Alternative Medicine, Issue 25, September 1998

Scientific American October 1999

Biscelgie, A.M. & Bacon, B.R., The Unmet Challenges of Hepatitis C, October 1999 Pages 80-85, Scientific American.

The Unmet Challenges of Hepatitis Some 1.8 percent of the U.S. adult population are infected with the hepatitis C virus, most without knowing it

 by Adrian M. Di Bisceglie and Bruce R. Bacon

 As recently as the late 1980s few people other than physicians had heard of hepatitis C, a slowly progressing viral infection that over a couple of decades can lead to liver failure or liver cancer. Today the condition is widely recognized as a huge public health concern. Some 1.8 percent of the U.S. adult population, almost four million people, are infected with the hepatitis C virus, most of them without knowing it. The virus is one of the major causes of chronic liver disease, probably accounting for even more cases than excessive alcohol use, and is the most common reason for liver transplants. Some 9,000 people die each year in the U.S. from complications of the infection, a number that is expected to triple by 2010. Information about the incidence of hepatitis C in other countries is less reliable, but it is clear that the virus is a major public health problem throughout the world.

 Physicians, historians and military leaders have long recognized hepatitis- inflammation of the liver-as a cause of jaundice. This yellow discoloration of the whites of the eyes and skin occurs when the liver fails to excrete a pigment called bilirubin, which then accumulates in the body. In recent decades, however, the diagnosis of hepatitis has progressively improved, and physicians can now distinguish several distinct forms. At least five different viruses can cause the condition, as can drugs and toxins such as alcohol.

 Researchers first studied viral hepatitis in the 1930s and 1940s in settings where jaundice was common, such as prisons and mental institutions. They identified two distinct forms with different patterns of transmission. One was transmitted by contact with feces of infected individuals and was called infectious hepatitis, or hepatitis A. The other appeared to be passed only through blood and was termed serum hepatitis, or hepatitis B.

 An important development occurred in the 1950s, when researchers devised tests for liver injury based on certain enzyrnes in blood serum. When liver cells- known as hepatocytes-die, they release these enzymes into the circulation, where their concentrations can be easily measured. Elevated serum levels of alanine aminotransferase (ALT) and, especially, aspartate aminotransferase (AST) became recognized as more reliable signs of liver trouble than jaundice. (In addition to hepatitis, some uncommon inherited metabolic diseases can cause elevated liver enzymes.)

 These things stood until Baruch Blumberg, working at the National Institutes of Health, made a breakthrough in the mid-1960s. Blumberg identified the signature of a viral agent, now known as hepatitis B virus, in the blood of patients with that disease. Blumberg's discovery won him a Nobel Prize and allowed researchers to develop reliable blood tests for the virus. A decade later Stephen M. Feinstone, a researcher at the same institution, identified a different viral agent in the stool of patients with hepatitis A. This work led quickly to the development of tests that accurately detect antibodies to hepatitis A virus in the blood of those infected.

 Hepatitis had long been a significant risk for recipients of blood transfusions and blood products. As many as 30 percent of patients receiving a blood transfusion in the 1960s developed elevated levels of ALT and AST, or even jaundice, some weeks later. Workers had suspected an infectious agent was responsible. When the new tests for hepatitis A and B became available in the 1970s, researchers soon found that a substantial proportion of cases of post-transfusion hepatitis were caused by neither of these two viruses. The new disease was labeled "non-A, non-B" hepatitis.

 Most investigators expected that the agent responsible for these cases would soon be discovered. In reality, it took nearly 15 years before Michael Houghton and his colleagues at Chiron Corporation, a biotechnology company in Emeryville, Calif., finally identified the hepatitis C virus, using samples of serum from infected chimpanzees provided by Daniel W Bradley of the Centers for Disease Control and Prevention. Hepatitis C accounts for most cases of viral hepatitis that are not types A or B, although a few result from other, rarer viruses.

 The Needle in an RNA Haystack

 Hepatitis C virus proved difficult to identify because it cannot be reliably grown in cell cultures, and chimpanzees and tamarins appear to be the only nonhuman animals that can be infected. Because both species are very expensive to use in research, only small numbers of animals can be employed. These obstacles, which still impede the study of the virus, explain why it was the first infectious agent discovered entirely by cloning nucleic acid.

 The Chiron researchers first extracted RNA from serum samples strongly suspected to contain the unknown viral agent. A chemical variant of DNA, RNA is used by many viruses as their genetic material. RNA is also found in healthy cells, so the problem was to identify the tiny fraction corresponding to the unknown viral genome.

