Liver biopsy is an important part of the evaluation of patients with a variety of liver diseases. Besides establishing the diagnosis, the biopsy is often used to assess the severity of the disease in ...terms of both grade and stage. The stage in most chronic liver diseases relates to the degree of scarring with the end stage being cirrhosis with its clinical complications. The grade relates to the severity of the underlying disease process, with features that vary with the pathogenetic mechanisms. Chronic viral hepatitis has been the object of the most extensive efforts at grading and staging, stimulated by the advent of new forms of therapy. Systems have also been developed for fatty liver disease, allograft rejection and chronic cholestatic diseases, but these have not been as widely used. Simple grading and staging systems for chronic hepatitis, including the IASL, Batts–Ludwig, and Metavir systems, are most appropriate for management of individual patients, while more complex systems such as the Histology Activity Index (HAI) are appropriate for evaluation of large cohorts of patients when statistical analysis is required.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Non-alcoholic steatohepatitis (NASH) is part of the spectrum of non-alcoholic fatty liver disease (NAFLD) that leads to progressive liver disease and presents a growing challenge to public ...health. Because of the increased prevalence of metabolic syndrome and obesity, NAFLD and NASH have expanded to a substantial extent. In NASH patients, advanced fibrosis is the major predictor of morbidity and liver-related mortality, and an accurate diagnosis of NASH is mandatory. Although there is currently no validated test of serum biomarkers available to diagnose NASH, and histologic evaluation with a liver biopsy remains the gold standard, screening for fibrosis is recommended in patients with suspicion of NASH. Clinical prediction models and serum biomarkers for advanced fibrosis have relatively good negative predictive value and can be useful for screening. Also, transient elastography is increasingly available to estimate fibrosis in NASH. Therefore, due to the lack of a reliable and accepted non-invasive diagnostic modality, screening for NASH in the general population is not currently recommended. Better understanding of the natural history of NASH is needed to evaluate the utility and cost-effectiveness of screening.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis constitute a spectrum of histologic lesions characterized by varying degrees of hepatocellular injury and fat accumulation with ...inflammation and scarring. Fibrosis associated with this disease may progress to cirrhosis and its complications. As there are no approved therapies, clinical trials to assess potential forms of drug therapy are conducted to assess drugs for efficacy and safety before submission to regulatory review. Liver biopsies are performed and evaluated to confirm the diagnosis of nonalcoholic steatohepatitis and to assess fibrosis stage for inclusion in trials.
The Society of Radiologists in Ultrasound convened a panel of specialists from radiology, hepatology, pathology, and basic science and physics to arrive at a consensus regarding the use of ...elastography in the assessment of liver fibrosis in chronic liver disease. The panel met in Denver, Colo, on October 21-22, 2014, and drafted this consensus statement. The recommendations in this statement are based on analysis of current literature and common practice strategies and are thought to represent a reasonable approach to the noninvasive assessment of diffuse liver fibrosis.
Despite the substantial gains in our understanding of NAFLD/NASH over the past 2 decades, there has been some dissatisfaction with the terminology “non‐alcoholic” which overemphasizes “alcohol” and ...underemphasizes the root cause of this liver disease, namely, the predisposing metabolic risk factors. As a potential remedy, a name change from NAFLD to metabolic associated fatty liver disease (MAFLD) has been proposed. Although MAFLD reflects the relevant risk factors for this liver disease, this term is still suboptimal, leaving a great deal of ambiguity. Here, we caution that changing the name without understanding its broad implications can have a negative impact on the field. In this context, changing the terminology without new understanding of the molecular basis of the disease entity, new insights in risk stratification or other important aspect of this liver disease, can create unnecessary confusion which could negatively impact the field. At a time when the field is facing substantial challenges around disease awareness as well as clarity of acceptable endpoints for drug development and biomarker discovery, changing the terminology from one suboptimal name to another suboptimal name without full assessment is expected to deepen these challenges. In the context of this debate about terminology, we recommend the creation of a true international consensus group to include all the relevant scientific liver societies (AASLD, EASL, ALEH, APASL), patient advocacy organizations, bio‐pharmaceutical industry, regulatory agencies and policy makers. A consensus meeting must assess the impact and consequences of changing the terminology based on the available evidence and make recommendations that will move the field forward. By this approach, a true collaborative international and inclusive consensus can be adopted by all stakeholders dealing with this important global liver disease.