BETA January 1998.
Hepatitis is a general term for inflammation of the liver. The liver is a large organ in the abdomen that processes many substances in the body, including hormones, drugs and poisonous substances. Hepatitis can be caused by a variety of agents, including viruses and toxins.
Hepatitis is often classified as acute or chronic. Acute hepatitis is the first phase of illness; all types of viral hepatitis have an acute phase. Chronic hepatitis is long-lasting (6 month or longer) and can lead to permanent liver damage. Hepatitis B, C and D may become chronic.
Hepatitis A, also known as infectious hepatitis, is the most common type of viral hepatitis. It is caused by the hepatitis A virus (HAV), which is primarily transmitted via the fecal-oral route. HAV is easily transmitted, for example, through the ingestion of contaminated food (particularly shellfish) or water, when changing diapers or through oral-anal sexual contact. The disease also may be transmitted by household contact (for example, sharing eating utensils).
Hepatitis A has a short incubation period (the time between infection and the development of symptoms) of 10-50 days. Initial symptoms may include fever, abdominal pain, nausea and fatigue. The illness may range from mild to debilitating. For 7-10 days, people with HAV shed the virus and can infect others. Some people with hepatitis A, especially young children, have no symptoms but can still transmit the disease. Hepatitis A usually completely resolves on its own, although complete recovery can take 6-12 months. Relapses occur in 15-20% of cases, but there is no chronic or carrier state. The disease is rarely fatal.
The Centers for Disease Control and Prevention (CDC) estimates that 125,000-200,000 new cases of hepatitis A and 100 deaths from the disease occur yearly in the U.S. One-third of the U.S. population has antibodies that indicate past infection with HAV; these people are protected against future episodes of hepatitis A. An effective hepatitis A vaccine is available.
Hepatitis B, previously known as serum hepatitis, is caused by the hepatitis B virus (HBV). HBV is transmitted through blood and other body fluids including semen, vaginal fluid, breast milk, saliva and urine. People may come into contact with infected body fluids through accidental needlesticks, sharing needles to inject drugs, use of unsterilized tattooing and piercing implements, sharing razors or toothbrushes, and unprotected sex. Some people were infected through blood transfusions before 1972, when a test was developed to screen donated blood. Mothers may transmit HBV to their infants late in pregnancy or during delivery. HBV is more easily transmitted than HIV, and the virus is harder to kill. HBV can live in dried blood for 7-10 days and on surfaces for up to 30 days. Some cases of transmission via household contact are known. Many people with HBV have no identifiable risk factors.
The incubation period for hepatitis B is 40-180 days; people with HBV may shed the virus and remain infectious for 50-60 days. Initial symptoms include fever, stomach cramps, nausea, vomiting, loss of appetite, and muscle and joint aches. About a third of people with hepatitis B have no symptoms. An estimated 5-10% of people infected with HBV as adults develop chronic hepatitis. Ninety percent of HBV-infected infants become chronic carriers. Carriers may or may not have symptoms, but in either case they can transmit HBV to others. People with chronic hepatitis B may experience long-term liver damage and are at a higher risk of developing liver cancer. Those who recover completely from hepatitis B are protected from subsequent HBV infection.
According to the CDC, nearly 300,000 people in the U.S. are infected with HBV each year and over 1 million people carry the virus. Acute HBV infection causes some 400 deaths each year in the U.S. An estimated 4,000-5,000 people die from HBV-related illnesses including cirrhosis (liver scarring) and liver cancer each year. An effective hepatitis B vaccine is available.
Hepatitis C is caused by the hepatitis C virus (HCV). It was formerly known as non-A, non-B hepatitis until HCV was identified in 1989. Various genotypes of the virus exist. HCV is transmitted primarily by blood and other body fluids and can be transmitted in the same ways as HBV. Hepatitis C is most common among injection drug users who have shared needles and hemophiliacs who have received blood product transfusions. A screening test for HCV in donated blood became available in 1990, and a more accurate test has been used since 1992. In August 1997, the U.S. Public Health Service issued a recommendation that anyone in the U.S. who had received a blood transfusion before 1992 should be tested for HCV. The virus is uncommonly transmitted through sexual contact. A recent study of heterosexual couples in which one partner was infected with HCV showed a transmission rate of 1% per year (see Research Notes, BETA, September 1997). HCV can be transmitted from mother to infant, and transmission through household contact is suspected. Many people with HCV -- probably more than initially believed -- have no identifiable risk factors.