 The Chiron workers used an enzyme to copy multiple fragments of DNA from the RNA, so that each carried some part of its genetic sequence. Next, they inserted this "complementary DNA" into virus like entities that infect Escherichia coli bacteria, which induced some bacteria to manufacture protein fragments that the DNA encoded. The researchers grew the bacteria to form colonies, or clones, that were then tested for their ability to cause a visible reaction with serum from chimpanzees and a human with non-A, non-B hepatitis. The hope was that antibodies in the serum would bind to any clones producing protein from the infectious agent. Out of a million bacterial clones tested, just one was found that reacted with serum from chimpanzees with the disease but not with serum from the same chimpanzees before they had been infected. The result indicated that this clone contained genetic sequences of the disease agent. Using the clone as a toehold, investigators subsequently characterized the remainder of the virus's genetic material and developed the first diagnostic assay, a test that detects antibodies to hepatitis C in blood. Since 1990 that test and subsequent versions have allowed authorities to screen all blood donated to blood banks for signs of infection.

 The antibody test soon showed hepatitis C to be a much bigger threat to public health than had generally been recognized. A remarkable feature-one that sets it apart from most other viruses-is its propensity to cause chronic disease. Most other viruses are self-limited: infection with hepatitis A, for example, usually lasts for only a few weeks. In contrast, nearly 90 percent of people with hepatitis C have it for years or decades.

 Few patients know the source of their virus, but on direct questioning many recall having a blood transfusion, an episode of injection drug use or an injury from a hypodermic needle containing blood from an infected individual. About 40 percent of patients have none of these clear risk factors but fall into one of several categories identified in epidemiological studies. These include having had sexual contact with someone with hepatitis, having had more than one sexual partner in the past year and being of low socioeconomic status.

 Whether hepatitis C is sexually transmitted is controversial. Instances of transmission between partners in stable, monogamous relationships are rarely identified, and the rate of infection in promiscuous gay men is no higher than in the population in general. These observations suggest that sexual transmission is uncommon, but they are hard to reconcile with the epidemiological findings. The paradox has not been resolved. Some patients who deny injection drug use may be unwilling or unable to recall it. Others might have been infected from unsterile razors or tattooing instruments. Shared straws put into the nose and used to snort street drugs might also transmit the virus via minute amounts of blood.

 Slow Progress

 The discovery of hepatitis C virus and the development of an accurate test for it mark an important victory for public health. The formerly substantial risk of infection from a blood transfusion has been virtually eliminated. Moreover, the rate of infection appears to be dropping among injection drug users, although this may be because anti-AIDS campaigns have discouraged sharing of needles. Yet hepatitis C still presents numerous challenges, and the prospects for eradicating the virus altogether appear dismal. Attempts to develop a vaccine have been hampered because even animals that successfully clear the virus from their bodies acquire no immunity to subsequent infection. Moreover, millions of people who are chronically infected are at risk of developing severe liver disease.

Long-Term Consequences

The mechanism of damage is known in outline. Viral infections can cause injury either because the virus kills
cells directly or because the immune system attacks infected cells. Hepatitis C virus causes disease through the second mechanism. The immune system has two
operating divisions. The humoral arm, which is responsible for producing antibodies, appears to be largely ineffective against hepatitis C virus.
Although it produces antibodies to various viral components, the antibodies fail to neutralize the invader, and their presence does not indicate immunity,
as is the case with hepatitis B.

It seems likely that hepatitis C virus evades this defense through its high mutation rate, particularly in regions of its genome responsible for the manufacture of proteins on the outside of the virus to which antibodies might bind. Two such hyper variable regions have been identified within the so-called envelope regions of the genome. As many as six distinct genotypes and many more subtypes of the virus have been identified; numerous variants exist even within a single patient.

In contrast to the humoral arm, the cellular arm of the immune system, which specializes in viral infections, mounts a vigorous defense against hepatitis C. It appears to be responsible for most of the liver injury. Cytotoxic T lymphocytes primed to recognize hepatitis C proteins are found in the circulation and in the liver of chronically infected individuals and are thought to kill hepatocytes that display viral proteins. Fortunately, liver tissue can regenerate well, but that from hepatitis patients often contains numerous dead or dying hepatocytes, as well as chronic inflammatory cells such as lymphocytes and monocytes.

If hepatitis persists for long enough- typically some years-the condition escalates, and normally quiescent cells adjacent to hepatocytes, called hepatic stellate cells, become abnormally activated. These cells then secrete collagen and other proteins, which disrupt the fine-scale structure of the liver and slowly impair its ability to process materials. This pathology is known as fibrosis. Stellate cells are similar in origin and function to the fibrosis-producing cells found in other organs, such as fibroblasts in the skin and mesangial cells in the kidney. They store vitamin A as well as produce the liver's extra cellular matrix, or framework. It is likely that many of the processes that initiate the fibrotic response in the liver occur in these other tissues as well.

