GTx (United States)

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&percnt;20Practice%20Guidelines/HCCUpdate2010.pdf. Here, we briefly describe only new or changed recommendations. AASLD, American Association for the Study of Liver Diseases; BCLC, Barcelona Clinic Liver Cancer; HCC, hepatocellular carcinoma. 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 Diagnostic algorithm for suspected HCC. CT, computed tomography; MDCT, multidetector CT; MRI, magnetic resonance imaging; US, ultrasound. 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. 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.

Udgivelsesdato: 2007-Jun

The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) follow the guidelines jointly issued by the two societies in 2003 and 2007 [1,2]. Publication of a new document 6 years after the previous one was felt to be timely because, over this period, important studies have been conducted and many new results&#13;\nhave been published on both the diagnosis and treatment of individuals with an elevated blood pressure (BP), making refinements, modifications and expansion of the previous recommendations necessary.

Abstract This study extends the developing body of literature on supply chain integration (SCI), which is the degree to which a manufacturer strategically collaborates with its supply chain partners and collaboratively manages intra‐ and inter‐organizational processes, in order to achieve effective and efficient flows of products and services, information, money and decisions, to provide maximum value to the customer. The previous research is inconsistent in its findings about the relationship between SCI and performance. We attribute this inconsistency to incomplete definitions of SCI, in particular, the tendency to focus on customer and supplier integration only, excluding the important central link of internal integration. We study the relationship between three dimensions of SCI, operational and business performance, from both a contingency and a configuration perspective. In applying the contingency approach, hierarchical regression was used to determine the impact of individual SCI dimensions (customer, supplier and internal integration) and their interactions on performance. In the configuration approach, cluster analysis was used to develop patterns of SCI, which were analyzed in terms of SCI strength and balance. Analysis of variance was used to examine the relationship between SCI pattern and performance. The findings of both the contingency and configuration approach indicated that SCI was related to both operational and business performance. Furthermore, the results indicated that internal and customer integration were more strongly related to improving performance than supplier integration.

Nonalcoholic steatohepatitis (NASH), the lynchpin between steatosis and cirrhosis in the spectrum of nonalcoholic fatty liver disorders (NAFLD), was barely recognized in 1981. NAFLD is now present in 17% to 33% of Americans, has a worldwide distribution, and parallels the frequency of central adiposity, obesity, insulin resistance, metabolic syndrome and type 2 diabetes. NASH could be present in one third of NAFLD cases. Age, activity of steatohepatitis, and established fibrosis predispose to cirrhosis, which has a 7- to 10-year liver-related mortality of 12% to 25%. Many cases of cryptogenic cirrhosis are likely endstage NASH. While endstage NAFLD currently accounts for 4% to 10% of liver transplants, this may soon rise. Pathogenic concepts for NAFLD/NASH must account for the strong links with overnutrition and underactivity, insulin resistance, and genetic factors. Lipotoxicity, oxidative stress, cytokines, and other proinflammatory mediators may each play a role in transition of steatosis to NASH. The present "gold standard" management of NASH is modest weight reduction, particularly correction of central obesity achieved by combining dietary measures with increased physical activity. Whether achieved by "lifestyle adjustment" or anti-obesity surgery, this improves insulin resistance and reverses steatosis, hepatocellular injury, inflammation, and fibrosis. The same potential for "unwinding" fibrotic NASH is indicated by studies of the peroxisome proliferation activator receptor (PPAR)-gamma agonist "glitazones," but these agents may improve liver disease at the expense of worsening obesity. Future challenges are to approach NAFLD as a preventive public health initiative and to motivate affected persons to adopt a healthier lifestyle.

Abstract Rising international cooperation, vertical disintegration, along with a focus on core activities have led to the notion that firms are links in a networked supply chain. This novel perspective has created the challenge of designing and managing a network of interdependent relationships developed and fostered through strategic collaboration. Although research interests in supply chain management (SCM) are growing, no research has been directed towards a systematic development of SCM instruments. This study identifies and consolidates various supply chain initiatives and factors to develop key SCM constructs conducive to advancing the field. To this end, we analyzed over 400 articles and synthesized the large, fragmented body of work dispersed across many disciplines. The result of this study, through successive stages of measurement analysis and refinement, is a set of reliable, valid, and unidimensional measurements that can be subsequently used in different contexts to refine or extend conceptualization and measurements or to test various theoretical models, paving the way for theory building in SCM.

