in the spread of hepatitis A in both developing and developed countries. Among adults, however, it can cause much more substantial liver injury, including a violent hepatitis or even liver failure. It has been estimated that approximately 80% of adults who become infected with hepatitis A will develop symptomatic disease. Although it can cause extensive damage acutely, hepatitis A does not cause chronic liver disease.

The typical symptoms, like those of any hepatitis, include nausea, vomiting, vague abdominal discomfort, jaundice, fatigue, and generalized malaise. Laboratory studies are usually abnormal when patients are symptomatic and include rapid increases in liver enzymes reflecting hepatic necrosis (liver cell death), followed by a more gradual rise in serum bilirubin (a breakdown product of red blood cells normally processed and removed from the bloodstream by the liver) that is responsible for jaundice. The diagnosis is confirmed by a blood test revealing the presence of specific antibodies to the hepatitis A virus.

The typical presentation of hepatitis A includes a period without symptoms after initial exposure to the virus, usually lasting approximately 4 weeks, followed by a symptomatic period that may also last anywhere from 3 to 5 weeks. Rarely, this period can last up to 12 weeks, but then is usually followed by complete recovery. Very rarely, patients may develop an illness with a more prolonged jaundiced phase, lasting up to 3 months, or a prolonged relapsing hepatitis, with waxing and waning symptoms. This prolonged relapsing course can last up to as many as 12 months after initial presentation, but again, is typically followed by complete recovery. The last form of presentation, fulminant hepatitis, is very rare, but may cause so much damage as to require liver transplantation in as many as 50% of affected adults. Unfortunately, there is no other treatment option for patients with fulminant hepatitis A.

The risk of hepatitis A infection can be reduced by adequate sanitation, isolation of known or suspected infected individuals, and good hygienic practices particularly in restaurants, day cares, hospitals, and other institutions. In addition, groups at increased risk for hepatitis A, including health care workers, day-care workers, and travelers to endemic areas, such as missionaries and military recruits, should be vaccinated.

Individuals with other chronic hepatitis infections should also be vaccinated because of their reduced ability to tolerate additional injury to an already compromised liver. In addition, for people who have been exposed to hepatitis A, for example, family members of an infected individual, an immune globulin preparation (containing specific antibodies in high titers against hepatitis A) may prevent infection. Unfortunately, no specific treatment is available for patients with symptomatic hepatitis.


Hepatitis B was the first hepatitis virus to be discovered, in 1967. Hepatitis B is the most common hepatitis virus worldwide with some estimates suggesting that half of the world’s population may have been infected. In areas of high prevalence of infection, such as East Asia or sub-Saharan Africa, as many as 100% of the population may have been or may currently be infected with the hepatitis B virus. The most common mode of hepatitis B transmission is from mothers to their children around the time of childbirth. Other means of transmission include sexual transmission or via blood (e.g., needlestick injuries, intravenous drug use, or transfusions). In contrast, in low-prevalence countries such as the United States, the most common means of transmission is usually related to sexual contact with a chronically infected individual.

Unlike hepatitis A, which only has an acute form, hepatitis B infection may be acute or chronic. The age of acquisition of hepatitis B infection has implications regarding the likelihood of developing chronic infection. Infants who are infected shortly after birth may have a 90% chance of becoming chronically infected; in children between 1 and 5 years, the risk falls to 25-50%; and by adulthood, the risk falls to about 5%. Approximately 70% of patients with acute hepatitis B are either relatively asymptomatic or at least not jaundiced.

The time lag from an exposure to hepatitis B to the start of symptoms is usually between 1 and 4 months, and is accompanied by dramatic increases in liver enzymes, marking widespread destruction of the liver, then followed by jaundice. Over a period of several months, these enzymes gradually return to normal in the patients who recover completely. Less than 1% of patients will develop acute liver failure and either die or require a liver transplant.

Chronic hepatitis B is the persistence of the virus in the liver and is detected by the presence of markers of hepatitis virus infection in the serum, such as the hepatitis B surface antigen (one of the proteins made in high titers in the liver of an infected patient) or hepatitis B viral DNA. Approximately 5% of the world’s population is chronically infected, with the highest rates in the areas that have the highest rates of infection. In the United States or Western Europe, the overall rate of chronic infection is between 0.2% and 1%. The course of chronic hepatitis B is variable, depending on the age of acquisition of infection as well as other risk factors for liver disease (such as alcohol abuse) and the patient’s immune response to the virus. Some patients are almost asymptomatic (the so-called “healthy carrier” state), whereas others, for example, from endemic areas such as China, may have progressive liver damage, leading eventually to cirrhosis or liver cancer in as many as 40-50%. In regions where hepatitis B is endemic, liver cancer is the leading cause of cancerrelated death.

