False-Positive Hepatitis C Testing in Long-Term LVAD Support

Abstract

Left ventricular assist devices (LVAD) have revolutionized the field of mechanical circulatory support because this technology has been shown to extend life and improve outcomes in patients with advanced heart failure. It has turned out that many LVAD patients become immunologically activated because of serum antibodies directed against human leukocyte antigens (HLA). 1,2 Srivastava et al. 3 have recently described high rates of false-positive hepatitis C antibody tests in LVAD patients, thereby supporting the observation of broad immunologic reactions in these patients. However, there is a lack of information whether such immunologic reaction is limited to a certain laboratory test and whether such an effect is observed temporarily or consistently.In our center, LVAD surgery is performed since more than 20 years with more than 350 cases. We reviewed those patients who had an LVAD (HeartWare or HeartMate II) implanted between September 2011 and September 2013 (n = 37) with regard to hepatitis C (HCV) serology, which was controlled on demand during follow-ups. HCV was tested by ADVIA Centaur XP Anti-HCV Test, Siemens Healthcare Diagnostics, Germany. This test engages the HCV coding antigen c200 and NS5 as well as a synthetic HCV coding core peptide c22 and provides a specificity of 99.9%. In case of positive results, the blood was further analyzed by Anti-HCV Line Immunoblot DeciScan HCV PLUS, Bio-Rad, Germany, as confirmatory test. This immunoblot comprises analysis for the proteins NS3, NS4, C1, and C2.In six patients (five patients with HeartMate II and one patient with HeartWare LVAD), we found positive screening tests for HCV after postoperative intervals of up to 12 months. All these patients were negative for HCV in confirmatory immunoblot testing. Remarkably, on longitudinal analysis, the screening test did not prove to reveal consistent positive results but usually turned to become negative again.Our report is in line with the work of Srivastava et al. 3 and further points out that false-positive hepatitis C reaction and negative confirmatory analyses are not only limited to the tests reported earlier. 3 Even more remarkable, such an immunologic reaction is not constantly found but has the tendency to vanish, leaving the interesting question of immunologic processes initiated by LVAD therapy. However, as already pointed out by Srivastava et al., 3 hepatitis C testing should be carefully performed with regard to decision making toward heart transplantation.

Seroreversion of positive anti‐hepatitis C virus antibodies in left ventricular assist device recipients: Now you see them, now you don’t

“…On the other hand, disappearance of anti‐HCV antibodies, in the case of CF‐LVADs particularly after removal of the device, would significantly increase the likelihood of these being false positive antibodies probably formed in a nonspecific immune response to CF‐LVAD biomaterial. In our study, we found that about 19% of all LVAD recipients developed anti‐HCV antibodies with concomitantly undetectable HCV‐RNA, which was in keeping with the incidences reported in prior studies . Upon repeat testing, we found that all of the positive HCV‐antibody tests turned negative.…”

“…According to the International Society of Heart and Lung Transplant (ISHLT) guidelines, a positive screening HCV‐antibody test must be followed by a confirmatory HCV‐RNA test before a potential candidate can be listed, with additional HCV testing as needed while wait listed, often prolonging wait list times . Over the years and for unclear reasons, formation of anti‐HCV antibodies in the absence of HCV‐RNA has been a fairly common occurrence in patients with CF‐LVADs with the reported incidences ranging from 16% to 59% . This phenomenon has thus far been attributed to the increased alloantibody synthesis seen with exposure of monocytes to LVAD‐derived biomaterial and as such, in the few cross‐sectional studies published so far, anti‐HCV antibodies formed in the absence of detectable HCV‐RNA in patients with CF‐LVADs have been deemed “false positive” …”

“…Screening for hepatitis C virus (HCV) infection is mandatory for all heart transplant (HTx) candidates . Previous cross‐sectional studies have reported that around 16%‐59% of bridge‐to‐transplant left ventricular assist device (BTT‐LVAD) patients are found to have a positive screening anti‐HCV antibody test with concomitantly negative HCV‐ribonucleic acid (RNA) . In the absence of detectable HCV‐RNA, these anti‐HCV antibodies in the BTT‐LVAD population have simply been deemed “false positive” …”

“…1 Previous crosssectional studies have reported that around 16%-59% of bridgeto-transplant left ventricular assist device (BTT-LVAD) patients are found to have a positive screening anti-HCV antibody test with concomitantly negative HCV-ribonucleic acid (RNA). [2][3][4][5][6] In the absence of detectable HCV-RNA, these anti-HCV antibodies in the BTT-LVAD population have simply been deemed "false positive". [2][3][4][5][6] However, it is well known that up to 20% of all acute HCV infections resolve spontaneously and result in a positive anti-HCV antibody tests with negative HCV-RNA.…”

“…[2][3][4][5][6] In the absence of detectable HCV-RNA, these anti-HCV antibodies in the BTT-LVAD population have simply been deemed "false positive". [2][3][4][5][6] However, it is well known that up to 20% of all acute HCV infections resolve spontaneously and result in a positive anti-HCV antibody tests with negative HCV-RNA. 7 Also, successfully treated acute HCV infections similarly results in positive anti-HCV antibody test with negative HCV-RNA.…”