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Novel assay detects HBV closed circular DNA in donated livers
Researchers detected quantifiable levels of intrahepatic hepatitis B closed circular DNA in approximately half of deceased donated livers with occult HBV infection using a novel droplet digital polymerase chain reaction-based assay, according to recently published data.
“Occult hepatitis B virus (HBV) infection (OBI) refers to the presence of intrahepatic HBV DNA in the absence of detectable hepatitis B surface antigen (HBsAg),” Gian Paolo Caviglia, PhD, University Hospital of Turin, Italy, and colleagues wrote. “OBI has clinical significance; it can reactivate hepatitis B when the immune response of the host is compromised, as in liver transplants or under chemotherapy, may accelerate the progression of hepatic fibrosis in patients with chronic hepatitis C and has been considered a risk factor for hepatocellular carcinoma.”
Caviglia and colleagues analyzed the deceased donated livers of 100 individuals who were negative for HBsAg and positive for HBV core antibody (anti-HBc), as well as 18 liver biopsies from liver donors without HBV as controls. Fifty-two of the HBV-positive livers had positive nested-polymerase chain reaction (PCR) for at least two of four HBV genomic regions.
The droplet digital PCR method showed excellent linear correlation between expected and observed HBV closed circular DNA (cccDNA) copy number (105 to 1010 copies per reaction; R2 = 0.9998; P < .0001).
The researchers detected HBV cccDNA in 27 of the HBV-positive biopsies with a median of 13 copies per 105 cells (range, 5-25), whereas none of the OBI-negative livers were positive for HBV cccDNA (P < .001).
Intrahepatic HBV cccDNA levels correlated significantly with the four nested-PCRs for OBI detection (r = 0.545; 95% CI, 0.391-0.67). Median anti-HBc IgG levels increased significantly between OBI-negative livers and OBI-positive livers (5.1 vs. 13.7 cut-off index; P = .004).
Multivariate analysis showed that anti-HBc IgG higher than a 4.4 cut-off index significantly and independently correlated with measurable intrahepatic HBV cccDNA (OR = 8.516; 95% CI, 1.709-42.425). Lower antibody titers had a negative predictive value of 94.6% for the lack of measurable intrahepatic HBV cccDNA.
“The anti-HBc IgG antibody may not only identify by a low serological level the patients at no or a minor risk of OBI reactivation, it may also provide by its level above a cut-off of 4.4 [cut-off index] an unbiased numerical surrogate to discriminate the patients at the highest risk of OBI reactivation, helping clinicians to define individualized schemes of OBI prophylaxis,” the researchers concluded. – by Talitha Bennett
Disclosure: The authors report no relevant financial disclosures.