Hepatitis C -- The Newest Opportunistic Infection
HIV/Hepatitis C Co-infection in the Age of HAART
The dynamic course of the AIDS epidemic over the last nineteen years has been the site of many changes, some relatively minor and others more revolutionary in nature. The most recent major change has been the introduction of combination therapy that includes protease inhibitors -- highly active antiretrovirus therapy, or HAART -- which first appeared in the winter of 1996. The protease inhibitor revolution in HIV care has dramatically increased survival and decreased mortality. In fact, for many people with more than 200 CD4 cells, HIV has turned into a chronic controllable illness similar to diabetes and hypertension.
Now that people with HIV and AIDS are living longer, however, other diseases are taking their toll. One of these is the hepatitis C virus, or HCV. As many as one-half of all people with HIV may have HCV, and the presence of HIV can exacerbate HCV and dramatically accelerate its progress to cirrhosis and death. In fact, liver disease has become the leading cause of hospital admissions and death in patients with HIV. Some of the new drugs place their own strain, making HAART patients even more at risk for liver disease, and therefore making HCV treatment even more important.
The Spread of Hepatitis CHepatitis C was first recognized in the early 1970s as non-A non-B hepatitis, and in the late 1980s researchers named it hepatitis C. The statistics show the extent of the disease: 3.9 million Americans have been infected with hepatitis C, of whom 2.7 million have chronic hepatitis C, that is, infection that lasts for more than six months; 1.8 percent of Americans are currently infected with the virus; each year another 36,000 individuals are newly infected with HCV; 85 percent of those infected have chronic HCV; only 15 percent clear acute HCV spontaneously, that is, in these people the infection develops quickly and lasts less than six months -- the opposite of the statistics on hepatitis B; most of those infected are adults ages 30 to 50; HCV is the leading cause for liver transplantation in the United States.
It has been estimated that more than 200 million people are infected with HCV, an overall incidence of 3.3 percent of the world's population. The number of deaths from hepatitis C is expected to triple in the next ten to twenty years. Without early and aggressive treatment of infected individuals, the death toll from HCV is likely to surpass that of AIDS and could reach more than a million by the year 2020.
There are approximately 400,000 people in the United States co-infected with both HIV and HCV. The numbers are higher among injection drugs users, where 50 to 90 percent are co-infected. Among people attending New York City AIDS clinics, 40 percent are co-infected with HCV.
TransmissionLike HIV, HCV is transmitted through blood-to-blood contact. HCV, however, lives outside the body for a much longer time than HIV and is therefore much more easily spread. Sharing needles for injection drugs is a very high-risk behavior. Using only sterilized needles for tattoos is very important in guarding against HIV, but it may not be enough to prevent HCV infection. The reason is that when the tattoo artist dips the needle into the ink, a microscopic amount of blood from the person getting the tattoo can get into the ink itself. If that blood contains HCV, it is the ink, not the needle, that poses the danger to the next person being tattooed.
Women can pass on their own HCV to their babies at birth, but it is very rare, and breastfeeding does not seem to increase the risk of mother-to-child transmission.
Sexual transmission seems to be low, but it becomes a risk factor among those who have participated in other high-risk behavior such as anal intercourse and/or who have multiple sexual partners.
Hepatitis C and the LiverHCV is a very slow-developing chronic disease. Many people have HCV and never even know that they are infected until it is too late. It works silently over the years, causing irreversible liver damage without any signs. The most common symptom associated with hepatitis C is fatigue. Liver damage from HCV can take up to twenty years for cirrhosis and thirty years for liver cancer. These problems occur at a much faster rate -- perhaps twice as fast -- among those who are co-infected with HIV.
