Transient elastography with controlled attenuation parameter (CAP) for diagnosis of moderate or severe steatosis in people with suspected non-alcoholic fatty liver disease

Objectives: This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows: To determine the diagnostic accuracy of transient elastography with CAP for diagnosis of moderate and severe hepatic steatosis in people with suspected NAFLD when compared with liver biopsy as reference standard. To achieve this, we will compare none/mild hepatic steatosis (S0 to S1) versus moderate/severe hepatic steatosis (S2 to S3); and none/mild/moderate hepatic steatosis (S0 to S2) versus severe hepatic steatosis (S3). Secondary objectives: We aim to also identify the pooled sensitivity and specificity for the most common cut‐off values of CAP for diagnosis of none/mild hepatic steatosis (S0 to S1) and moderate/severe hepatic steatosis (S2 to S3); or none/mild/moderate hepatic steatosis (S0 to S2) and severe hepatic steatosis (S3) in people with suspected NAFLD, and to explore potential sources of heterogeneity influencing the diagnostic test accuracy of CAP (see: Investigations of heterogeneity)

MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice

Hepatic steatosis is a global epidemic that is thought to contribute to the pathogenesis of type 2 diabetes. MicroRNAs (miRs) are regulators that can functionally integrate a range of metabolic and inflammatory pathways in liver. We aimed to investigate the functional role of miR-155 in hepatic steatosis. Male C57BL/6 wild-type (WT) and miR-155−/− mice were fed either normal chow or high fat diet (HFD) for 6 months then lipid levels, metabolic and inflammatory parameters were assessed in livers and serum of the mice. Mice lacking endogenous miR-155 that were fed HFD for 6 months developed increased hepatic steatosis compared to WT controls. This was associated with increased liver weight and serum VLDL/LDL cholesterol and alanine transaminase (ALT) levels, as well as increased hepatic expression of genes involved in glucose regulation (Pck1, Cebpa), fatty acid uptake (Cd36) and lipid metabolism (Fasn, Fabp4, Lpl, Abcd2, Pla2g7). Using miRNA target prediction algorithms and the microarray transcriptomic profile of miR-155−/− livers, we identified and validated that Nr1h3 (LXRα) as a direct miR-155 target gene that is potentially responsible for the liver phenotype of miR-155−/− mice. Together these data indicate that miR-155 plays a pivotal role regulating lipid metabolism in liver and that its deregulation may lead to hepatic steatosis in patients with diabetes

Transient elastography with controlled attenuation parameter (CAP) for diagnosis of moderate or severe steatosis in people with suspected non-alcoholic fatty liver disease

© 2020 The Cochrane Collaboration. This article [Turankova T, Blyuss O, Brazhnikov A, Svistunov A, Gurusamy KS, Pavlov CS. Transient elastography with controlled attenuation parameter (CAP) for diagnosis of moderate or severe steatosis in people with suspected non-alcoholic fatty liver disease (Protocol). Cochrane Database of Systematic Reviews 2020, Issue 7. Art. No.: CD013670. DOI: 10.1002/14651858.CD013670.], has been published in final form at https://doi.org/10.1002/14651858.CD013670.Objectives: This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows:. To determine the diagnostic accuracy of transient elastography with CAP for diagnosis of moderate and severe hepatic steatosis in people with suspected NAFLD when compared with liver biopsy as reference standard. To achieve this, we will compare none/mild hepatic steatosis (S0 to S1) versus moderate/severe hepatic steatosis (S2 to S3); and none/mild/moderate hepatic steatosis (S0 to S2) versus severe hepatic steatosis (S3). Secondary objectives We aim to also identify the pooled sensitivity and specificity for the most common cut-off values of CAP for diagnosis of none/mild hepatic steatosis (S0 to S1) and moderate/severe hepatic steatosis (S2 to S3); or none/mild/moderate hepatic steatosis (S0 to S2) and severe hepatic steatosis (S3) in people with suspected NAFLD, and to explore potential sources of heterogeneity influencing the diagnostic test accuracy of CAP (see: Investigations of heterogeneity).Peer reviewe