Hepatitis C often begins with a flu-like illness after an incubation period of 1-3 months, although the majority of people with HCV (up to 75%) have mild or no symptoms. The initial symptoms of hepatitis C are generally milder than those of hepatitis B, but hepatitis C more frequently has long-term consequences, often decades after infection. CDC estimates that 85% of HCV-infected people will develop chronic hepatitis C.
The CDC estimates that there are 150,000 new HCV infections and over 12,000 deaths due to hepatitis C in the U.S. each year. An estimated 4 million people in the U.S. -- over 1.5% of the population -- have chronic hepatitis C, many of whom are undiagnosed. Some experts believe that the hidden hepatitis C epidemic will become an increasingly serious public health problem by the turn of the century, as more people currently infected with HCV are diagnosed and require care.
Hepatitis D, formerly known as delta hepatitis, is caused by the hepatitis D virus (HDV). Because HDV requires the help of HBV to enter host cells and replicate, hepatitis D occurs only in people who also have hepatitis B. People co-infected with HBV and HDV tend to have more severe acute hepatitis and are more likely to develop chronic hepatitis than those infected with HBV alone. HDV is primarily transmitted via blood, and in the U.S. is most often seen in injection drug users and those who have received blood transfusions. Sexual transmission may also occur. HDV is prevalent in the Mediterranean area and parts of Northern Africa and South America.
Hepatitis E, also called enteric or epidemic hepatitis, is most common in developing countries, particularly in parts of Africa and Southeast Asia, where it infects up to 30% of the population. Studies conducted by Eric Mast of the CDC found that 1Ð5% of blood donors in North Carolina and Northern California had antibodies against HEV, but the clinical significance of these positive test results is uncertain. Like HAV, HEV is primarily transmitted by the fecal-oral route, and the disease is most common in areas where sanitation is poor. HEV causes a form of acute hepatitis that is similar to hepatitis A. Hepatitis E infection is usually mild, except in pregnant women, who may have severe cases. No chronic or carrier state has been identified.
Hepatitis F virus (HFV) has been tentatively identified in persons who have hepatitis not caused by the A-E viruses. Validation of this initial report has been problematic, and little is currently known about HFV.
Hepatitis G virus (HGV; also known as HGBV-C) is a newly discovered virus which is distantly related to HCV. HGV is transmitted via blood, and is most common in injection drug users and blood transfusion recipients; it has been detected in 1Ð5% of U.S. blood donors. HGV can be transmitted from mother to infant, and is believed to be sexually transmitted. About 10-20% of people with HCV are co-infected with HGV. It is becoming increasingly clear that HGV does not cause either acute or chronic liver disease. According to Harvey J. Alter, MD, director of the National Institutes of Health infectious diseases division, "the vast majority of patients with prospectively observed HGV infection have no evidence of associated liver disease...One cannot conclude that HGV causes acute or chronic hepatitis."
In addition to the hepatitis viruses, the herpesviruses Epstein-Barr virus (EBV) and cytomegalovirus (CMV) uncommonly cause acute hepatitis in adults. These viruses may lead to severe liver damage, especially in people with compromised immune systems.
Type of Viral Hepatitis
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Because the liver processes toxic substances, it can become overwhelmed if the level of toxins in the body becomes too high. Many drugs -- including some anti-HIV drugs, antituberculosis drugs, sulfa drugs and the over-the-counter pain-reliever acetominophen (Tylenol) -- can damage the liver, as can excessive levels of hormones (e.g., testosterone). Toxic hepatitis can also be caused by certain herbs, poisonous mushrooms and industrial toxins. Different drugs and toxins cause different types of liver damage, and damage may occur immediately or up to 6 months after exposure. Short-term heavy use of alcohol can cause hepatitis, and long-term alcohol use can cause liver cirrhosis. Hepatitis that occurs shortly after starting a new drug should prompt one to consider an adverse drug reaction. In some cases, eliminating the drug or toxic substance will allow the liver to recover. In other cases, liver damage may be permanent.
