Another great show expected this week with Tony. Topics Covered are below:
- Monsanto guilty of chemical poisoning inFrance
- Free speech become too expensive!
- Systematic review- the diagnosis and staging of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis
- EFSA sets recommended EU protein intakes at 0.8g/kg per dayHome Made Protein Shakes
Monsanto guilty of chemical poisoning inFrance
Mon, Feb 13 2012–By Marion Douet
PARIS (Reuters) – A French court on Monday declared U.S. biotech giant Monsanto(MON.N: Quote, Profile, Research) guilty of chemical poisoning of a French farmer, a judgment that could lend weight to other health claims against pesticides.–In the first such case heard in court in France, grain grower Paul Francois says he suffered neurological problems including memory loss, headaches and stammering after inhaling Monsanto’s (MON.N: Quote, Profile, Research) Lasso weedkiller in 2004.—He blames the agri-business giant for not providing adequate warnings on the product label.–The ruling was given by a court in Lyon, southeast France, which ordered an expert opinion of Francois’s losses to establish the sum of damages.–Lawyers for Monsanto could not immediately be reached for comment.–Previous health claims from farmers have foundered because of the difficulty of establishing clear links between illnesses and exposure to pesticides.–“I am alive today, but part of the farming population is going to be sacrificed and is going to die because of this,” Francois, 47, told Reuters.–He and other farmers suffering from illness set up an association last year to make a case that their health problems should be linked to their use of crop protection products.—The agricultural branch of the French social security system says that since 1996, it has gathered farmers’ reports of sickness potentially related to pesticides, with about 200 alerts a year.—But only about 47 cases have been recognised as due to pesticides in the past 10 years. Francois, who suffers from neurological problems, obtained work invalidity status only after a court appeal.
LESS INTENSIVE NOW—The Francois case goes back to a period of intensive use of crop-protection chemicals in the European Union. The EU and its member countries have since banned a large number of substances considered dangerous.–Monsanto’s Lasso was banned in France in 2007 following an EU directive after the product had already been withdrawn in some other countries.-France, the EU’s largest agricultural producer, is now targetting a 50 percent reduction in pesticide use between 2008 and 2018, with initial results showing a 4 percent cut in farm and non-farm use in 2008-2010.—The Francois claim may be easier to argue than others because he can pinpoint a specific incident – inhaling the Lasso when cleaning the tank of his crop sprayer – whereas fellow farmers are trying to show accumulated effects from various products.”It’s like lying on a bed of thorns and trying to say which one cut you,” said a farmer, who has recovered from prostate cancer and asked not to be named.–The French association of crop protection companies, UIPP, says pesticides are all subject to testing and that any evidence of a cancer risk in humans leads to withdrawal of products from the market.[U1] –“I think if we had a major health problem with pesticides, we would have already known about it,” Jean-Charles Bocquet, UIPP’s managing director, said.–The social security’s farming branch this year is due to add Parkinson’s disease to its list of conditions related to pesticide use after already recognising some cases of blood cancers and bladder and respiratory problems.–France’s health and environment safety agency (ANSES), meanwhile, is conducting a study on farmers’ health, with results expected next year.(Writing by Gus Trompiz; Editing by Muriel Boselli, Sybille de La Hamaide and Jane Baird)
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Free speech become too expensive!
http://alexandramorton.typepad.com /
Tomorrow, a judge in a BC court will be asked to make an instantaneous decision on day 20 of a 20-day trial whether to grant an injunction against Don Staniford speaking about the fish farm industry.– Similarly, the proceedings in courtroom #52, Vancouver Law Courts would have little significance if you could not see the roles of Norway, China, Premier Christy Clark and shareholders. The defamation hearing Staniford vs. Mainstream is a test – can the corporate world tolerate democracy. –Big tobacco and Norwegian salmon feedlots hired the same strategist – Hill and Knowlton. The Tobacco Industry knew their product was suspect in killing people, and so it took skilled professionals to get people to keep buying cigarettes. Hill and Knowlton are top-flight, known for managing public relations for the Gulf War, the Exxon oil spill inAlaska, the Three Mile Island nuclear disaster and the massacre atTiananmen Square. The salmon farmers have spent millions advertising just in the last two years.