Prevalence of hepatic steatosis as diagnosed on unenhanced abdominal computed tomography

Background/Objectives: The prevalence of non-alcoholic fatty liver disease (NAFLD) has been found to be lower in the African American population when compared to European American or Hispanics, even after controlling for obesity and insulin resistance. The prevalence of hepatic steatosis in the local population is unknown. No studies looking at the association between metabolic syndrome and non-alcoholic fatty liver disease have been done in the local population. The aim of this study is to determine the prevalence of hepatic steatosis in patients undergoing unenhanced abdominal Computed Tomography (CT) at Aga Khan University Hospital, NairobiSubjects/Methods: A cross-sectional analytical study of resident indigenous African patients undergoing an unenhanced CT abdomen at Aga Khan University Hospital, Nairobi’s (AKUHN) Radiology department. Data from 246 patients who meet the inclusion and exclusion criteria was collected. Metabolic syndrome was diagnosed using the WHO definition.Results: Of the 246 patients, 39.3% were female and 60.7% were male. Only 77 patients consented to undergo testing for fasting lipid profile. This limited the number of patients who could be diagnosed with metabolic syndrome. Out of the 246 patients, 33 had hepatic steatosis giving a prevalence of 13.4%, at a P value of 0.05 and a confidence interval of 9.0 to 17.8.Although a large number of people reported occasional/social alcohol intake, only 10 patients had alcohol uptake threshold meeting the criteria used. The causes of hepatic steatosis were mainly attributable to non-alcoholic fatty liver disease; only 2.5% had hepatic steatosis due to alcohol consumption. Obesity was found to be a strong risk factor for hepatic steatosis and patients with elevated BMI were up to 4 times more likely to have hepatic steatosis. Diabetes was also found to be a strong risk factor for hepatic steatosis, diabetics were 3 times more likely to have steatosis when compared to non-diabetics.Conclusions: The prevalence of hepatic steatosis was 13.4%. There was a strong association of hepatic steatosis and diabetes, with diabetics 3 times more likely to have hepatic steatosis. An association was found between the components of metabolic syndrome and hepatic steatosis

Vitamin D to reduce liver fibrosis in non-alcoholic fatty liver disease

BACKGROUND: As the prevalence of metabolic risk factors in the American population has increased over time, so too has the diagnoses of non-alcoholic fatty liver disease (NAFLD). Within this spectrum of disease lies the potential for silent progression towards cirrhosis, leaving the patient with few options for treatment. Currently, the standard of care remains counseling on diet and exercise with the goal of reversing disease progression by addressing the underlying risk factors. LITERATURE REVIEW: Recent studies have shown that a correlation exists between low levels of serum 25-hydroxyvitamin D and hepatic injury from NAFLD. This has become an active area of research, due in part to the anti-inflammatory and immunoregulatory properties of vitamin D. The prospect of a simple and cost effective intervention that can exert its effects on the mechanisms behind the development of NAFLD is interesting and warrants further research. PROPOSED PROJECT: This proposal is for a double-blind, randomized, experimental study of vitamin D3 (cholecalciferol) versus placebo in a patient population of those with both clinically proven NAFLD and concomitant vitamin D deficiency. Liver fibrosis will be measured and staged with the use of FibroScan elastography. The statistical analysis thereafter will determine if a clinically significant reduction in hepatic fibrosis exists, compared with the results of the placebo group. CONCLUSIONS/SIGNIFICANCE: Should vitamin D prove to be an effective treatment option in reversing the progression of NAFLD, clinicians would be equipped with a simple and safe tool to augment their management of the patient. For those that experience barriers (i.e. lower socioeconomic status, other comorbidities, etc.) preventing them from improving diet and exercise, vitamin D would serve as an alternative therapy to aid in reducing their disease burden. Easier methods to treat their disease now projects improved quality of life years later

Racial/ethnic differences in hepatic steatosis in a population‐based cohort of post‐menopausal women: the Michigan Study of Women's Health Across the Nation