The course of chronic hepatitis B in North American patients generally can be divided into two phases—a so-called replicative phase in which the virus is actively multiplying and causing progressive liver damage, and a nonreplicative phase in which the virus lies dormant within the liver. Much of the variability of the course of hepatitis B stems from the duration of the replicative phase in which markers of active production of virus can be detected in the serum (such as the presence of envelope or E antigen). These markers are also an indication for higher infectivity and are usually accompanied by significant liver destruction. The clearance of E antigen, marked by the development of a specific antibody, results in a more quiescent phase of liver disease, often with lower or undetectable amounts of circulating virus and improvement in liver enzymes. These patients’ liver disease can flare, however, if they develop an illness requiring treatment with steroids or other medications that suppress the immune system. A small percentage of these patients will eventually clear all signs of infection, losing markers of infection (e.g., the surface antigen) at a rate of 0.5-2% per year. The outcome for those who do not clear the virus varies, based on the length of time they have been infected. In addition, although the risk in North American patients is fairly small, if patients already infected with hepatitis B were to become infected with another hepatitis virus, including hepatitis A, C, or D (a rare form of hepatitis B), they are at increased risk for developing severe liver disease or fulminant liver failure.

Several treatment options exist for hepatitis B patients. The first successful therapy was based on interferon and is effective in clearing markers of active disease from the blood in up to 40% of patients, but unfortunately has significant side effects.

More recently, several medications that interfere with the synthesis of hepatitis B viral DNA have been shown to reduce the damage of hepatitis B, causing loss of E antigen or seroconversion (i.e., development of an antibody to the E antigen) at similar rates. Although these drugs are much better tolerated, concern about the emergence of resistance has limited their use to patients with active disease.


Hepatitis C is a virus with a worldwide distribution, infecting almost 3% of the world’s population, including almost 4 million Americans. The virus is classified among the flaviviruses (a group which also includes West Nile virus, dengue, and yellow fever viruses). The genome of hepatitis C virus (HCV) codes for a long protein, about 3,000 amino acids in length, which is then processed into a number of structural proteins and enzymes necessary for replication. Based on sequence structure, an individual virus can be assigned to one of six different genotypes of hepatitis C; these have a varying geographic distribution. Most patients acquire hepatitis C infection via blood transfusion or blood exposures, such as needlestick injuries or intravenous drug use, or less commonly, from sexual exposure or in the perinatal period. Unlike infections with the other hepatitis viruses, hepatitis C virus is much more likely to become chronic, typically in about 80% of patients who are exposed. The reason why some patients are able to clear the infection is unknown, but it is speculated that these patients may have more vigorous immune responses to the infection than those who do not clear the virus.

Although hepatitis C virus infection usually becomes chronic, the likelihood that chronically infected patients will develop progressive liver disease is approximately 20%, typically occurring over a time period of about 20 years or more. Other factors that influence the rate of progression to cirrhosis (end-stage liver disease) include the amount of alcohol consumed, gender (disease in women tends to progress more slowly—possibly related to iron depletion), the age of acquisition (progression in younger patients may be slower), as well as some factors related to the virus type or the patient’s underlying immune status.

Although some develop typical hepatitis symptoms, most patients who acquire the infection are asymptomatic, and often remain so for years. Patients are therefore often identified when abnormal liver tests are found on screening tests or alerted after donating blood to the Red Cross. Most screening tests detect specific antibodies to the virus; confirmatory antibody tests or very sensitive tests to detect the viral RNA can be used to confirm the presence of ongoing infection. Quality of life studies often detect an increase in nonspecific symptoms such as fatigue, weight loss, or abdominal discomfort, as well as anxiety and depression in patients with chronic HCV. Ultimately, with the onset of clinical cirrhosis, symptoms and complications of end-stage liver disease (such as liver cancer) become apparent. As in hepatitis B, a wide range of manifestations of hepatitis C virus outside the liver has been found. Although somewhat uncommon, these include skin disease, rheumatologic disease, and endocrine and kidney diseases.

Treatment options for hepatitis C virus are currently based on the use of interferon. These are derived from a family of naturally produced proteins that have direct antiviral effects as well as effects on the immune system, and are used in conjunction with a second antiviral medication, ribavirin. However, treatment side effects as well as low overall efficacy rates prevent the majority of patients from completely eliminating the virus permanently. New therapies on the horizon offer great promise for these patients; intensive efforts are also under way to produce a vaccine to prevent infection.

SEE ALSO: Immunization, Injection drug use, Quality of life, Safer sex

Suggested Reading

  • Koff, R. S. (2003). Hepatitis A and E. In D. Zakim & T. D. Boyer (Eds.), Hepatology: A textbook of liver disease (pp. 939—958). Philadelphia: W.B. Saunders.
  • Nair, S., & Perrillo, R. P. (2003). Hepatitis B and D. In D. Zakim & T. D. Boyer (Eds.), Hepatology: A textbook of liver disease (pp. 959-1016). Philadelphia: W.B. Saunders.
  • Younossi, Z. M., Ong, J. P., & O’Shea R. (2003). Contemporary diagnosis and management of Hepatitis C. Newton, PA: Handbooks in Health Care.

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