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Modification of a simple clinical scoring system as a diagnostic screening tool for non-alcoholic steatohepatitis in Japanese patients with non-alcoholic fatty liver disease.

ABSTRACT: AIMS/INTRODUCTION: We reinvestigated the clinical usefulness of the modified NAFIC scoring system, modified by changing the weightage assigned to the fasting serum insulin level based on the importance of hyperinsulinemia in the pathogenesis of non-alcoholic steatohepatitis (NASH), in Japanese patients with non-alcoholic fatty liver disease (NAFLD) who had undergone liver biopsy. MATERIALS AND METHODS: The NAFIC score is conventionally calculated as follows: serum ferritin ?200 ng/mL (female) or ?300 ng/mL (male), 1 point; serum fasting insulin ?10 ?U/mL, 1 point; and serum type IV collagen 7 s ?5.0 ng/mL, 2 points. A total of 147 patients with NAFLD who had undergone liver biopsies were included in the estimation group. To validate the modified scoring system, 355 patients from nine hepatology centers in Japan were also enrolled. RESULTS: In the estimation group, 74 (50.3%) patients were histologically diagnosed as having NASH, whereas the remaining 73 (49.7%) were diagnosed as not having NASH. As the percentage of NASH patients increased not only among participants with serum insulin levels greater than 10 ?U/mL, but also in those with serum levels greater than 15 ?U/mL, we advocated use of the modified NAFIC score, as follows: serum fasting insulin 10-15 ?U/mL, 1 point and ?15 ?U/mL, 2 points. The modified NAFIC score showed improved sensitivity and negative predictive value for the diagnosis of NASH. This finding was also confirmed in the validation group. CONCLUSIONS: The modified NAFIC scoring system could be a clinically useful diagnostic screening tool for NASH.

SUBMITTER: Nakamura A

PROVIDER: S-EPMC4020262 | biostudies-other | 2013 Nov

REPOSITORIES: biostudies-other

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Modification of a simple clinical scoring system as a diagnostic screening tool for non-alcoholic steatohepatitis in Japanese patients with non-alcoholic fatty liver disease.

Nakamura Akinobu A Yoneda Masato M Sumida Yoshio Y Eguchi Yuichiro Y Fujii Hideki H Hyogo Hideyuki H Ono Masafumi M Suzuki Yasuaki Y Kawaguchi Takumi T Aoki Noriaki N Okanoue Takeshi T Nakajima Atsushi A Maeda Shin S Terauchi Yasuo Y

Journal of diabetes investigation 20130519 6

<h4>Aims/introduction</h4>We reinvestigated the clinical usefulness of the modified NAFIC scoring system, modified by changing the weightage assigned to the fasting serum insulin level based on the importance of hyperinsulinemia in the pathogenesis of non-alcoholic steatohepatitis (NASH), in Japanese patients with non-alcoholic fatty liver disease (NAFLD) who had undergone liver biopsy.<h4>Materials and methods</h4>The NAFIC score is conventionally calculated as follows: serum ferritin ≥200 ng/m ...[more]

PMID: 24843721

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Project description:This paper is based upon the "Charles Lieber Satellite Symposia" organized by Manuela G. Neuman at the Research Society on Alcoholism (RSA) Annual Meetings, 2013 and 2014. The present review includes pre-clinical, translational and clinical research that characterize alcoholic liver disease (ALD) and non-alcoholic steatohepatitis (NASH). In addition, a literature search in the discussed area was performed. Strong clinical and experimental evidence lead to recognition of the key toxic role of alcohol in the pathogenesis of ALD. The liver biopsy can confirm the etiology of NASH or alcoholic steatohepatitis (ASH) and assess structural alterations of cells, their organelles, as well as inflammatory activity. Three histological stages of ALD are simple steatosis, ASH, and chronic hepatitis with hepatic fibrosis or cirrhosis. These latter stages may also be associated with a number of cellular and histological changes, including the presence of Mallory's hyaline, megamitochondria, or perivenular and perisinusoidal fibrosis. Genetic polymorphisms of ethanol metabolizing enzymes such as cytochrome p450 (CYP) 2E1 activation may change the severity of ASH and NASH. Alcohol mediated hepatocarcinogenesis, immune response to alcohol in ASH, as well as the role of other risk factors such as its co-morbidities with chronic viral hepatitis in the presence or absence of human immunodeficiency virus are discussed. Dysregulation of hepatic methylation, as result of ethanol exposure, in hepatocytes transfected with hepatitis C virus (HCV), illustrates an impaired interferon signaling. The hepatotoxic effects of ethanol undermine the contribution of malnutrition to the liver injury. Dietary interventions such as micro and macronutrients, as well as changes to the microbiota are suggested. The clinical aspects of NASH, as part of metabolic syndrome in the aging population, are offered. The integrative symposia investigate different aspects of alcohol-induced liver damage and possible repair. We aim to (1) determine the immuno-pathology of alcohol-induced liver damage, (2) examine the role of genetics in the development of ASH, (3) propose diagnostic markers of ASH and NASH, (4) examine age differences, (5) develop common research tools to study alcohol-induced effects in clinical and pre-clinical studies, and (6) focus on factors that aggravate severity of organ-damage. The intention of these symposia is to advance the international profile of the biological research on alcoholism. We also wish to further our mission of leading the forum to progress the science and practice of translational research in alcoholism.