But truth is more powerful.—Staniford used cigarette pack imagery (http://salmonfarmingkills.com) to make the point that farm salmon contain cancer-causing chemicals, that they are spreading like a cancer, choking off wild salmon migration routes and otherwise harming oceans worldwide. Staniford never named Mainstream in these graphics, but BC salmon farming is 92% Norwegian owned andNorwayis the biggest shareholder in Mainstream’s parent company, Cermaq. So throughMainstream,Norwayis attempting to protect its industry, calling for an immediate gag orderon Staniford and $1 million in damages. —Why such a big response to a guy with big mouth and no money?–Under the watchful eye of Justice Adair, we saw evidence that the salmon farming industry knew cancer-causing chemicals are in their product, even as they targeted pregnant women to eat more farm salmon—In 2011, a multi-million dollar ad campaign put fish farm propaganda in our mailboxes saying-“Farmed salmon is natural, nutritious and free of contaminants[U2] ”–They know there are contaminants in farm salmon, but they paid huge bucks to tell British Columbians there are none.–While the salmon farming industry has the resources to hire Hill and Knowlton, Staniford’s tools are biting satire, superheroes, three websites, a Captain Condom suit and edgy, British humor. He knows people won’t read dry exposés on the industry. So he pushed the limits andNorwayis pushing back hard. Mr. Wotherspoon, commercial litigation lawyer for Fasken Martineau, with 9 offices around the world, is asking Justice Adair for an immediate gag order on Mr. Staniford to shut him up for the few remaining weeks he is inBritish Columbia, before he is deported.–Norwegians should be concerned about this. In 2010, the Norwegian Nobel Peace Prize was awarded to Chinese free speech dissident, Lui Xiaobo. When Norwegian actress Liv Ullmann accepted the award on Xiaobo’s behalf she said-“To strangle freedom of speech is to trample on human rights, stifle humanity, and suppress truth.” –Chinatook offence and imposed new rules concerning import of Norwegian farm salmon causing a 68% decline in shipments of Norwegian farm salmon to China.Massive stores of farm salmon rotted in warehouses. –While they are vulnerable to the trade winds they create, society’s rapacious corporate giants can save themselves from the spin of the vortex merely by leaning on another leg in another country. WhatNorway’s salmon feedlot operators lost inNorway, they gained in BC. BC farm salmon export toChinaskyrocketed from $249,000 in 2010 to more than $3.8 million in 2011 (VancouverSun, Feb 2012). –Now, however, free speech is threatening the profitable BC /Chinafarm salmon connection. Staniford keeps saying salmon farming spreads disease.Indeed the ISA virus, the most lethal virus known to salmon and a form of influenza spread from Norway to Chile in 2007 causing 2 $billion dollars of damage. When my colleagues and I reported European strain ISA virus positive tests here in BC, what did the provincial Minister of Agriculture, Don McRae do? He made a statement that Premier Christy Clark would personally tellChinawe do not have ISA virus in BC.The Canadian Food Inspection Agency testified at the Cohen Inquiry in December that if ISA virus is in BC, trade in farm salmon could cease. –Recent industry trade paper headlines make it clear the farm salmon market is collapsing, because there is too much uneaten farm salmon on the market driving prices down below cost.Two weeks ago the US lifted a 20-year 24% duty on Norwegian farm salmon. This will allow Norwegian companies to sell more farm salmon to the U.S. and might save the motherships, but it puts their BC companies at greater risk.[U3] Farm salmon companies in BC report firing people and downsizing, they cannot survive without the Chinese market.—And so gale force winds spawned on the other side of the planet, when Norway having awarded one man for free speech,have slammed into a small courtroom in Vancouver where Norway seeks to take free speech away from another man. The structure of the courts and democracy are creaking, rivets popping, paint peeling.—Norway, I want to say to you – ISA virus is in BC, cancer-causing chemicals are in your fish, you do use BC as a dump as your companies never shovel their manure and wild fish are being killed in your pens. —You can silence Staniford, but at what cost? You won’t hide these truths, because they are lying around in evidence everywhere. —Corporations are like addicts, they can’t stop themselves. They are blind to everything, but the next quarter. What does it mean when you hand out the Nobel Peace prize in one part of the world and then work to erode democracy where it has become inconvenient to business? —
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Systematic review- the diagnosis and staging of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis
J K Dowman,*† J W Tomlinson,‡ and PN Newsome*†
*Centre for Liver Research, 5th floor,InstituteofBiomedical Research,UniversityofBirmingham, Edgbaston,BirminghamB15 2TT,UK
†The Liver Unit,QueenElizabethHospitalBirmingham, Edgbaston,BirminghamB15 2TH,UK
‡Centre for Endocrinology, Diabetes and Metabolism,UniversityofBirmingham, Edgbaston,BirminghamB15 2TT,UK
Dr J. K. Dowman, Centre for Liver Research, 5th floor,InstituteofBiomedical Research,UniversityofBirmingham, Edgbaston,BirminghamB15 2TT,UK. E-mail: j.k.dowman@bham.ac.uk
This uncommissioned systematic review was subject to full peer-review.
Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms
Received September 7, 2010; Revised September 27, 2010; Revised December 2, 2010; Accepted December 6, 2010.
Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
This article has been cited by other articles in PMC.
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Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent cause of liver disease in Western countries. The development of non-alcoholic steatohepatitis (NASH) and fibrosis identifies an at-risk group with increased risk of cardiovascular and liver-related deaths. The identification and management of this at-risk group remains a clinical challenge.
Aim
To perform a systematic review of the established and emerging strategies for the diagnosis and staging of NAFLD.
Methods
Relevant research and review articles were identified by searching PubMed, MEDLINE and EMBASE.
Results—There has been a substantial development of non-invasive risk scores, biomarker panels and radiological modalities to identify at-risk patients with NAFLD without recourse to liver biopsy on a routine basis. These modalities and algorithms have improved significantly in their diagnosis and staging of fibrosis and NASH in patients with NAFLD, and will likely impact on the number of patients undergoing liver biopsy.
Conclusions
Staging for NAFLD can now be performed by a combination of radiological and laboratory techniques, greatly reducing the requirement for invasive liver biopsy.
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Introduction
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease ranging from simple steatosis, to inflammatory steatohepatitis (NASH) with increasing levels of fibrosis and ultimately cirrhosis. NAFLD is closely associated with obesity and insulin resistance, and is now recognised to represent the hepatic manifestation of the metabolic syndrome. Since the term NASH was first coined by Ludwig et al. in 1980,1 the prevalence of NAFLD has risen rapidly in parallel with the dramatic rise in population levels of obesity and diabetes,2 resulting in NAFLD now representing the most common cause of liver disease in the Western world.3—Despite recent advances in elucidating the complex metabolic and inflammatory pathways involved in NAFLD, the pathogenesis of steatosis and progression to steatohepatitis and fibrosis/cirrhosis is not yet fully understood.4, 5 While steatosis alone appears to be associated with a relatively benign prognosis,6 factors known to be involved in progression to more advanced and clinically relevant disease include inflammatory cytokines/adipokines, mitochondrial dysfunction and oxidative stress.7 Insulin resistance causes impaired suppression of adipose tissue lipolysis, leading to increased efflux of free fatty acids (FFA) from adipose tissue to the liver.Ø8 Hyperinsulinaemia also promotes hepatic de novo lipogenesis, which is markedly increased in NAFLD patients compared with normal individuals.9 It is now recognised that FFA promote insulin resistance, inflammation and oxidative stress,10, 11 and thus rather than being harmful, hepatic triglyceride accumulation may actually be protective by preventing the harmful effects of FFA.12 The important role of oxidative stress mechanisms, pro-inflammatory cytokines such as TNFalpha and interleukin 6, and adipokines such as leptin (proinflammatory and pro-fibrotic), and adiponectin (anti-inflammatory and insulin-sensitising), in promoting NASH are also becoming increasingly delineated.5 However, evidence that only a minority of patients with NAFLD progress to more advanced stages of NASH suggests that disease progression is likely to depend on a complex interplay between such factors and underlying genetic predisposition.4, 7—The causes, epidemiology and natural history of NAFLD will be covered briefly, before discussing the established and emerging means of assessing and staging patients with NAFLD.
