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      Nonalcoholic steatohepatitis: global impact and clinical consequences

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          Abstract

          Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver diseases ranging from simple fatty infiltration of liver parenchyma to the potentially progressive type of NAFLD called nonalcoholic steatohepatitis (NASH). Given the obesity epidemic, NAFLD and NASH have reached alarming levels globally. Recent data suggest that more than a quarter of the world population is affected by NAFLD; however, the disease prevalence is higher in certain patient population, that is, 55% prevalence rate among patients with type 2 diabetes (T2DM). Besides T2DM, NAFLD is also closely related to other metabolic abnormalities, such as visceral obesity, hypertension, and hyperlipidemia. It has been suggested that stage of liver fibrosis is the most important factor associated with mortality among patients with NAFLD. Additionally, patients with T2DM have increased risk of adverse outcomes. In addition to these metabolic abnormalities, older age and some genetic factors could pose additional risks. Patients with NAFLD and NASH have significantly impaired health-related quality of life than the general population. There is also a growing economical impact of NAFLD and NASH on healthcare systems around the globe. Despite a number of promising regimens as treatment options, healthy lifestyle modification with diet and exercise remains at the core of management of NAFLD and NASH.

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          Most cited references59

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          Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes.

          Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. We estimated the global prevalence, incidence, progression, and outcomes of NAFLD and nonalcoholic steatohepatitis (NASH). PubMed/MEDLINE were searched from 1989 to 2015 for terms involving epidemiology and progression of NAFLD. Exclusions included selected groups (studies that exclusively enrolled morbidly obese or diabetics or pediatric) and no data on alcohol consumption or other liver diseases. Incidence of hepatocellular carcinoma (HCC), cirrhosis, overall mortality, and liver-related mortality were determined. NASH required histological diagnosis. All studies were reviewed by three independent investigators. Analysis was stratified by region, diagnostic technique, biopsy indication, and study population. We used random-effects models to provide point estimates (95% confidence interval [CI]) of prevalence, incidence, mortality and incidence rate ratios, and metaregression with subgroup analysis to account for heterogeneity. Of 729 studies, 86 were included with a sample size of 8,515,431 from 22 countries. Global prevalence of NAFLD is 25.24% (95% CI: 22.10-28.65) with highest prevalence in the Middle East and South America and lowest in Africa. Metabolic comorbidities associated with NAFLD included obesity (51.34%; 95% CI: 41.38-61.20), type 2 diabetes (22.51%; 95% CI: 17.92-27.89), hyperlipidemia (69.16%; 95% CI: 49.91-83.46%), hypertension (39.34%; 95% CI: 33.15-45.88), and metabolic syndrome (42.54%; 95% CI: 30.06-56.05). Fibrosis progression proportion, and mean annual rate of progression in NASH were 40.76% (95% CI: 34.69-47.13) and 0.09 (95% CI: 0.06-0.12). HCC incidence among NAFLD patients was 0.44 per 1,000 person-years (range, 0.29-0.66). Liver-specific mortality and overall mortality among NAFLD and NASH were 0.77 per 1,000 (range, 0.33-1.77) and 11.77 per 1,000 person-years (range, 7.10-19.53) and 15.44 per 1,000 (range, 11.72-20.34) and 25.56 per 1,000 person-years (range, 6.29-103.80). Incidence risk ratios for liver-specific and overall mortality for NAFLD were 1.94 (range, 1.28-2.92) and 1.05 (range, 0.70-1.56).
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            The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases.

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              Design and validation of a histological scoring system for nonalcoholic fatty liver disease.

              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."

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                06 September 2021
                01 October 2021
                : 10
                : 10
                : R240-R247
                Affiliations
                [1 ]Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, Virginia , USA
                [2 ]Betty and Guy Beatty Center for Integrated Research , Inova Health System, Falls Church, Virginia, USA
                [3 ]Inova Medicine , Inova Health System, Falls Church, Virginia, USA
                Author notes
                Correspondence should be addressed to Z M Younossi: Zobair.Younossi@ 123456inova.org
                Author information
                http://orcid.org/0000-0001-9313-577X
                Article
                EC-21-0048
                10.1530/EC-21-0048
                8558888
                34486981
                ce839db0-57c0-4e0a-bbdf-c808432fc8a0
                © The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 27 August 2021
                : 06 September 2021
                Categories
                Review

                nonalcoholic steatohepatitis,pathophysiology,epidemiology,disease burden

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