To assess the technical success rate and diagnostic performance of liver magnetic resonance (MR) elastography.
This retrospective study was approved by the institutional review board with patient ...informed consent. A total of 1377 consecutive MR elastography examinations performed between 2007 and 2010 in 1287 patients for clinical indications were included. Medical records were used to retrieve liver stiffness as assessed with MR elastography, histologic analysis, blood work, and other liver disease-related information. Nonparametric Kruskal-Wallis tests and analysis of covariance methods were used to evaluate the diagnostic values and relationships of the collected data.
Hepatic MR elastography had a success rate of 94.4% (1300 of 1377 cases) and yielded reproducible measurements (r = 0.9716, P < .0001) in the study cohort, with a complex patient profile and multiple interpreters. Body mass index had no significant effect on success rate (P = .2). In 289 patients who underwent liver biopsy within 1 year of the MR elastography date, mean liver stiffness as assessed with MR elastography was significantly higher in patients with advanced fibrosis (stages F3, F4) than in those with mild to moderate fibrosis (stages F0, F1, F2) (5.93 kPa ± 2.31 standard deviation vs 3.35 kPa ± 1.44, P < .0001). Liver stiffness is associated with many factors other than fibrosis extent, including cause of fibrosis (viral hepatitis C vs nonalcoholic fatty liver disease, P = .025), inflammation (severe vs mild to moderate, P = .03), and hepatic metabolic and synthetic function (no fibrosis vs intermediate fibrosis, P ≤ .01).
In a general clinical practice environment, hepatic MR elastography is a robust imaging method with a high success rate in a broad spectrum of patients. It also shows the complex association between liver stiffness and hepatic pathophysiology.
Drug-induced liver injury Leise, Michael D; Poterucha, John J; Talwalkar, Jayant A
Mayo Clinic proceedings
89, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Drug hepatoxicity can be nonidiosyncratic (predictable), as in the case of acetaminophen, or idiosyncratic (unpredictable). This review article focuses primarily on idiosyncratic drug-induced liver ...injury (DILI). New epidemiologic data suggest that approximately 20 new cases of DILI per 100,000 persons occur each year. Idiosyncratic DILI accounts for 11% of the cases of acute liver failure in the United States. Risk factors for DILI include medication dose, drug lipophilicity, and extent of hepatic metabolism. There is mixed evidence to support the role of host factors such as age, sex, and chronic liver disease in the development of DILI. For specific drugs, a genetic predisposition appears to be a risk factor for DILI. Suspected cases of idiosyncratic DILI should be categorized as hepatitic, cholestatic, or mixed on the basis of the degree/ratio of abnormalities in the alanine aminotransferase and alkaline phosphatase. A careful evaluation for other causes of liver disease should be performed, though a liver biopsy is rarely needed. There is evidence that some patients with DILI may actually have hepatitis E and this diagnosis should be considered. Amoxicillin/clavulanate isoniazid, and nonsteroidal anti-inflammatory drugs are among the most common causes of DILI. Drug discontinuation or dechallenge should lead to an improvement in liver biochemistries in most patients, though a bilirubin value of more than 3 g/dL is associated with mortality of at least 10%. New biomarkers for DILI using proteomics and micro RNA appear promising but require further study. New studies on drugs with potential for causing DILI are reviewed herein, including tumor necrosis factor-alpha antagonists, fluoroquinolones, tyrosine kinase inhibitors, statins, and supplements. PubMed was used with search terms of drug induced liver injury OR DILI with filter settings of "English language" and "humans" and custom date range of "January 1, 2000." The authors also manually searched bibliographies from key references and included seminal references before the year 2000.