Causes of NAFLD
In the great majority of cases, NAFLD arises in association with one or more features of the metabolic syndrome, namely insulin resistance, glucose intolerance or diabetes, central obesity, dyslipidaemia and hypertension.13–15 However, after exclusion of a history of significant alcohol intake, which is conventionally <20 g/day,16 other causes of steatosis which should be considered include nutritional causes, e.g. rapid weight loss and total parenteral nutrition, rare metabolic disorders and drug-induced steatosis. Commonly implicated agents include glucocorticoids, amiodarone, synthetic oestrogens and highly active antiretroviral drugs (HAART).16–18 Steatosis is also frequently associated with hepatitis C, particularly genotype 3, and endocrine disorders such as polycystic ovary syndrome (PCOS),19, 20 hypopituitarism21 and hypothyroidism.22
Epidemiology—The prevalence of NAFLD is estimated to be between 20% and 30% in Western adults,23, 24 rising to 90% in the morbidly obese.25 NASH, the more advanced and clinically important form of NAFLD, is less common, with an estimated prevalence of 2–3% in the general population16 and 37% in the morbidly obese.25 Of concern, NAFLD now affects 3% of the general paediatric population, rising to 53% in obese children,26, 27 with considerable implications for future disease burden. Steatosis was present in 70% of a large unselected cohort of patients with type 2 diabetes.28
Non-alcoholic fatty liver disease affects all ethnic groups, although prevalence appears to be higher in Hispanic and European Americans compared with African-Americans. This difference remains after controlling for insulin resistance and obesity23, 29 and may be related to ethnic differences in lipid metabolism.23, 30—Natural history
Patients with a diagnosis of NAFLD have been shown across several studies to have a worse outcome when compared with an age and sex-matched general population.31 Of note, the excess mortality in this group is attributable to both cardiovascular and liver-related causes.32, 33 Since the description in 1999 of the prognostic relevance of different histological types of NAFLD,34 several subsequent studies have demonstrated that the presence of just simple steatosis, with no inflammation or fibrosis, is associated with a similar overall and liver-related mortality to that of an age and gender matched general population. This reinforces the need to stratify patients with NAFLD into simple steatosis or more advanced disease. More advanced disease can be defined as advancing levels of fibrosis and/or the presence/level of inflammation and hepatocyte ballooning. This distinction is pertinent as cohort studies thus far have only identified advanced fibrosis, and not inflammation, as a predictor of worse clinical outcome.32 This may be a type 2 error reflecting small sample sizes, or it may be attributed to additional factors such as PNPLA3 polymorphisms35 regulating the development of fibrosis.
Methods
A systematic literature search was performed to identify studies assessing methods for the diagnosis and staging of NAFLD/NASH. Relevant articles were identified by searching the PubMed database, MEDLINE and EMBASE, limited to articles published in the English language but not date-restricted. Search terms included fatty liver, NAFLD, NASH, steatosis, AND biomarkers, non-invasive, diagnosis, assessment, staging. Additional searches were also made for each of the individual methods described, e.g. NAFLD fibrosis score, transient elastography, Fibroscan, Fibrotest etc. Selected articles referenced in these publications were also examined.
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Inclusion criteria
Studies were included if:
they were meta-analyses, systematic reviews or primary studies of one or more relevant diagnostic/staging tool;
they included at least 30 subjects, to reduce the risk of including underpowered studies;
liver biopsy was used as the reference standard;
the diagnosis of NAFLD had been established with exclusion of other causes of liver disease.
Exclusion criteria
Studies were excluded if:
publications were not in English;
data on disease stage e.g. fibrosis stage, was not identifiable;
they were only presented in abstract form.
Using the search strategy described above, approximately 150 articles were considered. Following review, 68 articles met the selection criteria and were included in the analyses.
Data extraction
JD performed the data extraction, which was then checked by the remaining authors (PN and JT).
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NAFLD: making the diagnosis
The diagnosis of NAFLD should be strongly suspected in the presence of features such as obesity, diabetes and obstructive sleep apnoea (OSA); however, other causes should always be considered before attributing abnormal liver function tests (LFTs) to NAFLD alone (Figure 1). Alternative diagnoses which should be excluded by history and serological testing include the viral hepatitides, excess alcohol consumption, haemochromatosis, autoimmune liver disease, alpha-1 antitrypsin deficiency, Wilson’s disease and drug-induced liver dysfunction.
Figure 1
Making the diagnosis of NAFLD.