"Hepatitis" simply means inflammation of the liver. The disease is caused by a virus that mainly infects the liver cells. When a hepatitis virus infects a liver cell, spikes on its outer membrane (known as the "envelope") anchor to the outer surface of the liver cell. A core of viral genes is now able to pass from the envelope into the cell. Once inside, the virus can take over the normal function of the liver cell, forcing it to make more viruses. This process causes the cell to die . . . but not before thousands of viruses get released to infect healthy cells. Your immune system is designed to fight infection by making antibodies; a different antibody is produced for each different infection, and each type of antibody attacks just its particular virus or bacterium. Antibodies also help clear infection from the bloodstream. The antibodies our bodies produce against hepatitis C are similar to those we produce against HIV in that they are usually less effective in killing off these viruses than many other antibodies are in eliminating their target pathogens.
Your liver is a versatile organ that plays several different and vital roles in enabling your body to use nutrients and medications and cleanse itself of toxins. Your liver is the filter of the body. Everything you eat, drink, breathe, or inject gets filtered through the liver, which takes waste and poison out of the bloodstream. Your liver is also the warehouse of the body. It stores sugar and vitamins for your body to use when they're needed. Your liver takes nutrients and sends them into the bloodstream so that they can be distributed to the cells that need them. The liver also helps digest and stores fat, which makes it possible to keep going all day without eating each time your body needs more energy. The liver transforms medicine into a form that your body can handle; without the liver, medicines can't work properly. Your liver makes protein needed for muscle building and clotting factors to stop bleeding. The liver makes bile to absorb nutrients and vitamins. The liver also helps to detoxify the body.
Left untreated, HCV goes on to cause damage in the form of cirrhosis, fibrosis (scarring of the liver), cancer, and liver failure. Cirrhosis can cause varicose veins, called varices, in the esophagus that can cause bleeding. It can lead to fluid buildup in the abdomen. called ascites. Hepatic encephalopathy is a decreased mental state caused by liver failure. Liver cancer (hepatoma) occurs in people with HCV only in the presence of cirrhosis.
Diagnosing HCVLiver enzymes are a type of protein molecule, and persistent elevations indicate liver inflammation. But almost half -- over 45 percent -- of those infected with HCV have normal liver enzymes. Liver enzymes have no direct relationship to the condition of the liver or to serum HCV levels. Therefore, people known to be HCV-infected who have normal liver enzymes are encouraged to undergo liver biopsies to determine the exact amount of damage there really is in the liver.
Liver function tests include tests for the levels of albumin, bilirubin, and platelets. Albumin is a component of blood that helps prevent swelling. Platelets are responsible for aiding in the clotting of blood. Bilirubin accounts for the yellow skin, or jaundice, that is characteristic of liver problems. It is a yellow substance that builds up in your blood as red blood cells age and break down. Your liver is responsible for the breakdown of bilirubin. When your liver doesn't function properly and bilirubin builds up, the result is jaundice. Lab tests, however, often show normal albumin, bilirubin, and platelet levels, leading to a diagnosis of HCV being missed.
The most reliable way to diagnose hepatitis C is through an HCV antibody test. Who should be tested? Anyone who has ever shared a needle -- even one time -- is at risk. If you received a blood transfusion or an organ transplant before universal testing of the blood supply was initiated in 1992, you are at risk, as are people who have had long-term kidney dialysis. If you've been pierced or tattooed, if you are a healthcare worker who has ever been stuck with a patient's needle, if you have ever snorted cocaine or any other substance, shared a razor blade or a toothbrush, received a manicure or pedicure, undergone electrolysis, had acupuncture, you may have been exposed. Any blood on the outside of a syringe, on a tourniquet, on any surface at all, may increase your risk of exposure. So who should be tested? Everyone.
When you go in for an HCV antibody test, you should be tested for hepatitis A and B at the same time. [See "Hep Alphabet" by Raymond A. Smith.] If you have been tested and found to have no immunity to A and/or B, and are negative for their antibodies, ask your healthcare provider to give you vaccines to protect you against these viruses. Hepatitis A is spread through oral/anal contact. You get it by putting something in your mouth that is contaminated with feces. It can be transmitted if your food is touched by someone with the virus who doesn't wash his or her hands after going to the bathroom. It is also transmitted from unclean seafood, or when water is not filtered properly. Hepatitis A is sexually transmitted through "rimming," or anal/oral sex. Hepatitis A can be fatal when you have HCV. Hepatitis B is sexually transmitted similarly to HIV.
TreatmentThere is no vaccine for hepatitis C, as there are for hepatitis A and B. Effective treatment is available, however, that can help reduce the severity of this disease and decrease the death toll.
If you test positive for HCV, a viral load should be done to measure how much virus is in your bloodstream. Unlike HIV, which is measured in the thousands, HCV is measured in the hundreds of thousands to millions. Liver enzymes are measured but, as discussed above, may be normal; even if they measure five to ten times normal they may still not indicate liver damage. A liver biopsy is the most effective way of diagnosing liver damage, but it is not necessary to receive treatment. If your liver biopsy shows cirrhosis you can still be treated.
A revolution in hepatitis C therapy similar to the one that occurred in HIV took place a little more than two years ago. In June 1998, the FDA approved the combination of recombinant interferon alpha 2b and ribavirin, brand name Rebetron. Interferon is an injection and ribavirin comes in capsule form. This combination of drugs has dramatically changed the landscape of hepatitis C treatment from one of high side effects with low sustained viral response rates to one of nearly 50 percent sustained viral response rates.
Interferon is a natural substance that your body makes to help defend itself against infection by helping your body's immune response against virus and infected cells. Ribavirin is a nucleoside analogue similar to AZT. Ribavirin has no independent effect against the hepatitis C virus; it essentially enables the body to utilize interferon more effectively. The amount of drug that is prescribed depends on body weight and whether you are also anemic. Individuals with anemia may be treated with erythropoietin (Procrit), a drug the stimulates the bone marrow to make red blood cells, before treatment with ribavirin is begun. HCV sustained response rates (continuing normalization of liver enzymes and suppression of detectable HCV-RNA at least six months after the termination of therapy) in HIV patients are similar to those who have HCV only.
The standard of care in HCV treatment is changing rapidly, just as the care in HIV has changed dramatically in the last few years. Based on new information, less frequent medication at lower doses may soon become the norm, keeping the virus suppressed more effectively with fewer side effects.
HIV and HCVThe two viruses have many similarities in the way they are transmitted and the way they act in the body, and a few important differences: HCV and HIV are both blood-borne diseases, that is, they enter the body directly through the blood. It is much easier to get HCV through blood than HIV. Antibody testing is the backbone of screening for the presence of both viruses. In both viruses, the antibody is ineffective, providing no immunity and immune avoidance to the disease caused by the virus. Both are RNA viruses. Both viruses produce astronomical amounts of virus each day; HIV produces approximately 10 billion new viral particles per day and HCV about 10 trillion each day. The amount of both viruses is measured by viral load. The mutation rate is much faster in HIV -- 10,000 variants daily compared to 1,000 for HCV. Prior to seroconversion, HCV -- like HIV -- is associated with extremely high viral concentrations. After seroconversion HCV concentrations are reduced, sometimes to undetectable levels. One big difference is that HIV, so far, is not curable. HCV is. Treatment can totally eradicate this virus from your body and it will never come back!
If you are HIV-positive, your HCV infection worsens at a faster rate than if you have HCV alone. The hepatitis C virus multiplies faster in an HIV-positive person than in someone who is HIV-negative. HCV does not, on the other hand, make HIV multiply faster. The more controlled an individual's HCV is, the less strain there is on the liver and the better the prospects for effective HIV treatment. If your body can't absorb HIV medication, a process interfered with by HCV, then your HIV virus will start to replicate and impaired immune function will develop more rapidly.
Treating HIV/HCV Co-infectionThere are several things you should know before you begin treatment for HIV/HCV co-infection: First, protease inhibitors can be toxic to the liver; Norvir and Crixivan are the worst offenders. Of the NNRTIs, Viramune poses the greatest threat of liver toxicity. AZT, when used with ribavirin, can increase your risk for anemia. Ribavirin is very teratogenic, that is, it causes severe birth defects. Women who are pregnant should never take the drug; if you are being treated with ribavirin, wait at least six months after discontinuing the treatment before attempting to become pregnant. Other diseases such as arthritis, allergies, asthma, or depression may get worse during treatment with ribavirin.