Primary sclerosing cholangitis (PSC) is a chronic immune-mediated disease of the liver of unclear etiology, characterized by chronic inflammation and fibrosis of bile ducts. It primarily affects ...middle-aged men and is associated with 4-fold increased mortality as compared with an age- and sex-matched population. Progressive biliary and hepatic damage results in portal hypertension and hepatic failure in a significant majority of patients over a 10- to 15-year period from the initial diagnosis. In addition, PSC confers a markedly increased risk of hepatobiliary cancer, including cholangiocarcinoma and gallbladder cancer, as compared with the general population, and cancer is the leading cause of mortality in patients with PSC. It is associated with inflammatory bowel disease in 70% of patients and increases the risk of colorectal cancer almost 10-fold. Despite significant research efforts in this field, the pathogenic mechanisms of PSC are still incompletely understood, although growing evidence supports the role of genetic and immunologic factors. There are no proven medical therapies that alter the natural course of the disease. Thus, liver transplantation is the only available treatment for patients with advanced PSC, with excellent outcomes in this population.
Primary sclerosing cholangitis (PSC), first described in the mid-1850s, is a complex liver disease that is heterogeneous in its presentation. PSC is characterized by chronic cholestasis associated ...with chronic inflammation of the biliary epithelium, resulting in multifocal bile duct strictures that can affect the entire biliary tree. Chronic inflammation leads to fibrosis involving the hepatic parenchyma and biliary tree, which can lead to cirrhosis and malignancy. The etiology of PSC is not fully understood, which in part explains the lack of effective medical therapy for this condition. However, we have begun to better understand the molecular pathogenesis of PSC. The recognition of specific clinical subtypes and their pattern of progression could improve phenotypic and genotypic classification of the disease. We review our current understanding of this enigmatic disorder and discuss important topics for future studies.
Magnetic resonance elastography (MRE) is a noninvasive tool for staging liver fibrosis. We conducted a meta-analysis of individual participant data collected from published studies to assess the ...diagnostic accuracy of MRE for staging liver fibrosis in patients with chronic liver diseases (CLD).
Through a systematic literature search of multiple databases (2003-2013), we identified studies on diagnostic performance of MRE for staging liver fibrosis in patients with CLD with native anatomy, using liver biopsy as the standard. We contacted study authors to collect data on each participant's age, sex, body mass index (BMI), liver stiffness (measured by MRE), fibrosis stage, staging system used, degree of inflammation, etiology of CLD, and interval between MRE and biopsy. Through a pooled analysis, we calculated cluster-adjusted area under the receiver-operating curve, sensitivity, and specificity of MRE for any fibrosis (≥stage 1), significant fibrosis (≥stage 2), advanced fibrosis (≥stage 3), and cirrhosis (stage 4).
We analyzed data from 12 retrospective studies, comprising 697 patients (mean age, 55 ± 13 y; 59.4% male; mean BMI, 26.9 ± 6.7 kg/m(2); 92.1% with <1 year interval between MRE and biopsy; and 47.1% with hepatitis C). Overall, 19.5%, 19.4%, 15.5%, 15.9%, and 29.7% patients had stage 0, 1, 2, 3, and 4 fibrosis, respectively. The mean area under the receiver-operating curve values (and 95% confidence intervals) for the diagnosis of any (≥stage 1), significant (≥stage 2), advanced fibrosis (≥stage 3), and cirrhosis, were as follows: 0.84 (0.76-0.92), 0.88 (0.84-0.91), 0.93 (0.90-0.95), and 0.92 (0.90-0.94), respectively. A similar diagnostic performance was observed in stratified analysis based on sex, obesity, and etiology of CLD. The overall rate of failure of MRE was 4.3%.
Based on a pooled analysis of data from individual participants, MRE has a high accuracy for the diagnosis of significant or advanced fibrosis and cirrhosis, independent of BMI and etiology of CLD. Prospective studies are warranted to better understand the diagnostic performance of MRE.
