Evaluation of Liver Fibrosis Using Texture Analysis on Combined-Contrast-Enhanced Magnetic Resonance Images at 3.0T.

PURPOSE: To noninvasively assess liver fibrosis using combined-contrast-enhanced (CCE) magnetic resonance imaging (MRI) and texture analysis. MATERIALS AND METHODS: In this IRB-approved, HIPAA-compliant prospective study, 46 adults with newly diagnosed HCV infection and recent liver biopsy underwent CCE liver MRI following intravenous administration of superparamagnetic iron oxides (ferumoxides) and gadolinium DTPA (gadopentetate dimeglumine). The image texture of the liver was quantified in regions-of-interest by calculating 165 texture features. Liver biopsy specimens were stained with Masson trichrome and assessed qualitatively (METAVIR fibrosis score) and quantitatively (% collagen stained area). Using L 1 regularization path algorithm, two texture-based multivariate linear models were constructed, one for quantitative and the other for quantitative histology prediction. The prediction performance of each model was assessed using receiver operating characteristics (ROC) and correlation analyses. RESULTS: The texture-based predicted fibrosis score significantly correlated with qualitative (r = 0.698, P < 0.001) and quantitative (r = 0.757, P < 0.001) histology. The prediction model for qualitative histology had 0.814-0.976 areas under the curve (AUC), 0.659-1.000 sensitivity, 0.778-0.930 specificity, and 0.674-0.935 accuracy, depending on the binary classification threshold. The prediction model for quantitative histology had 0.742-0.950 AUC, 0.688-1.000 sensitivity, 0.679-0.857 specificity, and 0.696-0.848 accuracy, depending on the binary classification threshold. CONCLUSION: CCE MRI and texture analysis may permit noninvasive assessment of liver fibrosis.

Risk of nephrogenic systemic fibrosis is low in patients with chronic liver disease exposed to gadolinium-based contrast agents.

PURPOSE: To determine the risk of nephrogenic systemic fibrosis (NSF) in a cohort of patients with chronic liver disease. MATERIALS AND METHODS: This retrospective, Institutional Review Board (IRB)-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant study was performed at a single tertiary liver center. The study cohort comprised 1167 patients with chronic liver disease followed in a liver clinic and exposed to gadolinium-based contrast agents (GBCAs) between February 2004 and October 2007. A retrospective review of medical records was performed. For each patient, data were collected on demographics, history of GBCA exposure, presence of purported risk factors for NSF, and histopathological evidence of NSF. RESULTS: Of the 1167 patients with chronic liver disease, 58% (n = 678) had cirrhosis. The patients had a total of 2421 separate GBCA exposures. Fifty-five percent (n = 646) had a single exposure, 19% (n = 218) had two exposures, and 26% (n = 303) had three or more exposures. Seventy-two percent (n = 843) of patients had renal insufficiency, 25 patients (2.1%) had hepatorenal syndrome, 80 patients (6.8%) were in the perioperative liver transplant period, and 49 patients (4.2%) had one or more additional risk factors for NSF. None of the 1167 patients developed NSF. CONCLUSION: Chronic liver disease does not appear to be a significant risk factor for NSF.

Hepatocellular carcinoma screening rates vary by etiology of cirrhosis and involvement of gastrointestinal sub-specialists.

BACKGROUND: Regular screening of cirrhotic patients for hepatocellular carcinoma (HCC) has been suboptimal, but there is little data regarding specific risk factors for reduced screening. METHODS: From 1996 to 2010, patients with cirrhosis were retrospectively identified from outpatient gastroenterology and primary care practices. Data was obtained from the diagnosis of cirrhosis until the time of elevated alpha-fetoprotein (AFP) or lesion suspicious for HCC, death, liver transplantation, or end of the data collection period. Recommended screening was defined as abdominal imaging (ultrasound, contrast-enhanced CT, or MRI) with or without serum alpha-fetoprotein (AFP) at least once every 12 months based on professional guidelines. RESULTS: One hundred fifty-six patients with cirrhosis were identified. The etiologies of cirrhosis were viral hepatitis (n = 65), alcohol (n = 40), non-alcoholic steatohepatitis (NASH) (n = 27), and non-viral, non-alcoholic, non-NASH cirrhosis (n = 24). Of the 156 patients, 51% received recommended screening for HCC. Patients with NASH cirrhosis received recommended screening significantly less (p = 0.016) than cirrhotics with viral hepatitis, alcoholic cirrhosis, or non-viral, non-alcoholic, non-NASH cirrhosis and were less likely to receive gastroenterology referral (p < 0.001). Additionally, 20 patients were diagnosed with cirrhosis incidentally during a surgical procedure. These patients were significantly less likely to receive recommended HCC screening than those diagnosed non-surgically (10.0 vs. 56.6%; p < 0.001). Screening was significantly more likely to occur in patients seen regularly by a gastrointestinal subspecialist (66.7 vs. 22.8%; p < 0.001). CONCLUSIONS: Patients with NASH cirrhosis and incidentally discovered cirrhosis have low rates of HCC screening and are referred less often to gastroenterologists. These data suggest a need for increased education about NASH cirrhosis and better systems of communication among general practitioners, surgeons, and gastroenterologists.