Qualitative synthesis informs important aspects of evidence-based healthcare, particularly within the practical decision-making contexts that health professionals work in. Of the qualitative methodologies available for synthesis, meta-aggregation is most transparently aligned with accepted conventions for the conduct of high-quality systematic reviews. Meta-aggregation is philosophically grounded in pragmatism and transcendental phenomenology. The essential characteristics of a meta-aggregative review are that the reviewer avoids re-interpretation of included studies, but instead accurately and reliably presents the findings of the included studies as intended by the original authors. This study reports on the methodology and methods of meta-aggregation within the structure of an a priori protocol and standardized frameworks for reporting of results by over-viewing the essential components of a systematic review report.

UNLABELLED: To optimize the management of patients with chronic hepatitis C virus (HCV) infection, noninvasive tests to determine the degree of hepatic fibrosis have been developed. The aims of this study were (1) to validate a simple, inexpensive, noninvasive test called FIB-4, which combines standard biochemical values (platelets, ALT, AST) and age, in a series of 847 liver biopsies performed in HCV-monoinfected patients; and (2) to compare the results of 780 FIB-4 and FibroTests performed the same day in a series of 592 HCV-infected patients. The FIB-4 index enabled the correct identification of patients with severe fibrosis (F3-F4) and cirrhosis with an area under the receiver operating characteristic curve of 0.85 (95% CI 0.82-0.89) and 0.91 (95% CI 0.86-0.93), respectively. An FIB-4 index <1.45 had a negative predictive value of 94.7% to exclude severe fibrosis with a sensitivity of 74.3%. An FIB-4 index higher than 3.25 had a positive predictive value to confirm the existence of a significant fibrosis (F3-F4) of 82.1% with a specificity of 98.2%. Using these ranges, 72.8% of the 847 liver biopsies were correctly classified. The FIB-4 index was strongly correlated to the FibroTest results for a score <1.45 or >3.25 (kappa = 0.561, P < 0.01). A FIB-4 value <1.45 or >3.25 (64.6% of the cases) was concordant with FibroTest results in 92.1% and 76%, respectively. CONCLUSION: For values outside 1.45-3.25, the FIB-4 index is a simple, accurate, and inexpensive method for assessing liver fibrosis and proved to be concordant with FibroTest results.

Stiffness of elastic arteries like the aorta predicts cardiovascular risk. By directly reflecting arterial stiffness, having the best predictive value for cardiovascular outcome and the ease of its measurement, carotid-femoral pulse wave velocity is now considered the gold standard for arterial stiffness assessment in daily practice. Many different measurement procedures have been proposed. Therefore, standardization of its measurement is urgently needed, particularly regarding the distance measurement. This consensus document advises on the measurement procedures in general and provides arguments for the use of 80% of the direct carotid-femoral distance as the most accurate distance estimate. It also advises the use of 10 m/s as new cut-off value for carotid-femoral pulse wave velocity.

