LOS ANGELES (April 6, 1999) -- Scientists are studying new treatments to combat two viruses that cause chronic liver inflammation, can have catastrophic consequences, and are expected to become increasingly devastating over the next decade. Inflammation of the liver, or hepatitis, can result from a variety of activities or events such as drug and alcohol abuse, ingestion of toxic chemicals or medications, or exposure to one of several viruses that affect the liver.
Of the six known liver-related viruses, referred to as hepatitis A, B, C, D, E, and G, the hepatitis B and C strains pose the greatest threat because they can become chronic diseases, are easily transmitted and they often remain unrecognized until they have caused significant damage to the liver.
In fact, because the liver does not contain nerve endings to send signals of pain to the brain, patients can live without symptoms for many years from the time of infection to diagnosis. By then, scarring, or cirrhosis, of the liver may be so widespread and function so diminished that transplantation offers the only prospect of survival. Liver damage due to hepatitis B or C also can lead to liver cancer, called hepatocellular carcinoma.
"Patients with liver disease can appear relatively well from their perspective, as well as from the perspective of their families and their health-care providers until they reach a stage of complications," according to John M. Vierling, M.D., director of Hepatology at Cedars-Sinai Medical Center, medical director of the hospital's liver transplantation program, and chair of the board of directors of the American Liver Foundation.
Chronic hepatitis B is currently blamed for about 6,000 deaths a year in the United States, Dr. Vierling said. Hepatitis C is responsible for 10,000 deaths but those numbers are expected to jump sharply. "With hepatitis C, we have excellent evidence from the federal government that this rate could rise to approximately 30,000 deaths per year by the year 2010. We are looking at an increasing impact of chronic hepatitis C on mortality, and this mortality will be clustered in people of mid-adult years. These are people in the productive phase of their lives, who, if healthy, would be contributing to society and their families but instead may be seeking liver transplantation or dying."
Because both viruses can be acquired from small amounts of infected blood, hepatitis B and hepatitis C have several risk factors in common, although the degree of risk varies. For example, both viruses can be transmitted through heterosexual or male homosexual intercourse, but the sexual transmission rate of hepatitis B is high while that for hepatitis C is relatively low. On the other hand, another risk factor - sharing needles for injecting intravenous drugs or sharing straws for inhaling cocaine - is comparatively less for hepatitis B than for hepatitis C.
Also, while today's blood supply is safe, hepatitis C transmission could have occurred though blood transfusions performed before 1992; hepatitis B transmission may be linked to blood transfusions performed before 1975. The use of contaminated tattooing or body piercing equipment increases risk, as does the sharing of razors or toothbrushes that are contaminated with blood. Healthcare workers who handle blood are at increased risk, as are patients on hemodialysis for kidney failure.
"Anyone who has risk factors for the possible acquisition of hepatitis B and C should ask to be tested," said Dr. Vierling. "This would include anyone who has a history of having a large number of sex partners, sexually transmitted diseases, injection or inhalation drug use - even once in the past - blood-product transfusion before 1992, hemodialysis, or employment in a healthcare setting where there is contact with blood. People of low socioeconomic means who live in a crowded household where there is a great deal of sharing and potential exposure to blood may also be at increased risk."
For those at risk, specific blood tests for the hepatitis B and C viruses should be performed because routine lab work typically measures the levels of one or two liver-related enzymes that may be within normal ranges even if a patient is infected. Tests that offer a more definitive evaluation of liver function - such as albumin levels and prothrombin time (a blood clotting test) - are rarely performed on a routine basis.
One significant difference in the transmission risks of hepatitis B and C is in the rate of infection of newborns. When a mother is actively infected with hepatitis B at the time of delivery, her baby has a nearly 90 to 100 percent chance of being infected at birth. By contrast, hepatitis C is transmitted from infected mothers to newborns in only about four percent of cases, Dr. Vierling said.
Progression of the two diseases is markedly different, too. Babies who are born with or acquire hepatitis B have a 90 to 95 percent chance of developing chronic infection, while only about five percent of adults who become infected develop chronic disease. The immune systems of the other 95 percent of adults are able to mount an effective defense to overcome and eliminate the illness. The course of hepatitis C, on the other hand, is not age-sensitive. About 85 percent of those who contract the virus will have chronic, life-long liver disease because even the mature immune systems of adults are typically unable to effectively eliminate hepatitis C.
A persistent assault on the liver can lead to cirrhosis, which, in turn, can result in several complications. In a normal liver, for instance, blood flows unimpeded, but in a scarred liver, increased resistance causes increased blood pressure within the portal vein. This condition, called portal venous hypertension, can lead to fluid retention and swelling of the abdomen, abdominal infections, malnutrition, or bleeding from dilated veins inside the esophagus or in the hemorrhoidal plexus.
As a result of poor blood flow through the liver, substances produced by bacteria in the colon that should be metabolized by the liver may be shunted away from the organ through alternative channels. Remaining in the bloodstream, they may reach the brain and cause diminished mental acuity (encephalopathy) or even coma.
In addition to these complications associated with increased portal venous pressure - referred to as decompensating cirrhosis -- a cirrhotic liver may fail altogether or develop cancer, hepatocellular carcinoma. Because hepatitis can have such dire consequences, physicians emphasize prevention and early diagnosis and treatment. "Hepatitis B is a preventable disease and all children and adolescents should be vaccinated," said Dr. Vierling. "An individual who is successfully vaccinated has eliminated any possibility of contracting hepatitis B in the future. Patients who have the disease should be under a physician's care to determine whether it is appropriate for them to be treated with antiviral medications."
A manufactured form of interferon is the mainstay in treating hepatitis and other serious viral infections. The natural form of interferon is produced in the body to boost immunity and regulate other cell functions. As an alternative to interferon injections in the treatment of hepatitis B, a new drug called lamivudine has recently been approved by the Food and Drug Administration. Other new therapeutic antivirals are currently being tested for hepatitis B.
"This is a disease which we can prevent or alleviate with antivirals in order to stave off the potential complications of decompensated cirrhosis and, hopefully, hepatocellular carcinoma," said Dr. Vierling.
For treatment of hepatitis C, the FDA has approved three interferons, either alone or, in the case of one of the interferons, in combination with an oral drug called ribavirin. Several other clinical trials are underway.
Determining which patients would benefit from therapy and at what point treatment should begin continues to be a matter of discussion among physicians and researchers. There is agreement, however, that patients with liver biopsies showing progress toward cirrhosis and patients who have already developed cirrhosis that has not yet decompensated are urgent candidates for therapy.
For patients who do not respond to therapy and in cases of advanced, decompensating cirrhosis, liver transplantation may provide the only hope of survival. The United Network of Organ Sharing, an agency that is under contract of the federal government, sets minimum criteria for transplant eligibility of patients with cirrhosis due to chronic hepatitis B and C. According to Dr. Vierling, the criteria are based on a numerical score derived from blood test results and other factors such as the presence or absence of encephalopathy and fluid retention in the abdomen.
In general, only patients who have a score above a certain threshold may be included on a transplant list, although variations can occur in some circumstances, such as prior bleeding from varices (dilated veins) and a continued risk for rebleeding, or the presence of a small hepatocellular carcinoma.
Because the threat from hepatitis B and C is certain to rise during the next decade but the diseases are poorly understood, the American Liver Foundation offers free, accurate information by phone at 800-465-4837 (800-GO LIVER).
Materials provided by Cedars-Sinai Medical Center. Note: Content may be edited for style and length.
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