Simplified criteria for diagnosis of autoimmune hepatitis are based on autoantibodies, serum immunoglobulin G, histologic features, and negative viral serology. A score of 6 points is necessary for ...the designation of probable autoimmune hepatitis and 7 points or more for definite autoimmune hepatitis. The presence of three histologic features is required for categorizing a case as typical (2 points): interface hepatitis with portal lymphocytic/lymphoplasmacytic cells extending into lobule, emperipolesis, and rosettes. In the absence of all three features, a chronic hepatitis picture is considered compatible with autoimmune hepatitis (1 point). This study examines the validity of these histologic features for the diagnosis of autoimmune hepatitis. Clinical data and liver biopsies were reviewed for 88 autoimmune hepatitis, 20 primary biliary cholangitis, and 13 non-autoimmune acute hepatitis cases. Interface/lobular activity, number of plasma cells, copper/CK7 stains, and presence/absence of biliary features were assessed in autoimmune hepatitis and primary biliary cholangitis cases. The simplified criteria score was calculated. Modified histologic criteria were formulated on the basis of interface/lobular activity, number of plasma cells, and presence/absence of biliary features. Using the proposed histologic features, histologic score of 2 increased from 8 to 77%, while total simplified score of >6 increased from 69 to 86%. There was no increase in total simplified score for primary biliary cholangitis or non-autoimmune acute hepatitis. Rosettes and emperipolesis are difficult to interpret, and lack sensitivity and sensitivity for autoimmune hepatitis diagnosis. The current histologic criteria used in the current simplified score lead to underscoring of autoimmune hepatitis cases. The modified histologic criteria based on the inflammatory activity, extent of plasma cells, and results of copper/CK7 staining increased the histologic score in autoimmune hepatitis and led to a probable/definite diagnosis of autoimmune hepatitis in 17% of cases that would have otherwise been classified as non- autoimmune hepatitis by simplified score.
Utilizing Resource-Advantage Theory as the underlying theoretical foundation and drawing on literature from a variety of disciplines, we develop a market-oriented sustainability framework. By ...incorporating sustainability into market orientation, the goal of strategic alignment of sustainability with marketing strategies is achieved to create a competitive advantage. Three constructs identified in the model are DNA, stakeholder involvement, and performance management. These three constructs are the drivers of sustainability. DNA is used as an extended metaphor to clarify and illustrate the workings of an organization and how sustainability may be implemented. This construct includes core ideology, dynamic capabilities, and societal engagement. The firm’s DNA is communicated to both internal and external stakeholders, and stakeholders’ concerns should be an influence on strategic marketing planning. Performance management is the third major construct in the model and includes corporate social performance and corporate financial performance metrics. Within the model explication, we offer propositions to support market-oriented sustainability research and provide directions for sustainability theory, research, and practice.
Glypican-3 is a heparin sulfate proteoglycan normally expressed in fetal liver and placenta, but not in normal adult liver. Preliminary studies have shown that glypican-3 can be useful for the ...diagnosis of hepatocellular carcinoma. We performed immunohistochemistry for glypican-3 on 80 resection cases of hepatocellular lesions to examine the utility of glypican-3 immunohistochemistry in hepatocellular carcinoma at two ends of the differentiation spectrum. Staining was compared to Hep Par 1 in poorly differentiated cases. Glypican-3 was expressed in 46 (79%) hepatocellular carcinomas (56, 83 and 89% of well, moderately and poorly differentiated respectively) and seven (64%) fibrolamellar carcinomas. Of the 16 well differentiated cases, 10 closely resembled adenoma and were diagnosed due to focal abnormalities and/or loss of reticulin. Glypican-3 expression was seen in 50% in this group. Hepatocellular carcinomas arising in cirrhotic liver were more likely to be glypican-3 positive (91 vs 57%, P=0.004). All hepatic adenomas and macroregenerative nodules were negative, and three (43%) high grade dysplastic nodules were positive. Focal staining was seen in regenerative nodules in four (11%) cirrhosis cases. Glypican-3 was significantly more sensitive than Hep Par 1 for diagnosis of poorly differentiated hepatocellular carcinomas (89 vs 63%, P=0.02). The difference was more significant when only cases with diffuse positive staining were considered (83 vs 21%, P<0.001). In conclusion, glypican-3 has high sensitivity for the diagnosis of hepatocellular carcinoma, but is less sensitive in the extremely well differentiated hepatocellular carcinoma and fibrolamellar variant of hepatocellular carcinoma. Caution should be exercised in using glypican-3 in biopsy specimens as cirrhotic nodules can show strong expression. Glypican-3 can be especially useful in the identification of poorly differentiated hepatocellular carcinoma as it has higher sensitivity compared to Hep Par 1.
Purpose - To provide a comprehensive managerial framework to understand and provide a well balanced and integrated stakeholder orientation for implementing corporate social responsibility in ...marketing.Design methodology approach - Many published articles provide significant findings related to narrow dimensions of stakeholder orientation in marketing. This article utilizes existing knowledge on this topic to support a methodology to implement a well-integrated corporate social responsibility program that encompasses marketing.Findings - The findings provide a grounded framework based on previous research that provides a step-by-step approach for implementing corporate social responsibility from a marketing perspective.Research limitations implications - The framework developed in this paper provides an opportunity to examine to what extent the step-by-step methodology has been implemented in organizations as well as alternative approaches for implementation.Practical implications - This is a managerial guide for using a stakeholder model for implementing social responsibility in marketing.Originality value - This paper fulfils a need for advancing knowledge on implementing social responsibility in marketing and provides a practical framework for managers who desire to implement social responsibility.
Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of a history of significant alcohol use or other known liver disease. Nonalcoholic steatohepatitis (NASH) ...is the progressive form of NAFLD. The Pathology Committee of the NASH Clinical Research Network designed and validated a histological feature scoring system that addresses the full spectrum of lesions of NAFLD and proposed a NAFLD activity score (NAS) for use in clinical trials. The scoring system comprised 14 histological features, 4 of which were evaluated semi-quantitatively: steatosis (0-3), lobular inflammation (0-2), hepatocellular ballooning (0-2), and fibrosis (0-4). Another nine features were recorded as present or absent. An anonymized study set of 50 cases (32 from adult hepatology services, 18 from pediatric hepatology services) was assembled, coded, and circulated. For the validation study, agreement on scoring and a diagnostic categorization ("NASH," "borderline," or "not NASH") were evaluated by using weighted kappa statistics. Inter-rater agreement on adult cases was: 0.84 for fibrosis, 0.79 for steatosis, 0.56 for injury, and 0.45 for lobular inflammation. Agreement on diagnostic category was 0.61. Using multiple logistic regression, five features were independently associated with the diagnosis of NASH in adult biopsies: steatosis (P = .009), hepatocellular ballooning (P = .0001), lobular inflammation (P = .0001), fibrosis (P = .0001), and the absence of lipogranulomas (P = .001). The proposed NAS is the unweighted sum of steatosis, lobular inflammation, and hepatocellular ballooning scores. In conclusion, we present a strong scoring system and NAS for NAFLD and NASH with reasonable inter-rater reproducibility that should be useful for studies of both adults and children with any degree of NAFLD. NAS of > or =5 correlated with a diagnosis of NASH, and biopsies with scores of less than 3 were diagnosed as "not NASH."
Differentiation between benign and malignant lesions of the hepatic biliary tree may pose a diagnostic problem, as well-differentiated intrahepatic cholangiocarcinoma may mimic biliary hamartoma, ...bile duct adenoma, or parenchymal extinction. We evaluated Ki-67 proliferative index and p53 status by immunohistochemical staining to aid in exclusion of cholangiocarcinoma. 14 biliary hamartomas, 21 bile duct adenomas, and 11 livers with parenchymal extinction were compared to 26 intrahepatic cholangiocarcinomas (16 well-differentiated and 10 moderate- or poorly- differentiated tumors). We found an increased proliferative index in intrahepatic cholangiocarcinomas compared to benign biliary proliferations (average 23.0% in cholangiocarcinoma vs. 1.4% in all benign biliary lesions, n 26 vs. 46, P < .001). No difference in average proliferative index was observed between well-differentiated and moderately/poorly differentiated cholangiocarcinomas (average 22.7% vs. 23.3%, n 16 vs. 10, P = .92). Average proliferation indices of benign biliary lesions were uniformly low (biliary hamartoma 1.2%; bile duct adenoma 2%; parenchymal extinction 0.4%). The majority of cholangiocarcinomas (23/26, 88.5%), but none of the benign lesions (0/46, 0%) had proliferative indices greater than 10%. Strong nuclear p53 immunohistochemical staining was only seen in cholangiocarcinomas (9/26, 34.6%) and not in benign biliary lesions (0/46, 0%), though many of the benign lesions showed weak to moderate staining Immunohistochemical staining for Ki67 facilitates distinction between benign and malignant lesions of the intrahepatic biliary tree, whereas p53 immunohistochemical staining, is less helpful.
The Hunt-Vitell (H-V) model of marketing ethics has been validated over the last 30 years. The model explains how people make ethical decisions. Artificial intelligence (AI), involving machine ...learning, is replacing humans and making decisions based on algorithms or rules developed by programmers. The challenge is how to program the ethical component of AI decisions normally provided by humans. H-V is a descriptive model that can be applied to making AI ethical decisions. A blueprint and revised H-V model is developed as a guide to implementing AI ethics.
While non-alcoholic steatohepatitis is a slowly progressive disease, patients may rarely present in acute liver failure. We describe six patients who developed severe hepatic dysfunction following ...rapid weight loss or malnutrition. Rapid weight loss (18 to 91 kg) occurred after Roux-en-Y gastric bypass in four patients and starvation-like dieting or hypoalbuminemia was noted in two patients. Four patients either died or received an urgent liver transplant. Pathologic findings were characterized by advanced alcoholic steatohepatitis-like features, including extensive/circumferential centrizonal pericellular fibrosis, central scar with perivenular sclerosis/veno-occlusion with superimposed hepatocellular dropout, abundant/prominent hepatocellular balloons, and numerous Mallory–Denk bodies, but there was no history of excess alcohol consumption. This study characterizes clinicopathologic features of aggressive non-alcoholic steatohepatitis following rapid weight loss or malnutrition, which should be included in the differential diagnosis with alcohol when a patient is considered for liver transplantation. The mechanism of liver injury in aggressive steatohepatitis is unknown, but rapid fat mobilization in obese patients may potentially cause oxidative stress to the liver and further study is needed to determine if there is a genetic predisposition to this form of injury and if antioxidants may protect the liver during rapid weight loss/malnutrition.
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