Aims The prevalence of hepatic steatosis may differ between post‐menopausal African‐American women and non‐Hispanic white women and by sex hormone binding globulin level. We examined prevalence of hepatic steatosis by race/ethnicity and associations with sex hormone binding globulin. Methods Participants included post‐menopausal women who underwent hepatic ultrasound ( n  = 345) at the Michigan site of the Study of Women's Health Across the Nation, a population‐based study. We examined hepatic steatosis prevalence by race/ethnicity and used logistic regression models to calculate the odds of hepatic steatosis with race/ethnicity and sex hormone binding globulin, after adjustment for age, alcohol use, waist circumference, high density lipoprotein cholesterol, triglycerides, systolic blood pressure and use of medications reported to lower intrahepatic fat. Results Fewer African‐American women than non‐Hispanic white women had hepatic steatosis (23 vs. 36%, P  = 0.01). African‐American women had lower triglyceride and low‐density lipoprotein cholesterol levels, but higher blood pressure and follicle‐stimulating hormone levels ( P  < 0.05). In the optimal‐fitting multivariable models, women in the highest tertile of sex hormone binding globulin (60.2–220.3 nmol/l) had a lower odds of hepatic steatosis (odds ratio 0.43, 95% CI 0.20–0.93) compared with women in the lowest tertile of sex hormone binding globulin (10.5–40.3 nmol/l). There was an interaction between race/ethnicity and medication use whereby non‐Hispanic white women using medications had three times higher odds of hepatic steatosis compared with African‐American women not using medications (odds ratio 3.36, 95%  CI 1.07–10.58). Interactions between race/ethnicity and other variables, including sex hormone levels, were not significant. Conclusions Hepatic steatosis on ultrasound may be more common in post‐menopausal non‐Hispanic white women than African‐American women and was associated with lower levels of sex hormone binding globulin. What's new? Although hepatic steatosis is common in post‐menopausal women, previous studies have not examined risk factors in this population, particularly sex steroids and sex hormone binding globulin. We report that increased sex hormone binding globulin, the primary binding protein of sex hormones and a risk factor for diabetes, was strongly associated with decreased odds of hepatic steatosis in both race/ethnicities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101792/1/dme12225.pd

MRI overview for fat quantification in non-alcoholic fatty liver disease in the clinical and research settings

The general purpose of this master’s thesis is to describe the MRI techniques used in scanning and post processing for quantifying liver fat percentages for the purpose of diagnosis and research. At the onset we will look at epidemiological data regarding nonalcoholic fatty liver disease, which is often called by the name of hepatic steatosis. Based on the prevalence of this disease it is worthwhile to fully understand non-invasive (MRI) analysis, and its use in the clinical and research setting. Following an introductory section regarding the basis of magnetic resonance imaging, we will take a more in-depth look at current methods utilized for liver fat quantification. Due to the massive population of those of suffer from this disease worldwide it is prudent to analyze current methods, as well as the implications that such research has and will have on the pharmaceutical approach to treating this disease. The purpose of this thesis is to elucidate the MRI techniques utilized for liver fat quantification and provide a comprehensive view of how these techniques are used for diagnosis in the clinical setting, and longitudinal studies in the research setting to measure liver fat levels and how they react to various treatment approaches

Vitamin D Signaling through Induction of Paneth Cell Defensins Maintains Gut Microbiota and Improves Metabolic Disorders and Hepatic Steatosis in Animal Models.