The majority of patients with NAFLD are asymptomatic and the diagnosis suspected after finding elevated transaminases on routine testing. Hepatic steatosis is also a frequent incidental finding on ultrasound scan (US) performed for other reasons such as suspected gallstone disease. The most common symptoms are right upper quadrant discomfort and fatigue, although the latter may also be caused by OSA which is frequently observed in the typically obese population with NAFLD. Hepatomegaly is the most common clinical finding, with signs of chronic liver disease rarely present in the absence of cirrhosis. A recent study reported the novel finding that increased dorsocervical lipohypertrophy was the anthropometric parameter most strongly associated with severity of steatohepatitis.36
Although NAFLD is often diagnosed after the finding of mildly abnormal LFTs, more than two thirds of patients have normal aminotransferase levels at any given time37 and the entire histological spectrum of NAFLD can be observed in patients with normal alanine aminotransferase (ALT) values.38, 39 ALT is usually greater than aspartate aminotransferase (AST), and rarely more than three times the upper limit of normal. An AST:ALT ratio greater than 1.0 suggests the presence of more advanced disease.40 Alkaline phosphatase can be slightly elevated but is rarely the only liver function test abnormality.41Gamma-glutamyltransferase (GGT) is frequently elevated and may also be a marker of increased mortality.42, 43 Low albumin and hyperbilirubinaemia indicate advanced liver disease and are not otherwise features of NAFLD.44 Iron studies may show an elevated ferritin in up to 50% of patients and elevated transferrin saturation in approximately 10%.40 However, such findings do not appear to correlate with elevated hepatic iron concentration, and the role of hepatic iron in the pathogenesis of NASH remains unclear.45–The Fatty Liver Index (FLI) was developed as a simple algorithm to predict fatty liver on USS in the general population.46 The FLI uses four variables of BMI, waist circumference, GGT and serum triglyceride levels, and achieved an accuracy of 0.84 in detecting fatty liver.46 The FLI has since been utilised by several groups in population studies of NAFLD.47–49 Ultrasound (USS) is a commonly used test in patients with suspected NAFLD, with steatosis typically appearing as a hyperechogenic liver. A recent study examined the accuracy of USS in 235 patients with suspected liver disease who underwent liver biopsy, and showed a sensitivity of 64% and specificity of 97%, rising to 91% and 93% respectively in patients with at least 30% steatosis.50 However, the presence of morbid obesity considerably reduces sensitivity and specificity.51 USS is unable to quantify the amount of fat present or provide any staging of disease,52 and is operator-dependent with significant intra- and inter-observer variability.53
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Staging of NAFLD
Having made a diagnosis of NAFLD, the next step is to determine the severity, as that provides important information on prognosis. Historically this has required liver biopsy, although there have been many recent advances which allow non-invasive management for many patients. When staging patients with NAFLD, there are two aspects to consider; (i) the level of fibrosis and (ii) the level of inflammation/ballooning (Table 1).
Table 1
Methods for assessing fibrosis and NASH
The histological spectrum of NAFLD ranges from simple steatosis through steatohepatitis to fibrosis and cirrhosis. There are no pathological changes which can definitively distinguish NAFLD from alcoholic liver disease (ALD), thus an accurate alcohol history is essential to distinguish between these two common conditions.54 The histological changes in NAFLD are mainly parenchymal and in a perivenular location, although portal and periportal lesions may occur.54 Simple steatosis is usually macrovesicular resulting from accumulation of triglycerides within hepatocytes.44 Features of steatohepatitis include hepatocellular injury, characterised by ballooned hepatocytes, with inflammation and fibrosis.54 Mitochondrial abnormalities may occur in NASH, but rarely in simple steatosis,11 supporting a role for mitochondrial defects in the pathogenesis of NAFLD-related liver injury.54, 55 The typical histological features of steatosis and inflammation often disappear in advanced disease,56, 57 thus many cases of ‘cryptogenic’ cirrhosis are likely caused by NASH.56–58 Hepatocellular carcinoma is a well-recognised complication of NASH-related cirrhosis,59, 60 but can also be associated with precirrhotic NAFLD.61, 62 Several systems have been proposed for the histological assessment of NAFLD, of which the Kleiner NAFLD activity score (NAS)63 is probably the most well established. The NAS provides a composite score based on the degree of steatosis (0–3), lobular inflammation (0–3) and hepatocyte ballooning (0–2), with an additional score for fibrosis. A score of ≥5 suggests probable or definite NASH, and ❤ indicates that NASH is unlikely.63 However, although liver biopsy currently remains the gold standard for diagnosis of NASH, limitations of this technique include intra-observer variation63, 64 and sampling variability,65, 66 with features such as fibrosis often not uniformly distributed.54[U4]