This position paper has been approved by the AASLD and represents the position of the association. These recommendations provide a data-supported approach. They are based on the following: (1) formal review and analysis of the recently published world literature on the topic; (2) American College of Physicians Manual for Assessing Health Practices and Designing Practice Guidelines1; (3) guideline policies, including the AASLD Policy on the Development and Use of Practice Guidelines and the American Gastroenterological Association Policy Statement on Guidelines2; and (4) the experience of the authors in the specified topic. Intended for use by physicians, these recommendations suggest preferred approaches to the diagnostic, therapeutic, and preventive aspects of care. They are intended to be flexible, in contrast to standards of care, which are inflexible policies to be followed in every case. Specific recommendations are based on relevant published information. To more fully characterize the quality of evidence supporting recommendations, the Practice Guidelines Committee of the AASLD requires a Class (reflecting benefit versus risk) and Level (assessing strength or certainty) of Evidence to be assigned and reported with each recommendation (Table 1, adapted from the American College of Cardiology and the American Heart Association Practice Guidelines3).4 AASLD, American Association for the Study of Liver Diseases; AIH, autoimmune hepatitis; ALF, acute liver failure; ALT, alanine aminotransferase; ANA, antinuclear antibody; CT, computed tomography; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HVPG, hepatic venous pressure gradient; IgG, immunoglobulin G; INR, international normalized ratio; NAFLD, nonalcoholic fatty liver disease; PBC, primary biliary cirrhosis; PSC, primary sclerosing cholangitis; PT, prothrombin time; US, ultrasound. Histological assessment of the liver, and thus, liver a in the and of with liver and has been to be of the and to and liver liver a of the liver has in and in use of liver in with to assessment of the of liver be to liver a has been in to (Table liver to and the of liver in the of with liver and to be a of the of guideline to the of liver and recommendations This guideline with liver to liver liver a the of and the of for with liver liver and assessment of the liver has on in of liver has (1) for (2) for assessment of (3) to in to a hepatitis B or hepatitis C liver a in the of of liver assessment be to a on a in primary biliary liver and in with the of and and fatty liver or and and be with are in Liver in with liver autoimmune hepatitis and nonalcoholic fatty liver in with of alanine immunoglobulin a antinuclear Liver be in with and or or of with liver a in the of the with a This the with liver of or the in a liver has been has been with a of to and Liver be in with in which the liver to be of the liver in with and be the with of the pressure Liver provide in with acute liver liver in a in AIH, and which in more Liver in with or a or of hepatitis by of a of and a of use of liver in a to the of of and and Evidence in the of the of assessment in hepatic hepatic of which are with more in with are by evidence and of in with liver in with to of and to be to the Evidence assessment in in in a of with PBC, for every of a on liver a in or of in to the in with and with are of hepatocellular and be Liver in with provide the for with to be for with be from assessment of liver by analysis information. of liver be in with and these which be of This the to the of liver to for liver more to has of the for with a of liver a be in a a in the of with liver be on the the the with a more analysis of the liver in with the of which in to the liver with liver for with to of be or Liver in of with the of and liver to of the of in with evidence of evidence with with to with or of more and for liver on the of analysis in the of liver for and and in which liver be are in and to the of analysis of the liver in the of with liver to for assessment of are more in the on the of liver and analysis in liver and in published AASLD to Liver has been in the of liver of a and to a liver in a of to a and to a in in liver to liver of with NAFLD, liver primary and biliary AIH, liver primary sclerosing and and of a liver to of and of in of liver and a for liver the of liver in the of liver and analysis information. in with liver with a for a liver of a and a liver nonalcoholic and Histological liver the in of the liver to the the and more Liver be in the of liver in the of liver of the and of a liver be and the to a liver be or of to be the assigned in of with has including or AIH, and on of to evidence of and based on of the of in autoimmune to be a more in of for been on the of the and on of versus of and a of with the use of these for of liver liver of in to a in the of liver to or liver or Liver in the of including to the of of the liver liver on a in with liver evidence to evidence be by liver in liver in with of with with and of with more a of with or assessment to be in of the liver and been with liver in and with liver with be by liver has for of in and are in the of a fatty Liver and of hepatic in of a of liver of the liver and including hepatitis in in in and in of including of with fatty liver a of the of use of liver for of liver a by and of liver be or and in the and use of liver on the of requires of the has liver or the has a liver of of liver in the the liver has with and of venous and the liver be of the of the with liver the with This be in with a in with a with with the use of liver (1) the in (2) liver with B or C and and (3) to be a of of the which the the of the for liver to the to thus, by these the reported recommendations liver in with HCC, the AASLD guideline review on of the liver in with from in and the of of the of This to and in with a of which in the of liver in in the of biliary or a a the biliary or the hepatic to a be by or the of liver the be or be the be to primary hepatic from a more primary or a on the of and in which to the and in the or in of the of or more hepatic in the of liver This to or or for to with the hepatic liver and in a hepatic of the in of these be or are the in liver hepatic on the these on liver a has on the and with computed and has a of hepatic are and on the of contrast for of or more liver be with by primary be or are of on and be to the to the has be from from the to with on the of the more liver and a in liver be in with Liver be in in in and of a to the Level Liver in the of with liver in the to liver in these be to of the and of the Level to liver has the liver on or the been in the or the a the and of liver liver experience the the be the (1) by and the be (2) of be to the or be (3) of be and the and the (4) the to of and to the and the be and by be to the and these are to of the and in the a of including and be to liver to of liver be liver and liver provide and Level to of liver be the including and be Level of the including prothrombin normalized in the a to the a of be in of with in these to be to the of the on the and the of these in and by the the of more in which are by of with to be with and are to the of more of of and be to (1) in the hepatic and (2) biliary of these to in to be to and to on the are evidence a liver a or the to a fatty to the of the the and the of the in the of a recommendations evidence recommendations a of by be the liver the are to more by from the by in of in the of or use of be to the are from for a of pressure and in from the of and the of liver are with which to the of of the to these from in which are are and the these be from to to the be the liver from these and of be the of in with are to be the the to a be are for with in the of of be on a and in the of these be the of liver each the and of versus the for assessment of liver be the of the with the of a of the use of or or in the are these are and be to be in a of or the of which with liver these the or are of to be in the the to the are with which to the of been to liver be with of the of liver the the and with of suggest the be to liver the for of be on a the with use in the of liver Level be to liver be to liver and be to the of be the of liver Level be liver Level be the liver Level liver be in a with for the or for Use of or or are or be be to the of to the in a be the the benefit of This be in of and (Table of the the has been in with the in of of approach. with a or a with a or in and hepatic pressure are be to liver by the has been in the literature and be and of are a or the liver to be in to or the of in with or by the has been of to to the liver with of by with be of a and the use of and of the in to in with the of the benefit of of or and and the for liver and be from be to liver of the liver with liver for in a of for been or with of has been to be for with or a a of the in which the with or the from a the the and to liver with and liver and of the by in of of with of Liver in the and in the liver for and of with liver are the or and or to a in to of the of recently and the liver a or to a of This with or the for the to or been to more in the of and the the of the be and the of be for analysis the on a in with a or a or to a of liver pressure of from to more and be in the of recently these a of the which to the and the for be liver with the in a and be the in a use of liver and to use be to be a of and and with a from the to the to the the be by the the the of the and a the to of with of the liver be a or in the of the of the liver be of the by the and the a be to the the in the a to the and liver the of the the liver the liver be and the of the in the to the of and to the of been the of and liver formal has the use of a or which the liver has been the and by the are every for the and every the in the position to the liver to the and a of a of to the the or the position in each followed by the to the position of of with and for and a in more the for on the in a of liver thus, be the the of the liver has been of in liver the from to to with with the of the the of by for liver in the position and for in the the for a to and of to be liver be of liver are of the of the of liver requires and for Level use of and to Level be every for the liver Level to and on and Level the liver from the and and has the to the use of has been in or a the has liver the a of by to by to a in of benefit of in a in which and in of the to of in the versus a in with in the the of to published a of with HCV, in the with versus the use of to be more in the of liver be on the of assessment of the liver to a in the of the in of use of US, or in for liver and in the has of with quality recommendations and with of the by the the the of from liver Level to liver with the of in of the be to in the be on the and of the are to be (Table the are of the to the in for and the are liver the be with and the the in the liver, a or in the of are to liver the by the to be or the use of liver with and and are to or the of be to are with which to the in the of liver in with a the liver to the in with or the of in with or in with with of for liver in with to or or which be the has been the of liver for of liver to be a and to provide information. are to by a be or are of the be a of which has liver in with be of be of be a be be the liver and the of be with are more to with to the and liver be and of with a of the a in to in in a more of of a for HCC, by in of and to on evidence of the the of to be the to be with use of a a and a these the in of has been the of (Table represents to of be with suggest of these with to and for the to the to liver based on the of liver in with a to the of to the of in with acute liver a of liver a the to of by with in the PT, or liver and and and in with liver of from of authors the PT, and are of the of liver are of in to or to are in of liver has been or be more relevant to are of the the of of the in with liver with a for or the of to be a to a with liver and of liver or a in with a more to with in of the of or to in with by the and are Use of to has in and the of has in with liver disease; in of in with of the a a for the in or to the for liver for in or to a are by with the a of with with or on the of in the use of the been to in of liver by the with liver in the of in these the of from the liver in the of in with liver a of experience with liver in the including more the and a review of in a of including of liver to a and of the from and to liver are in the and a of a of or the of or a be in are the with liver for be in of the with in the with of and the with or or the of the to these in with of and and for of the in liver of represents a or are to more the in these of in liver has recently been the the from a of with liver has been the provide a of to be and are to the of including and in of which has been of for a of in to be and This by the of Health and the Study of in intended to with of to hepatic or to be assigned of the or and to be by a in or the for to the of of with to liver to are more with of and These with or and and with with liver a be liver or be in these the be on a of of the liver or in with liver in these are to recommendations and thus, be on liver with or in and be in Level liver the or the Level with a liver a of or are Level liver and a on the Level to liver in the of of to be the of and of the and of liver or which be Level assessment of in liver by the in the reported on with and with to the of for liver for the of assessment of hepatic This of the be in the of a (Table are and the are based on experience and the of liver in to of including with be more in with a of to be to versus the with liver to be be with of to in a of and the of a or of a of or from the liver with the for to with to the for to be on a to US, to be more of liver which by a in with evidence of and requires the of or or has been to in in to in for liver (Table in to the (Table to or pressure or or in in to to liver has been to a in in with has been on of liver and by in of be to and to the the of or are reported to be to the of and the of and a or be with of based on the suggest a and a in the use of the of of the of with of recommendations of and by the of to are of a to on are liver with a in with a or to be review of the literature the of to to be to with to the of with a and reported in and of be of the to liver and to to be of be for of be of with or with to in or with in Use of liver in with has the of in with or use of has been on to liver of use of in with on recently are experience and on the use of in with suggest be the be liver be in with and of the to the liver to in the literature (Table to be of in with or to in liver in in a of the of for of been reported liver These of of and with to be in liver to to and of and to of these has of a be the of of to the the pressure suggest or evidence of are of and or in with evidence of with be more on the of be in the of and or in the of liver be of liver and these with Level be are or Level use of or or be in to be Level with or on be use to be in on Level on be to liver and be Level for liver the in with by and use for the liver of the more in with hepatitis C or use for the of the liver has been by the (1) which (2) which be and (3) for the the which has been be in or to the position of the liver in the of for liver or in be in with and in with of or in the be in (1) with are to (2) are to the liver by or (3) with or be for preferred to and and use of for for with a of which are or on for the the liver a of liver for of the liver with of the to the liver be by a to a in the or for aspects of are to and the following: (1) of a or the (2) use of a the hepatic or and (3) the a the hepatic has been or evidence or to the to which are the of be by and with liver the in with the of to the liver to the the hepatic the and the be to in to position the liver in a more This be in in which the the the hepatic and a or approach. the in with be a and the This with a of which be by the the the of the the to the the be on of liver in the and and of use of of the liver has the to a of liver to the in or the liver be of the to the has the hepatic to the This be by the by a the the to the in the has of of of of the in provide a of and be with a of the the quality of and the for of and liver liver in including in with and in with liver be in the with are to and with Level to the in the the liver be to This the be of to a of and of of has been to be the of to be literature has on and in with a from with of liver of from to in a be to a of the are be in liver are and with a more of for of be from in of by from in from a be in the to to a of to the of the to the of for to be to in which more in and of hepatitis with of the of of be with This by the be and reported by the the reported on the the the of the in with hepatitis and in or in a of liver from with hepatitis B and C liver to in the of with in with a or in with and in in in with a or and in a be for liver in in with to a to in to of To for the of are to and with a are the of the the the with use of a be and a a be with are to a of be in for and of liver use of a to in to of has been be with the to of liver with and in for and of hepatitis and are to provide for a in with of a a in with of a in with a a in with a in with a on the liver by be for a of the be of the be in or preferred by the the of and and of be of the for of the in to or or a analysis of be of of the be for the be of in from for on has the more with from the be to of use in with the in and in a of the be in and for a of the be in for to and in and or for to be by of the be for or be for or the for analysis of to of for and for a of of the and of a of are the of be for with or a and with to the for to hepatic in the are or the of which has recently been in of for in in for in and the to the of are for the of in for of these for in for more in and for the of and are for of HCC, the of with and has been to the a in liver the in with the the for the the of by been reported in more of use of from liver of with liver by of the and the been for and of and a for these are and are for analysis of of in to use and with to of Association for Study of the Liver or (Table which for and to be the in which the of or be or with to the more This in which more and of liver on a of in and in Level the of be in the with and be to Level a a Level use of a or Level liver and and be liver be with in a of with and liver of by of by a liver to from and the by or the be for in the be the of a to be of the of liver the of liver a of has been of liver review of the approaches the of for and been and are are for or for or They are and are for or the of the of the liver more the use of in has been of including the of liver and the for and to hepatic to and be more in Liver a in the of with liver for of liver and use are and Level the of the of these authors in liver by for in liver are based on evidence and experience the of the the of to the of liver the for a and Committee has the of to in liver with the for for in the on the American Gastroenterological Association to on the of the the and of the to more liver to or a by of the of in be of the for liver Use of to the liver for or in requires which to a has in the use of and the use of in of by to liver in to the liver and the for the (1) a the to (2) with the of the liver, and and the and Use of and to to use of to a the of experience by a of including in Specific for liver and for Level Liver be to by in the of liver and of Level the of to Level in liver in of liver and Level liver be to by and experience with the Level use of liver to for a of the and of and a for and to which are has been the of and the to to and which approaches and are to in of more of and of in the of This in and in the to in the of requires liver and the requires more which or are or the to which the of to assessment of by and in of the (1) are to the of (2) preventive (3) of to of or to a of in to the and of Use of or in a preventive to a the of these to to liver in the of are to are for to to of the from to of and and of liver Study of the of liver in or Study to characterize the of liver in of the of in in of of to liver This guideline in with the Practice Guidelines Committee of the This of the of the AASLD Practice Guidelines Committee and for the or of supporting by the be to the for the