Certain signs and symptoms of liver damage are common to all types of hepatitis. However, many people with hepatitis experience no noticeable symptoms at all.
Acute hepatitis typically begins with a prodromal phase that resembles the flu. Common symptoms include low-grade fever, nausea, vomiting, loss of appetite, fatigue, a general feeling of malaise, and muscle and joint pain. Some people with hepatitis experience pain in the upper right part of the abdomen and pruritus, a feeling of itchiness of the skin or internal organs. People with acute hepatitis typically develop high levels of certain substances in the blood. High levels of 2 liver enzymes called transaminases in the serum suggest liver inflammation (see section below on "Diagnosis of Hepatitis").
A small number of people with HAV, HBV (especially if also infected with HDV), and HCV experience acute fulminant hepatitis, a condition involving massive necrosis, or death of liver tissue. In such cases, liver failure leads to metabolic imbalances in body chemistry and the inability to remove toxic substances, which may result in brain damage, collapse of the circulatory system, coma or death.
In more typical cases, as initial symptoms begin to subside -- usually within a few weeks -- people with hepatitis may develop jaundice. Jaundice is a yellowing of the skin and the whites of the eyes. It is a sign that the liver is not properly processing bilirubin, a yellowish pigment (coloring agent) released when old red blood cells are broken down. Bilirubin is normally processed by the liver and eliminated in the feces. If the liver is not working properly, bilirubin builds up in the blood and colors the skin and eyes. Some of the excess bilirubin is eliminated in the urine, which may appear dark brown; at the same time, because the pigment is not making its way through the intestines, feces may appear unusually pale or clay-colored. Although it is commonly thought of as a characteristic sign of hepatitis, jaundice occurs only in a minority of people with the disease.
As liver enzyme levels fall and jaundice fades, most people with acute hepatitis enter a recovery phase, which may last from 2-12 weeks or longer. During this time a person may continue to experience fatigue and abdominal tenderness.
In some cases, people with certain types of hepatitis do not completely recover and virus persists. Hepatitis B and C infection can lead to chronic hepatitis and long-term complications including cirrhosis, liver cancer and fatal liver failure.
Some 5-10% of people infected with HBV go on to develop chronic hepatitis. This rate is higher in those who are superinfected with HDV. Chronic hepatitis B is more likely to develop in those who are infected as young children -- up to 90% become chronic carriers.
The rate of persistent hepatitis C is higher -- an estimated 85%, according to the CDC. Some people with chronic hepatitis C show no signs of liver damage themselves but can transmit HCV to others. Other people undergo progressive liver damage. Chronic HBV and HCV infection are more likely in people with compromised immune systems.
Chronic hepatitis is often asymptomatic, but some people with chronic hepatitis B or C may experience continual or intermittent elevated liver enzyme levels, fatigue, nausea, abdominal tenderness and liver swelling. Long-term liver damage may develop over a period of years or decades, and may include inflammation, fibrosis (fibrous tissue in the liver), cirrhosis (scarring and fat build-up in the liver), necrosis (death of liver cells) and a type of liver cancer known as hepatocellular carcinoma. Some of the symptoms and liver damage resulting from hepatitis may be caused by the body's immune response to hepatitis viruses, rather than by the viruses themselves.
In some cases chronic hepatitis leads to liver failure, in which the liver cannot carry out its essential metabolic functions such as filtering toxins and producing proteins. Liver failure due to chronic hepatitis is the major reason for liver transplants in the U.S. Untreated liver failure may result in brain damage, coma and death.
Diagnosis of viral hepatitis -- and what type of hepatitis a person has -- is based on several factors. The prodromal flu-like illness is common to all types of acute hepatitis, but it is characteristic of many other diseases as well, so is a poor basis for diagnosis. In addition to these symptoms, other outward signs of hepatitis (or of liver damage in general) include jaundice, dark-colored urine and visible masses of skin surface blood vessels called spider angiomas. Some people with cirrhosis develop dilated veins in the esophagus, which may bleed easily.