MR imaging of liver fibrosis: current state of the art.

Chronic liver disease is a major public health problem worldwide. Liver fibrosis, a common feature of almost all causes of chronic liver disease, involves the accumulation of collagen, proteoglycans, and other macromolecules within the extracellular matrix. Fibrosis tends to progress, leading to hepatic dysfunction, portal hypertension, and ultimately cirrhosis. Liver biopsy, the standard of reference for diagnosing liver fibrosis, is invasive, costly, and subject to complications and sampling variability. These limitations make it unsuitable for diagnosis and longitudinal monitoring in the general population. Thus, development of a noninvasive, accurate, and reproducible test for diagnosis and monitoring of liver fibrosis would be of great value. Conventional cross-sectional imaging techniques have limited capability to demonstrate liver fibrosis. In clinical practice, imaging studies are usually reserved for evaluation of the presence of portal hypertension or hepatocellular carcinoma in cases that have progressed to cirrhosis. In response to the rising prevalence of chronic liver diseases in Western nations, a number of imaging-based methods including ultrasonography-based transient elastography, computed tomography-based texture analysis, and diverse magnetic resonance (MR) imaging-based techniques have been proposed for noninvasive diagnosis and grading of hepatic fibrosis across its entire spectrum of severity. State-of-the-art MR imaging-based techniques in current practice and in development for noninvasive assessment of liver fibrosis include conventional contrast material-enhanced MR imaging, double contrast-enhanced MR imaging, MR elastography, diffusion-weighted imaging, and MR perfusion imaging.

Nephrogenic systemic fibrosis in liver disease: a systematic review.

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.

Noninvasive assessment of hepatic steatosis.

Hepatic steatosis, the accumulation of lipids within hepatocytes, is a common condition. The prevalence of its most frequent manifestation, nonalcoholic fatty liver disease (NAFLD), has been estimated to be as high as 35% in some populations. Currently, liver biopsy is the gold standard for the diagnosis and assessment of severity of hepatic steatosis, staging of fibrosis, and is the only modality able to differentiate bland steatosis from steatohepatitis. However, its invasiveness, significant side effect profile, and susceptibility to sampling error ultimately make it a suboptimal tool. Accordingly, focus has been placed on noninvasive radiologic techniques for hepatic fat detection and quantification. The rationale, performance characteristics, and limitations of traditional noninvasive measures, including ultrasound, computed tomography, and magnetic resonance (MR) spectroscopy and imaging, are reviewed. A novel MR method, the spectrally modeled relaxation-invariant technique, overcomes the inherent weaknesses of conventional MR to diagnose and quantify hepatic steatosis over its entire range of severity. Noninvasive radiologic techniques, particularly MR, can be applied broadly, including in the diagnosis of NAFLD in asymptomatic patients with elevated serum aminotransferase levels, longitudinal monitoring of disease progression or response to treatment, population-based epidemiologic or observational studies, and drug discovery.

Hemodynamic evaluation before liver transplantation: insights into the portal hypertensive syndrome.

The cardiac hemodynamics of patients awaiting liver transplantation is complex. Coronary atherosclerosis, a hyperdynamic circulatory state and cirrhotic cardiomyopathy are present to a variable degree in this population. In this contribution to the Symposium on Portal Hypertension, we expand on our published experience with coronary angiography and cardiac hemodynamics at the time of evaluation of candidacy for liver transplantation in a cohort of 161 patients. Although we confirmed the relation of systemic hemodynamics with the degree of liver failure, we noted a higher prevalence of high output heart failure, defined as an increased left ventricular end-diastolic pressure in the setting of an elevated cardiac output, most notably in patients classified as Child C. Most patients with high pulmonary artery pressure also exhibited evidence of elevated left ventricle filling pressures. A low systemic vascular resistance, a marker of arterial vasodilatation, was similar in the presence of atherosclerosis, a condition where impaired vasorelaxation occurs as a result of endothelial dysfunction. The high prevalence of coronary artery disease in this series supports the observations that atherosclerosis is a major issue in the current population with cirrhosis awaiting liver transplantation. A lower sensitivity of noninvasive screening tools for the detection of coronary atherosclerosis is likely the result of the interaction of the hyperdynamic circulation with the performance of these tests.