Non-invasive assessments of NAFLD severity—Such assessments can provide information on the amount of liver fibrosis and/or the presence of NASH, features which are usually, but not always, found together. The focus on fibrosis is based on cohort studies which demonstrate that fibrosis, rather than inflammation, predicts outcome. Several non-invasive diagnostic panels and scoring systems have been developed with varying diagnostic utility. The uneven distribution of fibrosis throughout the liver in NAFLD indicates that such scoring systems may potentially represent a more accurate reflection of global liver fibrosis severity than is permitted by the current gold standard liver biopsy,67[U5] which samples only 1/50 000th of the organ and is prone to significant sampling error.65, 66
Assessment of fibrosis
(i) Demographic factors and simple blood tests: Several diagnostic panels have been developed to facilitate the non-invasive assessment of NAFLD and differentiation between different stages of disease. These are generally based on a number of laboratory measurements, often in combination with clinical parameters such as age, sex and BMI. Such scoring systems have generally demonstrated greater utility in the detection of advanced fibrosis than intermediate and early stages of fibrosis, a group potentially more likely to benefit from therapeutic interventions.37–The BARD score is a simple scoring system designed to identify NAFLD patients with a low risk of advanced disease. It combines three variables of BMI, AST/ALT ratio (AAR) and the presence of diabetes into a weighted sum (BMI ≥28 = 1 point,AARof ≥0.8 = 2 points, DM = 1 point), to generate a score from 0 to 4. In the original study, a score of 2–4 was shown to be associated with an odds ratio for advanced fibrosis of 17 and a negative predictive value of 96%.68 A further study of the BARD score in 138 patients with biopsy-proven NAFLD revealed an area under the receiver operating curve (AUROC) of 0.67 (95% CI, 0.56–0.77), with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 51%, 77%, 45% and 81% respectively.69 In a recent study including 145 patients with biopsy-proven NAFLD, McPherson et al. compared the diagnostic performance of five simple non-invasive tests [BARD score, NAFLD fibrosis score, FIB-4 score, AST to platelet ratio index (APRI) and ALT/AST ratio], for the identification of NASH-related advanced fibrosis. Here the BARD score demonstrated an AUROC of 0.77, with sensitivity 89%, specificity 44%, NPV 95% and PPV 25%.70 The BARD score was also validated in a Polish NAFLD cohort, where an NPV of 97% was demonstrated,71 but appeared less useful in a Japanese cohort, where the AUROC was 0.73 with NPV 77%.72 The BARD score is easily calculated and thus represents a simple tool for excluding the presence of advanced fibrosis in NAFLD patients. The AST-to-platelet ratio index (APRI),73 AST/ALT ratio,74 and FIB-4 score75 have previously demonstrated utility in the non-invasive assessment of fibrosis in a number of chronic liver diseases. Several recent studies have also examined the role of these markers in NAFLD, as will be described.–The APRI was originally developed for use in chronic hepatitis C,73 but its utility in NAFLD has since been studied by a number of groups. Using this score, Cales et al. demonstrated an AUROC of 0.866 for significant fibrosis, 0.861 for severe fibrosis and 0.842 for cirrhosis in a study of 235 NAFLD subjects.76 However, significantly lower values were obtained in other studies, where AUROCs of 0.564 for significant fibrosis, 0.568 for advanced fibrosis,77 and 0.786 for predicting cirrhosis78 were demonstrated. In their study of 145 NAFLD patients, McPherson et al. reported an AUROC of 0.67 for the diagnosis of advanced fibrosis.70