Metabolic syndrome (MetS), characterized as obesity, insulin resistance, and non-alcoholic fatty liver diseases (NAFLD), is associated with vitamin D insufficiency/deficiency in epidemiological studies, while the underlying mechanism is poorly addressed. On the other hand, disorder of gut microbiota, namely dysbiosis, is known to cause MetS and NAFLD. It is also known that systemic inflammation blocks insulin signaling pathways, leading to insulin resistance and glucose intolerance, which are the driving force for hepatic steatosis. Vitamin D receptor (VDR) is highly expressed in the ileum of the small intestine, which prompted us to test a hypothesis that vitamin D signaling may determine the enterotype of gut microbiota through regulating the intestinal interface. Here, we demonstrate that high-fat-diet feeding (HFD) is necessary but not sufficient, while additional vitamin D deficiency (VDD) as a second hit is needed, to induce robust insulin resistance and fatty liver. Under the two hits (HFD+VDD), the Paneth cell-specific alpha-defensins including α-defensin 5 (DEFA5), MMP7 which activates the pro-defensins, as well as tight junction genes, and MUC2 are all suppressed in the ileum, resulting in mucosal collapse, increased gut permeability, dysbiosis, endotoxemia, systemic inflammation which underlie insulin resistance and hepatic steatosis. Moreover, under the vitamin D deficient high fat feeding (HFD+VDD), Helicobacter hepaticus, a known murine hepatic-pathogen, is substantially amplified in the ileum, while Akkermansia muciniphila, a beneficial symbiotic, is diminished. Likewise, the VD receptor (VDR) knockout mice exhibit similar phenotypes, showing down regulation of alpha-defensins and MMP7 in the ileum, increased Helicobacter hepaticus and suppressed Akkermansia muciniphila. Remarkably, oral administration of DEFA5 restored eubiosys, showing suppression of Helicobacter hepaticus and increase of Akkermansia muciniphila in association with resolving metabolic disorders and fatty liver in the HFD+VDD mice. An in vitro analysis showed that DEFA5 peptide could directly suppress Helicobacter hepaticus. Thus, the results of this study reveal critical roles of a vitamin D/VDR axis in optimal expression of defensins and tight junction genes in support of intestinal integrity and eubiosis to suppress NAFLD and metabolic disorders

Cathelicidin suppresses lipid accumulation and hepatic steatosis by inhibition of the CD36 receptor.

Background and objectivesObesity is a global epidemic which increases the risk of the metabolic syndrome. Cathelicidin (LL-37 and mCRAMP) is an antimicrobial peptide with an unknown role in obesity. We hypothesize that cathelicidin expression correlates with obesity and modulates fat mass and hepatic steatosis.Materials and methodsMale C57BL/6 J mice were fed a high-fat diet. Streptozotocin was injected into mice to induce diabetes. Experimental groups were injected with cathelicidin and CD36 overexpressing lentiviruses. Human mesenteric fat adipocytes, mouse 3T3-L1 differentiated adipocytes and human HepG2 hepatocytes were used in the in vitro experiments. Cathelicidin levels in non-diabetic, prediabetic and type II diabetic patients were measured by enzyme-linked immunosorbent assay.ResultsLentiviral cathelicidin overexpression reduced hepatic steatosis and decreased the fat mass of high-fat diet-treated diabetic mice. Cathelicidin overexpression reduced mesenteric fat and hepatic fatty acid translocase (CD36) expression that was reversed by lentiviral CD36 overexpression. Exposure of adipocytes and hepatocytes to cathelicidin significantly inhibited CD36 expression and reduced lipid accumulation. Serum cathelicidin protein levels were significantly increased in non-diabetic and prediabetic patients with obesity, compared with non-diabetic patients with normal body mass index (BMI) values. Prediabetic patients had lower serum cathelicidin protein levels than non-diabetic subjects.ConclusionsCathelicidin inhibits the CD36 fat receptor and lipid accumulation in adipocytes and hepatocytes, leading to a reduction of fat mass and hepatic steatosis in vivo. Circulating cathelicidin levels are associated with increased BMI. Our results demonstrate that cathelicidin modulates the development of obesity

Hepatic steatosis and fibrosis: Non-invasive assessment

Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality. Therefore, there is a clear need for safe and noninvasive assessment modalities to determine hepatic steatosis, inflammation and fibrosis. This review covers key mechanisms and the importance of fibrosis and steatosis in the progression of liver disease. We address non-invasive imaging and blood biomarker assessments that can be used as an alternative to information gained on liver biopsy