Better treatment, low awareness for hepatitis C

The current state of hepatitis C virus (HCV) infection in the U.S. offers both bad news and good news. While the number of patients who have been infected for more than 20 years has been increasing, treatments have become more effective. The main challenge now, according to experts, is increasing awareness and getting appropriate therapy to those who need it.

Hepatitis C “is beating all others in going from untreatable to curable,” said John G. Bartlett, MD, MACP, a professor of medicine in the division of infectious diseases at Johns Hopkins University in Baltimore.

The cure rate, or sustained virologic response, for genotype 1, the most common HCV infection in the United States, has increased from about 40% to 50% with dual therapy only a few years ago to about 70% with triple therapy today. New drugs in the pipeline are expected to be even more potent and better tolerated, Dr. Bartlett said.

And yet, 70% of the estimated 3.1 million Americans with HCV are never offered treatment because they don't know they are infected, he said. About 75% of HCV-related deaths between 1999 and 2007 occurred among people 45 to 64 years old, and without a more aggressive effort to identify new cases, the Centers for Disease Control and Prevention (CDC) expects the number of deaths from HCV to double and the public health burden to increase over the next two decades.

Identifying risk

The CDC currently recommends antibody screening of people with past behaviors that may place them at risk, as well as those who have been exposed to blood products. People at risk for HCV include not only those who ever used an IV drug but also those who received a blood transfusion before 1992.

Health care workers can be at risk due to exposure to blood products and needlesticks. And sharing drug paraphernalia, even decades in the past, is a big risk factor, said Jose Franco, MD, FACP, professor of medicine and medical director of hepatology at the Medical College of Wisconsin in Milwaukee. But HCV is unlikely to be transmitted through sexual contact.

“Sexual transmission of HCV is not like HIV and hepatitis B, which are efficiently transmitted sexually,” said Dr. Franco, who recently completed an update to ACP's Physicians' Information and Education Resource (PIER) module on HCV. “In fact, if you call the CDC and say you are hepatitis C positive, are in a monogamous relationship, and want to know what precautions to take, they will say that the risk is so low in a monogamous relationship that you don't have to take any precautions.”

According to HCV experts, diagnosis should begin with primary care physicians who are aware of the risk factors and ask their patients the most important questions:

• Were you were born between 1945 and 1965?
• Have you ever used IV drugs?
• Did you receive a blood transfusion prior to 1992?
• Have you been exposed to blood products?
• Have you ever worked in a health care setting?
• Have any of your sexual partners been diagnosed with HCV?

Patients who answer “yes” to any of these questions should undergo a screening antibody test. If the test is positive, the next step is getting an HCV viral load confirmation of active disease and evaluation for genotype and presence of liver disease. Internists should also counsel their patients with HCV to adopt some preventive lifestyle changes: Give up alcohol and don't share toothbrushes, razors or nail clippers, Dr. Franco said.

Any patient with HCV should be screened for HIV and hepatitis B, according to experts. And for HIV, Dr. Franco said, the reverse is also true: About 20% to 30% of people infected with HIV are also HCV positive, with HIV apparently accelerating the progression of HCV.

Patients with confirmed HCV infection are usually referred to a gastroenterologist, an infectious disease specialist, or a hepatologist because treatment and monitoring are complex. But more internists will need to get involved in treatment in the coming years, Dr. Franco predicted.

“There is no way that the large number of patients can all be treated by specialists; it is simply too large a number,” he said. (For more on primary care physicians treating HCV, see “Project ECHO expands reach of primary care” in the September 2011 ACP Internist, available online. )

Damage over decades

People with HCV usually have no symptoms besides brief flu-like symptoms early in the infection, but the virus causes damage over decades.

“The disease chips away ... even though the patient never really feels poorly. They may feel fatigued, but the symptoms are easy to ignore as the patient gets older,” Dr. Franco said.

Not all patients will need treatment; about 20% will spontaneously clear the virus. However, 80% will develop chronic disease, and of this group, 20% will develop cirrhosis within about 20 years, according to Dr. Franco. Progression to cirrhosis can be accelerated with the use of alcohol. Unfortunately, there is no way to predict which patients will eventually develop cirrhosis or hepatocellular carcinoma, another potential consequence of HCV.

