Observational Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 28, 2016; 8(36): 1623-1628
Published online Dec 28, 2016. doi: 10.4254/wjh.v8.i36.1623
Prevalence of significant liver disease in human immunodeficiency virus-infected patients exposed to Didanosine: A cross sectional study
Sarah Logan, Alison Rodger, Laura Maynard-Smith, James O’Beirne, Thomas Fernandez, Filippo Ferro, Colette Smith, Sanjay Bhagani
Sarah Logan, Alison Rodger, Laura Maynard-Smith, Thomas Fernandez, Filippo Ferro, Sanjay Bhagani, the Ian Charleson Day Centre, Ground Floor, Royal Free London NHS Foundation Trust, London NW3 2PF, United Kingdom
Alison Rodger, Colette Smith, Research Department of Infection and Population Health, University College London, London NW3 2PF, United Kingdom
James O’Beirne, Department of Hepatology, Nambour General Hospital, Sunshine Coast Hospital and Health Service, Nambour, Queensland 4560, Australia
Author contributions: Logan S, Rodger A, O’Beirne J, Smith C and Bhagani S contributed to study conception and design; Logan S, Maynard-Smith L, Fernandez T and Ferro F contributed to data acquisition; Logan S, Rodger A, Smith C and Bhagani S analysed and interpreted the data; Logan S and Rodger A wrote the article; O’Beirne J and Bhagani S contributed to editing reviewing; all authors gave final approval of the manuscript.
Supported by The British HIV Association Research Award 2009-£7800 in total awarded.
Institutional review board statement: The study was reviewed and approved by the NHS/HSC Research Ethics Committee in North West London. The reference number is 10/H0720/54.
Informed consent statement: All study participants provided their informed consent in writing prior to study enrollment.
Conflict-of-interest statement: None of the authors has any conflict of interest to declare.
Data sharing statement: In order to avoid deductive disclosure of confidential information in patents with HIV, individual level patient data will not be available. Please contact the authors directly if you wish to discuss access to the data.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Sanjay Bhagani, Consultant in Infectious Diseases and HIV Medicine, the Ian Charleson Day Centre, Ground Floor, Royal Free London NHS Foundation Trust, Rowland Hill Street, London NW3 2PF, United Kingdom. s.bhagani@nhs.net
Telephone: +44-207-7940500 Fax: +44-207-4726558
Received: June 30, 2016
Peer-review started: July 3, 2016
First decision: August 5, 2016
Revised: September 16, 2016
Accepted: November 1, 2016
Article in press: November 2, 2016
Published online: December 28, 2016

To identify significant liver disease [including nodular regenerative hyperplasia (NRH)] in asymptomatic Didanosine (DDI) exposed human immunodeficiency virus (HIV) positive patients.


Patients without known liver disease and with > 6 mo previous DDI use had liver stiffness assessed by transient elastography (TE). Those with alanine transaminase (ALT) above upper limit normal and/or TE > 7.65 kPa underwent ultrasound scan (U/S). Patients with: (1) abnormal U/S; or (2) elevated ALT plus TE > 7.65 kPa; or (3) TE > 9.4 kPa were offered trans-jugular liver biopsy (TJLB) with hepatic venous pressure gradient (HVPG) assessment.


Ninety-nine patients were recruited, median age 50 years (range 31-70), 81% male and 70% men who have sex with men. Ninety-five percent with VL < 50 copies on antiretroviral therapy with median CD4 count 639 IU/L. Median DDI exposure was 3.4 years (range 0.5-14.6). Eighty-one had a valid TE readings (interquartile range/score ratio < 0.3): 71 (88%) < 7.65 kPa, 6 (7%) 7.65-9.4 kPa and 4 (6%) > 9.4 kPa. Seventeen (17%) met criteria for TJLB, of whom 12 accepted. All had HVPG < 6 mmHg. Commonest histological findings were steatosis (n = 6), normal architecture (n = 4) and NRH (n = 2), giving a prevalence of previously undiagnosed NRH of 2% (95%CI: 0.55%, 7.0%).


A screening strategy based on TE, liver enzymes and U/S scan found a low prevalence of previously undiagnosed NRH in DDI exposed, asymptomatic HIV positive patients. Patients were more likely to have steatosis highlighting the increased risk of multifactorial liver disease in this population.

Keywords: Nodular regenerative hyperplasia, Human immunodeficiency virus, Steatosis, Non-cirrhotic portal hypertension, Didanosine

Core tip: Human immunodeficiency virus positive patients are at increased risk of liver disease. The aetiology is often multifactorial and includes exposure to antiretroviral therapy. We used a simple screening strategy based on transient elastography, liver enzymes and ultrasound scan to identify that 2% of asymptomatic patients exposed to Didanosine in a clinical cohort had undiagnosed nodular regenerative hyperplasia. A further 6% had undiagnosed steatosis. Implementation of a screening strategy enables identification of liver disease and initiation of earlier targeted interventions in this high-risk group.