The Modification of Diet in Renal Disease (MDRD) equations provide a rapid method of assessing GFR in patients with chronic kidney disease (CKD). However, previous research indicated that modification of these equations is necessary for application in Chinese patients with CKD. The objective of this study was to modify MDRD equations on the basis of the data from the Chinese CKD population and compare the diagnostic performance of the modified MDRD equations with that of the original MDRD equations across CKD stages in a multicenter, cross-sectional study of GFR estimation from plasma creatinine, demographic data, and clinical characteristics. A total of 684 adult patients with CKD, from nine geographic regions of China were selected. A random sample of 454 of these patients were included in the training sample set, and the remaining 230 patients were included in the testing sample set. With the use of the dual plasma sampling (99m)Tc-DTPA plasma clearance method as a reference for GFR measurement, the original MDRD equations were modified by two methods: First, by adding a racial factor for Chinese in the original MDRD equations, and, second, by applying multiple linear regression to the training sample and modifying the coefficient that is associated with each variable in the original MDRD equations and then validating in the testing sample and comparing it with the original MDRD equations. All modified MDRD equations showed significant performance improvement in bias, precision, and accuracy compared with the original MDRD equations, and the percentage of estimated GFR that did not deviate >30% from the reference GFR was >75%. The modified MDRD equations that were based on the Chinese patients with CKD offered significant advantages in different CKD stages and could be applied in clinical practice, at least in Chinese patients with CKD.

