Systematic Review: Non A-E, seronegative or indeterminate hepatitis; what is this deadly disease?

Paul Brennan (Lead / Corresponding author), Mhairi C. Donnelly, Kenneth J. Simpson

Research output: Contribution to journalReview articlepeer-review

21 Citations (Scopus)
295 Downloads (Pure)


Background: A significant proportion of cases of acute liver failure (ALF) do not have an identifiable cause; so called “non A-E”, “non-A, non B, non C”, “seronegative” or “indeterminate” hepatitis. However, this entity is clinically not well described.
Aim: To collate the known incidence and outcomes in indeterminate hepatitis. This systematic review sought to identify potential aetiologies that ought to be considered, and identify likely future objectives in classification and treatment strategies for indeterminate hepatitis.
Methods: Literature review to determine aetiological factors, prevalence and outcomes relating to indeterminate hepatitis.
Results: There is significant heterogeneity within the reported cases of indeterminate hepatitis in the literature. Some of the potential infective aetiologies which are reviewed here include; parvovirus B19 (PVB19), herpes simplex virus (HSV), Toga-Like Virus and the Annelloviridae (including SEN-V). Interestingly, this condition predominately affects middle aged women, with subacute progression of the liver failure. In addition, the prognosis of indeterminate hepatitis is poor, with reduced spontaneous survival compared with other causes of acute liver failure and increased need for emergency liver transplantation.
Conclusions: Whilst various pathological processes have been implicated in the development of indeterminate hepatitis, the specific cause remains elusive. There is an urgent need for general consensus on a specific definition and exclusion of confounding aetiologies with coordinated multicentre investigation of this rare condition to identify aetiology and develop therapies to reduce the significant mortality and need for emergency liver transplantation associated with this condition.
Original languageEnglish
Pages (from-to)1079-1091
Number of pages13
JournalAlimentary Pharmacology & Therapeutics
Issue number8
Early online date21 Feb 2018
Publication statusPublished - Apr 2018


  • Indeterminate hepatitis
  • seronegative hepatitis
  • non A-E hepatitis

ASJC Scopus subject areas

  • Pharmacology (medical)


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