If fibrosis progresses far enough, it results in cirrhosis, which is characterized by bands of fibrosis enclosing nodules of regenerating hepatocytes. Progression is faster in people over age 50 at the time of infection, in those who consume more than 50 grams of alcohol a day, and in men, but cirrhosis can result even in patients who never drink alcohol. Fibrosis and cirrhosis are generally considered irreversible, although recent findings cast some doubt on that conclusion.

About 20 percent of patients develop cirrhosis over the first 20 years of infection. Thereafter some individuals may reach a state of equilibrium without further liver damage, whereas others may continue to experience very slow but progressive fibrosis. End-stage liver disease often manifests itself as jaundice, ascites (accumulation of fluid within the abdomen), bleeding from varicose veins within the esophagus, and confusion. Hepatitis C infection has also come to be recognized as a major indirect cause of primary liver cancer. The virus itself seems not to put people at increased risk, but cirrhosis induced by the virus does.

Cirrhosis is responsible for almost all the illness caused by the hepatitis C virus. Although a small proportion of patients recollect an episode of jaundice when they probably acquired their infection, chronic hepatitis C is often asymptomatic. When symptoms do occur, they are nonspecific: patients sometimes complain of vague feelings of fatigue, nausea or general unwellness. The insidious nature of the condition is probably another reason why hepatitis C remained undiscovered for as long as it did. The disease plays out over decades. An aspect confounding investigators is that not all infected individuals react in the same way. Some may carry the virus for decades without significant injury; others experience serious damage within only a few years.

Liver transplantation can save some end-stage patients, but the supply of human livers available for transplant is woefully inadequate. Researchers are therefore working intensively to develop treatments that will eradicate the virus in patients.

The first therapeutic agent shown to be effective was alpha interferon, a protein that occurs naturally in the body. Interferon appears to have a nonspecific antiviral action and may also enhance immune system activity. The drug is generally given by subcutaneous injection three times a week for 12 months. Only 15 to 20 percent of patients, however, exhibit a sustained response, as defined by the return of ALT and AST to normal levels and the absence of detectable hepatitis C RNA in serum for at least six months after stopping treatment. Why treatment fails in most patients is essentially unknown, although some viral genotypes seem to be more susceptible to interferon than others.

Last year the Food and Drug Administration approved another drug, ribavirin, to treat hepatitis C in conjunction with interferon. Ribavirin, which can be swallowed in pill form, inhibits many viruses. Interestingly, though, it appears to have no effect against the hepatitis C virus by itself and is thought somehow to enhance interferon's effects on the immune system. Interferon and ribavirin given together for six to 12 months can expunge the virus in about 40 percent of patients, and clinical workers are now studying how to maximize the benefits from these two agents. Long-acting forms of interferon that require administration only once a week are one focus of interest.

A new drug is now being tested in small numbers of patients. Vertex Pharmaceuticals in Cambridge, Mass., is investigating a compound that inhibits a human enzyme called ionosine mono-phosphate dehydrogenase. The hepatitis C virus relies on this enzyme to generate constituents of RNA. No results from these trials are yet available.

In the absence of medications capable of dependably eliminating the virus, the NIH recently embarked on a study to determine whether long-term administration of alpha interferon can slow liver damage in patients who fail to clear the virus. And we and other researchers are studying the simple expedient of taking a pint of blood from patients on a regular basis. This treatment reduces the amount of iron in the body, a manipulation that can reduce serum ALT and AST levels. Whether it slows liver damage is still uncertain.

Targeting the Virus

The best prospects for future treatment for hepatitis C appear to be agents targeted specifically against the virus, just as successful treatments for HIV target that agent. With that goal in mind, researchers have elucidated the structure of the hepatitis C virus in detail. Its genetic material, or genome, consists of a single strand of RNA. In size and organization the genome is similar to that of yellow fever and dengue fever viruses; hepatitis C virus has therefore been classified with them as a member of the family Flaviviridae. Enzymes in an infected cell use the viral RNA as a template to produce a single large protein called a polyprotein, which then cleaves to yield a variety of separate proteins with different functions. Some are structural proteins that go to form new viral particles; others are enzymes that replicate the original infecting RNA. At either end of the genome are short stretches of RNA that are not translated into protein. One of these terminal regions seems to prompt infected cells to manufacture the viral polyprotein; it is an important target for diagnostic assays. The other appears to play a role in initiating the replication of viral RNA. The structural proteins include the core protein, which encloses the RNA in a viral particle within a structure known as the nucleocapsid, and two envelope proteins that coat the nucleocapsid. The nonstructural proteins include a viral protease responsible for cleaving the polyprotein, as well as other enzymes responsible for chemically readying the components of viral RNA (triphosphatase), for copying the RNA (polymerase) and for unwinding the newly manufactured copy (helicase).