The AST/ALT ratio (AAR) is calculated using two widely available laboratory liver function tests. In addition to its utility as an individual marker, theAARis also a component of several other fibrosis scoring systems including the NAFLD Fibrosis score and BARD score. Despite its simplicity, using a cut-off of 0.8 McPherson et al. demonstrated an AUROC of 0.83, with sensitivity 74%, specificity 78% and NPV of 93% for the diagnosis of advanced fibrosis in NAFLD using the AAR.70 The United States Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) recently investigated the utility of readily available clinical and laboratory variables to predict histological severity of NASH in >600 patients with biopsy-proven NAFLD. In this study, a combination of serum AST, ALT and theAARperformed only modestly (AUROC 0.59) for predicting steatosis, but was able to predict cirrhosis with an AUROC of 0.81. However, the addition of demographic data, comorbidities and several other routinely measured laboratory tests increased the AUROCs to 0.79 for NASH and 0.96 for cirrhosis.79–The FIB-4 test combines age with three standard biochemical values (platelets, ALT and AST) to assess fibrosis. In NAFLD FIB-4 has demonstrated similar results to the AST/ALT ratio where, using a cut-off of 1.3, an AUROC of 0.86, sensitivity 85%, specificity 65% and NPV of 95% were demonstrated for the diagnosis of advanced fibrosis.70 In a US-based comparison of several non-invasive markers of fibrosis in 541 NAFLD patients, FIB-4 had the highest AUROC of 0.802, with PPV and NPV of 80% and 90% respectively for diagnosis of advanced fibrosis. In this study, AUROCs for the NAFLD fibrosis score, AAR, APRI, AST:platelet ratio and BARD score were 0.768, 0.742, 0.73, 0.72 and 0.70 respectively.80—Increased serum GGT level has also been shown to be associated with advanced fibrosis in NAFLD, with a study of 50 NAFLD patients demonstrating an AUROC of 0.74 for the prediction of advanced fibrosis. Using a cut-off serum GGT value of 96.5 U/L, GGT predicted advanced fibrosis with 83% sensitivity and 69% specificity.81–FibroMeter is a panel of serum markers which was originally developed for staging fibrosis in chronic HCV.82 However, FibroMeter NAFLD has since been developed which has shown good diagnostic accuracy in staging NASH-related fibrosis. This panel combines seven variables (age, weight, fasting glucose, AST, ALT, ferritin and platelet count), and in a study of 235 NAFLD patients demonstrated AUROCs of 0.943 for significant fibrosis, 0.937 for severe fibrosis and 0.904 for cirrhosis respectively. The sensitivity, specificity, PPV and NPV of FibroMeter for diagnosing significant fibrosis were 78.5%, 95.9%, 87.9 and 92.1%.76
The NAFLD fibrosis score (NFS) is a panel comprising six variables of age, hyperglycaemia, BMI, platelet count, albumin and AST/ALT ratio, which was constructed using a large panel of 733 biopsy-proven NAFLD patients across several centres worldwide. Two cut-off scores were generated to predict the likelihood of the presence or absence of advanced fibrosis respectively.67 In the original study, by applying the low cut-off score (−1.455), the NFS had an NPV of 93% and 88% in the estimation and validation groups respectively for excluding the presence of advanced fibrosis. By applying the high cut-off score (0.676), PPVs of 90% and 82% in the estimation and validation groups respectively were achieved for predicting the presence of advanced fibrosis. The AUROC was 0.84, and application of this model to the
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EFSA sets recommended EU protein intakes at 0.8g/kg per day The European Food Safety Agency (EFSA) has published population reference intakes (PRIs) for protein, the latest stage of its work on dietary reference values (DRVs), with a particular focus on levels needed during pregnancy and childhood. A PRI indicates the amount of an individual nutrient that the majority of people in a population need for good health depending on their age and sex.—The population reference intake for adults of all ages was estimated to be 0.83g protein/kg body weight per day [U6] and,” said the Parma-based assessor. .In delivering an opinion on EU is applicable both to high quality protein and to protein in mixed diets protein intakes, EFSA’s Panel on Dietetic Products, Nutrition and Allergies (NDA) also acknowledged that intakes twice the 0.83 level were, regularly consumed from mixed diets by some physically active and healthy adults in Europe [U7] The NDA said such levels are considered safe “Data from food consumption surveys show that actual mean protein intakes of adults in Europe are at, or more often above, the PRI of 0.83g/kg body weight per day,” the NDA wrote.—But less positively for industry, the panel said dietary reference values (DRVs) could not be established for several health conditions due to insufficient data The available data on the effects of an additional dietary protein intake beyond the PRI on muscle mass and function, on body weight control and obesity (risk) in children and adults, and on insulin sensitivity and glucose homeostasis do not provide evidence that can be considered as a criterion for determining DRVs for protein,” it said.