title: David Tua

text: In 2004, Tua's accountant learned that the boxer's finances with his boxing company, Tuaman Inc. Ltd., were tangled with company expenses; Tua no longer has most of his $NZ 20 million in purses from his professional matches, and important assets Tua thought he owned alone were anything but, including a piece of coastal land at Pakiri. Tuaman Inc. Ltd had business expenses flowing in various directions, involving companies and clients Tua had no knowledge of. Tua's own home was purchased with borrowed money, and the boxer's purses were linked to renovation costs for Martin Pugh's property. These findings were based on documents from Pugh's offices.


title: David Tua

text: In 2005 Tua took Kevin Barry and Martin Pugh to court over their business arrangements. Barry and Pugh accused Tua of manipulating them to collect revenue, yet Tua maintained that he knew little of the men's affairs and did what they told him to do out of trust. The dispute gave both sides legal victories: over the issue of the coastal land property, the court ruled in favor of Barry and Pugh, since Tua failed to properly clarify his ownership over the land; on the issue of the terminated 2003 contract, the court ruled in Tua's favour, concluding he clearly owed no expenses to his former management from that contract. In October 2009, it was reported in "The New Zealand Herald" that the parties had settled all previously unresolved matters arising from the protracted litigation.


title: David Tua

text: In May 2007, Cedric Kushner, president of Gotham Boxing Inc. and Tua's promoter, filed a $5 million lawsuit against IBF heavyweight champion Wladimir Klitschko and promoter Shelly Finkel among others – and while the lawsuit is unrelated to Tua, Kushner has stated he will drop the lawsuit if Tua is given a title bout against Klitschko in 2008, which ultimately failed to materialize.


title: David Tua

text: In September 2009, Tua's aunt was killed in the Samoa tsunami. In early October he travelled to Samoa with cousin Va'aiga Tuigamala to see how they could help.


title: David Tua

text: In the 2019 Queen's Birthday Honours, Tua was appointed an Officer of the New Zealand Order of Merit, for services to youth, boxing and the community, having previously been appointed a Member of the New Zealand Order of Merit, for services to boxing, in the 2001 New Year Honours.


title: David Tua

text: In 1996, Tua was honored by the country of Tuvalu, with a stamp commemorating the 1996 Summer Olympic Games in Atlanta, Georgia, United States bearing Tua's likeness and name on it.


title: Banastre Tarleton

text: Sir Banastre Tarleton, 1st Baronet, GCB (21 August 175415 January 1833) was a British general and politician. He is best known as the lieutenant colonel leading the British Legion at the end of the American Revolution. He later served in Portugal and held commands in Ireland and England. Consequently, he had hoped to command British forces fighting the French in the Peninsular War. However, that position was given to Arthur Wellesley.


title: Banastre Tarleton

text: Tarleton's cavalrymen were colloquially known as "Tarleton's Raiders". During most of his service in North America, he led the British Legion, a provincial unit organised in New York in 1778. After returning to Great Britain in 1781 at the age of 27, Tarleton was elected a Member of Parliament for Liverpool and returned to office in the early 19th century. As such, Tarleton became a prominent Whig politician despite his young man's reputation as a "roué". Tarleton came from a family of slavers, and reflected that during his political career, where he was a prominent opponent of British abolitionists.


title: Banastre Tarleton

text: Banastre Tarleton was the third of seven children born to merchant John Tarleton (1718–1773), who served as Mayor of Liverpool in 1764 and was involved in the transatlantic slave trade. His paternal grandfather Thomas Tarleton had been a shipowner and slave trader.


title: Banastre Tarleton

text: Banastre's younger brother John (1755–1841) entered the family business. He was elected as a member of Parliament (MP).


title: Banastre Tarleton

text: Tarleton was educated at the Middle Temple, London and went to University College, Oxford, in 1771, preparing for a career as a lawyer. In 1773 at the age of 19, he inherited £5,000 on his father's death. He squandered almost all of it in less than a year on gambling and women, mostly at the Cocoa Tree club in London. In 1775 he purchased a commission as a cavalry officer (cornet) in the 1st Dragoon Guards (effective from 2 May 1775), where he proved to be a gifted horseman and leader of troops. Owing to his abilities, he worked his way up through the ranks to lieutenant colonel without having to purchase any further commissions.


title: Banastre Tarleton

text: In December 1775, at the age of 21, the volunteer-soldier Banastre Tarleton sailed from Cork to North America, where the American War of Independence (1775–83) had broken out. Tarleton sailed with Lord Cornwallis as part of an expedition to capture the southern city of Charleston, South Carolina. After that expedition failed, at the Battle of Sullivan's Island (28 June 1776), Tarleton joined the main British Army under command of General William Howe, in New York


title: Banastre Tarleton

text: Under the command of Colonel William Harcourt, Tarleton, as a cornet, was part of a scouting party sent to gather intelligence on the movements of General Charles Lee, in New Jersey. On 13 December 1776, Tarleton surrounded a house in Basking Ridge, and forced Gen. Lee, still in dressing gown, to surrender, by threatening to burn down the house; the prisoner of war, General Lee, was taken to New York, and later was used in an exchange of prisoners.


title: Banastre Tarleton

text: In the course of the colonial war in North America, Cornet Tarleton's campaign service during 1776 earned him the position of brigade major at the end of the year; he was twenty-two years old. He was promoted to captain on 13 June 1778. Major Tarleton was at the Battle of Brandywine and at other battles in the campaigns of 1777 and 1778. One such battle, in 1778, was an attack upon a communications outpost in Easttown Township, Chester County, Pennsylvania, which was guarded by troops commanded by Capt. Henry Lee III, of the Continental Army, who repulsed the British attack, and in which Major Tarleton was wounded.


