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      Use of Liver Imaging and Biopsy in Clinical Practice

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      New England Journal of Medicine

      New England Journal of Medicine (NEJM/MMS)

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          Most cited references 77

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          Management of hepatocellular carcinoma: An update

          Since the publication of the American Association for the Study of Liver Diseases (AASLD) practice guidelines on the management of hepatocellular carcinoma (HCC) in 2005, new information has emerged that requires that the guidelines be updated. The full version of the new guidelines is available on the AASLD Web site at http://www.aasld.org/practiceguidelines/Documents/Bookmarked%20Practice%20Guidelines/HCCUpdate2010.pdf. Here, we briefly describe only new or changed recommendations. Surveillance and Diagnosis In the previous guideline, groups were specified for which surveillance was likely to be cost-effective because the hepatocellular carcinoma (HCC) incidence was high enough. New data on defining HCC risk have emerged for hepatitis B virus,1,2 hepatitis C virus,3 and autoimmune hepatitis.4 Surveillance is deemed cost-effective if the expected HCC risk exceeds 1.5% per year in patients with hepatitis C and 0.2% per year in patients with hepatitis B. Analysis of recent studies show that alpha-fetoprotein determination lacks adequate sensitivity and specificity for effective surveillance (and for diagnosis).5,6 Thus, surveillance has to be based on ultrasound examination. The recommended screening interval is 6 months. Diagnosis of HCC should be based on imaging techniques and/or biopsy.The 2005 diagnostic algorithm has been validated and the diagnostic accuracy of a single dynamic technique showing intense arterial uptake followed by “washout” of contrast in the venous-delayed phases has been demonstrated.7-9 Contrast-enhanced US may offer false positive HCC diagnosis in patients with cholangiocarcinoma and thus, has been dropped from the diagnostic techniques. The diagnostic algorithm is shown in Fig. 1. The application of dynamic imaging criteria should be applied only to patients with cirrhosis of any etiology and to patients with chronic hepatitis B who may not have fully developed cirrhosis or have regressed cirrhosis. Interpretation of biopsies and distinction between high-grade dysplatic nodules and HCC is challenging. Expert pathology diagnosis is reinforced by staining for glypican 3, heat shock protein 70, and glutamine synthetase, because positivity for two of these three stains confirms HCC.10 Fig. 1 Diagnostic algorithm for suspected HCC. CT, computed tomography; MDCT, multidetector CT; MRI, magnetic resonance imaging; US, ultrasound. Staging and Treatment of HCC The BCLC staging system (Fig. 2)11 has come to be widely accepted in clinical practice and is also being used for many clinical trials of new drugs to treat HCC. Therefore, it has become the de facto staging system that is used. Fig. 2 The BCLC staging system for HCC. M, metastasis classification; N, node classification; PS, performance status; RFA, radiofrequency ablation; TACE, transarterial chemoembolization. The recommendations for liver transplantation have not changed. No new data have emerged that can be used to define a new limit for expanding the patient selection criteria. The usefulness of portal pressure measurement to predict the outcome of patients and define optimal candidates for resection has been validated in Japan.12 Thus, resection should remain the first option for patients who have the optimal profile, as defined by the BCLC staging system. Although resection can be performed in some of these patients with advanced liver disease, the mortality is higher and they might be better served by liver transplantation or ablation. A cohort study of radiofrequency ablation demonstrated that complete ablation of lesions smaller than 2 cm is possible in more than 90% of cases, with a local recurrence rate of less than 1%.13 These data should be confirmed by other groups before positioning ablation as the first-line approach for very early HCC. The recommendations regarding patient selection and method of administration of chemoembolization are unchanged. Radioembolization, i.e., the intra-arterial injection of yttrium-90 bound to glass beads or to resin, has been shown to induce tumor necrosis, but there are no data comparing its efficacy to transarterial chemoembolization or to sorafenib treatment for those with portal vein invasion. However, for patients who have either failed transarterial chemoembolization or who present with more advanced HCC, new data indicates the efficacy of sorafenib (a multikinase inhibitor with activity against Raf-1, B-Raf, vascular endothelial growth factor receptor 2, platelet-derived growth factor receptor, c-Kit receptors, among other kinases) in prolonging life.14,15 Sorafenib induces a clinically relevant improvement in time to progression and in survival The magnitude of the improvement in survival compares with other established molecular targeted therapies for other advanced cancers, and the associated toxicity is easily managed without treatment-related mortality. The most frequent adverse events were diarrhea (sorafenib versus placebo: 11% versus 2%) and hand–foot skin reaction (sorafenib versus placebo: 8% versus <1%), fatigue, and weight loss. Sorafenib is now considered first-line treatment in patients with HCC who can no longer be treated with potentially more effective therapies. In summary, in the past decade HCC has gone from being an almost universal death sentence to a cancer that can be prevented, detected at an early stage, and effectively treated. Physicians caring for patients at risk need to provide high-quality screening, proper management of screen-detected lesions, and provision of therapy that is most appropriate for the stage of disease.
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            Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions.

