Hepatitis B virus (HBV) was discovered in patients receiving liver transplants, despite donors testing negative for the virus, CDC researchers found.

From 2014 to 2019, the agency received reports of 20 patients who contracted HBV after liver transplants from donors who had no evidence of prior HBV infection, according to Danae Bixler, MD, and colleagues from the CDC.

History of injection drug use was the most common risk factor for HBV in 100% of participants from 2014 to 2018 and in 86% of those studied in 2019, the authors wrote in the Morbidity and Mortality Weekly Report.

“The increase in HBV donor-derived infections reported in 2019 among liver recipients might be related to increased numbers of donors with hepatitis C infection or recent injection drug use,” Bixler told MedPage Today.

She noted an increase in overdose deaths from opioids/stimulants during that time period, as well as an increase in liver transplants both from hepatitis C virus (HCV)-seropositive donors and HCV RNA-positive donors currently infected with the virus.

For years, liver transplantation has been known as the most effective treatment option for chronic HBV-related liver failure, cirrhosis, and even hepatocellular carcinoma, but reactivation of HBV post-transplantation remains a clinical challenge affecting survival, the authors noted.

Data provided by Bixler and colleagues reinforced current guidelines on testing for liver transplant recipients due to the rare reported cases of HBV infections, the authors said.

“In addition to testing for HBV DNA at 4-6 weeks after transplantation, clinicians caring for liver transplant recipients should consider testing for HBV DNA 1 year after transplantation or at any time if signs and symptoms of viral hepatitis develop, even if previous tests were negative,” Bixler and coauthors stated while urging the spread of awareness on delayed HBV infections.

CDC looked into 30 suspected cases of unexpected HBV infections among liver recipients from 2014 to 2019. After excluding false-positive test results or non-reproducible HBV DNA tests, only 20 cases remained. The average donor age upon death was 31. Nineteen donors were white and 11 were men. Among the 18 donors where positive toxicology results and injection drug use was confirmed, drug intoxication was the most frequent cause of death.

Sixteen of these donors tested seropositive for the HCV antibody, including 13 donors from 2019. Eleven of these donors had both an injection drug use history and confirmed positive toxicology. Stimulants, such as cocaine and amphetamines, were the most commonly detected drug class in donors.

“These findings suggest that donor injection drug use is an important risk factor for hepatitis B infection in liver recipients post-transplant,” Bixler told MedPage Today.

CDC researchers found 18 new HBV infections in liver recipients as well as two liver-kidney recipients a median of 41 weeks after transplant. They did not find new HBV infections among 31 recipients of non-liver organ transplants from the same 20 donors.

Authors noted reactivation of HBV is possible after transplantation, if a liver donor tested positive for total anti-HBV core antibody prior to organ procurement, had a previous HBV infection, or developed a primary infection. For both HBV and HCV, injection drug use remains the predominant risk factor.

“Donors might have been exposed to HBV through injection drug use shortly before death; thus organ procurement might have occurred during the eclipse period, before HBV DNA was detectable in donor serum,” the authors added.

CDC researchers defined the “eclipse period” as being 1 to 12 weeks after HBV exposure to the initial serum identification of HBV DNA.

“In 20% of HBV or HCV co-infections, patients can test negative for all HBV serum markers,” the authors stated. Subsequent immunosuppression or liver recipient HCV treatment may result in HBV reactivation post-transplant, they added.

Bixler and colleagues cited limitations of this study, which included the variability in testing or reporting on infections from transplant centers and a difference in the timeframe in which recipients are tested or screened for HBV infection after liver transplantations in accordance with the Public Health Service Guidelines (2013), which may have underestimated HBV donor infections. There were no universal screening requirements among liver recipients prior to transplant and liver biopsy specimens were also not available for most liver donors, they said.