How Long Does Acute Hepatitis C Remain in the Pre-Seroconversion Window?

FEBRUARY 15, 2017
Caitlyn Fitzpatrick
infectious disease, hepatitis C, HCV, hepatology, acute hepatitis, liver disease, CROI 2017

In acute hepatitis C infection, the amount of time when a patient is virologically positive but IgG antibody (Ab) negative, referred to as the pre-seroconversion window, differs depending on the method used. Researchers from Johns Hopkins School of Medicine and the National Institute of Allergy and Infectious Diseases in Baltimore, Maryland used various assay algorithms to better understand that window period.

The researchers pulled data from studies on commercially available hepatitis C seroconversion panels. They evaluated primary viral infection and subsequent IgG Ab seroconversion and presented their findings were presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2017) in Seattle, Washington.

Laboratory results were gathered from 82 repeat donors, making up 754 visits. Thirty-nine of them were excluded—23 were hepatitis C RNA positive at baseline, 12 remained hepatitis C negative during the study period, and four whose interval to estimate the initial infection date more than 30 days.

The 43 donors who remained had acute hepatitis C infection with a median of four days in between clinic visits.

Date of detectable infection was estimated using hepatitis C RNA positivity (nucleic acid testing (NAT) by any assay) and Murex HCV Ag/Ab Combo Assay. Date of detectable seroconversion was estimated using the Architect Anti-HCV Assay, Ortho HCV Version 3.0 ELISA, and Murex 4.0 ELISA.

“The average time spent in the RNA +/Ab- stage prior to positivity by the Murex HCV Ag/Ab Combo assay was estimated to be 18 days and 25 days from the binomial regression models fitted with logit-cubic link function and log-log link function, respectively,” the researchers explained.

The team estimated the mean duration of recent infection (MDRI) prior to seroconversion with six different testing algorithms. The results showed that MDRI point estimates with the NAT (considered the gold standard) ranged from 29 to 41 days. The Murex HCV Ag/Ab Combo assay showed 25 to 45 days.

The Architect Anti-HCV assay and Murex 4.0 ELISA had equivalent MDRI point estimates and 95% confidence intervals—40 to 45 days—for patients tested with all assays, except Ortho. NAT and Murex HCV Ag/Ab Combo assay also had similar MDRI estimates.

“Our estimates regarding the pre-seroconversion window period of acute hepatitis C infection are in agreement with the published literature (~45 days), including previous estimates calculated among people who inject drugs,” the team confirmed.

The assays had fairly consisted MDRI point estimates. The Ag/Ab assay may be a more cost-effective option than NAT for the hepatitis C seronegative populations. Confidence intervals were also similar, but more investigation is needed due to some inconsistency, the researchers said.

Although up to 80% of acute hepatitis C infections develop into chronic cases, concentrating on the short-term infections is important in order to reach the World Health Organization’s (WHO) goal of 90% reduction in hepatitis C cases by 2030.

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