The protease and helicase enzymes have been well characterized and their detailed three-dimensional structure elucidated through x-ray crystallography, necessary first steps for designing drugs to inhibit an enzyme. Several drug companies, including Schering Plough, Agouron Pharmaceuticals, and Eli Lilly and Vertex Pharmaceuticals, are now studying potential hepatitis C protease or helicase inhibitors. Clinical trials are probably only a few years away. Another viral enzyme, the polymerase, is also a possible target. Whether the virus will evolve resistance to such agents remains to be seen.

Developing anti-hepatitis C therapies may be about to get easier. Three months ago Ralf Bartenschlager and his colleagues at Johannes-Gutenberg University in Mainz, Germany, published details of an RNA genetic construct that includes the regions coding for the virus's enzymes and reproduces itself in liver cancer cell lines. This construct may prove valuable for testing drugs targeted at these enzymes.

Another possible therapeutic avenue being investigated is disruption of the process that activates hepatic stellate cells and causes them to instigate fibrosis. This mechanism is known to involve cytokines, or signaling chemicals, that cells in the liver called Kupffer cells release when they are stimulated by lymphocytes. Turning this process off once it has started should prevent most of the untoward consequences of hepatitis C infection.

Some workers are trying to develop therapeutics aimed at the short terminal regions of the virus's genome. One idea, being pursued by Ribozyme Pharmaceuticals, is to develop therapeutic molecules in that can specific constant sequences there.  Ribosomes, short lengths of RNA or chemical close relative, can accomplish this feat.  The main challenge may be getting enough ribosomes into infected cells. Delivering adequate quantities of a therapeutic agent is also a problem for some other innovative treatment concepts, such as and gene therapy to make a liver cells resistant to infection, "antisense" RNA that can inhibit specific genes, and engineered proteins that activate a cells self-destruct mechanisms when they are cleaved by the hepatitis c protease.

All these attempts to counter hepatitis c are hampered by a serious shortage of funds for research. The amount of federal support, considering the threat to millions of patients, is relatively small. We are confident that much improved therapies, and possibly a vaccine, will in time be available. An expanded research program could ensure that these developments come soon enough to help patients.

 {Sidebar: Pictures available on request.} Hepatitis C infection starts when viral particles in the circulation find their way to susceptible cells, particularly hepatocytes. A viral protein called E2 appears to facilitate entry by latching onto a specific receptor. On entering, the virus loses its lipid coat and its protein envelope, freeing the RNA cargo. Enzymes in the cell then use this RNA as a template to make a large viral protein, the polyprotein. It is cleaved into a variety of small proteins that goes on to form new viral particles and help to copy the viral RNA.

 The original RNA is copied to yield a "negative-stranded" RNA that carries the inverse, or complement, of the original sequence. This serves as a template to make multiple copies of the original RNA, which are incorporated into new viral particles, along with structural proteins, at a body called the Golgi complex. Complete viral particles are eventually released from the infected cell, after acquiring a lipid surface layer.Recent studies suggest that a patient produces as many as 1,000 billion copies of hepatitis C virus a day, most of them from the liver.     -A.M.D. and B.R.B.

 Sidebar:  HEPATITIS C VIRUS GENOME consists of a single RNA gene plus two terminal regions. The gene encodes a polyprotein,which subsequently cleaves to form a variety of smaller proteins. Some of these are used to make new virus particles; others are enzymes that help to replicate the viral RNA for inclusion into new viruses.

 Sidebar: How the Hepatitis C Virus Was Discovered

 Researchers identified the hepatitis C virus by making DNA copies of RNA from the cells of infected chimpanzees.They cloned the DNA by using bacteriophages to carry it into bacteria. Colonies were then tested with serum from infected chimps. One produced an immune reaction, indicating it carried viral genetic sequences. -A.M.D.andB.R.B.

Cosmopolitan October 1999

Hepatitis C

Each year, more and more young women are being infected with hepatitis C, a deadly virus that, like HIV, can be contracted during sex but also through something as seemingly harmless as sharing a toothbrush—or getting a manicure. Here’s what you need to know to protect yourself now. By Julia Califano

“Having grown up in the shadow of AIDS, I was always careful when it came to sex,” says Carol Ragas, a 26-year-old financial adviser from Hollywood, Florida. “I had my share of sex partners, but I never went to bed with anyone without using a con­dom. I was so paranoid, I wouldn’t even share a boyfriend’s toothbrush unless I knew he’d been tested for just about every­thing.” And sex wasn’t the only thing Carol was careful about. She never got into drugs, wasn’t a big drinker, and always ex­ercised and ate right. In fact, the closest she came to doing anything “wild” was two years ago when she decided to surprise her boyfriend by getting a tattoo. She went to a clean, respectable-looking tattoo par­lor in town and asked the artist to etch two small roses on her ankle. “When my boyfriend saw it, lie thought it was so sexy. He was all over me in three seconds.”

Six months later, the couple was talking marriage, but Carol wasn’t feeling quite right. “I had come down with a low-grade stomach flu that I just couldn’t seem to shake.” When she still felt slightly sick a few months later, she decided to check in with her doctor. He suspected it might be a thyroid problem but ordered a full battery of blood tests just to make sure,” she says. When Carol returned to his office a week later, the nurse whisked her behind closed doors. “She gave me the proverbial good news/bad news speech. The good news was that my thyroid was fine. ‘[he bad news was that I’d tested positive for hepatitis C,” she recalls. “I was dumb-founded. All I could say was ‘What’s that?” And the nurse didn’t help matters much.

“She told me it was a virus of the liver, said not to worry, and shooed me out of the door with a referral to a gastroenterologist.” When Carol got home she started doing some research on the disease over the Internet, and it wasn’t long before her concern blossomed into full—fledged panic.

The Web sites revealed one frightening fact after another. She learned that she’d probably have the virus for the rest of her life, that it could cause severe scarring to the liver (called cirrhosis) and liver can­cer within 20 years of infection, and that it could ultimately be fatal. “My head was spinning,” she recalls. “I just couldn’t be­lieve that it could happen to me,”

The Next AIDS?

A decade ago, hepatitis C didn’t even have a name. Now, four million men and women (a whopping 1 in 50 Americans) are believed to be infected. In fact, hep C than by HIV infects four times as many people—largely because there are more possible mutes of transmission. Like HIV, hep C is spread through  with infected blood, so needle sharing and un­protected sex are known culprits. But that’s where the similarities end. Unlike lily, the hep C virus doesn’t (lie when exposed to air: It can live for days in a spot of dried blood, and that may mean it’s possible to contract it from a toothbrush or razor or by being tattooed, pierced, or manicured.

While experts believe that HIV is always eventually fatal, hep C kills only roughly lout of 10 of the people it infects—about 10,0(X) people a year die. But experts pre­dict that when the millions of symp­tomless victims who have recently been infected become sick in the next 10 to 20 years, the death toll will triple—resulting in more deaths from hep C than from AIDS.

Carol (who believes she contracted the virus from the tattoo) was diagnosed within a year of infection, when i the treatments for hepatitis C are usually the most effective. But she’s an exception. “Most patients become infected in their 20s but don’t find out until their 4Os or 50s,” says Julie Lehane, Ph.D), director of education and infor­mation for the American Liver Foundation. At that point, it may be too late for some to save their livers—or even their lives.

How HepC Kills Quietly

People are still in the dark about hepatitis C, not only because it was just identified in 1989 but also because carriers may not be sick for years or even decades after they are infected. “Hepatitis C is a silent predator,” says Bruce R. Bacon, M.D., di­rector of the division of gastroenterology and hepatology at Saint Louis University School of Medicine in Missouri. “It can be passed to people who have no idea they’ve been infected, take up resi­dence in the liver, and slowly hut pro­gressively damage it.” Experts believe that as many as 70 percent of the women and men in their 20s and 30s who are carry­ing the virus have absolutely no clue that they’re infected or that they may l)e spreading the disease to others.

Those who do find out typically learn the way Ellen Cotton did—completely by ac­cident. “When I was 28 and doing PR for a medical group, I organized and donated blood for a company-wide blood drive,” says the now 35-year—old Dallas mother. A few weeks later; she received a letter stat­ing that her blood had tested positive for hepatitis C and that she should  her doctor. “I was stunned. Even after my doc­tor confirmed the diagnosis, I had a hard time believing it was true,” says Ellen, who suspects she ed the virus from blood transfusions she received after a car accident when she was 19. “1 kept thinking, How could I be walking around with such a serious illness and not even feel sick?”

Even when patients do experience signs of trouble, the symptoms are usually vague, intermittent, and easily attributed to other causes. When she was in her mid-20s, Rosalie Cacioppo, a New York City ad­ministrative assistant, always seemed tired, but she simply chalked it up to stress and trying to do too much on too little sleep. “I’d typically foci pretty energetic in the morning, then by afternoon, I’d he struggling to stay awake at my desk. By the time work was over~ I usually ditched any plans and just sacked out on the couch,” she says.

