In the JournalsPerspective

HCV nucleic acid test offers ‘opportunity’ to increase liver transplant pool

Utilizing hepatitis C antibody-positive but nucleic acid test-negative liver donors for HCV-negative liver transplant recipients opens up liver transplant options, allowing for the use of livers available due to drug overdose, according to experts.

Khurram Bari, MD
Khurram Bari

“Now that we have [nucleic acid testing (NAT)] available, that should be considered in labeling the donors rather than hepatitis C-positive or not,” Khurram Bari, MD, from the University of Cincinnati, told Healio Gastroenterology and Liver Disease. “NAT testing is a better indicator of hepatitis C positivity or negativity in donors, not just antibody. The antibody test can be nonspecific; it can positive, but if the NAT is negative there is a much lower risk for hepatitis C transmission.”

In 2015, the University of Cincinnati Medical Center began offering liver transplant candidates without HCV the option to receive an organ from HCV seropositive, non-viremic liver donors to decrease waiting times on the transplant list.

According to Bari and colleagues, a recent guide from the Disease Transmission Advisory Committee of Organ Procurement and Transplantation Network estimated the risk for HCV transmission from positive donors with immediate needle exposure to be as high as 3%.

To estimate the incidence of HCV transmission from positive donors to negative recipients, the researchers enrolled 26 liver transplant candidates who were negative for HCV antibody (n = 25) or negative for serum NAT (n = 1). The researchers excluded one patient who died of primary graft failure 18 days after transplantation.

Median age of the remaining 25 patients was 62 years (range, 36-69 years) and the median MELD score was 22. One patient was successfully treated for HCV prior to transplant, whereas the rest were HCV antibody negative at baseline.

Median age of donors was 41 years and most were white (88%) and had died of a presumed drug overdose (60%).

HCV transmission , SVR

At a median follow-up of 11 months (range, 5-18 months), four transplant recipients developed HCV viremia. The researchers determined that none of the recipients had behavioral risk factors or health care exposures that could have served as a source for HCV infection and that the infections were from a new source rather than a “mutation over time.”

Two of the newly infected patients achieved SVR at 12 weeks of treatment with DAAs. One patient achieved an end of treatment response with DAAs and follow-up SVR is pending.

The fourth patient underwent retransplantation after primary graft failure. At 9 months after retransplantation, he died due to complications of pneumonia. The patient had not initiated antiviral therapy because of his complicated clinical course and severe debility.

“There is definitely a risk for hepatitis C, which was higher than we thought, but it’s not 100%. It’s not like you are giving true hepatitis C-positive organs,” Bari said. “This is an opportunity. As there is an intravenous epidemic in drug use ... we have a lot of these donors who are antibody positive and NAT-negative. If these donors are considered to be hepatitis C-positive, these organs can go to waste. With this approach we can use those organs in patients who do not have hepatitis C and, if the donors do transmit, we can treat those patients later.”

The researchers also noted that one-time NAT for HCV in donors had a limited predictive value for transmission to transplant recipients and that donor characteristics, such as age, sex, increased-risk behavior and cause of death, may also affect outcomes.

“This is a big question of how these patients are transmitting hepatitis C,” Bari said. “The question is and the next step is: How do we think they are transmitting? If we can figure that out, we may be able to minimize that transmission.” – by Talitha Bennett

Disclosure: The authors report no relevant financial disclosures.

Utilizing hepatitis C antibody-positive but nucleic acid test-negative liver donors for HCV-negative liver transplant recipients opens up liver transplant options, allowing for the use of livers available due to drug overdose, according to experts.

Khurram Bari, MD
Khurram Bari

“Now that we have [nucleic acid testing (NAT)] available, that should be considered in labeling the donors rather than hepatitis C-positive or not,” Khurram Bari, MD, from the University of Cincinnati, told Healio Gastroenterology and Liver Disease. “NAT testing is a better indicator of hepatitis C positivity or negativity in donors, not just antibody. The antibody test can be nonspecific; it can positive, but if the NAT is negative there is a much lower risk for hepatitis C transmission.”

In 2015, the University of Cincinnati Medical Center began offering liver transplant candidates without HCV the option to receive an organ from HCV seropositive, non-viremic liver donors to decrease waiting times on the transplant list.

According to Bari and colleagues, a recent guide from the Disease Transmission Advisory Committee of Organ Procurement and Transplantation Network estimated the risk for HCV transmission from positive donors with immediate needle exposure to be as high as 3%.

To estimate the incidence of HCV transmission from positive donors to negative recipients, the researchers enrolled 26 liver transplant candidates who were negative for HCV antibody (n = 25) or negative for serum NAT (n = 1). The researchers excluded one patient who died of primary graft failure 18 days after transplantation.

Median age of the remaining 25 patients was 62 years (range, 36-69 years) and the median MELD score was 22. One patient was successfully treated for HCV prior to transplant, whereas the rest were HCV antibody negative at baseline.

Median age of donors was 41 years and most were white (88%) and had died of a presumed drug overdose (60%).

HCV transmission , SVR

At a median follow-up of 11 months (range, 5-18 months), four transplant recipients developed HCV viremia. The researchers determined that none of the recipients had behavioral risk factors or health care exposures that could have served as a source for HCV infection and that the infections were from a new source rather than a “mutation over time.”

Two of the newly infected patients achieved SVR at 12 weeks of treatment with DAAs. One patient achieved an end of treatment response with DAAs and follow-up SVR is pending.

The fourth patient underwent retransplantation after primary graft failure. At 9 months after retransplantation, he died due to complications of pneumonia. The patient had not initiated antiviral therapy because of his complicated clinical course and severe debility.

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“There is definitely a risk for hepatitis C, which was higher than we thought, but it’s not 100%. It’s not like you are giving true hepatitis C-positive organs,” Bari said. “This is an opportunity. As there is an intravenous epidemic in drug use ... we have a lot of these donors who are antibody positive and NAT-negative. If these donors are considered to be hepatitis C-positive, these organs can go to waste. With this approach we can use those organs in patients who do not have hepatitis C and, if the donors do transmit, we can treat those patients later.”

The researchers also noted that one-time NAT for HCV in donors had a limited predictive value for transmission to transplant recipients and that donor characteristics, such as age, sex, increased-risk behavior and cause of death, may also affect outcomes.

“This is a big question of how these patients are transmitting hepatitis C,” Bari said. “The question is and the next step is: How do we think they are transmitting? If we can figure that out, we may be able to minimize that transmission.” – by Talitha Bennett

Disclosure: The authors report no relevant financial disclosures.

    Perspective
    Allison J. Kwong, MD

    Allison J. Kwong

    The recent availability of effective antiviral therapy for hepatitis C has resulted in much lower rates of graft loss due to HCV after transplantation and thus improved posttransplant outcomes. As a result, there has been greater interest in using donor livers that are potentially infected with HCV. Donor livers that are HCV antibody positive but not viremic (by nucleic acid testing, or NAT) are not thought to be at high risk for HCV transmission, though the possibility remains if NAT is falsely negative or the donor is in the window, or eclipse, period at the time of donation.

    This report shows that the intentional use of HCV antibody positive donor livers for non-viremic recipients is possible — though the risk of donor-derived HCV infection in their sample was 16%, higher than previously estimated. Recipients who become infected with HCV can be treated effectively after transplantation. Posttransplant outcomes using these grafts (particularly those from increased-risk donors) should continue to be closely monitored and studied, but this is a promising option to help expand the donor pool, shorten waiting times, and alleviate the organ shortage.

    • Allison J. Kwong, MD
    • Division of Gastroenterology and Hepatology
      Stanford University School of Medicine