            Steatohepatitis is a morphological pattern of liver injury that may be seen in alcoholic or nonalcoholic liver disease. This pattern may occur with obesity, diabetes, the use of certain drugs, or the cause may be idiopathic. The well-recognized histopathological features of nonalcoholic steatohepatitis (NASH) include hepatocellular steatosis and ballooning, mixed acute and chronic lobular inflammation, and zone 3 perisinusoidal fibrosis. Currently, there are no systems for grading necroinflammatory activity or for staging fibrosis as exist for various other forms of chronic liver disease. The purpose of this study was to develop such a grading and staging system and was based on review of liver biopsies from 51 patients with nonalcoholic steatohepatitis from Saint Louis University Health Sciences Center. For determination of grade, 10 histological variables of activity were initially analyzed; an overall impression of mild, moderate, and severe was made and the variables considered to be most significant were used to develop the necroinflammatory grade. The histological lesions considered to be significant were: steatosis, ballooning, and intra-acinar and portal inflammation. A staging score was developed to reflect both location and extent of fibrosis. The fibrosis score was derived from the extent of zone 3 perisinusoidal fibrosis with possible additional portal/periportal fibrosis and architectural remodeling. Fibrosis stages are as follows: Stage 1, zone 3 perisinusoidal fibrosis; Stage 2, as above with portal fibrosis; Stage 3, as above with bridging fibrosis; and Stage 4, cirrhosis. We propose a grading and staging system that reflects the unique histological features of nonalcoholic steatohepatitis.
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              The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD.

              Patients with nonalcoholic fatty liver disease (NAFLD) and advanced liver fibrosis are at the highest risk for progressing to end-stage liver disease. We constructed and validated a scoring system consisting of routinely measured and readily available clinical and laboratory data to separate NAFLD patients with and without advanced fibrosis. A total of 733 patients with NAFLD confirmed by liver biopsy were divided into 2 groups to construct (n = 480) and validate (n = 253) a scoring system. Routine demographic, clinical, and laboratory variables were analyzed by multivariate modeling to predict presence or absence of advanced fibrosis. Age, hyperglycemia, body mass index, platelet count, albumin, and AST/ALT ratio were independent indicators of advanced liver fibrosis. A scoring system with these 6 variables had an area under the receiver operating characteristic curve of 0.88 and 0.82 in the estimation and validation groups, respectively. By applying the low cutoff score (-1.455), advanced fibrosis could be excluded with high accuracy (negative predictive value of 93% and 88% in the estimation and validation groups, respectively). By applying the high cutoff score (0.676), the presence of advanced fibrosis could be diagnosed with high accuracy (positive predictive value of 90% and 82% in the estimation and validation groups, respectively). By applying this model, a liver biopsy would have been avoided in 549 (75%) of the 733 patients, with correct prediction in 496 (90%). a simple scoring system accurately separates patients with NAFLD with and without advanced fibrosis, rendering liver biopsy for identification of advanced fibrosis unnecessary in a substantial proportion of patients.
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                Author and article information

                Journal
                New England Journal of Medicine
                N Engl J Med
                New England Journal of Medicine (NEJM/MMS)
                0028-4793
                1533-4406
                August 24 2017
                August 24 2017
                : 377
                : 8
                : 756-768
                Article
                10.1056/NEJMra1610570
                28834467
                © 2017
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