An abdominal exam may reveal an enlarged liver, or a small or shrinking liver, and a person with hepatitis may report tenderness in the upper right part of the abdomen. Computed tomography or ultrasound scans may be done to evaluate liver size and density. A biopsy (removing a sample of liver tissue with a needle for examination) may be necessary to assess the amount of liver damage present.
The most distinctive signs of hepatitis are not visible, but rather involve laboratory blood tests. Lab tests for hepatitis are of 2 types: liver function tests that measure liver enzymes and other substances in the blood, and assays that measure hepatitis antigens, antibodies and genetic material.
Liver function tests measure the level of enzymes called transaminases that process amino acids in the liver. When the liver is inflamed, these enzymes can leak into the blood. Higher than normal levels of aspartate transaminase (AST, also known as SGOT) and alanine transaminase (ALT, also known as SPGT) in the blood serum indicate liver damage. In people with acute hepatitis, liver enzyme levels decrease as the liver recovers. In people with chronic hepatitis, liver enzymes may fluctuate or may remain consistently elevated.
Because the liver plays a key role in processing many substances in the body, changes in liver function can be detected by looking at levels of different breakdown products and chemical components in the blood. High levels of bilirubin and alkaline phosphatase usually reflect liver damage, as does a low level of serum albumin (a blood protein). Prolonged prothrombin time, a measure of the time it takes for blood to coagulate, is a sign of severe liver damage.
Each hepatitis virus is associated with unique antigens and antibodies. Blood tests that measure antigen and antibody levels can determine which type of hepatitis a person has, and often the status of disease.
A person who is infected with hepatitis A will typically have HAV antigens in their blood during acute infection. Those who have been infected with HAV in the past usually have anti-HAV antibodies. Hepatitis A has no chronic or carrier state.
Hepatitis B presents a more complicated picture. HBV has several different antigens, to which the body responds by producing several different antibodies. A person is not reported as being simply antibody positive or negative for HBV. Rather, the combinations of positive and negative measurements of the various HBV antigens and antibodies give a complex picture of hepatitis B disease status.
Soon after a person is infected with HBV -- even before the development of symptoms -- the hepatitis B surface antigen (HBsAg) can be measured in the blood. The immune system produces an antibody against HBsAg, called anti-HBs. HBV virus has 2 other detectable antigens known as HBcAg (core antigen) and HBeAg. The corresponding antibodies are anti-HBc and anti-HBe, respectively. The presence of HBsAg in the blood indicates current active hepatitis B. The presence of HBeAg indicates that HBV is actively replicating and that a person is highly infectious. The presence of anti-HBs and anti-HBc antibodies in the absence of HBsAg signals that a person was previously infected with HBV, but no longer has active disease and is no longer infectious.
Antibodies against HCV, HDV and HEV can be detected in the blood of people who have had these types of hepatitis. The enzyme immunoassay for HCV can detect antibodies within 3 months of exposure.
More recently developed tests measure hepatitis virus genetic material (DNA or RNA) rather than antigens and antibodies. Polymerase chain reaction (PCR) and branched DNA (bDNA) assays -- familiar as tests used to measure HIV viral load -- are also used to test for HBV and HCV. The presence of detectable virus sequences indicates that the virus is actively replicating. These tests are highly accurate and can detect hepatitis viruses soon after infection. Hepatitis viral load tests may be used to monitor the course of HBV and HCV disease. However, because these tests are new, researchers are still learning how to interpret hepatitis viral load results.
The first line of protection against hepatitis is avoiding contact with the viruses that cause the disease. For HAV and HEV, this means maintaining good hygiene (especially always washing hands after using the toilet) and being cautious about potentially contaminated food and water (especially when travelling). HBV, HCV and HDV can be avoided by not sharing injection drug needles, cocaine straws or crack pipes, using sterile implements for tattooing, piercing and acupuncture, not sharing personal items like razors and toothbrushes, and exercising universal precautions (such as wearing gloves and face protection) in healthcare settings. Any spilled body fluids should be carefully cleaned up. In the U.S., donated blood and tissues are screened for HBV and HCV. Because some types of hepatitis are transmitted by sexual activity, precautions to prevent sexually transmitted diseases (including the use of condoms for penile and vaginal intercourse, and barriers such as dental dams for oral-genital and oral-anal contact) can prevent transmission of these viruses.