title: Banastre Tarleton

text: After becoming commander of the British Legion, a force of American Loyalist cavalry and light infantry, also called Tarleton's Raiders, Tarleton went to South Carolina, at the beginning of 1780. There, Tarleton's Raiders supported Sir Henry Clinton in the siege operations that culminated in the capture of Charleston. The siege and capture of the city were part of the British strategy in the southern military theatre meant to restore royal authority over the southern colonies of British North America.


title: Banastre Tarleton

text: On 29 May 1780, Colonel Tarleton, with a force of 149 mounted soldiers, overtook a detachment of 350 to 380 Virginia Continentals, led by Colonel Abraham Buford, who refused to surrender or to stop his march. Only after sustaining many casualties did Buford order the American soldiers to surrender. Nonetheless, Tarleton's forces ignored the white flag and massacred the soldiers of Buford's detachment; 113 American soldiers were killed, 203 were captured, and 150 were severely wounded. The British army casualties were 5 soldiers killed and 12 soldiers wounded. From the perspective of the British Army, the affair of the massacre is known as the Battle of Waxhaw Creek. In that time, the American rebels used the phrase "Tarleton's quarter" (shooting after surrender) as meaning "no quarter offered".


title: Banastre Tarleton

text: An eye-witness, the American field surgeon Robert Brownfield, wrote that Colonel Buford raised the white flag of surrender to the British Legion, "expecting the usual treatment sanctioned by civilized warfare"; yet, while Buford called for quarter, Colonel Tarleton's horse was shot with a musket ball, felling horse and man. On seeing that, the Loyalist cavalrymen believed that the Virginia Continentals had shot their commander – while they asked him for mercy. Enraged, the Loyalist troops attacked the Virginians with an "indiscriminate carnage never surpassed by the most ruthless atrocities of the most barbarous savages"; in the aftermath, the British Legion soldiers killed wounded American soldiers where they lay.


title: Banastre Tarleton

text: Colonel Tarleton's account, published in 1787, said that his horse had been shot from under him, and that his soldiers, thinking him dead, engaged in "a vindictive asperity not easily restrained".


title: Banastre Tarleton

text: Regardless of the extent to which they were true or false, the reports of British atrocities motivated Whig-leaning colonials to support the American Revolution. On the other hand, Tarleton advocated repression of the civilian population, and criticized the mildness of Lord Cornwallis's methods, because moderation "did not reconcile enemies, but ... discourages friends". In either event, on 7 October 1780, at the Battle of Kings Mountain, South Carolina, soldiers of the Continental Army, having heard of the slaughter at Waxhaw Creek, killed American Loyalists who had surrendered after a sniper killed their British commanding officer, Maj. Patrick Ferguson.


title: Banastre Tarleton

text: In South Carolina, Col. Tarleton's British Legion were harried by Francis Marion, "The Swamp Fox", an American militia commander who practiced guerrilla warfare against the British. Throughout the campaigns, Tarleton was unable to capture him or thwart his operations. Marion's local popularity among anti-British South Carolinians ensured continual aid and comfort for the American cause. In contrast, Colonel Tarleton alienated the colonial citizens with arbitrary confiscations of cattle and food stocks.


title: Banastre Tarleton

text: Tarleton materially helped Cornwallis to win the Battle of Camden in August 1780. On 22 August, he was promoted to major in the 79th Regiment of Foot (Royal Liverpool Volunteers). He defeated Thomas Sumter at Fishing Creek, aka "Catawba Fords", but was less successful when he encountered the same general at Blackstock's Farm in November 1780.


title: Banastre Tarleton

text: On 17 January 1781 Tarleton's forces were virtually destroyed by American Brigadier General Daniel Morgan at the Battle of Cowpens. Tarleton and about 200 men escaped the battlefield. William Washington commanded the rebel cavalry; he was attacked by the British commander and two of his men. Tarleton was stopped by Washington himself, who attacked him with his sword, calling out, "Where is now the boasting Tarleton?" A cornet of the 17th, Thomas Patterson, rode up to strike Washington but was shot and killed by Washington's orderly trumpeter. Washington survived this assault and in the process wounded Tarleton's right hand with a sabre blow, while Tarleton creased Washington's knee with a pistol shot that also wounded his horse. Washington pursued Tarleton for sixteen miles, but gave up the chase when he came to the plantation of Adam Goudylock near Thicketty Creek. Tarleton was able to escape capture by forcing Goudylock to serve as a guide.


title: Banastre Tarleton

text: He was successful in a skirmish at Torrence's Tavern while the British crossed the Catawba River (Cowan's Ford Skirmish 1 February 1781) and took part in the Battle of Guilford Courthouse in March 1781. With his men, Tarleton marched with Cornwallis into Virginia.


title: Banastre Tarleton

text: There he carried out a series of small expeditions while in Virginia. Among them was a raid on Charlottesville, where the state government had relocated following the British occupation of the capital at Richmond. He was trying to capture Governor Thomas Jefferson and members of the Virginia legislature. The raid was partially foiled by the ride of Jack Jouett, with Jefferson and all but seven of the legislators escaping over the mountains. Tarleton destroyed arms and munitions and succeeded in dispersing the Assembly.


title: Banastre Tarleton

text: Tarleton was brevetted to lieutenant-colonel in the 79th Foot on 26 June 1781. In July 1781 some of his forces allegedly were involved in Francisco's Fight, an alleged skirmish between colonial Peter Francisco and nine of Tarleton's dragoons, which resulted in one dead, eight wounded and Francisco capturing eight horses. After other missions, Cornwallis instructed Tarleton to hold Gloucester Point, during the Siege of Yorktown. On 4 October 1781, the French Lauzun's Legion and the British cavalry, commanded by Tarleton, skirmished at Gloucester Point. Tarleton was unhorsed, and Lauzun's Legion drove the British within their lines before being ordered to withdraw by the Marquis de Choisy. The Legion suffered three Hussars killed with two officers and eleven Hussars wounded. Fifty British were killed or wounded, including Tarleton. The British surrendered Gloucester Point to the French and Americans after the surrender at Yorktown in October 1781. After the surrender, the senior British officers were invited to dinner by their American captors, and the only one not to get an invitation was Tarleton. He returned to Britain on parole, finished with this war at the age of 27.