Drug‐induced liver injury (DILI) is considered to be a diagnosis of exclusion. Liver biopsy may contribute to diagnostic accuracy, but the histological features of DILI and their relationship to ...biochemical parameters and outcomes are not well defined. We have classified the pathological pattern of liver injury and systematically evaluated histological changes in liver biopsies obtained from 249 patients with suspected DILI enrolled in the prospective, observational study conducted by the Drug Induced Liver Injury Network. Histological features were analyzed for their frequency within different clinical phenotypes of liver injury and to identify associations between clinical and laboratory findings and histological features. The most common histological patterns were acute (21%) and chronic hepatitis (14%), acute (9%) and chronic cholestasis (10%), and cholestatic hepatitis (29%). Liver histology from 128 patients presenting with hepatocellular injury had more severe inflammation, necrosis, and apoptosis and more frequently demonstrated lobular disarray, rosette formation, and hemorrhage than those with cholestasis. Conversely, histology of the 73 patients with cholestatic injury more often demonstrated bile plugs and duct paucity. Severe or fatal hepatic injury in 46 patients was associated with higher degrees of necrosis, fibrosis stage, microvesicular steatosis, and ductular reaction among other findings, whereas eosinophils and granulomas were found more often in those with milder injury. Conclusion: We describe an approach for evaluating liver histology in DILI and demonstrate numerous associations between pathological findings and clinical presentations that may serve as a foundation for future studies correlating DILI pathology with its causality and outcome. (Hepatology 2014;59:661–670)
Objectives
We conducted an individual participant data (IPD) pooled analysis on diagnostic accuracy of MRE to detect fibrosis stage in patients with non-alcoholic fatty liver disease (NAFLD).
Methods
...Through a systematic literature search, we identified studies of MRE (at 60–62.5 Hz) for staging fibrosis in patients with NAFLD, using liver biopsy as gold standard, and contacted study authors for IPD. Through pooled analysis, we calculated the cluster-adjusted AUROC, sensitivity and specificity of MRE for any (≥stage 1), significant (≥stage 2) and advanced (≥stage 3) fibrosis and cirrhosis (stage 4).
Results
We included nine studies with 232 patients with NAFLD (mean age, 51 ± 13 years; 37.5 % males; mean BMI, 33.5 ± 6.7 kg/m
2
; interval between MRE and biopsy <1 year, 98.3 %). Fibrosis stage distribution (stage 0/1/2/3/4) was 33.6, 32.3, 10.8, 12.9 and 10.4 %, respectively. Mean AUROC (and 95 % CIs) for diagnosis of any, significant or advanced fibrosis and cirrhosis was 0.86 (0.82–0.90), 0.87 (0.82–0.93), 0.90 (0.84–0.94) and 0.91 (0.76–0.95), respectively. Similar diagnostic performance was observed in stratified analysis based on sex, obesity and degree of inflammation.
Conclusions
MRE has high diagnostic accuracy for detection of fibrosis in NAFLD, independent of BMI and degree of inflammation.
Key points
•
MRE has high diagnostic accuracy for detection of fibrosis in NAFLD.
•
BMI does not significantly affect accuracy of MRE in NAFLD.
•
Inflammation had no significant influence on MRE performance in NAFLD for fibrosis.
The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing. The health care burden resulting from the multidisciplinary management of this complex disease is unknown. We assessed the ...total health care cost and resource utilization associated with a new NAFLD diagnosis, compared with controls with similar comorbidities. We used OptumLabs Data Warehouse, a large national administrative claims database with longitudinal health data of over 100 million individuals enrolled in private and Medicare Advantage health plans. We identified 152,064 adults with a first claim for NAFLD between 2010 and 2014, of which 108,420 were matched 1:1 by age, sex, metabolic comorbidities, length of follow‐up, year of diagnosis, race, geographic region, and insurance type to non‐NAFLD contemporary controls from the OptumLabs Data Warehouse database. Median follow‐up time was 2.6 (range 1‐6.5) years. The final study cohort consisted of 216,840 people with median age 55 (range 18‐86) years, 53% female, 78% white. The total annual cost of care per NAFLD patient with private insurance was $7,804 (interquartile range IQR $3,068‐$18,688) for a new diagnosis and $3,789 (IQR $1,176‐$10,539) for long‐term management. These costs are significantly higher than the total annual costs of $2,298 (IQR $681‐$6,580) per matched control with similar metabolic comorbidities but without NAFLD. The largest increases in health care utilization that may account for the increased costs in NAFLD compared with controls are represented by liver biopsies (relative risk RR = 55.00, 95% confidence interval CI 24.48‐123.59), imaging (RR = 3.95, 95% CI 3.77‐4.15), and hospitalizations (RR = 1.87, 95% CI 1.73‐2.02). Conclusion: The costs associated with the care for NAFLD independent of its metabolic comorbidities are very high, especially at first diagnosis. Research efforts shouldfocus on identification of underlying determinants of use, sources of excess cost, and development of cost‐effective diagnostic tests.