UNLABELLED: Diagnosis of autoimmune hepatitis (AIH) may be challenging. However, early diagnosis is important because immunosuppression is life-saving. Diagnostic criteria of the International Autoimmune Hepatitis Group (IAIHG) were complex and purely meant for scientific purposes. This study of the IAIHG aims to define simplified diagnostic criteria for routine clinical practice. Candidate criteria included sex, age, autoantibodies, immunoglobulins, absence of viral hepatitis, and histology. The training set included 250 AIH patients and 193 controls from 11 centers worldwide. Scores were built from variables showing predictive ability in univariate analysis. Diagnostic value of each score was assessed by the area under the receiver operating characteristic (ROC) curve. The best score was validated using data of an additional 109 AIH patients and 284 controls. This score included autoantibodies, immunoglobulin G, histology, and exclusion of viral hepatitis. The area under the curve for prediction of AIH was 0.946 in the training set and 0.91 in the validation set. Based on the ROC curves, two cutoff points were chosen. The score was found to have 88% sensitivity and 97% specificity (cutoff > or =6) and 81% sensitivity and 99% specificity (cutoff > or =7) in the validation set. CONCLUSION: A reliable diagnosis of AIH can be made using a very simple diagnostic score. We propose the diagnosis of probable AIH at a cutoff point greater than 6 points and definite AIH 7 points or higher.