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Nonalcoholic fatty liver disease (NAFLD) is a spectrum comprised of isolated steatosis, nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. The majority of NAFLD subjects do not ...have NASH and do not carry a significant risk for liver‐related adverse outcomes (cirrhosis and mortality). Globally, the prevalence of NAFLD is approximately 25%. In Asia, a gradient of high to low prevalence rates is noted from urban to rural areas. Given the prevalence of NAFLD, the clinical and economic burden of NAFLD and NASH can be substantial. With increasing recognition of NASH as an important liver disease, the diagnosis of NASH still requires a liver biopsy that is suboptimal. Although liver biopsy is the most accurate modality to diagnose and stage the severity of NASH, this method suffers from being invasive, costly, associated with potential complications, and plagued with interobserver variability of individual pathological features. A number of noninvasive modalities to diagnose NASH and stage liver fibrosis are being developed. These modalities include predictive models (NAFLD fibrosis score) and serum biomarkers such as enhanced liver fibrosis (ELF). Other tests are based on radiological techniques, such as transient elastography (TE) or magnetic resonance elastography (MRE), which are used to estimate liver stiffness as a potential surrogate of hepatic fibrosis. Although a dynamic field of research, most of these diagnostic modalities have area under the curve ranging between 0.76 and 0.90%, with MRE having the best predictive performance. In summary, developing safe and easily accessible noninvasive modalities to accurately diagnose and monitor NASH and associated fibrosis is of utmost importance in clinical practice and clinical research. These tests are not only important to risk stratify subjects at the greatest risk for progressive liver disease, but also to serve as appropriate surrogate endpoints for therapeutic clinical trials of NASH. (Hepatology 2018;68:349‐360).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Nonalcoholic fatty liver disease (NAFLD) and its progressive form non‐alcoholic steatohepatitis (NASH), are rapidly becoming among the top causes of cirrhosis, hepatocellular carcinoma, and ...indications for liver transplantation. Other than lifestyle modification through diet and exercise, there are currently no other approved treatments for NASH/NAFLD. Although weight loss can be effective, it is difficult to achieve and sustain. In contrast, bariatric surgery can improve metabolic conditions associated with NAFLD, and has been shown to improve liver histology. To have approved regimens for the treatment of NASH/NAFLD, several issues must be addressed. First, all stakeholders must agree on the most appropriate clinical trial endpoints for NASH. Currently, resolution of NASH (without worsening fibrosis) or reduction of fibrosis stage (without worsening NASH) are the accepted endpoints by the regulatory authorities. It is important to recognize the prognostic implication of histologic features of NASH. In this context, although histologic NASH has been associated with advanced fibrosis, it is not an independent predictor of long‐term mortality. In contrast, there are significant data to suggest that fibrosis stage is the only robust and independent predictor of liver‐related mortality. In addition to the primary endpoints, several important secondary endpoints, including noninvasive biomarkers, long‐term outcomes, and patient‐reported outcomes must be considered. In 2018, a few phase 3 clinical trials for the treatment of NASH have been initiated. Additionally, a number of phase 2a and 2b clinical trials targeting different pathogenic pathways in NASH are in the pipeline of emerging therapies. Conclusion: Over the next 5 years, some of these regimens are expected to provide potential new treatment options for patients with NASH/NAFLD. (Hepatology 2018;68:361‐371)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
The neutrophil-to-lymphocyte ratio (NLR) is a trans-prognostic biomarker of physiologic stress and inflammation linked to muscle weakness in older adults. Generation of grip force coincides ...with sustained activity in the primary sensorimotor cortex (SM1). The current study investigates whether whole-brain functional connectivity, that is, degree centrality (CD) of SM1 relates to grip strength and whether both functional measures are predicted by advancing age as a function of the NLR. A structural regression model investigated the main and interactive effects of age and NLR on grip strength and CD of SM1 in 589 adults aged 21–85 years (M = 45.87, SD = 18.06). The model including the entire sample had a good fit (χ 2(4) = 1.63, p = .804). In individuals aged 50 years and older, age predicted lower grip strength and SM1 CD as a function of increasing NLR. In a model stratified by sex, the effect of age, NLR, and their interaction on grip strength are significant for older men but not older women. Analyses support CD of SM1 at rest as a neural biomarker of grip strength. Grip and its neural underpinnings decrease with advancing age and increasing NLR in mid to late life. Age-related decrements in grip strength and functional connectivity of brain regions involved in the generation of dynamic grip appear to be accelerated as a function of systemic physiological stress and inflammation, particularly in older men.