Although she brought up her fatigue to several doctors, she received conflicting responses. “At various times, I Was told I had the flu, mono, chronic fatigue syndrome, I hypoglycemia, and depression.” Over the years, she tried going on special diets and exercise programs and taking different nutritional supplements. “Nothing seemed to make any difference,” she says. It wasn’t until she was 35 and ~vent for a company physical that she finally learned the truth.

She had hepatitis C and had probably been infected for at least 10 years. Though the diagnosis solved one mystery, it opened up a new one, says Rosalie. “I couldn’t imagine how I could have contracted it.”

What’s Sex Got to Do With It?

Like 20 percent to 40 percent of all hep C patients, Rosalie doesn’t fall into a high-risk categories)~ which include IV drug users, health-care workers, and recipients of blood transfusions before 1992 (the blood banks are now safe, but before 1992, tests didn’t always accurately pick up the virus). “Of course, now that I know you might be able to get it from a speck of dried blood, I realize the possibilities are pretty wide open,” she says. Indeed, since unlike HIV, hep C can remain viable in a drop of dried blood for days, it may he possible that transmission can occur any time infected dried blood (as well as “live” blood) comes into  with your bloodstream. Surprising case in point: sharing a straw to snort cocaine. “When the straw rubs against the delicate lining of the nose, it can dislodge droplets of blood-tinged mucus. As the straw is passed around, it can transfer the one from one person to the next,” explains Willis C. Maddrey, M.D., a professor of internal medicine at the University of Texas Southwestern Medical Center at Dallas.

And of course, getting a tattoo, piercing any body part, and even having a manicure (if they clip your cuticles) can possibly expose you to hep C, since the needles and clippers can harbor dried infected blood if they’re not sterilized. “And even if the tattoo artist uses a newly sterilized needle, the reservoir of ink can harbor the virus for an extended period of time, though it’s not clear how long,” explains Dr. Bacon.

Finally, although hepc is harder tom trans­mit sexually than HIV, the Centers for Disease Control and Prevention estimates that 20 percent of new infections occur through sex practices. According to Dr. Bacon, however, unless sex involves  with infected blood—as can happen, for example, when both partners have open sores from a sexually transmitted disease— the transmission risk is relatively low. “Any sexual behavior that can cause trauma, such as very rough sex or anal sex is con­sidered the riskiest,” he says, because a tear in the vaginal or anal lining could allow transmission of the virus if your sex part­ner also has a sore or cut on his genital area.

The bottom line: To keep yourself free of hep C, practice safe sex, steer clear of IV and inhaled drugs, and opt not to share razors, toothbrushes, nail files, and clip­pers with boyfriends—or girlfriends. If you do have a manicure, get a body part pierced, or get a tattoo, make sure the establishment you choose sterilizes any skin ­piercing tools with an autoclave (a machine that looks like a metal toaster oven and kills bacteria and viruses by exposing them to extreme heat); alcohol and those blue disinfectant solutions are not likely to kill the virus. Also, check to be certain that the tattoo parlor you pick uses fresh ink and needles for each customer.

The Sooner the Better

While there is no sure cure for hep C, the earlier you’re diagnosed the better. “As soon as you know you’re infected, you can make lifestyle changes that will slow the disease’s progression by not exposing the liver to anything that could damage it,” ex­plains Alan Brownstein, the American Liver Foundation’s president and CEO. Since hep C does its deadly damage by crippling the organ that filters toxins from your system, it makes sense that avoiding things like alcohol and excessive use of over-the-counter drugs can help ward off progression of the sickness. Since alcohol actually prompts the virus to reproduce itself, every drink is like throwing gasoline on a flame, say experts. And all medications are filtered through the liver, so even pop­ping aspirin regularly may put additional strain on an already weakened organ.

Andi Thomas, a 40-year-old mother from Plantation, Florida, who believes she contracted hep C in her early 20s while working as a medical assistant, only learned she was positive two and a half years ago. “I spent most of my20s and ear1y 30s drink­ing on Friday and Saturday nights, then nursing the inevitable Sunday-morning hangover with steady doses of extra-strength acetaminophen,” she recounts. “Little did I know, I was slowly killing my­self. And despite growing public aware­ness of hep C, many doctors aren’t completely up to speed on the disease. ‘They don’t always recognize the signs and symptoms, SO they don’t order the tests that can detect it early,” explains Dr. Bacon.

That’s why the Centers for Disease Control and Prevention strongly urges anyone who has ever injected drugs (even once),had a blood transfusion before 1992, has had multiple sex partners (especially if rough or unprotected sex was involved), or has ever worked in the health-care field to ask their doctors for the simple blood test that can detect hep C. And of course, if you have any of hep C~ low-grade symp­toms—unexplained fatigue, soreness in the joints or abdomen, vomiting and nail-sea—mention them to your doctor.