Hepatitis vaccines involve the injection of inactivated hepatitis virus antigens. These stimulate the body to produce its own antibodies against the virus.
A killed-virus vaccine (Havrix, made by SmithKline Beecham; VAQTA, made by Merck and Company) is highly effective in preventing hepatitis A. The vaccine involves an initial injection followed by a booster 6-18 months later. Protection lasts at least 4 years, and may last as long as 20 years. The vaccine is safe for children and adults, including people with HIV. The U.S. Public Health Service's Advisory Committee on Immunization Practices (ACIP) recommends anti-HAV vaccine for men who have sex with men regardless of HIV status, as well as for international travelers, injection drug users, military personnel, healthcare workers, day-care center workers and children living in communities with high rates of hepatitis A. Because HAV infection is more often fatal in HIV positive people co-infected with HBV or HCV, many AIDS-experienced physicians recommend the HAV vaccine for all people with HIV.
A vaccine against hepatitis B (Recombivax HB, made by Merck and Company; Energix-B, made by SmithKline Beecham) is widely available and highly effective. ACIP originally recommended the HBV vaccine for high-risk adults including healthcare workers, men who have sex with men and injection drug users. Today, the HBV vaccine is also recommended as a routine childhood vaccination and for sexually active adolescents who were not vaccinated as children. The vaccine involves a series of 3 intramuscular injections; the second injection is given 1 month after the first, and the third is given 5 months later. Protective immunity lasts 5-10 years in people with healthy immune systems. It is not known how long immunity lasts in immunocompromised people. If a pregnant women is infected with HBV, her infant should receive the first of the anti-HBV vaccine series plus anti-HBV immune globulin (HBIG) within 12 hours after birth.
There are currently no vaccines against hepatitis C or E; people who have been vaccinated against HBV are also protected against HDV. Researchers are working to develop a vaccine against HCV. Such work is proving difficult because HCV (like HIV) can persist despite the presence of antibodies, mutates rapidly, and several different genotypes or subtypes can co-exist in the body.
The vaccine that protects against HAV does not protect against HBV and vice versa. It is recommended that people receive both vaccines. A combination HAV/HBV vaccine from SmithKline Beecham is currently in clinical trials in the U.S. and is available in Canada.
If a person has been exposed to hepatitis, postexposure prevention (PEP) using immune globulin (injected antibodies) can help prevent the development of clinical illness or reduce the length and severity of illness. For hepatitis A, PEP may begin within 2 weeks of exposure. Household contacts of a person with hepatitis A and travelers to developing countries are often given preventive anti-HAV immune globulin (also called gamma globulin). Anti-HBV immune globulin (HBIG) is used less often since the advent of the hepatitis B vaccine. PEP for hepatitis B should be started within 72 hours of exposure. Administration of the first of the HBV vaccine series plus HBIG starting immediately after birth can prevent transmission of HBV from mother to child. In its July 1997 Recommendations for Follow-Up of Health-Care Workers After Occupational Exposure to Hepatitis C Virus, the CDC does not recommend the use of immune globulin for postexposure prevention of hepatitis C. Anti-HEV immune globulin is under study.
PEP using immune globulin provides only temporary protection (a few months), since it involves the injection of foreign or manufactured antibodies which are eventually eliminated by the body. Vaccines confer longer-lasting protection because they stimulate the immune system to produce its own antibodies.
There is currently no known treatment for hepatitis A. The disease resolves on its own, although complete recovery may take as long as 6-12 months.
Treatment for hepatitis B and C is currently mediocre, but is evolving rapidly. Many factors may affect the decision whether to treat, including hepatitis viral load and extent of liver damage, and patient characteristics such as age and immune system status.