In this trial involving patients infected with hepatitis C virus (HCV) genotype 1 in whom previous treatment had failed, boceprevir plus peginterferon and ribavirin was more effective than ...peginterferon and ribavirin alone. Adverse effects of boceprevir included anemia and neutropenia.
More than 170 million people are chronically infected with hepatitis C virus (HCV) worldwide.
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The standard treatment is combination therapy with peginterferon and ribavirin.
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Of the six HCV genotypes, genotype 1 is the least responsive to currently approved therapies, with rates of sustained virologic response of less than 50%.
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Thus, there is a large population of patients with few therapeutic options, and direct-acting antiviral therapy has become the focus of investigations regarding treatment for HCV infection.
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Boceprevir is a structurally novel peptidomimetic ketoamide protease inhibitor that binds reversibly to the HCV nonstructural 3 (NS3) active site. . . .
Objective: The goal of this article is to describe a conceptual multilevel model that provides evidence of embodiment of a societal stressor on the health of the individuals and illustrate with ...simulated data how omitting components in the analysis model fails to properly capture how context influences health. Method: We describe a two-level model with variables at each level: stress at the group level and appraisal at the individual level. These factors are assumed to influence the blood pressure of individuals. Importantly, the person-level predictor is responsible for bringing the group-level predictor to the individual level by a cross-level interaction between stress and appraisal and/or a mediated effect of stress. When combined, the model components may be partitioned into a pure direct effect, a pure indirect effect, pure interaction effect, and an interaction-in-mediation effect. Data were generated in accordance with the model with each component accounting for some proportion of variance in blood pressure. Results: To the extent these components operate in the process of embodiment, a proposition we argue is reasonable, failure to specify the analytic model with all components leads to failure to characterize embodiment and misattribution of the effect and mechanism. Conclusions: To fully quantify embodiment of a societal stressor on a health outcome, studies should use multilevel designs and estimate cross-level interactions and mediated effects.
Objetivo: El objetivo de este artículo es describir un modelo conceptual multinivel que proporciona evidencia de la materialización de un factor estresante social en la salud de los individuos e ilustrar con datos simulados cómo la omisión de componentes en el modelo de análisis no logra capturar adecuadamente cómo el contexto influye en la salud. Métodos: Describimos un modelo de dos niveles con variables en cada nivel: Estrés a nivel grupal y Evaluación a nivel individual. Se supone que estos factores influyen en la presión arterial de los individuos. Es importante destacar que el predictor a nivel de persona es responsable de llevar el predictor a nivel de grupo al nivel individual mediante una interacción entre niveles entre el Estrés y la Evaluación y/o un efecto mediado del estrés. Cuando se combinan, los componentes del modelo pueden dividirse en un efecto directo puro, un efecto indirecto puro, un efecto de interacción puro y un efecto de interacción en mediación. Los datos se generaron de acuerdo con el modelo y cada componente tomando en cuenta alguna proporción de varianza en la presión arterial. Resultados: En la medida en que estos componentes operen en el proceso de encarnación/materialización, una proposición que sostenemos es razonable, no especificar el modelo analítico con todos los componentes conduce a no caracterizar la materialización y a una mal atribución errónea del efecto y mecanismo. Conclusiones: Para cuantificar completamente la materialización de un factor estresante social en un resultado de salud, los estudios deben utilizar diseños multinivel y estimar las interacciones entre niveles y los efectos mediados.
Public Significance StatementWe describe a data analysis framework that allocates the sources of health inequities such as the stress from structural racism to two levels: a community level where the stress occurs and the person's perception of the stress. Such allocation will help in designing interventions at the appropriate level.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK