March 29, 2013 | 11:52 am

A New Hope for Hepatitis C Infection

Posted by Albert Fuchs, M.D.

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The Hepatitis C virus is
what scientists call very
small. Here is an electron
micrograph of one. The
scale bar is 50 nanometers.
Photo credit: Wikimedia /
Rockefeller University

Hepatitis C is a viral infection that is usually spread through contact with infected blood. Prior to 1992, when testing of donated blood and organs became commonplace, many people were infected through blood transfusion and organ transplants. Now the most common method of infection is the sharing of needles or other equipment for injecting drugs. About 3.2 million people are estimated to have chronic hepatitis C infection in the U.S. Over decades, chronic infection can lead to liver failure and liver cancer. Hepatitis C is the leading indication for liver transplantation in the U.S. There is currently no vaccine.

Current medications for hepatitis C have some serious side effects and are sometimes only effective transiently, because the virus can develop resistance to the anti-viral medications. Current medications work by blocking the function of one of the virus’s components, so mutations in the virus can alter that component making the medicine ineffective.

A novel family of medicines has focused on targeting a part of the healthy liver cell that the virus uses to replicate. A specific kind of molecule called microRNA which is present in normal liver cells is required to bind to part of the hepatitis C for infection and viral replication to occur. This new family of medicines, called microRNA inhibitors, bind microRNA and prevent them from binding to hepatitis C.

A study published in this week’s New England of Medicine (NEJM) tested the effect of miravirsen, a microRNA inhibitor, in hepatitis C patients. This was a preliminary study designed to find the short-term effects on a small number of patients. Only 36 patients were enrolled in the study and they received five weekly injections of various doses of miraversen or of placebo.

The results were encouraging. The patients receiving miraversen had a large drop in the amount of hepatitis C virus detected in their blood. This effect lasted after the miraversen treatment was stopped. In a few patients the amount of hepatitis C in their blood fell below the limits of detection. There were no serious side effects, and none of the virus obtained from patients showed mutations suggesting resistance to the new drug.

Larger and more prolonged studies are needed before the miraversen is generally available, but besides the potential hope for hepatitis C patients, microRNA inhibitors may find utility in a number of other diseases.

Learn more:

A new drug shows promise of hepatitis C cure (Booster Shots, LA Times’ health blog)
'Sponge' Drug Shows Promise For Treating Hepatitis C (Shots, NPR’s Health blog)
Treatment of HCV Infection by Targeting MicroRNA (NEJM article)
Micromanaging Hepatitis C Virus (NEJM editorial)
Hepatitis C Information for the Public (Centers for Disease Control and Prevention)

Important legal mumbo jumbo:
Anything you read on the web should be used to supplement, not replace, your doctor’s advice.  Anything that I write is no exception.  I’m a doctor, but I’m not your doctor.

March 15, 2013 | 10:38 am

Azithromycin Might Kill You, but That’s Not Why You Shouldn’t Take It

Posted by Albert Fuchs, M.D.

This week the FDA issued a warning about the antibiotic azithromycin (Zithromax). The media stories have some patients terrified and some of them are calling me convinced that azithromycin is poison, a reliable agent for suicide.

What’s the hubbub about?

Azithromycin is in a family of antibiotics called macrolides, which also includes erythromycin and clarithromycin (Biaxin). Erythromycin and clarithromycin have long been known to very rarely cause fatal abnormal heart rhythms. It was thought that azithromycin didn’t have this rare side effect.

In May of last year the New England Journal of Medicine (NEJM) published a study that tried to confirm this. The study compared rates of sudden death while taking a course of azithromycin to the risk while taking amoxicillin, ciprofloxacin, levofloxacin, or no antibiotic. The study was not randomized. It simply matched hundreds of thousands of antibiotic prescriptions to death certificates.

The study found a tiny increased risk in patients taking azithromycin. How tiny? Compared to taking amoxicillin, taking azithromycin contributed 47 additional cardiovascular deaths per 1 million antibiotic courses. That’s one extra death per 21,276 courses. If you took 5-day azithromycin courses continuously, it would take 291 years to take that many courses of antibiotics. That’s a much slower way to die than, say, hemlock.

All patients did not have the same risk of having a fatal heart rhythm abnormality. Older patients, patients taking medications for heart rhythm abnormalities, and patients with heart disease, certain EKG abnormalities, and certain electrolyte abnormalities were at greater risk of this side effect. The patients at highest risk face one additional death every 4,100 courses of antibiotics, while those at lowest risk have one additional death every 110,000. These are very, very small risks.

So doctors should try to avoid all macrolides in high risk patients. But patients should probably forget the whole thing and avoid azithromycin for a different reason.

