Hepatitis C Screening for Patients With Cancer
In this podcast, Harrys A. Torres, MD, talks about his team's study that aimed to identify the optimal screening test for hepatitis C virus in patients with hematologic malignancies and/or prior hematopoietic cell transplant.
- Torres HA, Angelidakis G, Jiang Y, et al. Serologic vs. molecular testing for screening for hepatitis C virus infection in patients with hematologic malignancies with and without prior hematopoietic cell transplant recipients. Paper presented at: IDWeek 2020; October 21-25, 2020; Virtual. https://www.eventscribe.com/2020/IDWeek/fsPopup.asp?efp=VFhWUUpXVFA2ODg4&PosterID=292366&rnd=0.8516078&mode=posterinfo.
Harrys A. Torres, MD, is an infectious diseases physician at MD Anderson Cancer Center and an associate professor in the Department of Gastroenterology, Hepatology, and Nutrition at the University of Texas (Houston, Texas).
Amanda Balbi: Hello everyone, and welcome to another installment of Podcasts360—your go-to resource for medical news and clinical updates. I’m your moderator, Amanda Balbi with Consultant360 Specialty Network.
The prevalence of chronic hepatitis C virus infection among patients with cancer in the United States has been reported to be 1.5% overall and up to 10.6% in specific subgroups. Testing for hepatitis C virus antibody is a low-cost diagnostic method in widespread use worldwide. However, the optimal screening test for hepatitis C virus among patients with cancer has not been established. In a new study presented at IDWeek 2020, researchers sought to identify the optimal screening test for hepatitis C virus in this patient population.
We’re joined today by the lead author on the study, Dr Harrys Torres, who is an infectious diseases physician at MD Anderson Cancer Center and an associate professor in the Department of Gastroenterology, Hepatology, and Nutrition at the University of Texas in Houston.
Thank you so much for joining me today, Dr Torres. To start, can you tell us more about your study and its findings?
Harrys Torres: Thank you for inviting me. It's very exciting opportunity. The study is about hepatitis C and how we test patients with cancer. I practice at MD Anderson, which is a major referral center in the United States.
What is still unclear is how do we screen these patients for hepatitis C. The title of the study is “Serologic vs molecular testing for screening for hepatitis C virus infection in patients with hematologic malignancies with and without prior hematopoietic cell transplant recipients.”
And what we know is hepatitis C is carcinogenic, and it’s associated with several types of malignancy, not only liver cancer. It also can cause some significant problems, including morbidity and mortality, in cancer patients. And it’s estimated that the patients with cancer in the United States have a prevalence of hepatitis C between 1.5 and up to 10.6, as we have recently reported in [indecipherable 1:55] cancer patients.
This is of importance to multiple societies, including the American Society of Clinical Oncology (ASCO), because we know that these can affect cancer patients, and the reason ASCO recommendations and guidelines—I'm one of the authors there—what is recommended is to do a universal screening in cancer patients for 3 main reasons.
Number one is because we know that we're going to screen patients only based on the birth cohort or the risk-based screening; we’re going to miss at least one-third of the patients.
The problem is when we miss hepatitis C, these patients may develop reactivation of the infection, interruption of cancer due to that progression of fibrosis and cirrhosis, and some of these patients may develop a second primary cancer.
We also know that direct-active antivirals (DAAs) can eradicate most of the infection in these patients. We know that up to 91% to 95% of these patients, even with cancer, can get virologic cure of hepatitis C.
Universal screening is now recommended by the 2020 USPSTF recommendations. So it's really recommended to screen all adults, and that's what we have been doing at MD Anderson, at least since 2016.
We also know that by treating these infections, we can improve different types of outcomes on these patients. We can normalize the liver function tests. A very important point for cancer patients is that we cannot increase access to clinical trials for cancer care.
We can also increase access to bone marrow transplant. We can prevent reactivation, and a very important point for our oncologists is that we can improve the overall survival—not only the liver-related survival but the overall survival under these [indecipherable 2:46] survival in these patients. So there are important oncologic end points that we can improve by treating the hepatitis C.
The challenge is what to use for that. And we know that there are 2 different types of assays approved for diagnosis of hepatitis C. One is a serologic assay that detects hepatitis C antibody, and the second is a molecular assay that detects the hepatitis C RNA quantitative.
The cost is completely different in most countries. For example, in the United States, we know that the cost of serologic assays is between $0.50 and $1.70 vs in the molecular essays, which is between $30 and $200—depends on where you're getting that test done.
And the US national guidelines recommend screening with antibody in both immunocompetent and immunocompromised patients. But they only immunocompromised patient population that is included on these recommendations is the HIV population. So we don't really know how these well as applicable to cancer patients, including bone marrow transplant patients.
The background of this study is trying to identify the most appropriate screening test for chronic hepatitis C in patients who have cancer, any type of cancer, and with or without transplant.
What we did here is we enrolled prospectively all patients coming to the hematologic clinic at MD Anderson, including the lymphoma clinic, myeloma, leukemia, stem cell transplant. We enrolled these patients between February 2019 and November 2019. They had to be adults with any type of malignancy with or without transplant.