title: Banastre Tarleton

text: Tarleton had lost two fingers from a musket ball received in his right hand during the Battle of Guilford Courthouse in North Carolina, but "his crippled hand was to prove an electoral asset" back home. The condition of his hand is disguised in the pose of his 1782 portrait (shown in this article) by Sir Joshua Reynolds.


title: Banastre Tarleton

text: After his return to Great Britain, Tarleton wrote a history of his experience in the war in North America, entitled "Campaigns of 1780 and 1781 in the Southern Provinces of North America" (London, 1781). He portrayed his own actions in the Carolinas favourably and questioned decisions made by Cornwallis. It was criticized by Lieutenant Roderick Mackenzie in his "Strictures on Lieutenant-Colonel Tarleton's History" (1781) and in the "Cornwallis Correspondence".


title: Banastre Tarleton

text: In 1784, Tarleton stood for election as M.P. for Liverpool, but was narrowly defeated. In 1790 he succeeded Richard Pennant as MP, and, with the exception of a single year, was re-elected to the House of Commons until 1812. He was a supporter of Charles James Fox despite their opposing views on the British role in the American War of Independence.


title: Banastre Tarleton

text: Tarleton spoke on military matters and a variety of other subjects. Tarleton was noted for his proslavery attitudes, supporting the slave trade due to its importance to the Liverpool economy as a major shipping port in the triangular trade. He worked to preserve the slavery business with his brothers Clayton and Thomas, and he became well known for his taunting and mockery of the British abolitionists. He generally voted with the Parliamentary opposition. When the Fox-North Coalition came to power, he supported the government nominally headed by William Cavendish-Bentinck, 3rd Duke of Portland.


title: Banastre Tarleton

text: Tarleton continued to serve in the army and was promoted to colonel on 22 November 1790, to major-general on 4 October 1794 and to lieutenant-general on 1 January 1801. Whilst on service in Portugal, Tarleton succeeded William Henry Vane, 3rd Earl of Darlington as colonel of the Princess of Wales's Fencible Dragoons in 1799. Tarleton was appointed colonel of the 21st Light Dragoons on 24 July 1802. He was brevetted to general on 1 January 1812. He had hoped to be appointed to command British forces in the Peninsular War, but the position was instead given to Wellington. He held a military command in Ireland and another in England.


title: Banastre Tarleton

text: Tarleton had a 15-year relationship with the actress and writer Mary Robinson (Perdita) whom he initially seduced on a bet. She was an ex-mistress of the future King George IV while he was still Prince of Wales. Tarleton and Robinson had no children; in 1783 Robinson had a miscarriage. She was important to his parliamentary career, writing many of his speeches. His portrait was painted by both Joshua Reynolds, who showed him at battle in the American Revolution, and Thomas Gainsborough.


title: Banastre Tarleton

text: Tarleton ultimately married Susan Bertie, the young, illegitimate and wealthy daughter of the 4th Duke of Ancaster in 1798. Tarleton had no children with Bertie. Tarleton did however, father an illegitimate daughter in 1797, prior to his marriage. The child was named Banina Georgina (1797–1818), her mother being named simply as Kolina.


title: Banastre Tarleton

text: "We honor the rough soldier Ferguson for the fiat of instant death with which he would have requited the most infamous and dastardly outrage that brutalizes warfare." Tarleton, on the other hand, reveled in his own misconduct and that of his soldiers.


title: Banastre Tarleton

text: In November 2005, it was announced that four rare battle flags or regimental colours seized in 1779 and 1780 from American soldiers by Tarleton and still held in Britain, would be auctioned by Sotheby's in New York City in 2006. Two of these colours were the guidon of the 2nd Continental Light Dragoons, captured in 1779; and a "beaver" standard – possibly a Gostelowe List Standard No. 7 dating from 1778. The "Beaver" Standard and two other flags (possibly division colours) were apparently captured at the Battle of Waxhaws. The flags were sold at auction on Flag Day in the United States (14 June 2006).


title: Banastre Tarleton

text: Tarleton introduced to the British Legion, and wore himself, a leather helmet with antique style applications and a fur plume (woollen for lower ranks) protruding far into the upper front side. It is depicted in Sir Joshua Reynolds' portrait of Tarleton above and was named after the officer. The helmet was used by British horse artillery troops until the end of the Napoleonic Wars as well as by light dragoon regiments from about 1796 to 1812.


title: Banastre Tarleton

text: It was based the Continental European dragoon helmet that became popular in several other armies before it fell out of fashion.


title: Banastre Tarleton

text: One such design, the "" ("caterpillar helmet") became the standard-issue headgear of various units in the Bavarian Army until abolished and substituted by the German Reichs typical Pickelhaube after Ludwig II of Bavaria's death in 1886.


title: North Brabant

text: North Brabant ( ; Brabantian: ; ), also unofficially called Brabant, is a province in the south of the Netherlands. It borders the provinces of South Holland and Gelderland to the north, Limburg to the east, Zeeland to the west, and the Flemish provinces of Antwerp and Limburg to the south. The northern border follows the Meuse westward to its mouth in the Hollands Diep strait, part of the Rhine–Meuse–Scheldt delta. North Brabant has a population of 2,562,566 as of November 2019. Major cities in North Brabant are Eindhoven (pop. 231,642), Tilburg (pop. 217,259), Breda (pop. 183,873) and its provincial capital 's-Hertogenbosch (pop. 154,205).


