Public Health Feature -- March 2001
By Laurie Stoneham
He's a successful practicing lawyer in Houston. Seems to have it all. But this picture of health may be carrying a secret that could kill him. During his "hippie" days, he'd tried intravenous (IV) drugs a couple of times. No big deal - he was too smart to get hooked. He doesn't talk about this wildness with anyone - even with his family doctor. It just wouldn't look good.
Today, this 45-year-old yuppie could be walking around with a potentially fatal disease that he doesn't even know he has. He's in the same boat with millions of other Americans, because the most common symptom of hepatitis C is no symptom at all.
These are the kinds of patients Howard P. Monsour, MD, staff hepatologist at St. Luke's Texas Liver Institute in Houston, sees a lot. Dr. Monsour, director of hepatitis studies at Gastroenterology and Liver Associates, the largest liver transplant group in Houston, discusses the alarming figures of what's been called a "silent epidemic" that's starting to get very noisy:
- After alcohol use, hepatitis C is now the No. 1 cause of cirrhosis.
- Hepatitis C will quadruple the number of liver cancers in the next 10 to 15 years.
William M. Lee, MD, director of the Clinical Center for Liver Diseases at The University of Texas Southwestern Medical Center at Dallas, notes that hepatitis C already is the No. 1 reason for the nation's 2,000 annual liver transplants. He adds that the current 10,000 annual liver disease deaths are expected to triple by 2010.
The Centers for Disease Control and Prevention estimates that 1.89 percent of the total population, or 3.9 million Americans, have the hepatitis C virus. Some estimates go as high as 9 million. No one knows for sure. Worldwide, it's thought that as many as 200 million people have the disease. Its most popular demographic is men ages 30 to 54.
Based on these national epidemiological studies, in Texas it's estimated that some 300,000 people have hepatitis C, according to Gary Heseltine, MD, an epidemiologist with the Texas Department of Health (TDH) Infectious Disease Epidemiology and Surveillance Division. But these are just estimates.
The numbers are startling for prison inmates. A recent Texas Department of Corrections study found that 25 to 30 percent of incoming inmates tested positive for the hepatitis C virus. Nationally, 30 percent of men in prison and 54 percent of incarcerated women are living with the virus.
A risk profile
While the virus has been in existence for decades (it showed up in blood samples of World War II soldiers), it wasn't officially identified and cloned until 1989. The test to detect antibodies to the virus was developed in 1991. Blood banks began screening the blood supply for this virus in 1992. People who received blood transfusions or whole blood products before 1992 are at greatest risk of having hepatitis C -- like your 60-year-old patient who was given blood during her hysterectomy in 1985. She needs to be tested.
The other huge at-risk group is IV drug users -- anyone of any age who has injected drugs or anabolic steroids even once. According to national studies, 70 to 80 percent of IV drug users have hepatitis C.
In the past couple of years, it was thought that the virus couldn't be transmitted through sexual contact. The contrary facts are now in. People who have had multiple sex partners are at risk and need to be tested.
A number of unknowns about this disease exist, along with concern about what lurks in those mysteries.
"We don't know the complete natural history and course of the disease. We don't know all the ways it's transmitted," said Frank Adams, DO, a practicing gastroenterologist and director of the hepatology clinic at Brackenridge Hospital in Austin. "There are some people, for example, who have it who don't fall into any of the risk categories. We have no animal model for it, so research is difficult. The virus mutates once it gets into the body, so it's a very difficult target to hit. And because the disease has been discovered only recently, we can't predict with absolute surety how hepatitis C patients will respond as they age."
In its attempt to survive, the hepatitis C virus continues to mutate. At this point, there are six different genotypes around the world, along with a variety of subtypes. The most common genotype in the United States is 1, which accounts for 70 to 75 percent of the cases. Made up of two subgroups, 1a and 1b, this strain, unfortunately, is the most difficult to treat with standard therapies. Genotype 2 is seen in 20 to 25 percent of American patients.
Of those individuals who have hepatitis C, only about 20 percent will develop cirrhosis, which studies show usually appears an average of 24 years after initial viral contact. "There's a whole spectrum of severity," said Dr. Lee. "There are a lot of people -- in fact the majority -- who will not develop cirrhosis."
Drs. Lee and Monsour emphasize that cirrhosis is not an automatic death knell. From early cirrhosis to end-stage liver disease, Dr. Monsour says, scarring occurs usually over a 20-year period and typically involves 70 percent of the organ before death results, which is seen in only 10 to 20 percent of cases.
Why the disease behaves differently in individual patients is unknown. Studies are under way to learn why some people advance to cirrhosis, while others don't seem to be affected much by the virus. Dr. Monsour's study of the disease, including his own research, has shown that while the course of the disease varies from person to person, the following factors seem to influence its course.
- Viral levels appear to increase the longer a person has been infected.
- The progression to cirrhosis may depend on the patient's genetically inherited response to the virus; some will scar more than others will.
- Immune response may play a role in the ability of some people to clear the infection spontaneously.
- Alcohol use is a known cofactor for contributing to and accelerating the progression of liver disease. What's unclear is the amount of alcohol that can be tolerated. Therefore, abstinence is the best advice for all patients living with the virus.