In 2011, two new viral protease inhibitors, boceprevir and telaprevir, were approved for treatment of HCV. These oral medications, dosed three times daily, are used in combination with what had been standard therapy, pegylated interferon (a weekly injection) plus ribavirin (an oral medication dosed twice daily).

The addition of a protease inhibitor has dramatically improved efficacy of treatment for HCV genotype 1. With triple therapy, the viral counts can rapidly lower to an undetectable point, sometimes within four weeks, Dr. Franco said. If the patient remains virus free, the therapy can be shortened from 48 to 24 weeks.

Before protease inhibitors were available, dual therapy's relatively low cure rate and burdensome complications meant that only about 10% to 20% of patients opted for treatment, wrote Harvey J. Alter, MD, MACP, in a Feb. 21 editorial in Annals of Internal Medicine. Now that there is a 70% chance of cure with the triple therapy, the pendulum is shifting more toward treatment, said Dr. Alter, who is a distinguished National Institutes of Medicine (NIH) investigator and chief of clinical studies in the department of transfusion medicine at the NIH in Bethesda, Md.

“The higher the efficacy of the treatment, the less likely you are to wait around” to see whether a patient's HCV status will continue to progress, Dr. Alter said. He noted, however, that factors including black race, obesity, HIV co-infection, established cirrhosis, and specific host polymorphisms in the interleukin-28B gene can diminish treatment response.

Complications cause problems

Triple therapy is also more expensive, and complications, most of which are associated with interferon, remain a problem. Franjo Vladic, MD, a gastroenterologist at the Center for Digestive Health in Willoughby, Ohio, said that patients report increased fatigue, continuing flu-like symptoms, pain at the injection site, irritability and hair loss. Patients can also develop neutropenia, thrombocytopenia, anemia and thyroid and kidney problems. Dr. Franco added that treatment can also cause bone marrow suppression in some patients.

“What patients hate the most is the fatigue and taking the shot,” Dr. Alter said, particularly if they had no symptoms before treatment. Helping a patient stay on treatment can require reducing drug doses or even discontinuing treatment if side effects are intolerable, experts said.

Physicians also need to stay alert to potential drug interactions. Patients must stop taking certain medications, such as statins, while they are receiving treatment for HCV, and will then require increased monitoring, such as cholesterol tests, to keep tabs on these preexisting conditions. HCV therapy can also lead to marked depression or worsening of previously diagnosed depression, Dr. Vladic said. According to Dr. Franco, patients who develop significant depression during treatment will need to be managed with antidepressant therapy.

Dr. Bartlett recommends that patients with a fibrosis score higher than 2 may need to begin treatment. However, if treatment can be delayed for a year or two, a delay should be considered. By that time, he said, more potent and more tolerable treatments could be available. Research presented in April at the 47th International Liver Congress in Barcelona indicated that new oral polymerase inhibitors in clinical trials have better cure rates and, because they aren't used in combination with interferon, have less toxicity, Dr. Bartlett said.

Younger patients may respond better to treatment, but older age is not a contraindication, experts stressed. “The more damage in the liver, the lower the response, and I would never use the fact of a patient being older as a reason not to treat, if therapy is indicated,” Dr. Franco explained. “The best predictors of whether a patient will respond are the genotype and the viral load ... but viral load does not correlate with disease progress.”

Dr. Franco advises a liver biopsy every five years for a patient who is HCV positive but is not undergoing treatment.

“If I biopsy in 2007 and the patient is at stage 1 and then is still at stage 1 five years later, I would say the disease is mild and that the scope of damage is relatively flat,” he said. “However, if the patient five years ago was at stage 1 and now is at stage 2 and starting to border on stage 3, that patient is clearly one of those 20% who will probably progress to cirrhosis and should strongly consider treatment.”

Dr. Alter concurs that patients with a diagnosis of HCV should be followed closely and should undergo a biopsy every five years.

“We know the disease doesn't progress rapidly, and it doesn't matter too much whether you treat someone at year 20 of their infection or at year 15,” Dr. Alter said. “But the patient needs to have a liver biopsy up front and should be monitored closely.”