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The global epidemiology of viral-induced acute liver failure: a systematic review protocol
  1. Jenna Patterson1,2,
  2. Hannah Sophia Hussey1,2,
  3. Leila Hussein Abdullahi2,3,
  4. Sheetal Silal4,5,6,
  5. Liz Goddard7,
  6. Mashiko Setshedi8,
  7. Wendy Spearman9,
  8. Gregory D Hussey1,10,
  9. Benjamin Kagina1,2,
  10. Rudzani Muloiwa1,11
  1. 1 Vaccines for Africa Initiative, University of Cape Town, Cape Town, South Africa
  2. 2 School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa
  3. 3 Somaliland Country Office, Save the Children International, Nairobi, Kenya
  4. 4 Department of Statistical Sciences, University of Cape Town, Cape Town, South Africa
  5. 5 Modelling and Simulation Hub Africa, University of Cape Town, Cape Town, South Africa
  6. 6 Nuffield Department of Medicine, University of Oxford, Oxford, UK
  7. 7 Department of Paediatrics, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa
  8. 8 Department of Medicine, Division of Gastroenterology, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa
  9. 9 Department of Medicine, Division of Hepatology, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa
  10. 10 Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
  11. 11 Department of Paediatrics, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa
  1. Correspondence to Jenna Patterson; PTTJEN005{at}


Introduction The burden of viral-induced acute liver failure (ALF) around the world still remains unclear, with little to no data collected regarding the disease incidence in general and synthesised data on the relative contribution of different viruses to the aetiology of ALF is missing in the field. The aim of this review is to estimate the burden (prevalence, incidence, mortality, hospitalisation) of ALF following infection HAV, HBV, HCV, HDV, HEV, EBV), HSV1, HSV2, VZV, parvo-virus B19, HPIVs, YFV, HVV-6, CMV, CA16 and/or HAdVs. Establishing the common aetiologies of viral-induced ALF, which vary geographically, is important so that: (1) treatment can be initiated quickly, (2) contraindications to liver transplant can be identified, (3) prognoses can be deterined more accurately, and most importantly, (4) vaccination against viral ALF aetiologies can be prioritised especially in under-resourced regions with public health risks associated with the relevant attributable diseases.

Methods and analysis EBSCOhost, PubMed, ScienceDirect, Scopus and Web of Science databases will be searched for relevant literature published and grey literature from 2009 up to 2019. Published cross-sectional and cohort studies will be eligible for inclusion in this review. Qualifying studies will be formally assessed for quality and risk of bias using a standardised scoring tool. Following standardised data extraction, meta-analyses will be carried out using STATA. Depending on characteristics of included studies, subgroup analyses and meta-regression analyses will be performed. This review will be reported according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines.

Ethics and dissemination No ethics approval is required as the systematic review will use only published data already in the public domain. Findings will be disseminated through publication in a peer-reviewed journal.

PROSPERO registration number CRD42018110309

  • global
  • epidemiology
  • acute liver failure

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  • Contributors JP, GDH, BK and RM conceived this study. JP developed the study protocol with the help of BK and RM. JP will implement the review under the supervision of RM. JP and HSH will perform the study search, screening and extraction of data under the guidance of RM. LHA and BK will provide methodological expertise for this review. SS, LG, WS, MS and GDH will provide content expertise for this review and all authors will provide comments on the final manuscript before publication. JP will be the guarantor of this review.

  • Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. The Vaccines for Africa Initiative (VACFA) has funded the costs associated with the research and dissemination of the results, including publications.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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