What we did is, at the same time when the patients were coming for cancer care, we screened them simultaneously for hepatitis C RNA and hepatitis C antibody. The hepatitis C antibody was performed by using the ARCHITECT Anti-HCV assay by Abbot Laboratories, with a specificity of 99.6 and sensitivity of 99.1.
This is a commercially available assay, and we also used an older commercially available assay for hepatitis C quantitative. We used a hepatitis C RNA test called the cobas® HCV test by Roche Molecular Systems.
The quantitative range between 15 and 100 million international units or ML. The interpretation [indecipherable 5:20] If the patient has positive antibody and positive RNA, the patient is infected.
What we were looking for in particular were patients with seronegative infection, meaning that patients who have negative antibody and positive RNA. Those are specifically the ones we were looking for.
And what we did is we calculated the power of the study on the basis of the diagnostic performance of these 2 tests—the antibody and the RNA—in HCV-infected patients. Unfortunately, we didn't have data on any other immunocompromised population. So, we have to use the data on HIV-infected patients.
We have found in the literature that 6.9% of patients were tested negative for hepatitis C antibody. However, they were infected because they had detectable RNA. We used for a statistical analysis, the McNemar test where 214 patients were needed to enroll with a yield of 90% of power to detect significant difference.
The agreement between the 2 tests was [indecipherable 6:24] Cohen Kappa statistical analysis and the McNemar test. These tests were performed. The study was funded in part by Merck Inc. and also by the NCI (National Cancer Institute), partially for each of these 2 groups. This study sponsors have no role in study design, collection, analysis, or interpretation of the data.
We did 214 patients, as was requested for the enrollment. The median age was 64 years old, and year of age within range between 27 and 84 years.
Most patients were male, with a 69%. Most patients were Caucasian, with 84%. Eight percent of the patients were Black. Most patients had lymphoid malignancies, with 70% of them. Seven percent of the patients had bone marrow transplant.
And what we found is, in terms of the diagnostic performance, we identified of the 214 patients evaluated, 3 patients had positive hepatitis C antibodies and 2 patients had positive hepatitis C RNA test. The overall percentage agreement was 99.5%, with a confidence interval of 97.4 to 99.9.
Of the 3 patients with positive hepatitis C antibody test results, 2 had positive RNA and one had negative RNA. There were no cases, so seronegative hepatitis C infection. The positive agreement between the two tests was 66.7%, and the negative percentage agreement was 100%.
In brief, we identified in 3 patients with hepatitis C antibody, 2 patients with hepatitis C RNA, and the agreement was 99.5%. And the Cohen Kappa coefficient was 0.80, indicating substantial agreement between the hepatitis C antibody and the hepatitis C RNA.
Why is this important? This is important because this is the first prospective study comparing different methods for hepatitis C screening in cancer patients. We found that serologic and molecular testing have similar diagnostic performance in this patient population. We also found that there were no cases of seronegative hepatitis C infection, meaning false negative hepatitis C infection, if we use only hepatitis C antibody.
And this is important because seronegative hepC infection may have significant implications in cancer care, including [indecipherable 8:59] chronic hepC infection that may lead to multiple complications.
And why is this important? This is really important because WHO has set the goal to eliminate hepatitis might 2030. One of the most efficient strategies that WHO mentioned is to eliminate the hep C by 2030 is to expand hep C testing, that 90% of people can get screened and also offered treatment. So, our findings favor the use of hepatitis C antibody—a relatively affordable test to be used worldwide to screen hepatitis C, even in cancer patients.
Our study is limited by the power—that was low, 214 patients only. Unfortunately, the sample size, even though was based on the power we use for HIV-positive studies, is still a low power. That has to do probably with the fact that the individuals we used to calculate the power were HIV-infected patients.
We know that they are immunocompromised, but at the same time, they are patients at high risk for hepatitis C infection, which is not necessarily the case for cancer patients.
Also, we expect that different results may be expected if serologic and molecular assays are different from the one we used are used on different studies. Another detail from our study is that we were not able to perform a cost-effectiveness analysis. And the reason is that granted that with the special pricing for laboratory testing not reflect the true market price.
In conclusion, we know that the diagnostic yield for screening of hepatitis C in severely immunocompromised cancer patients is similar for serologic and molecular testing, and the use of diagnostic methods with low cost like hepatitis C antibody will contribute, even in cancer patients, to the long-term goal of eliminating hepC in the United States and globally.
Amanda Balbi: And what is the next step in this research?
Harrys Torres: The next step here is to take these to other institutions. So, we do have a consortium with other NCI cancer centers in the United States and also some other cancer centers globally, including in France, Canada, and Italy. The plan is now to expand this to other institutions as well, so they will know how to screen these patients and they will also apply to their own centers. And, certainly, that will allow us to validate our findings in the multinational setting.
Amanda Balbi: Thank you so much for speaking with me today and answering my questions.
Harrys Torres: Thank you, Amanda, for inviting me.