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Hepatitis C Can Occur in Patients Within Normal ALT Ranges

By Marie Rosenthal, MS

Boomers have lived through a period of high risk for exposure to hepatitis C; within this demographic, there’s a particularly high incidence of the disease.

Hepatitis C is truly an enigma. About 75% of the estimated 4 million U.S. patients with hepatitis C virus (HCV) have not been diagnosed because they are asymptomatic or symptoms are so vague HCV is not recognized until liver disease develops.1 “We are experiencing an epidemic of liver disease because of the long latency period between the time you acquire infection and the time it takes for the scarring in the liver to progress to cirrhosis and life-threatening complications like liver failure or liver cancer,” says Ira M. Jacobson, MD, of the Weill Cornell Medical College and the Center for the Study of Hepatitis C in New York.

About two-thirds of those with HCV are baby boomers who acquired HCV when they were younger.1 “Individuals between 45 and 65 lived through a time that was a high risk for exposure to hepatitis C, and thus have the highest disease incidence,” says Nancy Reau, MD, an associate professor of medicine at the University of Chicago Medical Center.

Many people were infected with HCV by blood products or organ transplants they received before widespread testing was instituted in the 1990s. The other major risk factor is drug use; sharing dirty needles and perhaps snorting cocaine are major contributors to spreading the disease.

Public health policies have instituted the following steps to decrease the spread of HCV:

• The blood supply and organs intended for transplanting are tested and therefore safer.

• Universal precautions were instituted to prevent the spread of diseases among patients.

• Sterilized needle distribution programs have been implemented in many areas.

Physicians often test for HCV when a person has an elevated alanine aminotransferase (ALT) blood test that signals some sort of injury to the liver, but up to 40% of HCV patients have ALTs that fall within the normal laboratory range. Hepatologists consider an ALT of 19 mcg/L in women and 30 mcg/L in men as a normal cut off, but many laboratories continue to report ALT levels of 50 or 60 as being normal.

“It would be helpful if physicians had a greater appreciation of the fact that what constitutes a normal ALT has been revised downward even if it is not reflected in the lab reports,” Jacobson says.

Since some geriatricians and primary care physicians do not think of their older patients as possible former IV drug users, they often do not include HCV in their discussions with them. It may be because that is not who they are today or because of the inherent awkwardness of raising issues of patients’ prior engagement in high-risk behaviors.

“Internists are given 10 to 15 minutes to talk to a complex patient. The chances are slim that they will ask invasive questions about lifestyle like ‘Did you ever do IV drugs?’” Reau says. “They are concentrating on issues like high blood pressure, diabetes risk, smoking cessation, obesity, and regular vaccinations. These problems are more in the forefront of their normal practice.”

Because so few older patients are being diagnosed, the Centers for Disease Control and Prevention is considering an age-based recommendation for HCV screening that would require those older than the age of 50 to be screened for hepatitis C.

In the meantime, internists should ask patients about risky events that might have occurred in their youth, particularly IV drug use, snorting cocaine, and receiving blood products before 1992. “Otherwise, you are looking at an individual that might not tell you that when he was in Vietnam, he used IV drugs or had high-risk sex,” Reau says.

The earlier HCV is diagnosed, the better opportunity there is to stop the progression to end-stage liver disease and clear the virus.

“If people are exposed to HCV when they are older than 45, they are more likely to have aggressive HCV, and as they age, even if they were first infected at a young age, the HCV will become aggressive,” Reau says. “Therefore, age appears to be important both in terms of when you got it and how it progresses.”

For many years, the backbone of HCV treatment was a combination of peginterferon and ribavirin. This year, the FDA approved telaprevir (Incivek) and boceprevir (Victrelis) to treat patients with genotype 1 HCV, the most common strain of the virus.

When either of these protease inhibitors (PIs) is added to the traditional regimen, there is a sharp rise in sustained virologic response rates. In phase 3 trials in treatment-naïve patients, response rates went from 38% to 46% to 66% to 79% in those who received a PI.2,3 

Being unable to detect the virus 24 weeks after therapy stops is tantamount to virologic cure in more than 99% of patients. “Relapse, when it occurs after treatment in a patient who has undetectable virus after therapy, almost always occurs within the first three months,” Jacobson says.

PIs have also decreased treatment from 48 to 24 weeks in patients whose viral levels become undetectable early during therapy, which is good news for patients because these regimens can have serious or unpleasant side effects, and the PIs tend to amplify them.

Telaprevir and boceprevir were not studied in patients over the age of 65, but they are approved for older patients.

The cure rates are lower in older patients and those who have extensive liver scar tissue, but Jacobson says this should not be a contraindication for treatment. “These patients have an urgent need to arrest the complications of their liver disease. Treatment can be truly lifesaving,” he says.

Reau says physicians should discuss the risks vs. the benefits of treatment. Patients must understand that these medications, although lifesaving, are not benign. Side effects include anemia, rashes, and gastrointestinal effects.

Jacobson says he orders a cardiac stress test in an older patient before beginning treatment to ensure there is no occult cardiac disease. “I don’t want my treatment to be the patient’s first cardiac stress test as I watch that patient’s blood count go down,” he explains.

Since many older patients are taking medications for comorbidities, physicians should be aware of drug-drug interactions that can occur during antiviral therapy. “If a patient comes in with a complaint, you do not want to pick up that prescription pad as quickly as you might if the person was not on HCV therapy,” Reau says.

In addition to treatment, lifestyle recommendations for HCV patients include the following:

• Although rare, HCV can be sexually transmitted, so recommend that sexual partners be tested.

• Alcohol consumption needs to be discussed. Some hepatologists ban all alcohol; some allow the occasional drink if scarring is not advanced. However, all alcohol should be avoided during treatment.

• Patients should stop smoking because smoking can accelerate liver scarring.

• Patients should eat a well-balanced diet and lose weight to avoid fatty liver disease.

“I cannot emphasize the importance of physicians spending significant time with patients so they can understand the nature and ramifications of HCV infection and the pros and cons of treatment,” Jacobson says.

HCV management should be individualized because patients have different comorbidities, take different medications, suffer differing degrees of liver scarring, and may have different genetic strains.

Emphasizing the importance of tailoring the management approach to the constellation of considerations that apply to each patient, Jacobson says, “Every patient with HCV is as unique as a fingerprint.”

Marie Rosenthal, MS, is a freelance medical writer in New Jersey.

1. Armstrong GL, Wasley A, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006;144(10):705-714.

2. Jacobson IM, McHutchison JG, Dusheiko G, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364(25):2405-2416.

3. Poordad F, McCone J Jr, Bacon BR, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2001;364(13):1195-1206.