The only FDA-approved treatment for chronic hepatitis B and C is interferon-alpha (Intron A, Roferon A, Infergen). Interferons are messenger proteins produced by the body in response to viral infection. Interferon-alpha is thought to work by inhibiting viral replication and by enhancing the activity of the immune system. Interferon-alpha is effective in about 50% of cases of hepatitis B. Relapses after completion of treatment are common, especially in the case of hepatitis C.
A course of interferon-alpha therapy is typically administered by injection under the skin 3 days a week for 12 months. Treatment with interferon-alpha is more effective in people who have a low hepatitis viral load, who have HCV genotypes other than type 1, and who are early in the course of infection and have not yet sustained extensive liver damage. The NIH recommends that if no benefits are seen after 3 months of interferon-alpha monotherapy, treatment should be changed or discontinued. Side effects of interferon-alpha include flu-like symptoms, fatigue, psychological depression and anxiety.
Interferon-alpha has been shown to be more effective when used with a nucleoside analog drug called ribavirin (Virazol). Some studies have shown that ribavirin alone may have some benefit against HCV, although others studies show little or no benefit. Clinical trials have shown that the combination works well against HCV, particularly in people who have relapsed after being treated with interferon-alpha alone, with many participants achieving undetectable HCV viral loads. Recent research by Ola Weiland of the Karolinska Institute in Stockholm suggests that interferon-alpha/ribavirin combination therapy is most effective in people with high HCV viral loads, while treatment with interferon-alpha alone may be sufficient for people with low HCV viral loads. Common side effects of ribavirin include mild anemia and gastrointestinal upset.
Many drugs have been studied, alone and in combination, as treatments for chronic viral hepatitis. 3TC (Epivir) is a nucleoside analog drug best known as a component of combination anti-HIV regimens. 3TC kills HBV in the laboratory, and clinical trials have shown promise in treating hepatitis B. In one study, J. Dienstag and colleagues found that 100% of 32 patients with HBV who received 100 or 300 mg daily of 3TC achieved an undetectable HBV viral load; however, most experienced an increase in viral load and liver enzyme levels when treatment was stopped. Lobucavir, another nucleoside analog, has shown activity against HBV in laboratory tests and in human studies. The nucleotide analog adefovir dipivoxil (Preveon) has been shown in studies to reduce HBV viral load in the blood.
The antiherpes drugs ganciclovir (Cytovene), penciclovir and famciclovir (Famvir) can suppress HBV replication; further study is needed on how best to use these agents. Some studies have suggested that the immunomodulatory drug thymosin-alpha (Zadaxin) and the amino acid precursor N-acetylcysteine (NAC) have beneficial effects when combined with interferon-alpha. Other experimental drugs for hepatitis include L-FMAU and BMS-200475.
Certain alternative and complementary therapies can help to ÒsupportÓ the liver, including the herb milk thistle (silymarin). The symptom of pruritus can be relieved by the drugs cholestyramine (Questran), lorazepam (Ativan) and naltrexone (Revia). People with hepatitis should not consume alcohol or recreational drugs, which may further damage the liver.
When liver damage is extensive, a liver transplant may be necessary. However, new livers typically become infected with hepatitis viruses -- which remain in the body when the old liver is removed -- and many facilities will not perform transplants on people with HIV.
As with HIV, it is likely that combination therapy using 2-3 or more drugs will be more effective than monotherapy against chronic viral hepatitis. It is also probable that people with chronic HBV or HCV will require long-term -- possibly life-long -- suppressive antiviral therapy.
Because HIV affects the immune system, it can influence the body's response to other infections. Hepatitis A more likely to be fatal in HIV positive people who are also infected with HBV or HCV.
HBV and HCV are transmitted in many of the same ways as HIV, and it is common for people to be co-infected with both HIV and these hepatitis viruses. An estimated 9-36% of people with HIV are also infected with HCV.