title: North Brabant

text: The Duchy of Brabant was a state of the Holy Roman Empire established in 1183 or 1190. It developed from the Landgraviate of Brabant and formed the heart of the historic Low Countries, part of the Burgundian Netherlands from 1430 and of the Habsburg Netherlands from 1482, until it was split up after the Dutch revolt. After the War of Independence, Catholics in the Southern Netherlands were systematically and officially discriminated against by the Northern Protestant government until the second half of the 19th century, which had a major influence on the economic and cultural development of the southern part of the Netherlands.


title: North Brabant

text: Present-day North Brabant ("Staats-Brabant") was adjudicated to the Generality Lands of the Dutch Republic according to the 1648 Peace of Westphalia, while the reduced duchy remained in existence with the Southern Netherlands until it was conquered by French Revolutionary forces in 1794.


title: North Brabant

text: Until the 17th century, the area that now makes up the province of North Brabant was mostly part of the Duchy of Brabant, of which the southern part is now in Belgium. During the 14th and 15th centuries, the area experienced a golden age—especially the now-Belgian cities of Brussels, Mechelen, Leuven and Antwerp, and the Dutch cities of Breda, Bergen op Zoom and 's-Hertogenbosch.


title: North Brabant

text: After the Union of Utrecht was signed in 1579, Brabant became a battlefield between the Protestant Dutch Republic and Catholic Spain, which occupied the southern Netherlands. As a result of the Peace of Westphalia, the northern part of Brabant became part of the Netherlands as the territory of Staats-Brabant (Statal Brabant) under federal rule, in contrast to the founding provinces of the Dutch Republic, which were self-governing.


title: North Brabant

text: Attempts to introduce Protestantism into the region were largely unsuccessful; North Brabant remained strongly Catholic. For over a century, North Brabant served mainly as a military buffer zone. In 1796, when the confederate Dutch Republic became the unitary Batavian Republic, Staats-Brabant became a province as "Bataafs Brabant". This status ended with the reorganisation by the invading French, and the area was united into the "département" of Deux-Nèthes (present province of Antwerp).


title: North Brabant

text: In 1815, Belgium and the Netherlands were united in the United Kingdom of the Netherlands, and the province of North Brabant was established and so named to distinguish it from South Brabant in present-day Belgium, which seceded from the Kingdom in 1830. This boundary between the Netherlands and Belgium is special in that it does not form a contiguous line, but leaves a handful of tiny enclaves (and enclaves inside enclaves) on both sides of the border. In fact, the Dutch government generally used the pre-Napoleonic borders in 1815 to divide its provinces, in hommage to the principle of Restoration. A few of these irregularities were corrected (Luyksgestel was exchanged for Lommel), Huijbergen became totally Dutch, but some remain, notably Baarle-Hertog (Belgian) and Baarle-Nassau (Dutch).


title: North Brabant

text: When the present province was instituted, its territory was expanded with a part of the province of Holland and the former territory of Ravenstein, which had previously belonged to the Duchy of Cleves, as well as several small, formerly autonomous entities.


title: North Brabant

text: In World War II the area was liberated by the allies during Operation Pheasant between October 20 to November 4, 1944.


title: North Brabant

text: The period from 1900 until the late 1960s is called "Het Rijke Roomse Leven" (translated as 'the rich Roman life', with 'Roman' meaning 'Roman Catholic'), an era of strong religious belief. "Het Rijke Roomse Leven" came about as result of the emancipatory drive of the province's disadvantaged Catholic population and was supported by a Roman Catholic pillar, which was directed by the clergy, and not only encompassed churches, but also Roman Catholic schools and hospitals, which were run by nuns and friars. In those days every village in North Brabant had a convent from which the nuns operated. Politically, the province was dominated by Catholic parties: the Roman Catholic State Party and its post-war successor, the Catholic People's Party, which often held around 75% of the vote.


title: North Brabant

text: In the 1960s secularisation and the actual emancipation of the Catholic population brought about the gradual dissolution of the Catholic pillar, as church attendance decreased in North Brabant as elsewhere in Western Europe. The influence of "Het Rijke Roomse Leven" (The Rich Roman [Catholic] Life) remains in the form of education where some schools are still Roman Catholic (today run by professional teachers and not by nuns) and in North Brabant's culture, politics, mentality and customs, such as carnival.


title: North Brabant

text: The interpretation of the Roman Catholic identity in North Brabant has shifted during the last 65 years from religious to cultural, but the province still has a distinct Catholic atmosphere when compared to the provinces north of the major rivers. A cultural divide is still found between the "Catholic" south and the "Protestant" north, but with a total of 1.5 million people and 20% of the industrial production in the Netherlands the southern "Catholic" area BrabantStad has become one of the major economically important, metropolitan regions of the Netherlands. As of 2010, Catholics were no longer a majority of the population in the province of North Brabant. Only 1–2% of the total population of the Catholic area attend mass, and these churchgoers consist mostly of people over 65 years old.


title: North Brabant

text: With a population density of 501/km, North Brabant is above average urbanized. The urbanization is at the center of the province at largest, where the 'kite' (the Brabantse Stedenrij Breda, Tilburg, Eindhoven and 's-Hertogenbosch) is located, the rest of the province has a more rural character. The province has preserved some of its scenic nature well. National parks are found at the Loonse and Drunen Dunes, De Biesbosch and De De Groote Peel, on the marshes of the Meierij at Oisterwijk and Boxtel (within an area called Het Groene Woud), the border park Zoom-Kalmthoutse Heide, and in the forested area around Breda. Also, south of Eindhoven named De Kempen is an area with farmlands and forests. In Heeze, also south of Eindhoven, are the heath areas the "Groote Heide" (333 ha) and Strabrechtse Heath (1500 ha) located. The "Strabrechtse Heide" holds also the largest fen of the Netherlands. The "Beuven" (Beu fen) measures 85 hectares.


