== Demographic and clinical characteristics of the 41 published (Sep 2000 Aug 2008) NSF patients with concomitant liver disease. The lone NSF patient in the medical literature with concomitant liver disease and mild-moderate renal insufficiency. Liver disease etiology: EtOH = Alcoholic liver disease; HBV = Hepatitis B viral infection; HCV = Hepatitis C viral infection, PBC= Primary biliary cirrhosis. Renal disease etiology: ARF= Acute renal failure; CSA toxicity = Nuciferine Cyclosporine toxicity; DM = diabetes mellitus; FSGS= Focal segmental slomerulosclerosis; GN= Glomerulonephritis; HRS = Hepatorenal syndrome; HTN = Hypertension; MPGN= Membranoproliferative glomerulonephritis; RF= Renal failure. LT= Liver transplant; HD= Hemodialysis; PD= Peritoneal dialysis; RT= Renal transplant; ?= NOX1 Uncertain. == NSF Patients with Liver Disease and Concomitant Severe Renal Insufficiency == Among the 35 patients with liver disease and known renal status, 34 had severe renal insufficiency. containing case descriptions on 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/1.73m2or 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 peri-liver transplantation. The published medical literature demonstrates that patients with liver disease who develop NSF also have severe renal insufficiency, suggesting Nuciferine that liver disease does not confer a risk for NSF beyond that of the underlying renal insufficiency. Keywords:Nephrogenic systemic fibrosis, NSF, Nephrogenic fibrosing dermopathy, Dialysis-associated systemic fibrosis, Liver disease == INTRODUCTION == Initially recognized in 1997 and later published as a case series of 15 patients in 2000, Cowper et al. described a novel scleromyxedema-like dermatologic condition in patients with severe renal insufficiency that eventually came to be known asnephrogenic fibrosing dermopathy(1). Subsequent autopsy studies demonstrated more widespread fibrosis, involving the diaphragm, renal tubules, rete testes, psoas muscle, myocardium, and dura mater, ultimately yielding the more inclusive diagnostic termnephrogenic systemic fibrosis(NSF) (23). The principle manifestation, however, remains cutaneous, marked by plaque-like induration, thickening, and hyperpigmentation of the skin of the extremities and trunk, with facial sparing and lack of paraproteinemia. Progressive disease may result in joint contractures, limited range-of-motion, severe disability, and death. Similar to its clinical description, the understanding of NSF causation has also become increasingly refined. In 2006, two retrospective case series detailing 18 combined patients suggested a robust association between the administration of gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI) or angiography (MRA) and the development of NSF in patients with renal disease (45). Since then, the vast majority of published case reports have found a Nuciferine consistent association of NSF with GBCA exposure (6). Due to mounting evidence, the United States Food and Drug Administration (FDA) released a public health advisory cautioning against the use of GBCAs in patients with kidney failure (defined as either requiring dialysis or having a glomerular filtration rate [GFR] < 15 mL/min/1.73m2) in June 2006 (7). Subsequently, in May 2007, the FDA ordered a black box warning added to the labeling of GBCAs, expanding the prior advisory to include those patients with acute or chronic severe renal insufficiency (GFR < 30 mL/min/1.73m2), or acute renal insufficiencyof any severitydue to the hepato-renal syndrome or in the perioperative liver transplantation period (8). This expanded warning has two major implications: 1) liver disease confers a risk of NSF beyond that associated with renal insufficiency alone, and 2) liver patients with only mild or moderate renal insufficiency (non-dialysis patients with GFR 31 mL/min/1.73m2) are also at risk for NSF. Taken together, these assertions greatly increase the number of patients considered at risk for developing NSF and introduce a new set of patients those with liver disease to closer scrutiny. In clinical practice, GBCA-enhanced MR plays a crucial role in monitoring for hepatocellular carcinoma in the pre-transplantation period, mapping of the vasculature prior to transplantation, and diagnosing post-operative transplantation complications. Limiting its use, therefore, may have deleterious consequences to the care of these tenuous patients. Despite the implications of this expanded warning, the risk of NSF in patients with liver disease is not well known beyond anecdotal descriptions in some case reports and case series. Accordingly, in this paper, we systematically review the English medical literature of all published cases of.