These practice guidelines on the management of arterial hypertension are a concise summary of the more extensive ones prepared by a Task Force jointly appointed by the European Society of Hypertension and the European Society of Cardiology. These guidelines have been prepared on the basis of the best available evidence on all issues deserving recommendations; their role must be educational and not prescriptive or coercive for the management of individual subjects who may differ widely in their personal, medical and cultural characteristics. The members of the Task Force have participated independently in the preparation of these guidelines, drawing on their academic and clinical experience and by objective examination and interpretation of all available literature. A disclosure of their potential con?ict of interest is reported on the websites of the ESH and the ESC

UNLABELLED: Nonalcoholic steatohepatitis (NASH) is a serious liver disease associated with obesity. Characterized by metabolic syndrome, hepatic steatosis, and liver inflammation, NASH is believed to be under the influence of the gut microflora. Here, the composition of gut bacterial communities of NASH, obese, and healthy children was determined by 16S ribosomal RNA pyrosequencing. In addition, peripheral blood ethanol was analyzed to monitor endogenous ethanol production of patients and healthy controls. UniFrac-based principle coordinates analysis indicated that most of the microbiome samples clustered by disease status. Each group was associated with a unique pattern of enterotypes. Differences were abundant at phylum, family, and genus levels between healthy subjects and obese patients (with or without NASH), and relatively fewer differences were observed between obese and the NASH microbiomes. Among those taxa with greater than 1% representation in any of the disease groups, Proteobacteria, Enterobacteriaceae, and Escherichia were the only phylum, family and genus types exhibiting significant difference between obese and NASH microbiomes. Similar blood-ethanol concentrations were observed between healthy subjects and obese non-NASH patients, but NASH patients exhibited significantly elevated blood ethanol levels. CONCLUSIONS: The increased abundance of alcohol-producing bacteria in NASH microbiomes, elevated blood-ethanol concentration in NASH patients, and the well-established role of alcohol metabolism in oxidative stress and, consequently, liver inflammation suggest a role for alcohol-producing microbiota in the pathogenesis of NASH. We postulate that the distinct composition of the gut microbiome among NASH, obese, and healthy controls could offer a target for intervention or a marker for disease.

