Diagnosis of Hepatitis C


An introduction to diagnosing hepatitis C and understanding the difference between a positive antibody test and positive viral load


  • The Pathophysiology and Symptoms of Hepatitis C
  • Overview and Risk Factors of Hepatitis C

Christian B. Ramers, MD, MPH, AAHIVS: Bhavesh, let's get into the tests that we actually have at our disposal. What are the tests available, and how do we use them in diagnosing hepatitis C?

Bhavesh Shah, RPh, BCOP: At the institutional level, we're pretty spoiled where we actually have a lab that you can send a blood test to, but absolutely at the community setting there are different ways of getting that test done. There is a quick test you can do—a blood test or a quick that we’ve heard of, which takes about 20 minutes—but you still need a confirmatory blood test that you send out to the lab before getting viral load, genotyping, all that stuff. I think there’s still complexity in getting the diagnosis of hepatitis C, so it’s not something that’s widely utilized by every single provider.

Christian B. Ramers, MD, MPH, AAHIVS: Let’s get into some of the nuances here about testing. There are situations in which you might have a negative antibody test and a positive viral load or a positive antibody test and a negative viral load. Let’s go through each of those scenarios.

Caroline, what would it mean to you if somebody had a positive hepatitis C antibody but a negative viral load?

Caroline Derrick, PharmD, BCPS: A positive hepatitis C antibody means that there was an exposure, so the viral means that there would be current infection. If a patient has a positive viral load, then there would be active infection going on. You may often have someone with a positive antibody who does not have the viral load. That would be no present or active infection. It does not mean that the patient is immune to re-exposure or reinfection, and we might talk about that a little later. That’s something that patients may get confused on.

Christian B. Ramers, MD, MPH, AAHIVS: Patients that I’ve seen are generally surprised when you tell them you’ve been exposed to hepatitis C, because often they don’t know what the risk factors are. But then they come back for the viral load result, and if it’s negative, you don’t have it. Does that mean it’s just dormant or that they don’t have hepatitis C in their bodies?

Caroline Derrick, PharmD, BCPS: No, that means they don’t have hep C in their bodies, so this is a completely curable disease. It’s not something like hepatitis B, where you have covalently closed circular DNA hiding out in the liver cells. This is something that’s very different and exciting, that we can cure this disease state.

Christian B. Ramers, MD, MPH, AAHIVS: Bhavesh, I know your institution has treated thousands of patients now. What does their pattern look like—let’s say years after they’ve gone through treatment, in terms of the antibody and the viral load?

Bhavesh Shah, RPh, BCOP: We've luckily been able to capture the viral load in probably at least 76% of our patients. A lot of times it's hard to get that SBR [Scarff-Bloom-Richardson grading system] in a lot of patients who don't show up for their visit. From those patients who have been able to clear the viral load, we've been seeing that they've been cured long term.

Christian B. Ramers, MD, MPH, AAHIVS: They'll still have that antibody positive, but that viral load will be negative forever.

Bhavesh Shah, RPh, BCOP: Exactly.

Christian B. Ramers, MD, MPH, AAHIVS: One other tricky situation. Chris, let's say somebody comes to you who knows of an exposure, maybe a month ago, feels really sick and their primary care provider checks their liver enzymes, and they're really high. The initial hepatitis C antibody is negative. A provider says, "I'm not sure what's going on," and they send a viral load that's positive. What is going on there?

Christopher Hulstein, PharmD, CSP: There is a lag time between exposure to the virus and being able to produce an antibody that's detectable by tests. It is standard where if you have a positive viral load and negative antibody, especially if a patient has presenting signs and symptoms, they are going through an acute phase of infection.

The virus itself can lie dormant as well for several weeks before any symptoms or anything like that pop up, so it's important to understand that there is a little bit of lag time with those tests and the clinical picture behind it as a whole, not just looking at the test itself. It's very important.

Christian B. Ramers, MD, MPH, AAHIVS: That's a good point. Generally when we have a negative antibody, we can safely tell the patient, "Well, you don't have hepatitis C," but there's one asterisk to that, which is that if somebody has had a very recent exposure, we want to think twice about whether this is an acute infection.

I don't want to advise everyone to send viral loads on every negative antibody, because it's going to be rare that you catch that. But in certain populations, such as people who are injecting drugs and men who have sex with men, they may have a presentation of acute hepatitis C, and you might catch it. We've caught it several times in our clinic.

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