The reason you should avoid azithromycin is the same as the reason you should avoid all antibiotics. The risk of Clostridium difficile infection and the risk of antibiotic resistance is much greater than the miniscule risk of a fatal rhythm abnormality. That’s what should be scaring you about antibiotics. This is especially true of azithromycin because its convenient 5-day course, the Z Pack, has become a household name and patients ask for it even when antibiotics are very unlikely to help. It is very likely that the last Z Pack you took was for a cold, or for acute bronchitis, or for an early sinus infection, all of which resolve without antibiotics.

It would be a sad irony if we needed the irrational fear of extremely rare side effects to counter the irrational exuberance that patients have for unnecessary antibiotics. I hope instead that educated patients armed with reliable information will make good decisions.

Learn more:

F.D.A. Raises Heart Alert on Antibiotic in Wide Use (New York Times)
FDA Strengthens Warnings On Pfizer Antibiotic (Wall Street Journal)
FDA says Zithromax can cause fatal irregular heart rhythm (Reuters)
Azithromycin (Zithromax or Zmax) and the risk of potentially fatal heart rhythms (FDA Drug Safety Communication)
Azithromycin and the Risk of Cardiovascular Death (NEJM, May 2012)

Important legal mumbo jumbo:
Anything you read on the web should be used to supplement, not replace, your doctor’s advice.  Anything that I write is no exception.  I’m a doctor, but I’m not your doctor.

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March 1, 2013 | 12:50 pm

Normal Test Results are Often Not Reassuring

Posted by Albert Fuchs, M.D.

A CT scanner. Not a good test for anxiety. Photo by 1weezie23/Wikipedia.

Every primary care doctor has been faced with this situation. A patient reports vague symptoms and is very worried that they are a sign of a catastrophic illness. The symptoms aren't even slightly suggestive of the disease the patient is worried about, but the patient’s neighbor’s brother-in-law was just diagnosed with the same disease, and so the patient is pretty sure that he has it too. The doctor is not at all suspicious that the patient has this disease. The doctor believes that the patient is simply anxious, and that his symptoms are either caused by his anxiety or are normal bodily sensations that are being magnified and given lots of attention because of the news about the neighbor’s brother-in-law.

What can the doctor do? One option is to order a test – a CT, a MRI, blood tests, whatever would rule out the specific disease the patient is worried about. The doctor is not ordering the test because he is actually curious about the results. He thinks the probability of an abnormal result is extremely low. He is ordering the test simply in the hopes that a normal result will reassure the patient, decrease the anxiety, and maybe even lead to the resolution of the symptoms by letting the patient focus on something else.

The temptation to order the test is pretty great (especially if the doctor owns the testing equipment). But will it work? Will the normal test result fix the problem?

A study published this week in JAMA Internal Medicine attempted to answer that question. Researchers compiled all previous published randomized trials that assessed diagnostic testing done for symptoms that were unlikely to represent serious illness. They found that on average the patients’ reported anxiety and symptom severity did not decrease after the result was normal.

So when the disease being investigated is very unlikely, ordering a test just to reassure a patient doesn't actually reassure the patient.

It might be more effective to take the time to understand the cause of the anxiety. Perhaps the patient is actually very close to the neighbor’s brother-in-law and is himself devastated by the bad news and simply needs to express how sad he is for his friend. Or perhaps he has health anxiety (hypochondriasis) and has been to a dozen doctors in the last six months with different symptoms getting myriad normal tests. The former just needs some sympathetic listening. The latter needs cognitive behavioral therapy. Neither benefit from diagnostic testing.

Another reason to avoid testing for a disease that is very unlikely in a given patient has to do with math. I wrote last year that screening for most diseases is not helpful. One of the reasons is that no test is perfect. If the likelihood that the disease is present is extremely small, an abnormal test is more likely to be caused by an test error than by the disease being present. So testing patients that are almost certainly healthy raises the possibility of false positives due to test errors. That won’t reassure anyone and will likely lead to more tests to pursue the spurious abnormal result.

Doctors need to learn to say to patients “That doesn't sound worrisome. Let’s just keep an eye on it.” without being dismissive. Patients need to learn that a system that pays more for testing than listening will deliver more testing than listening.

Learn more:

In many patients, diagnostic testing isn't reassuring after all (LA Times)
'Worried Well' Often Ignore Negative Test Results: Study (US News)
Reassurance After Diagnostic Testing With a Low Pretest Probability of Serious Disease (JAMA Internal Medicine)
Doctor, Test Me for Everything (My post from last year explaining why some screening tests are harmful)
It’s Not All in Your Head: How Worrying about Your Health Could Be Making You Sick and What You Can Do about it (A very helpful and authoritative book for patients with health anxiety)

Important legal mumbo jumbo:
Anything you read on the web should be used to supplement, not replace, your doctor’s advice.  Anything that I write is no exception.  I’m a doctor, but I’m not your doctor.

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