The impact of fishing on chondrichthyan stocks around the world is currently the focus of considerable international concern. Most chondrichthyan populations are of low productivity relative to teleost fishes, a consequence of their different life-history strategies. This is reflected in the poor record of sustainability of target shark fisheries. Most sharks and some batoids are predators at, or near, the top of marine food webs. The effects of fishing are examined at the single-species level and through trophic interactions. We summarize the status of chondrichthyan fisheries from around the world. Some 50% of the estimated global catch of chondrichthyans is taken as by-catch, does not appear in official fishery statistics, and is almost totally unmanaged. When taken as by-catch, they are often subjected to high fishing mortality directed at teleost target species. Consequently, some skates, sawfish, and deep-water dogfish have been virtually extirpated from large regions. Some chondrichthyans are more resilient to fishing and we examine predictions on the vulnerability of different species based on their life-history and population parameters. At the species level, fishing may alter size structure and population parameters in response to changes in species abundance. We review the evidence for such density-dependent change. Fishing can affect trophic interactions and we examine cases of apparent species replacement and shifts in community composition. Sharks and rays learn to associate trawlers with food and feeding on discards may increase their populations. Using ECOSIM, we make some predictions about the long-term response of ecosystems to fishing on sharks. Three different environments are analysed: a tropical shelf ecosystem in Venezuela, a Hawaiian coral reef ecosystem, and a North Pacific oceanic ecosystem.

Current guidelines identify people with chronic kidney disease (CKD) as being at high risk for cardiovascular and all-cause mortality. Because as many as 19 million Americans may have CKD, a comprehensive summary of this risk would be potentially useful for planning public health policy. A systematic review of the association between non-dialysis-dependent CKD and the risk for all-cause and cardiovascular mortality was conducted. Patient- and study-related characteristics that influenced the magnitude of these associations also were investigated. MEDLINE and EMBASE databases were searched, and reference lists through December 2004 were consulted. Authors of 10 primary studies provided additional data. Cohort studies or cohort analyses of randomized, controlled trials that compared mortality between those with and without chronically reduced kidney function were included. Studies were excluded from review when participants were followed for < 1 yr or had ESRD. Two reviewers independently extracted data on study setting, quality, participant and renal function characteristics, and outcomes. Thirty-nine studies that followed a total of 1,371,990 participants were reviewed. The unadjusted relative risk for mortality in participants with reduced kidney function compared with those without ranged from 0.94 to 5.0 and was significantly more than 1.0 in 93% of cohorts. Among the 16 studies that provided suitable data, the absolute risk for death increased exponentially with decreasing renal function. Fourteen cohorts described the risk for mortality from reduced kidney function, after adjustment for other established risk factors. Although adjusted relative hazards were consistently lower than unadjusted relative risks (median reduction 17%), they remained significantly more than 1.0 in 71% of cohorts. This review supports current guidelines that identify individuals with CKD as being at high risk for cardiovascular mortality. Determining which interventions best offset this risk remains a health priority.

Nephrogenic systemic fibrosis is a new, rare disease of unknown cause that affects patients with renal failure. Single cases led to the suspicion of a causative role of gadodiamide that is used for magnetic resonance imaging. This study therefore reviewed all of the authors' confirmed cases of nephrogenic systemic fibrosis (n = 13) with respect to clinical characteristics, gadodiamide exposure, and subsequent clinical course. It was found that all had been exposed to gadodiamide before the development of nephrogenic systemic fibrosis. The delay from exposure to first sign of the disease was 2 to 75 d (median 25 d). Odds ratio for acquiring the disease when gadodiamide exposed was 32.5 (95% confidence interval 1.9 to 549.2; P < 0.0001). Seven (54%) patients became severely disabled, and one died 21 mo after exposure. No other exposure/event than gadodiamide that was common to more than a minority of the patients could be identified. These findings indicate that gadodiamide plays a causative role in nephrogenic systemic fibrosis.