Project description:The mechanisms underlying the progression of non-alcoholic steatohepatitis (NASH) are not completely elucidated. In this study we have integrated gene expression profiling of liver biopsies of NASH patients with translational studies in a mouse model of steatohepatitis and with pharmacological interventions in isolated hepatocytes to identify a novel mechanism implicated in the pathogenesis of NASH. By using high-density oligonucleotide microarray analysis we identified a significant enrichment of known genes involved in the multi-step catalysis of long chain polyunsaturated fatty acids, including delta-5 and 6 desaturases. A combined inhibitor of delta-5 and delta-6 desaturases significantly reduced intracellular lipid accumulation and inflammatory gene expression in isolated hepatocytes. Gas chromatography analysis revealed impaired delta-5 desaturase activity toward the omega-3 pathway in livers from mice with high-fat diet (HFD)-induced NASH. Consistently, restoration of omega-3 index in transgenic fat-1 mice expressing an omega-3 desaturase, which allows the endogenous conversion of omega-6 into omega-3 fatty acids, produced a significant reduction in hepatic insulin resistance, hepatic steatosis, macrophage infiltration and necroinflammatory liver injury, accompanied by attenuated expression of genes involved in inflammation, fatty acid uptake and lipogenesis. These results were comparable to those obtained in a group of mice receiving a HFD supplemented with EPA/DHA. Of interest, hepatocytes from fat-1 mice or supplemented with EPA exhibited synergistic anti-steatotic and anti-inflammatory actions with the delta-5/ delta-6 inhibitor. Conclusion: These findings indicate that both endogenous and exogenous restoration of the hepatic balance between omega-6 and omega-3 fatty acids and/or modulation of desaturase activities exert preventive actions in NASH. The complete database comprised the expression measurements of 18185 genes for liver sample groups: 8 non-alcoholic steatohepatitis (NASH ) and 7 control samples. This dataset is part of the TransQST collection.

Project description:Background & aimsThere is currently no data on physician preferences regarding future therapies for non-alcoholic steatohepatitis (NASH); this study explores these preferences and characteristics that are relevant to physician decision-making when choosing a potential therapy for a patient with NASH. The results were compared with those from a similar patient preference survey which was conducted in parallel.MethodInitial exploratory 30-minute telephone interviews were conducted to inform the design of a 15-minute quantitative online specialist physicians survey, containing direct questions and a preference survey. This was based on a best-worst scaling (BWS) experiment to assess the relative importance of different treatment characteristics (attributes), followed by several paired comparison questions to understand the preference for 5 hypothetical product profiles.ResultsThe answers come from 121 physicians from Canada (n = 31), Germany (n = 30), the UK (n = 30) and the USA (n = 30). The primary driving element in NASH treatment decision-making was efficacy (49.23%), defined as "[hypothetical product] impact on liver status" and "[slowing of] progression to cirrhosis". Physicians reported the common use of non-invasive NASH diagnostic tests and 81% reported performing liver biopsy. In 57% of cases, physicians reported that "concerns related to the available diagnostic methods" limit the number of patients with biopsy-confirmed NASH.ConclusionsThis first physician preference study reveals that efficacy will be the main driver for physicians in selecting future NASH drugs. The findings also confirm the widespread use of non-invasive diagnostic tests and the reluctance to perform confirmatory liver biopsy despite guideline recommendations, mainly due to limited therapeutic options and patient refusal.Lay summaryThis study explores physician preferences in relation to future therapies for non-alcoholic steatohepatitis (NASH) and characteristics that are relevant to physician decision-making when choosing a potential therapy for a patient with NASH. The results of a short online survey completed by 121 specialist physicians determined that the primary factor that influences treatment decision-making is efficacy, and that a wide range of non-invasive techniques are used to diagnose NASH, while confirmatory liver biopsy is not performed by all physicians despite guideline recommendations.

Dataset Information

Modification of a simple clinical scoring system as a diagnostic screening tool for non-alcoholic steatohepatitis in Japanese patients with non-alcoholic fatty liver disease.

Publications

Modification of a simple clinical scoring system as a diagnostic screening tool for non-alcoholic steatohepatitis in Japanese patients with non-alcoholic fatty liver disease.

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