title: North Brabant

text: Like most of the Netherlands, North Brabant is mostly flat but nearly every part of North Brabant is above sea level; therefore, there are not as many canals as in the lower parts of The Netherlands. Although most of the population lives in urban areas, the province is scattered with villages around which most of the land is cultivated.


title: North Brabant

text: The Biesbosch (from "bies", "rushes", and "bosch", "woodland") is an area southwest of Dordrecht formed when the dike on the Meuse burst and the St. Elizabeth's floods on 19 November 1421 engulfed great tracts of land in the southwestern Netherlands and altered the geography of the whole area, inundating over 40,000 hectares/100,000 acres of land. More than four-fifths of the flooded land has been reclaimed since the 18th century. An area of 6,000 hectares/15,000 acres was left as it was, and now forms the Biesbosch nature reserve and bird sanctuary.


title: North Brabant

text: Until the end of the 1960s the Biesbosch was directly connected with the sea and subject to changing tide levels. As a result, it developed a flora which tolerated brackish water and was the home of numerous waterfowl. Since the damming of the Haringvliet there is no variation in water level, and both flora and fauna have adapted to the new environment.


title: North Brabant

text: The Biesbosch is crisscrossed by a network of footpaths and bikepaths and by countless rivers and streams which offer excellent facilities for water sports (sailing, surfing). In spite of the large numbers of visitors the natural environment has remained largely unspoiled.


title: North Brabant

text: The Biesbosch nature reserve can be reached by car only from the east (preferably via Werkendam). The southwest part of the area, with its three large reservoirs of drinking water, is closed to road traffic. The Biesbosch can also be reached by boat from Drimmelen, Geertruidenberg or Lage Zwaluwe.


title: North Brabant

text: The historical region of Kempen occupies the southern part of the province of Noord-Brabant and extends south of Eindhoven far into northern Belgium. To the east it reaches as far as the Meuse valley. The surface topography of De Kempen is very uniform. Most of it lies between 5m/15 ft and 35m/115 ft above sea level. The basement rocks are Cretaceous and Tertiary sediments, which are overlaid by Ice Age gravels and sands carried here by rivers of melt-water from the retreating glaciers. It is a typical area of sandy heathland.


title: North Brabant

text: The infertile soil is suitable only for undemanding crops such as rye, oats, potatoes and fodder plants; this limits the profitability of agriculture. Until a few decades ago Kempen was a region of heathland and sand drifts with a sparse growth of pines, a few scattered villages subsisting on the poor soil and some small towns; and this is still the pattern in much of the region.


title: North Brabant

text: In recent years, however, the rapid advance of industry has brought about profound changes in this agricultural region. The origins of this industrial development go back 70–100 years. The main concentrations of industry are along the southern frontier of the Netherlands, e.g., at Eindhoven, Helmond, Tilburg, Breda, 's-Hertogenbosch.


title: North Brabant

text: In the east of Noord-Brabant, near the Limburgish border, is the Peel area, an expanse of moorland extending from Eindhoven to Venlo, on the border with Limburg. Southeast of Asten is a nature reserve (1,300 hectares/3,250 acres; visitor center at Ospeldijk) which has escaped destruction by peat cutting. Mostly boggy, it will appeal to nature lovers with its interesting flora and fauna. Apart from this small area almost the whole of the Peel has been brought into cultivation.


title: North Brabant

text: The province is bordered by the river Meuse in the north. Its delta flows through De Biesbosch area, a national park.


title: North Brabant

text: North Brabant has been divided into 56 municipalities since 2022. Traditionally, almost every town was a separate municipality, but their number was reduced greatly in the 1990s by incorporating smaller towns into neighbouring cities or by other mergers. The municipalities in North Brabant are:


title: North Brabant

text: On 1 January 2004 the municipalities of Geldrop and Mierlo merged into a new municipality called Geldrop-Mierlo.


title: North Brabant

text: On 1 January 2015 the municipality of Maasdonk merged into the existing municipalities of 's-Hertogenbosch and Oss.


title: North Brabant

text: On 1 January 2017 the municipalities of Veghel, Schijndel, and Sint-Oedenrode merged into a new municipality called Meierijstad, creating the largest municipality of the province of North Brabant in terms of land area.


title: North Brabant

text: On 1 January 2019 the municipalities of Aalburg, Werkendam, and Woudrichem merged into a new municipality called Altena, an even larger municipality in terms of land area.


title: North Brabant

text: On 1 January 2021 the municipality of Haaren merged into the existing municipalities of Boxtel, Oisterwijk, Tilburg, and Vught.


title: North Brabant

text: On 1 January 2022 the municipalities of Landerd and Uden merged into the new municipality of Maashorst, and the municipalities of Boxmeer, Cuijk, Grave, Mill en Sint Hubert, and Sint Anthonis merged into the new municipality of Land van Cuijk.


title: North Brabant

text: The Gross domestic product (GDP) of the province was 116.1 billion € in 2018, accounting for 15.0% of the Netherlands economic output. GDP per capita adjusted for purchasing power was €39,900 or 132% of the EU27 average in the same year.


title: North Brabant

text: Employment is found in the agricultural, industrial and service sectors, with agricultural and food processing companies such as Agrifirm, Bavaria, FrieslandCampina, Mars Incorporated, Nutreco, Royal Canin all having large production sites or their headquarters located in the province. The main agricultural products are sweetcorn, wheat and sugar beet, while cows and pigs are held as livestock.


title: North Brabant

text: An important economical activity is electronics industry, which developed as a spin-off from Philips. Several companies originated from Philips, such as Signify (formerly Philips Lighting), NXP (producer of semiconductors), and the world's largest supplier of photolithography systems, ASML.