To evaluate the diagnostic accuracy of magnetic resonance (MR) elastography as a method to help diagnose clinically substantial fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) and, ...by using MR elastography as a reference standard, to compare various laboratory marker panels in the identification of patients with NAFLD and advanced fibrosis.
This retrospective study was institutional review board approved and HIPAA complaint. Informed consent was waived. This study was conducted in patients with NAFLD, who were identified by imaging characteristics consistent with steatosis in a prospective database that tracks all MR elastographic examinations. Six laboratory-based models of fibrosis were compared with MR elastographic results as well as fibrosis stage from liver biopsy results. The area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value, and negative predictive value of each data set were compared.
Among 325 patients with NAFLD with MR elastographic data, there were 142 patients who underwent liver biopsy within 1 year of MR elastography. When comparing MR elastography results with liver biopsy results, the best cutoff for advanced fibrosis (stage F3-F4, 46 32.4% of 142) was 4.15 kPa (AUROC = 0.954, sensitivity = 0.85, specificity = 0.929). This cutoff value identified 104 patients with advanced fibrosis (32.0% of 325 patients). The FIB-4 score (AUROC = 0.827) and NAFLD fibrosis score (AUROC = 0.821) had the best diagnostic accuracy for advanced fibrosis, with high negative predictive values (NAFLD fibrosis score = 0.90 and FIB-4 score = 0.899).
MR elastography is a useful diagnostic tool for detecting advanced fibrosis in NAFLD. Of the laboratory-based methods, the NAFLD fibrosis and FIB-4 scores can most reliably detect advanced fibrosis.
Purpose To evaluate the diagnostic performance and examination success rate of magnetic resonance (MR) elastography and vibration-controlled transient elastography (VCTE) in the detection of hepatic ...fibrosis in patients with severe to morbid obesity. Materials and Methods This prospective and HIPAA-compliant study was approved by the institutional review board. A total of 111 patients (71 women, 40 men) participated. Written informed consent was obtained from all patients. Patients underwent MR elastography with two readers and VCTE with three observers to acquire liver stiffness measurements for liver fibrosis assessment. The results were compared with those from liver biopsy. Each pathology specimen was evaluated by two hepatopathologists according to the METAVIR scoring system or Brunt classification when appropriate. All imaging observers were blinded to the biopsy results, and all hepatopathologists were blinded to the imaging results. Examination success rate, interobserver agreement, and diagnostic accuracy for fibrosis detection were assessed. Results In this obese patient population (mean body mass index = 40.3 kg/m
; 95% confidence interval CI: 38.7 kg/m
, 41.8 kg/m
), the examination success rate was 95.8% (92 of 96 patients) for MR elastography and 81.3% (78 of 96 patients) or 88.5% (85 of 96 patients) for VCTE. Interobserver agreement was higher with MR elastography than with biopsy (intraclass correlation coefficient, 0.95 vs 0.89). In patients with successful MR elastography and VCTE examinations (excluding unreliable VCTE examinations), both MR elastography and VCTE had excellent diagnostic accuracy in the detection of clinically significant hepatic fibrosis (stage F2-F4) (mean area under the curve: 0.93 95% CI: 0.85, 0.97 vs 0.91 95% CI: 0.83, 0.96; P = .551). Conclusion In this obese patient population, both MR elastography and VCTE had excellent diagnostic performance for assessing hepatic fibrosis; MR elastography was more technically reliable than VCTE and had a higher interobserver agreement than liver biopsy.
RSNA, 2016 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on January 25, 2017.
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