Daijiworld Media Network - New Delhi
New Delhi, Oct 2: Advanced viral sequencing may help identify infections missed by conventional diagnostic tests in some cases of hepatitis of unknown origin, according to a study involving 49 patients in China.
Researchers at Beijing Ditan Hospital detected hepatitis C virus (HCV) in one patient whose initial antibody and RNA tests were negative. Subsequent testing confirmed an acute HCV infection, allowing the case to be reclassified. However, the study did not identify any common novel pathogen among the wider group of patients.
The study included 48 adults and one 16-year-old adolescent who were enrolled between June and December 2024. All participants had undergone initial investigations that ruled out recognised causes of hepatitis, including hepatitis A–E, alcohol-related liver disease, drug-induced liver injury, autoimmune hepatitis, metabolic disorders and biliary obstruction.
Researchers analysed 59 clinical specimens, including 44 plasma and 15 faecal samples, using targeted RNA sequencing and unbiased metagenomic sequencing. The targeted approach screened for 139 viruses, while metagenomic sequencing examined a broader range of viral genetic material.
Targeted sequencing detected HCV in one plasma sample. The patient had initially tested negative for HCV antibodies and RNA and had been diagnosed with hepatitis of unknown origin.
Further metagenomic sequencing identified a near-complete HCV genome covering 94.5 per cent of the reference sequence. Follow-up testing 14 days later confirmed HCV RNA positivity, with a viral load of 420,000 IU/mL, along with antibody seroconversion. The findings established that the patient had an early HCV infection that had not been detected during the initial testing.
Metagenomic sequencing also detected hepatitis B virus sequences in another patient despite negative conventional HBV testing at enrolment. Researchers suggested this could represent occult HBV infection, although they could not establish whether it was responsible for the hepatitis.
A goose circovirus-like sequence was identified in one faecal sample, but there is currently no evidence that the virus causes hepatitis in humans. An additional low-level influenza A-like signal was detected in one plasma sample, but it could not be confirmed through follow-up PCR testing.
Overall, the researchers found no common pathogenic virus that could explain the unexplained hepatitis cases in the cohort.
The study also found differences in viral signals between plasma and faecal samples, suggesting that testing multiple sample types could provide complementary information.
However, the researchers noted several limitations, including the small sample size, lack of a healthy control group and absence of liver biopsy specimens. The findings do not establish new viral causes of hepatitis or support routine metagenomic sequencing for all patients.
The researchers suggested that advanced sequencing could instead complement established diagnostic methods in selected unresolved cases, particularly when early infection or inconclusive conventional testing is suspected. Larger controlled studies are needed to determine its clinical usefulness and whether broader sequencing can reduce the number of hepatitis cases whose causes remain unexplained.