Testing for the virus
The experts urge physicians to keep hepatitis C on their radar screens. If interviewing patients and reviewing medical records reveal risks, then tests should be conducted.
Several tests can be performed to detect the presence of the hepatitis C virus and then to determine the amount of liver damage. Dr. Monsour emphasizes that patients can and do have normal liver enzymes and still have the virus.
The first is a blood test that detects antibodies for various proteins in the virus. The standard Enzyme-Linked Immunosorbent Assay (ELISA) anti-HCV is sensitive but has low specificity. The most advanced, specific test is the recombinant immunoblot assay (RIBA).
Test for presence of virus
The HCV-RNA test measures for the virus. With these tests, the genotype of the virus also can be identified. The two specific tests are HCV-RNA by PCR and HCV-RNA by b-DNA. These tests also give an estimate of the amount of virus in the bloodstream.
Once the virus is known to be present, a liver biopsy is usually performed to assess the condition of the liver and the stage of the disease.
The standard treatment of choice has involved the use of interferons. As a monotherapy, interferon produced a sustained response -- not detecting the virus for up to six months after treatment -- in less than 12 percent of all patients.
Combination therapy, using interferon and ribavirin, has improved the results significantly. Injections are given three times a week for six months to a year. In genotypes 1a and 1b, the most common and least responsive strains in the United States, this combination therapy produces sustained response rates in 29 percent of cases. In the other genotypes, long-term responses range from 65 to 85 percent.
Treating hepatitis C is expensive, ranging from $13,000 to $15,000 per course of therapy. All insurance pays for the treatment, including Medicaid and Medicare.
This is rigorous therapy, though, with unpleasant, sometimes debilitating side effects. Chronic fatigue, mild to moderate depression, and aching joints are the most common side effects. Dr. Monsour says the key to ensuring the patient completes the total regimen is to monitor and treat the side effects efficiently.
New treatment horizons
Clinical trials have been under way for several years, and the U.S. Food and Drug Administration (FDA) approved a new form of interferon known as peginterferon in late January. This is a longer-acting interferon requiring only one injection a week. Dr. Lee explains that trials have shown that the pegylated interferon alone produced sustained response rates in 38 percent of the type 1 genotypes, and when combined with ribavirin, its effectiveness increased to 50 percent. Today's combination therapy for type 1 is effective in 29 percent of cases. For the other genotypes, the new interferon's effectiveness ranges from 65 to 80 percent.
Schering-Plough's new interferon has received FDA approval, and Hoffmann-La Roche and Amgen are in the approval pipeline. But there's a rub. Dr. Lee says the FDA has approved the use of ribavirin only in a bundled package with Schering's interferon under the brand name Rebetron. This means that LaRoche and Amgen don't have access to ribavirin to use with their new interferons.
Dr. Lee says LaRoche is making ribavirin in Switzerland, and it will probably be approved for use in this country by this summer. He also believes that Schering will "unbundle" its Rebetron to make ribavirin available to patients without requiring the purchase of the company's interferon.
"It's going to be marketing warfare for a while, though," Dr. Lee said.
While there is a cure for hepatitis C for some, what about the 50 to 70 percent of patients who don't respond at all? What's available for them? Dr. Lee's group is one of 10 sites throughout the nation studying this dilemma through a National Institutes of Health grant.
Caring for indigent patients
Dr. Adams has been working with indigent patients for years. He uses an algorithmic approach to testing, diagnosing, and learning whether these individuals are suitable for treatment. But he doesn't have the resources or the dollars to initiate treatment.
"I find it amazing that there's this large population of people we can diagnose, and we can tell them they have a disease that's cost-effective to treat, and there aren't funds around to treat them," he said.
Schering and other manufacturers do underwrite treatment for individuals who are unable to pay for the therapy. "We can't rely on the generosity of a drug company to provide treatment for indigent patients," Dr. Adams said.
Sharilyn Stanley, MD, associate commissioner for disease control and prevention for TDH, said, "Some of these issues in the treatment realm are beyond public health and will actually require a federal response along the lines of the Ryan White program for HIV-infected folks."
The Ryan White Title III program is a federally funded grant program providing ongoing primary care services to HIV-positive patients who do not have access to appropriate health insurance.
To put it in perspective, Dr. Monsour says that the number of people with hepatitis C is three to five times greater than the number of those with HIV, while there is only about a tenth the funds available to deal with it.
Texas is leading the nation in addressing hepatitis C. During the last session of the Texas Legislature, Rep. Glen Maxey (D-Austin) won passage of HB 1652 to fund screening and educational efforts.
TDH has been carrying out that mission through 20 contractors operating about 200 counseling and testing sites throughout the state. Dr. Heseltine says these are not just "conventional brick and mortar sites." Counselors go to bars, parks, and other places where high-risk groups congregate to tell them about the services available and to offer testing.
"We were the first state in the country to get state funding to address hepatitis C," Dr. Stanley said. "The Centers for Disease Control, as well as other states, is looking to us to learn from our experience."