–likewise, the available evidence does not permit the conclusion that an additional protein intake might affect bone mineral density and could be used as a criterion for the setting of DRVs for protein.”–In this way it added that DRVs could not be set for amino acids because they “are not provided as individual nutrients but in the form of protein.”“In addition, the Panel notes that more data are needed to obtain sufficiently precise values for indispensable amino acid requirement. ”Demographic breakdown The panel recommended PRIs for population groups such as pregnant women who should consume 1, 9 and 28g of protein per day in the first, second and third trimesters of pregnancy respectively.Lactating women should consume 19g/d for the first six months and 13g/d afterwards.-[U8] Children should also increase intake above the PRI depending on their age.-” Patent pending Magtein promises to be the next key ingredient for memory and cognitive health. Two published studies indicate Magtein’s role in short–term and long–term memory improvement and alleviating anxiety response-Data from dietary surveys show that the average protein intakes in European countries vary between 67-114g/d in adult men and 59-102g/d in women – between 12-20% of total energy intake for both sexes. The NDA said accurate European protein intake data per/kg was scarce but varied between 0.8 to 1.25g/kg for adults. EFSA has raised a number of positive points about protein, not least the possibility that the PRV should be increased for pregnant and lactating women, claims Suzane Leser, nutrition manager, Volac Lifestyle Ingredients. Labelling misalignment? Leser said that on reading the Opinion we see a potential misalignment between EFSA recommendations and the new Food Information Regulation (FIR”The EFSA opinion states that when the aim is to indicate a product’s potential to supply amino acids, the use of the NCF specific to the food is more relevant. For dairy products this is x 6.38 as established in Directive 92/46/EEC for the sale of milk and milk products. However, to aid the simplicity of the labelling process the new Food Information Regulation states that a standard conversion rate should be used for all protein sources: x 6.25. This means that protein levels based on N x 6.25 typically underestimate the true protein contribution from high quality protein sources and, most critically, significantly overestimate the contribution from protein sources of low quality.[U9] ” She argues it is not just a consumer labelling issue but potentially one of resource efficiency. ”In line with the above Directive, dairy products are commonly traded with protein NCF x 6.38. Assuming all customers declare protein in compliance with labelling regulations as N x 6.25, there must be unnecessary over-supply. This is uneconomical because protein is the most costly of the food elements to consumers, and from a sustainability perspective hardly in line with the European Sustainable Consumption and Production Policies
Home Made Protein Shakes—will give some ideas to make a good protein shake ( meal ) take 30 grams ( or one scoop of a container for protein ) of gelaton— and add to 2 cups of water in a pot and boil and when water is boiling add the gelaton—in the blender add 3-4 eggs ( whole eggs with no shells) 1 tsp of oil or a slice of butter—add herbs or condiments of choice to this ( garlic and onion powders—sea salt—tumeric—pepper –paprika) once the gelaton is dissolved then get the blender going with the eggs –leave the lid on top and open center of lid where you can pour into the blender while blending—once the pot is emptied then allow for blending for about 2-4 minutes—when done you will have cooked the egg in that solution and it will have blended—you have now a protein shake with the equivalency of 45 grams of protein—
Take ¼ container of cottage cheese add to blender –add water 1 ½ cup – 2cup-add berries or fruit—add 1 tablespoon of oil of your choice—and add gelaton 15 grams—blend for 3 minutes—you have 40 grams of protein
- Take yogurt ( Balkan Style original) and take half the container and add 1 multiple vitamin complete with B’s and other nutrients add 2 capsules—add fat ( of choice) and add water 2 cups—and add cocoa and 1 scoop of dried egg protein—blend together for 3 minutes—when done you have made a meal replacement with a complete meal 30 grams of protein
ØIn the Morning consume 3 eggs and 2 oz of yogurt and add fat to either the eggs or yogurt—-have some fruit like apples or berries or citrus—have a tea—this will give you 20 grams of protein
So you can see how it is easy to get your daily requirement of protein—
ØDuring the day consume a adequate amount of protein from nut –animal –dairy sources –and always ad fat with the protein
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