Circovirus Hepatitis Infection in Heart-Lung Transplant Patient, France

Abstract

In March 2022, a 61-year-old woman in France who had received a heart-lung transplant sought treatment with chronic hepatitis mainly characterized by increased liver enzymes. After ruling out common etiologies, we used metagenomic next-generation sequencing to analyze a liver biopsy sample and identified an unknown species of circovirus, tentatively named human circovirus 1 (HCirV-1). We found no other viral or bacterial sequences. HCirV-1 shared 70% amino acid identity with the closest known viral sequences. The viral genome was undetectable in blood samples from 2017–2019, then became detectable at low levels in September 2020 and peaked at very high titers (10 10 genome copies/mL) in January 2022. In March 2022, we found >10 8 genome copies/g or mL in the liver and blood, concomitant with hepatic cytolysis. We detected HCirV-1 transcripts in 2% of hepatocytes, demonstrating viral replication and supporting the role of HCirV-1 in liver damage.

Circovirus infection, transplantation, hepatitis and zoonosis: a new disease and a new concern

“…[5] The mode of transmission of the new circovirus infection to humans is unknown, but it is thought to be a zoonosis. [4] The infection is most commonly seen in animals. Piglets are typically affected.…”

“…This illness has just been identified as a potential cause of transplant recipient hepatitis that goes undiagnosed in 2023. [4] In actuality, posttransplant hepatitis poses a serious risk to the transplant patient. [5] The problem can be caused by known hepatitis viruses, and protection against those pathogens is standard practice in clinical transplantation.…”

Human Circovirus is not detected in plasma pools for fractionation

“…In a recent study, we identified a novel Circovirus, known as HCirV-1, which was responsible for hepatitis in a patient immunosuppressed following a heart-lung transplantation. 1 A closely related virus was later reported in China in intravenous drug users (HCirV-2). 2 The origin and prevalence of these circoviruses in the human population remains unclear, as it could either be a circulating human virus or a zoonotic virus only occasionally transmitted from animals to patients, potentially favored by their compromised immune system.…”

“…In addition, samples were tested with PCR primers HCirV1-Fw1 5 0 -ACCTGGATG-GACCCTGGAAT-3 0 and HCirV1-Rv1 5 0 -AGAGTTCCAC CAGGTTCTGC-3 0 targeting the capsid gene of HCirV-1, as described in. 1 The estimated sensitivity of these two PCR tests was 300-600 genome copies per mL of plasma (Supplementary data).…”

“…In a recent study, we identified a novel Circovirus, known as HCirV‐1, which was responsible for hepatitis in a patient immunosuppressed following a heart‐lung transplantation 1 . A closely related virus was later reported in China in intravenous drug users (HCirV‐2) 2 .…”