Waiting For a Cure

As serious as hep C can be, a positive test result isn’t a death sentence. It’s not clear when but in 15 to 20 percent of cases, the immune system is able to launch a suc­cessful attack on this superbug and the virus goes away on its own. In up to 1 out of 3 infected people, however, the microbe goes on to cause severe damage. For many of those patients, a liver trans­plant—which is not easy to come by—is their only hope of long-term survival. “But in just the last few years, we’ve made in­credible strides in treating and manag­ing this disease,” says Dr. Maddrey.

Two years ago, the only therapy doctors had to offer hep C patients was inter­feron, an inject able drug that can cause bothersome side effects and only helps about 10 to 15 percent of patients. But just last year, the FDA approved a new treatment that combines interferon with an antiviral, ribavirin. The combo treatment has been known to eradicate the virus—at least in many- in about 40 percent of patients.

When Deanna Simpson (who asked that changed her name), a product manager m Cleveland, was diagnosed last year, she was 28, about to be married, and just getting her life off the ground. “I felt my life was snatched away from me,” says the 29-year-old, who believes she contracted hep C from a sex partner when she was 22. Now, after six months of being on the combination therapy, Deanna feels like she has her life—and her future—back.. The treatment itself was dreadful. I had jab myself in the thigh with a needle three times a week,” she recounts. But it paid off. “I’ve been off the drugs for eight months now, and there’s no sign of the virus in my blood,” she says.

Though doctors use the word cure very hesitantly with hep C (viruses have a way hiding out for years before rearing their ugly heads again), the studies are on Deanna’s side. “Research shows that 96 percent of patients who are virus-free six months after treatment are still free of the virus four years later,” says Dr. Bacon. “And those patients probably are cured.”

Carol, who has been on the combo treatment for five months, is hoping that she, too, will be one of the lucky 40 percent. And so, things are looking good. “The level of the virus in my system has dropped significantly, so the drugs are definitely working,” she says. For the first three months of therapy, she felt worse than ever, but now she is her spunk—and her hope—back. When I was first diagnosed, I thought my life was over. Now, I realize that you can have the disease and can still lead a normal, full e,” she says. “But a major reason why I’m feeling well is because I caught it early. So I made it my mission to tell everyone I know about this virus. If it can happen to me, it can happen to anyone.”

ALTERNATIVE MEDICINE, ISSUE 25, September 98

HEPATITIS C

DOCTORS have started calling it the “sur­prise infectious disease of the decade.” Hepatitis C. which affects an estimated 4 million Americans and possibly millions more worldwide, may smolder in the body for years before any symptoms become apparent. By the time sufferers discover they have been infected with this liver-scarring virus (spread through shared in­travenous drug needles, blood transfu­sions, occupational exposure. or other  with an infected person’s bodily fluids). The damage is often irreversible.

At least, that’s the view of conven­tional medicine. For an alternative medicine physician like Jesse Stoff. M.D., director of IntegraMed in Tucson. Arizona, hepatitis C is a treatable and often re­versible condition, as this case shows.

Mildred. 44. began experiencing di­gestive problems, abdominal tenderness, and nausea nearly 20 years after her brief experimentation with recreational drugs in the 19⁷0s. As a first measure, Dr. Stoff tested Mildred’s blood for levels of a liv­er enzyme known as GGT (serum gam­ma-glutamyl-transferase).

In a typical case of chronic active hep­atitis. GGT levels are on average seven times higher than the upper limit of nor­mal: in acute cases. GGT levels are the last among other liver enzymes) to return to normal. These facts make the GGT anal­ysis a useful marker for the presence of hepatitis, says Dr. Stoff.

When Mildred’s GGT enzyme test came back high (76. compared to the nor­mal. 45. Dr. Stoff ordered more specific blood tests. The blood test for hepatitis C antibodies (immune system defense pro­teins) confirmed that Mildred had been exposed to the hepatitis C virus and that impaired liver function was most likely behind her digestive difficulties.

In treating Mil­dred. Dr. Stoff took a three-pronged ap­proach. He would improve her liver function, bolster her immune system, and prevent the virus from spreading. For this, he designed a treatment pro­gram that incorporated dietary changes, nutritional supplements, herbs. and home­opathic remedies.

Mildred had to make significant changes in her eating habits. Her regular diet included plenty of red meat, but this can pose problems for many patients with liver dysfunction. Dr. Stoff explains. ‘When somebody has hepatitis, it’s easy to overload him or her on protein.” he says. ‘You can’t digest all that protein and soon your ammonia level starts going up. That can get you in big trouble in terms of your cen­tral nervous system.”