TDH also has spearheaded a broad-based educational campaign aimed at promoting awareness of facts and dispelling the myths about the disease through its Web site (http://www.dshs.state.tx.us/idcu/disease/hepatitis/hepatitis_c/professional/) and media releases. It also is planning to establish a hepatitis C hotline by this spring. The agency also contracted with Dr. Lee and the Department of Internal Medicine at UT Southwestern to conduct didactic continuing medical education programs for physicians and health care professionals.
Legislative efforts are under way to expand TDH services, says Dr. Heseltine. "We have a large cohort of infected people we're dealing with, and at the same time, we want to blunt any further progression of hep C through counseling and testing in the population. We also want to integrate hep C into the department's existing HIV/STD infrastructure that includes some 60 contractors." In addition, the agency wants to secure funding to offer those infected with hepatitis C immunizations against hepatitis A and B.
Beyond health care
All the experts agree that more funding is necessary both for research and treatment. The sheer numbers of people involved make this a massive dilemma.
"This issue transcends the medical community," Dr Monsour said. "It's really a societal dilemma. We're going to have to decide where the health care dollars are going to come from to pay for managing this disease."
Hepatitis C: the 'silent epidemic'
Known hepatitis C risk factors
The following individuals are considered to be at high risk for developing hepatitis C:
- Intravenous drug users, including athletes who have injected anabolic steroids;
- Recipients of blood transfusions or solid organ transplants before July 1992;
- Recipients of blood products before 1987;
- Those who have had sexual relations with multiple partners;
- Health care workers, especially those who are victims of needle-stick accidents;
- Long-term dialysis patients; and
- People who have body piercings and/or tattoos.
U.S. Public Health Service guidelines for hepatitis C patients
- Everyone who has tested positive for the antibody or the hepatitis C virus (HCV) itself should be considered potentially infectious.
- HCV-positive patients should not donate blood, body organs or tissue, or semen.
- Razors and toothbrushes should not be shared.
- Cuts and lesions should be covered.
- Patients should inform their dentists and physicians of their HCV status.
- Sexual partners of HCV-positive patients should be tested for the antibody.
- Hepatitis C is not known at this time to have a deleterious effect on pregnancy.
Hepatitis C facts
- Incubation from inoculation to detection of virus is 30 to 90 days.
- The average time from virus inoculation to cirrhosis is 24 years.
- The most common genotypes in the United States are 1a and 1b, the most resistant to treatment and thought to result in more severe disease states.
- Alpha interferon/ribavirin therapy produces sustained response rates in 29 percent of genotype 1 cases.
- Clinical trial results show peginterferon/ribavirin therapy to be effective in about 50 percent of type 1 cases.
Source: Howard P. Monsour, MD, Hepatitis in the Year 2000
TMA Advantage: Educational opportunities
The Texas Medical Association's Committee on Infectious Disease has focused on educating Texas physicians about hepatitis C, its risk factors, diagnosis, and treatment for years. "There are not enough gastroenterologists in the state to handle the treatment of this disease," said Gayle Love, director of TMA's public health department. "The goal has been to bring more primary care physicians into the fold to free up specialists for more serious cases." Last year TMA received a $60,895 grant from Schering-Plough to provide educational programs on hepatitis C screening, treatment, and patient management. The program was conducted throughout Texas last year, and several are scheduled for 2001.
The Centers for Disease Control and Prevention also has an online training program available for continuing medical education credit. You can access this site by visiting the TMA Web site at www.texmed.org and clicking on the "Health & Science" section, or by going directly to www.cdc.gov/ncidod/diseases/hepatitis/index.htm .
A one-day CME conference on hepatitis C will be held on the campus of The University of Texas Southwestern Medical Center at Dallas on Saturday, May 19. This program has been designated for up to 6 hours Category 1 credit toward the AMA Physician's Recognition Award and 7.2 Type II Nursing Contact Hours. For more information or to register, contact Lisa Dunlevy, continuing education coordinator, UT Southwestern, at firstname.lastname@example.org , or call (214) 648-3138.
For medical questions, UT Southwestern has established a hotline for health care professionals at (214) 648-4801.
Public service announcements featuring singer Waylon Jennings, whose son has hepatitis C, whipped up controversy late last year. Houston-based Hep C Hope Foundation says the intent was to inform and increase awareness of hepatitis C. But the message was mangled with misinformation, suggesting that anyone who had ever had a blood transfusion, oral surgery, or received an immunization was at risk. Other at-risk groups listed included military personnel, anyone with pierced ears, and firefighters.
The Texas Department of Health (TDH) responded quickly with news releases to set the record straight. TDH officials said in the releases that the ads were "unduly alarming," adding that universal safety precautions and sterilization practices followed in operating rooms and dental offices make the chances of transmitting the hepatitis C virus during surgery or dental work "virtually nil."
Gary Heseltine, MD, an epidemiologist with the TDH Infectious Disease Epidemiology and Surveillance Division, says this sort of exaggeration is dangerous, and creating a run on testing resources is not in the public interest. "What we don't want to do is screen everyone because not everyone is at risk for hepatitis C," he said.
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