title: North Brabant

text: There are eight 'innovation campusses' in North Brabant, including the High Tech Campus Eindhoven. In 2017, Brabantian companies applied for 3655 patents, earning a spot in the regional top 5 in Europe.


title: North Brabant

text: Other important industries are automobile production (e.g. General Motors in Breda, Tesla in Tilburg) and DAF in Eindhoven, textile and shoes.


title: North Brabant

text: In the 20th century, tourism has become an important sector for North Brabant. A tourist attraction is theme park Efteling in Kaatsheuvel, the largest of the Benelux.


title: North Brabant

text: Safaripark Beekse Bergen is an Safaripark located between Tilburg and Hilvarenbeek. In terms of area, it is the largest Safaripark in the Benelux. More than 150 animal species are kept, ranging from small mammals to large birds. It is best known for its diversity. You can explore the park on foot, by boat, bus or with your own car.


title: North Brabant

text: BrabantStad is a partnership between the municipalities of Breda, Eindhoven, Helmond, 's-Hertogenbosch and Tilburg and the province of North Brabant. According to national rules, BrabantStad is defined as the area of Eindhoven, 's-Hertogenbosch and Tilburg.


title: North Brabant

text: Brabantian is not a minority language in the Netherlands. It can be divided in two main dialects: East Brabantian and . Along with the Hollandic dialects it is one of the two most spoken versions of Dutch. Brabantian has, as compared to the other main Dutch dialects, had a big influence on the development of Standard Dutch. This is because Brabant was the dominant region in the Netherlands when the standardization of Dutch started in the 16th century. The first major formation of standard Dutch also took place in Antwerp, where a Brabantian dialect is spoken. The default language having been developed around this time, it therefore had mainly Brabantian influences. The early modern Dutch written language was initially influenced primarily by Brabantian, with strong influence from Hollandic emerging after the 16th century. Since the Brabantian dialect has developed faster than 16th- and 17th-century Dutch, it has become more diverse than modern Standard Dutch but is still quite similar and very understandable.


title: North Brabant

text: About one third of the Dutch-speaking population lives in the Brabantian dialect zone. Both in large Brabantian towns such as Breda and Eindhoven and in rural areas many people still speak the original dialect or colloquial Dutch with a typical "southern" tongue. Tilburg and 's-Hertogenbosch have a large number of people speaking the Brabantian dialect.


title: North Brabant

text: There are many museums, especially in the larger towns which include the North Brabant Museum in 's-Hertogenbosch, the Van Abbemuseum in Eindhoven, the Museum of the Image in Breda, Noordbrabants Natuurmuseum in Tilburg. Also a few towns have a large theater like the Chassé Theater in Breda and the Eindhoven Park Theatre. Large, reputable music venues like the 013 in Tilburg, which boasts the largest space of music venues in the Netherlands, and the Effenaar in Eindhoven offer concerts by major artists. Smaller venues like Mezz Breda, W2 Concert in 's-Hertogenbosch and the smaller halls of the 013 and the Effenaar offer concerts by emerging artists and bigger names in an intimate setting.


title: North Brabant

text: The Southern Dutch cuisine constitutes the cuisine of the Dutch provinces of North Brabant and Limburg and the Flemish Region in Belgium. It is renowned for its many rich pastries, soups, stews, and vegetable dishes and is often called "Burgundian", which is a Dutch idiom invoking the rich Burgundian court which ruled the Low Countries in the Middle Ages and was renowned for its splendor and great feasts.


title: North Brabant

text: It is the only Dutch culinary region which developed an "haute cuisine", as it is influenced by both German cuisine and French cuisine, and it forms the base of most traditional Dutch restaurants including typical main courses such as "Biefstuk", "Varkenshaas", or "Ossenhaas", which are premium cuts of meat, generally pork or beef, accompanied by various sauces and potatoes which have been double fried in the traditional Dutch (or Belgian) manner.


title: North Brabant

text: Stews, such as "hachee", a stew of onions, beef and a thick gravy, contain a lot of flavour and require hours to prepare. Vegetable soups are made from richly flavored stock or bouillon and typically contain small meatballs alongside a variety of different vegetables. Asparagus and "witlo(o)f" are highly prized and traditionally eaten with cheese and/or ham.


title: North Brabant

text: Pastries are abundant, often with rich fillings of cream, custard or fruits. Cakes, such as the "Moorkop" and "Bossche Bol" from Brabant, are typical pastries. There are also savory pastries, especially the popular "worstenbroodje" (a roll with a sausage of ground beef).


title: North Brabant

text: The traditional alcoholic beverage of the region is beer. There are many local brands, ranging from "Trappist" to "Kriek". Beer, like wine in French cuisine, is also used in cooking, often in stews.


title: North Brabant

text: North Brabant is home to 8 professional football clubs, more than any other province in the Netherlands. Two clubs (PSV and RKC Waalwijk) play in the Eredivisie, the highest professional football league in the Netherlands. Six clubs (Helmond Sport, Willem II, FC Den Bosch, FC Eindhoven, TOP Oss and NAC Breda) play in the Eerste Divisie, the second-highest division of professional football in the Netherlands. PSV Eindhoven is the biggest club of North Brabant, and most successful with 24 Eredivisie titles, 1 European Cup and 1 UEFA Cup, among many other domestic cups, and is one of the traditional "big three" clubs in the Netherlands.


title: North Brabant

text: North Brabant is home to 3 hockey clubs that play in the Hoofdklasse. HC Den Bosch ('s-Hertogenbosch), Oranje Zwart (Eindhoven) and MOP (Vught). Oranje Zwart is the most successful of these clubs with many prizes, in the regular competition as well as in Europe. The most recent prizes are National Champions in 2014–2015, 2015-2016 and European Champions in 2014–2015.