There is conflicting evidence about whether HIV positive people who are co-infected with HBV or HCV are likely to experience more severe illness or faster progression of hepatitis or HIV disease. Henri Portier, MD, presented evidence at the September 1997 Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) showing that co-infection with HIV and HCV accelerates HIV disease progression. Arvind Gupta of Lehigh Valley Hospital in Allentown, PA, also presented data showing that HCV infection may worsen HIV infection and speed progression to AIDS. Javier Garcia-Samaniego and colleagues of the Instituto de Salud Carlos III in Madrid reported in the American Journal of Gastroenterology that people co-infected with HCV and HIV experience more aggressive hepatitis and more extensive liver damage than those without HIV. At ICAAC, V. Di Martino and colleagues reported similar results. On the other hand, some researchers have suggested that liver inflammation and damage may be less in people with compromised immune systems, since the body's immune response itself may be responsible for some of the liver damage seen in chronic hepatitis; this theory remains unproven.
In terms of viral transmission, researchers from the Womens and Infants Transmission Study found that women co-infected with HCV and HIV are more likely to transmit HIV to their infants (26%) than HIV positive women without HCV (16%). Conversely, researchers from the University of Turin in Italy found that co-infected women were more likely to transmit HCV (15.5%) than HCV-infected women without HIV (3.7%).
With regard to treatment, some studies of 3TC for hepatitis B indicate that treatment is similarly effective in HIV positive and HIV negative people. However, other studies suggest that hepatitis treatment -- particularly with interferon-alpha -- is less effective in HIV positive people than in HIV negative people, and further research is indicated.
Use of anti-HIV therapy has been shown in some studies to have an effect on HBV and HCV hepatitis viral load as well. This may be because effective anti-HIV therapy strengthens the immune system and allows it to better fight hepatitis viruses, or because some anti-HIV drugs are also active against hepatitis viruses (for example, nucleoside analog drugs inhibit the replication of HBV as well as HIV). A. Pastor, of the Medical College of Virginia, reported at ICAAC that 2 out of 24 patients who were treated with anti-HIV protease inhibitors for 6 months experienced a 3-fold or greater decrease in both HIV and HCV viral load. However, Oliver Rutschmann of University Hospital in Geneva found that protease inhibitor therapy (using indinavir, ritonavir, or ritonavir plus saquinavir) led to a short-term rise in HCV viral load, even as HIV viral load fell and CD4 T-cell count rose.
Many of the antiretroviral drugs used to treat HIV disease are processed by the liver and have been associated with liver toxicity. High levels of nucleoside analog, non-nucleoside reverse transcriptase inhibitor and protease inhibitor drugs can damage the liver, and existing liver damage due to hepatitis can affect how well anti-HIV drugs work.
N. Brau and colleagues reported in March 29, 1997 issue of The Lancet on 3 cases of severe drug-induced hepatitis in patients with advanced HIV disease taking the protease inhibitor indinavir (Crixivan). One was a chronic HBV carrier, one had chronic hepatitis C and one had no evidence of HBV or HCV infection. The patient with chronic hepatitis B died, and the other 2 recovered after they stopped taking indinavir. However, according to Merck and Company, there were no reported cases of severe hepatitis in over 2,000 participants in pre-marketing clinical trials of indinavir, so this adverse event appears uncommon.
Some physicians have reported increases in liver enzyme levels in patients using combination anti-HIV regimens that include a protease inhibitor. Some people with acute hepatitis or with liver damage due to chronic hepatitis may not be able to take protease inhibitors or other types of anti-HIV drugs. HIV-infected people with hepatitis should consult their doctors for appropriate recommendations.
Treatment for hepatitis remains inadequate, but research has advanced considerably in recent years and several potential new therapies are being developed. Although it remains uncurable, many people with chronic hepatitis live long and mostly symptom-free lives. Perhaps the best news regarding hepatitis is the ease with which hepatitis A and B can be prevented by a vaccine. Vaccination against HAV and HBV is strongly recommended, whether a person is HIV positive or HIV negative.
Liz Highleyman is Assistant Editor of BETA.
Thanks to Teresa Wright, MD, for helpful comments on this article.
There are currently very few clinical trials available for people co-infected with hepatitis and HIV. Teresa Wright, MD, chair of the Medical Advisory Board of the American Liver Foundation, calls this a "huge need," and is working with several drug companies to develop such trials. General clinical trial information can be obtained by calling 1-800-TRIALS-A.