Common side effects of the medications used to treat HCV include depression, irritability, body aches, hair thinning, canker sores, abnormal thyroid function, anemia, weight loss, muscle wasting, loss of appetite, changes in taste (which can lead to poor nutrition), increased mucous production, weakness, low-grade temperature, fatigue, concentration problems, nausea, neutropenia (low white blood cell count), and trouble breathing. An individual may suffer from none of these effects . . . or from all of them.
Most of these side effects can be managed. If you have any history of depression, you should be treated with antidepressants before starting treatment. If you are already on antidepressant medication, your dose may need to be increased. Anti-inflammatory medication such as Tylenol or Advil can help reduce aches and fever. Appetite stimulants such as Megace or Marinol are helpful in maintaining and/or gaining weight. Procrit may be used to treat anemia, or the amount of ribavirin prescribed may be reduced, or both. Vitamin B12 can be used to treat fatigue. Inhalers are useful for breathing problems related to bronchospasms caused by interferon.
The reason for treating HCV in most cases is to prevent liver damage or keep it to a minimum. Cirrhosis of the liver is irreversible, and liver cancer is very difficult to treat. Every time your viral load is lowered, your liver has the chance to do some healing, thus buying some time. Also, HCV might exacerbate the hepatotoxic effects of HAART, which provides a compelling reason for treating co-infected people aggressively.
There have been questions about the use of ribavirin in HIV-positive individuals on HAART. An old study (from 1987, when ribavirin was being evaluated for its HIV effect) showed that ribavirin inhibited the effects of AZT in vitro. In current studies, however, it appears that ribavirin does not inhibit AZT or D4T (Zerit). HIV-RNA levels did not change when ribavirin was introduced into combination therapy in the treatment of HIV, while HCV levels dropped dramatically when ribavirin was used with interferon for the treatment of HCV. Long-term response rates in co-infected individuals are being evaluated now. Eighteen-month data of those who have completed treatment show that individuals who had undetectable HCV viral loads have remained undetectable. Clinicians are starting to use the word "cure" when talking about HCV treatment.
Genotypes are used in hepatitis C as a way of identifying how effective a proposed treatment may be. Genotypes predict therapeutic response, disease progression, and optimal treatment duration. Six genotypes have been identified, and their relative prevalence varies by geographic location. Unfortunately, some 80 percent of people in the United States fall into one of two genotypes that are difficult to treat because of poor response to interferon-based therapies. They do, however, respond to interferon and ribavirin treatment, and often an undetectable viral load can be achieved.
Treatment with interfereon and ribavirin can be very difficult. It is important that the physician who is treating your HCV is familiar with the side effects (see above) and is able to get you through the treatment course. The treatment course for HCV can be six to twelve months, depending on your genotype and on how quickly your viral load responds to treatment.
Looking AheadAdvances are being made in understanding the causes and development of HCV, thereby opening new avenues for treatment therapies. The latest and most widely publicized is pegylated interferon. Pegylation is a process whereby polyethylene glycol -- PEG -- is attached to the interferon and slows the rate at which the interferon is eliminated from the body. Normally interferon stays in the body for about 24 hours, but PEG stays in the body for up to seven days, and at higher levels, permitting the drug to be injected once a week. Pegylated interferon is currently in clinical trials. The FDA approval of this drug with ribavirin is expected soon, with its release to follow sometime this year. Other promising drug developments include neutralizing antibodies, protease inhibitors, helicase inhibitors, replicase inhibitors, antisense molecules, and ribozymes . . . but these drugs are years away from approval.
Public education programs are now tracking cases of HCV in the hope of finding infected individuals and treating them -- and treating them early. The bottom line is that if infected people are treated and treated early, the epidemic will prove far less costly to the nation in terms of individual lives, quality of life, and healthcare dollars.
Back to the September 2000 Issue of Body Positive Magazine.
This article was provided by Body Positive. It is a part of the publication Body Positive.