title: North Brabant

text: The States of North Brabant ("Staten van Noord-Brabant") have 55 seats and are headed by the King's Commissioner ("Commissaris van de Koning"), currently Ina Adema. Whereas the provincial council (the States-Provincial - "Provinciale Staten") is elected by the inhabitants, the Commissioner is appointed by the King and the cabinet of the Netherlands. With 10 seats, People's Party for Freedom and Democracy is the largest party in the council, closely followed by Christian Democratic Appeal and Socialist Party, both with 9 seats.


title: North Brabant

text: The daily affairs of the province are taken care of by the Provincial-Executive ("Gedeputeerde Staten"), which are also headed by the Commissioner; its members (commissioners - "gedeputeerden") can be compared with ministers.


title: North Brabant

text: Traditionally the province of North Brabant was strongly Roman Catholic. Following the independence of the Netherlands, Catholics faced discrimination by the Protestant government until the mid-19th century. During the 1960s the relatively strong demarcation between the Catholic south on one side and the Calvinist west and north on the other side of the Netherlands started to diminish. In the second half of the 20th century a rapid secularization took place in North Brabant.


title: North Brabant

text: In 2006 slightly more than half of the Brabantian people reported adhering to Catholicism. For example, in the Diocese of 's-Hertogenbosch, the eastern part of North Brabant and part of the province of Gelderland, 1,167,000 people reported an association with Roman Catholicism (56.8 percent of the population). However, only 45,645 residents of this area attended the mass on average, which was only 2 percent of the total population of the area. In western North Brabant (Diocese of Breda) the number of people associating themselves with Catholicism also strongly decreased; only 52 percent of the West Brabantians identify as Roman Catholic. Church attendance was even lower in the west, with only 1 percent of the West Brabantian population attending Mass. North Brabant is mostly Roman Catholic by tradition. Residents still use the term and certain traditions as a base for their cultural identity rather than as a religious identity, and the vast majority of the Catholic population is now largely irreligious in practice. Research among Catholics in the Netherlands in 2007 showed that only 27% of the Dutch Catholics could be regarded as theist, while 55% were ietsist or nontheist and 17% were agnostic.


title: North Brabant

text: In 2010, about 6% of the population of North Brabant claimed adherence to Protestantism, while 4.5% of the population was Muslim; the latter mainly live in the larger and medium-sized municipalities.


title: Non-alcoholic fatty liver disease

text: Non-alcoholic fatty liver disease (NAFLD), also known as metabolic (dysfunction) associated fatty liver disease (MAFLD), is excessive fat build-up in the liver without another clear cause such as alcohol use. There are two types; non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), with the latter also including liver inflammation. Non-alcoholic fatty liver is less dangerous than NASH and usually does not progress to NASH. When NAFL does progress to NASH, it may eventually lead to complications such as cirrhosis, liver cancer, liver failure, or cardiovascular disease.


title: Non-alcoholic fatty liver disease

text: Obesity and type 2 diabetes are strong risk factors for NAFLD. Other risks include being overweight, metabolic syndrome (defined as at least three of the five following medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum HDL cholesterol), a diet high in fructose, and older age. NAFLD and alcoholic liver disease are types of fatty liver disease. Obtaining a sample of the liver after excluding other potential causes of fatty liver can confirm the diagnosis.


title: Non-alcoholic fatty liver disease

text: Treatment for NAFLD is weight loss by dietary changes and exercise. There is tentative evidence for pioglitazone and vitamin E; and bariatric surgery can improve or resolve severe cases. Those with NASH have a 2.6% increased risk of dying per year.


title: Non-alcoholic fatty liver disease

text: NAFLD is the most common liver disorder worldwide and is present in approximately 25% of the world's population. It is very common in developed nations, such as the United States, and affected about 75 to 100 million Americans in 2017. Over 90% of obese, 60% of diabetic, and up to 20% of normal-weight people develop NAFLD. NAFLD is the leading cause of chronic liver disease and the second most common reason for liver transplantation in the US and Europe as of 2017. NAFLD affects about 20 to 25% of people in Europe. In the United States, estimates suggest between 30 and 40% of adults have NAFLD, and about 3 to 12% of adults have NASH. The annual economic burden was approximately US$103 billion in the US in 2016.


title: Non-alcoholic fatty liver disease

text: An abnormal accumulation of fat in the liver in the absence of secondary causes of fatty liver, such as significant alcohol use, viral hepatitis, or medications that can induce fatty liver characterizes non-alcoholic fatty liver disease (NAFLD). The term NAFLD encompasses a continuum of liver abnormalities, from non-alcoholic fatty liver (NAFL, simple steatosis) to non-alcoholic steatohepatitis (NASH). These diseases begin with fatty accumulation in the liver (hepatic steatosis). A liver can remain fatty without disturbing liver function (NAFL), but by various mechanisms and possible insults to the liver, it may also progress into non-alcoholic steatohepatitis (NASH), a state in which steatosis is combined with inflammation and sometimes fibrosis (steatohepatitis). NASH can then lead to complications such as cirrhosis and hepatocellular carcinoma.


title: Non-alcoholic fatty liver disease

text: A new name, metabolic dysfunction associated fatty liver disease, was proposed after 70% of a panel of experts expressed support for this name.


title: Non-alcoholic fatty liver disease

text: People with NAFLD often have no noticeable symptoms, and NAFLD is often only detected during routine blood tests or unrelated abdominal imaging or liver biopsy. In some cases, NAFLD can cause symptoms related to liver dysfunction such as fatigue, malaise, and dull right-upper-quadrant abdominal discomfort. Mild yellow discoloration of the skin may occur, although this is rare. NASH can severely impair liver function, leading to cirrhosis, liver failure, and liver cancer.