Various studies are underway to evaluate the safety and effectiveness of lobucavir, an oral antiviral drug, in reducing hepatitis B viral load levels. Different studies have various sites around the country and varying inclusion criteria. In San Francisco, call ViRx at 415-353-5623 (participants in this study may be HIV positive). For the San Francisco Veteran's Administration Medical Center study site, call 415-750-2105.
This is an open-label study of the safety and efficacy of BM 80.1003 alone and in combination with interferon-alpha. In San Francisco, call ViRx at 415-353-5623 for information and inclusion criteria (patients in this study must be HIV negative).
Schering-Plough is running several trials of the safety and efficacy of ribavirin in combination with interferon-alpha. There are varying study designs and inclusion criteria. The company is working to develop trials for people co-infected with HCV and HIV. For information, inclusion criteria and study sites call 1-800-890-4839.
Alter HJ. The cloning and clinical implications of HGV and HGBV-CNew England Journal of Medicine 334 (23): . 1536-7. June 1996.
Brau N and others. Severe hepatitis in three AIDS patients treated with indinavir. Lancet 349: 924-925. March 29, 1997.
Centers for Disease Control and Prevention. "Recommendations for follow-up of healthcare workers after occupational exposure to hepatitis C virus." Morbidity and Mortality Weekly Report 46: 603-606. July 4, 1997.
Dienstag J and others. A preliminary trial of lamivudine for chronic hepatitis B infection. New England Journal of Medicine 333: 1657-1661. 1995.
Di Martino V and others. Detrimental influence of HIV infection on the outcome of chronic hepatitis C: a multivariate analysis. 37th Interscience Conference on Antimicrobial Agents and Chemotherapy. Toronto, Ontario. September 28-October 1, 1997. Abstract H-37.
Garcia-Samaniego J and others. Influence of HCV genotypes and HIV infection on histological severity of chronic hepatitis C. American Journal of Gastroenterology 92: 1130-1134. July 1997.
Gupta A and others. Relationship between hepatitis C virus viral load and HIV viral load: a case control study. 37th Interscience Conference on Antimicrobial Agents and Chemotherapy. Toronto, Ontario. September 28-October 1, 1997. Abstract I-162.
Hershow RC and others. Increased vertical transmission of HIV from hepatitis C co-infected mothers. Journal of Infectious Diseases 176 (2): 414-420. August 1997.
Horstman J. Hepatitis C: the hidden epidemic. Medscape (www.medscape.com). October 17, 1997.
Martinot-Peignouz M and others. Pretreatment serum hepatitis C virus RNA levels and hepatitis C virus genotype are the main and independent prognostic factors of sustained response to interferon-alpha therapy in chronic hepatitis C. Hepatology 22: 1050-1056. 1995.
National Institites of Health Consensus Development Conference Panel. Management of hepatitis C. Hepatology 26 (3 Suppl 1): 2S-10S. September 1997.
Pastor A and others. Hepatits C virus and HIV viral load in co-infected patients undergoing anti-HIV retroviral therapy. 37th Interscience Conference on Antimicrobial Agents and Chemotherapy. Toronto, Ontario. September 28-October 1, 1997. Abstract I-163.
Piroth L and others. Does hepatitis C virus (HCV) coinfection accelerate clinical and biological evolution of HIV-infected patients? 37th Interscience Conference on Antimicrobial Agents and Chemotherapy. Toronto, Ontario. September 28-October 1, 1997. Abstract H-36.
Roger PM and others. Influence of HIV infection on chronic hepatitis C: support for immune-mediated pathogenesis of hepatitis C infection. 37th Interscience Conference on Antimicrobial Agents and Chemotherapy. Toronto, Ontario. September 28-October 1, 1997. Abstract I-167.
Rutschmann O and others. Impact of HIV protease inhibitors on HCV viremia. 37th Interscience Conference on Antimicrobial Agents and Chemotherapy. Toronto, Ontario. September 28-October 1, 1997. Abstract I-165.
This information is designed to support, not replace, the relationship that exists between you and your doctor.