Nephrogenic systemic fibrosis in liver disease: a systematic review

Abstract

Nephrogenic systemic fibrosis (NSF) may develop in patients with liver disease, a fact highlighted by Food and Drug Administration (FDA) announcements cautioning against the use of gadolinium-based contrast agents (GBCAs) in select liver disease patients. The purpose of this systematic literature review is to characterize the risk of NSF in patients with liver disease. All published articles on NSF from September 2000 through August 2008, were identified via PubMed searches and examination of articles' reference lists. Two reviewers independently read each article and identified unique patients with biopsy-proven or suspected NSF. Data on demographics, liver status, renal status, and GBCA exposure were collected. A total of 324 articles were reviewed, with 108 articles containing case descriptions of 335 unique NSF patients. After excluding the 95/335 (28%) patients in whom the presence or absence of liver disease was uncertain, liver disease was confirmed present in 41/239 (17%) patients. Renal insufficiency could be assessed in 35 of the liver disease patients; severe renal insufficiency, defined as a glomerular filtration rate (GFR) or estimated GFR (eGFR) <30 mL/min/1.73 m(2) or dialysis requirement, was present in 34/35 (97%) patients. The lone patient who developed NSF with mild/moderate renal insufficiency was atypical and received a total gadodiamide load of 0.76 mmol/kg over a 10-week period periliver transplantation. The published medical literature demonstrates that patients with liver disease who develop NSF also have severe renal insufficiency, suggesting that liver disease does not confer a risk for NSF beyond that of the underlying renal insufficiency. J. Magn. Reson. Imaging 2009;30:1313-1322. (c) 2009 Wiley-Liss, Inc.

Fig. 1. Characterization of NSF in the medical literature relative to concomitant liver disease and renal insufficiency

Mild/Mod = mild/moderate renal insufficiency

Fig. 2

Fig. 2A. Etiologies of liver disease in the 41 NSF patients with concomitant liver disease. HBV = hepatitis B viral infection, HCV = hepatitis C viral infection, EtOH = alcoholic liver disease. ^* α1-antitrypsin deficiency, hemochromatosis, amiodarone hepatotoxicity, primary biliary cirrhosis, “biliary disease,” and HELLP syndrome. Fig. 2B. Etiologies of renal disease in the 41 NSF patients with concomitant liver disease. HRS = hepatorenal syndrome, Glomerular Dz = glomerular disease, CSA toxicity = cyclosporine toxicity, HTN = hypertension, DM = diabetes mellitus. ^†Interstitial nephritis, polycystic kidney disease, and post-partum eclampsia.