Abstract There has been an increase in interest towards corporate activities aimed at reducing or eliminating the waste created during the production, use and/or disposal of the firm’s products. Prior research has focused on the need for such activities, while current research tries to identify those components that encourage or discourage such activities. As a result of the introduction of ISO 14001, attention has turned to corporate environmental management systems (EMS). The underlying assumption is that such a system is critical to a firm’s ability to reduce waste and pollution while simultaneously improving overall performance. This study evaluates this assumption. Drawing on data provided by a survey of North American managers, their attitudes toward EMS and ISO 14001, this study assesses the relative effects of having a formal but uncertified EMS compared to having a formal, certified system. The results strongly demonstrate that firms in possession of a formal EMS perceive impacts well beyond pollution abatement and see a critical positive impact on many dimensions of operations performance. The results also show that firms having gone through EMS certification experience a greater impact on performance than do firms that have not certified their EMS. Additionally, experience with these systems over time has a greater impact on the selection and use of environmental options. These results demonstrate the need for further investigation into EMS, the environmental options a firm chooses, and the direct and indirect relationships between these systems and performance.

UNLABELLED: Nonalcoholic steatohepatitis (NASH) is a chronic progressive liver disease that is strongly associated with obesity. Currently, there is no approved therapy for NASH. Weight reduction is typically recommended, but efficacy data are lacking. We performed a randomized controlled trial to examine the effects of lifestyle intervention using a combination of diet, exercise, and behavior modification, with a goal of 7% to 10% weight reduction, on clinical parameters of NASH. The primary outcome measure was the change in NASH histological activity score (NAS) after 48 weeks of intervention. Thirty-one overweight or obese individuals (body mass index [BMI], 25-40 kg/m(2)) with biopsy-proven NASH were randomized in a 2:1 ratio to receive intensive lifestyle intervention (LS) or structured education (control). After 48 weeks of intervention, participants assigned to LS lost an average of 9.3% of their weight versus 0.2% in the control group (P = 0.003). A higher proportion of participants in the LS group had a reduction of NAS of at least 3 points or had posttreatment NAS of 2 or less as compared with the control group (72% versus 30%, P = 0.03). NAS improved significantly in the LS group (from 4.4 to 2.0) in comparison with the control group (from 4.9 to 3.5) (P = 0.05). Percent weight reduction correlated significantly with improvement in NAS (r = 0.497, P = 0.007). Participants who achieved the study weight loss goal (>or=7%), compared with those who lost less than 7%, had significant improvements in steatosis (-1.36 versus -0.41, P < 0.001), lobular inflammation (-0.82 versus -0.24, P = 0.03), ballooning injury (-1.27 versus -0.53, P = 0.03) and NAS (-3.45 versus -1.18, P < 0.001). CONCLUSION: Weight reduction achieved through lifestyle intervention leads to improvements in liver histology in NASH.

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in affluent countries. Accurate noninvasive tests for liver injury are urgently needed. The aim of this study was to evaluate the accuracy of transient elastography for the diagnosis of fibrosis and cirrhosis in patients with NAFLD and to study factors associated with discordance between transient elastography and histology. Two hundred forty-six consecutive patients from two ethnic groups had successful liver stiffness measurement and satisfactory liver biopsy specimens. The area under the receiver-operating characteristics curve (AUROC) of transient elastography for F3 or higher and F4 disease was 0.93 and 0.95, respectively, and was significantly higher than that of the aspartate aminotransferase-to-alanine aminotransferase ratio, aspartate aminotransferase-to-platelet ratio index, FIB-4, BARD, and NAFLD fibrosis scores (AUROC ranged from 0.62 to 0.81, P < 0.05 for all comparisons). At a cutoff value of 7.9 kPa, the sensitivity, specificity, and positive and negative predictive values for F3 or greater disease were 91%, 75%, 52%, and 97%, respectively. Liver stiffness was not affected by hepatic steatosis, necroinflammation, or body mass index. Discordance of at least two stages between transient elastography and histology was observed in 33 (13.4%) patients. By multivariate analysis, liver biopsy length less than 20 mm and F0-2 disease were associated with discordance. CONCLUSION: Transient elastography is accurate in most NAFLD patients. Unsatisfactory liver biopsy specimens rather than transient elastography technique account for most cases of discordance. With high negative predictive value and modest positive predictive value, transient elastography is useful as a screening test to exclude advanced fibrosis. Liver biopsy may be considered in NAFLD patients with liver stiffness of at least 7.9 kPa.