Dr. Stoff put Mildred on a “low-stress liver diet” that eliminated all fried foods, red meat, alcohol and coffee, while em­phasizing cooked vegetables and grains along with limited amounts of chicken, fish or turkey. By eliminating alcohol and cof­fee—which are potentially irritating to the liver—Mildred could effectively reduce the toxic load on this important organ.

Although a largely vegetarian diet is “critically important” for patients with chronic liver disease, some protein is required to provide the body with the amino acids (protein building blocks) it needs to make antibodies against the illness, says Dr. Stoff.

Next Mildred was advised to restrict her intake of sugar and baked goods, as Dr. Stoff discovered that she suffered from candidiasis,  an overgrowth of the yeast-like fungus Candida albicans. This yeast thrives on sugar and simple carbohydrates such as those in cakes and cookies, and a diet that limits these items helps to “starve” the microorganism. It is not uncommon for people with a chronic viral infection to suffer from yeast overgrowth as well. Dr. Stoff notes.

To further improve liver function. Mildred began supplementing with Thioptic, a product containing alpha-lipoic acid -one capsule. three times daily). “Alpha-lipoic acid is always useful in treat­ing chronic liver inflammation.," says Dr. Stoff. “The Thioptic helped detoxify Mildreds liver and stimulate the regener­ation of delicate liver tissue.”

Aipha-lipoic acid occurs naturally in potatoes, carrots, yams. sweet potatoes. and red meat. When given as a supple-

ment, it can increase the body’s produc­tion of glutathione, an enzyme that pro­tects the cells from damage by harmful free radicals.

Mildred also took a series of homeo­pathic remedies to help balance and de­congest her liver as well as reduce in­flammation. These included Erysiodoron II. a combination of Apis and Belladonna (one tablet, three times daily):

Hepatodoron 4X (one tablet. three times daily): Liver Formula, an extract of crude liver in a vitamin B and herbal base (one tablet, three times daily ~: and Stanum 10X, a liquid homeopathic preparation de­rived from tin (seven drops directly into the mouth, three times daily). “Tin is a metal that when given in the right form. is specifically beneficial to liver function.” says Dr, Stoff.

As an added support for Mildred’s liv­er. Dr. Stoff prescribed Ecliptex. This is a Chinese herbal formula designed to help decongest basic life force energy (qi) that has stagnated in the diseased liver, ac­cording to Dr, Stoff. Mildred took three tablets of this formula, three times a day.

Dr. Stoff also prescribed products to enhance Mildred’s immune system. She took a combination of vitamins and Chinese herbs called Immune Booster (one tablet, three times daily with meals. as well as homeopathic Echinacea Compound. an immune stimulant based on this versatile herb and available in liq­uid form: she was to take it at the rate of seven drops daily.

To assist liver function. Dr. Stoff suggested a combination of digestive enzymes and amino acids. Mildred also took NK Support (with vegetable juice. twice daily and Biomune OSF Plus (one capsule. three times daily), a combination of astragalus and bovine colostrum and whey. to enhance NK (natural killer) cell function, according to Dr. Stoff.

Healthy NK cell activity is a key as­pect of effective immune system func­tioning. NK cells have potent cell-killing ability, being “armed” with an estimated 100 different biochemical poisons for de­stroying foreign cells, As with antibodies. their role includes surveillance: they iden­tify and then rid the body of aberrant or foreign cells before they can grow and pro­duce cancer or virally infected cells. They also search out and destroy cancer cells. "If someone has a chronic viral infection, then your primary line of defense is to re­store natural killer cell function,” Dr. Stoff explains.

Finally, Dr. Stoff prescribed Virusine, another amino acid formula which is “ex­tremely supportive of the immune system, especially the B cells,” he says. As an added benefit, Virusine helps slow viral replication, thereby preventing Mildred’s hepatitis from growing worse, says Dr. Stoff. The progress of the hepatitis C virus was further slowed with the herbal reme­dy colchicine, which Mildred took at a dosage of 500mg daily, and with the amino acid formula Liver Cleanse (two capsules, three times daily).

Mildred’s was an involved treatment program. but she followed it conscien­tiously. After nearly two years of gradual progress. Mildred’s GGT liver enzyme levels were back in the normal range and her symptoms had subsided. A year and a half later—three and a half years into the treatment—Mildred tested negative for hepatitis and a liver biopsy performed by her gastroenterologist confirmed these pos­itive results. Mildred’s hepatitis C is now completely reversed and she no longer suf­fers from her original symptoms.