title: Non-alcoholic fatty liver disease

text: NAFLD is strongly associated with or caused by type 2 diabetes, insulin resistance, and metabolic syndrome (defined as at least three of the five following medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein). It is also associated with hormonal disorders (panhypopituitarism, hypothyroidism, hypogonadism, polycystic ovary syndrome), persistently elevated transaminases, increasing age and hypoxia caused by obstructive sleep apnea, with some of these conditions predicting disease progression.


title: Non-alcoholic fatty liver disease

text: The majority of normal-weight people affected by NAFLD ("lean NAFLD") have impaired insulin sensitivity, are sedentary, and have increased cardiovascular disease risk and increased liver lipid levels. These are the consequences of a decreased capacity for storing fat and reduced mitochondrial function in adipose tissue and increased hepatic de novo lipogenesis. A recent systematic review has reported an increased risk of severe COVID-19 infection in NAFLD patients; however, no difference in mortality was observed between NAFLD and non-NAFLD patients.


title: Non-alcoholic fatty liver disease

text: Two-thirds of families with a history of diabetes type 2 report more than one family member having NAFLD. There is a higher risk of fibrosis for family members where someone was diagnosed with NASH. Asian populations are more susceptible to metabolic syndrome and NAFLD than their western counterparts. Hispanic persons have a higher prevalence of NAFLD than white individuals, whereas the lowest prevalence is observed in black individuals. NAFLD is twice as prevalent in men as in women, which might be explained by lower levels of estrogen in men.


title: Non-alcoholic fatty liver disease

text: Genetic variations in two genes are associated with NAFLD: non-synonymous single-nucleotide polymorphisms (SNPs) in PNPLA3 and TM6SF2. Both correlate with NAFLD presence and severity, but their roles for diagnosis remain unclear. Although NAFLD has a genetic component, the American Association for the Study of Liver Diseases (AASLD) does not recommend screening family members as there is not enough confirmation of heritability, although there is some evidence from familial aggregation and twin studies.


title: Non-alcoholic fatty liver disease

text: According to the Asia-Pacific Working Group (APWG) on NAFLD, overnutrition is a major factor of NAFLD and NASH, particularly for lean NAFLD. Diet composition and quantity, in particular omega-6 fatty acid and fructose, have important roles in disease progression from NAFL to NASH and fibrosis. Choline deficiency can lead to the development of NAFLD.


title: Non-alcoholic fatty liver disease

text: Habitual snoring may be a risk factor for NAFLD, even after accounting for established risk factors in individuals. Severe cases of snoring lead to airway blockage or difficulty breathing when sleeping, and usually signals the presence of obstructive sleep apnea (OSAS), a much more serious breathing condition. Blockage or narrowing of the airways, even temporarily, can cause the body to experience lowered oxygen levels in the blood, and these conditions of hypoxia are recurring in those with obstructive sleep apnea (OSAS). Constant hypoxia may cause a variety of changes within the body, such as tissue inflammation, increased insulin resistance, and liver injury. A prospective cohort study found the association between habitual snoring and NAFLD development to be significant, and the trend was noted to be most prominent in lean individuals.


title: Non-alcoholic fatty liver disease

text: The primary characteristic of NAFLD is the accumulation of lipids in the liver, largely in the form of triglycerides. However, the mechanisms by which triglycerides accumulate and the reasons that accumulation can lead to liver dysfunction are complex and incompletely understood. NAFLD can include steatosis along with varied signs of liver injury: either lobular or portal inflammation (a form of liver injury) or ballooning degeneration. Similarly, NASH can include histological features such as portal inflammation, polymorphonuclear cell infiltrates, Mallory bodies, apoptotic bodies, clear vacuolated nuclei, microvesicular steatosis, megamitochondria, and perisinusoidal fibrosis. Hepatocyte death via apoptosis or necroptosis is increased in NASH compared with simple steatosis, and inflammation is a hallmark of NASH.


title: Non-alcoholic fatty liver disease

text: One debated mechanism proposes that hepatic steatosis progresses to steatosis with inflammation following some further injury, or "second hit". Oxidative stress, hormonal imbalances, and mitochondrial abnormalities are potential causes of this "second hit" phenomenon. A further nutrigenomics model named "multiple hit" extends the "second hit" model, suggesting that multiple disease biomarkers and factors such as genes and nutrition influence NAFLD and NASH progression. This model attempts to use these factors to predict the impact of lifestyle changes and genetics for the evolution of the NAFLD pathology. Many researchers describe NAFLD as a "multisystem" disease, as it impacts and is influenced by organs and regulatory pathways other than the liver.


title: Non-alcoholic fatty liver disease

text: The accumulation of senescent cells in the liver is seen in persons with NAFLD. In mice, liver senescent hepatocytes result in increased liver fat deposition. Treatment of NAFLD mice with senolytic agents has been shown to reduce hepatic steatosis.


title: Non-alcoholic fatty liver disease

text: Based on gene knockout studies in murine models, it has been suggested that, among many other pathogenic factors, TGF beta signals may be crucially involved in promoting the progression of NASH.


title: Non-alcoholic fatty liver disease

text: Non-alcoholic and alcoholic fatty liver disease share similar histological features, which suggests that they might share common pathogenic pathways. Fructose can cause liver inflammation and addiction similarly to ethanol by using similar metabolic pathways, unlike glucose. Therefore, some researchers argue that non-alcoholic and alcoholic fatty liver diseases are more alike than previously thought. Furthermore, high fructose consumption promotes fat accumulation in the liver by stimulating "de novo" lipogenesis in the liver and reducing the beta-oxidation of fat. Unlike the sugar glucose, the enzyme fructokinase rapidly metabolizes fructose. This leads to a decreased level of intracellular adenosine triphosphate (ATP). The decrease in ATP increases oxidative stress and impairments in proper protein synthesis and mitochondrial function in the liver.


title: Non-alcoholic fatty liver disease

text: Insulin resistance contributes to the accumulation of toxic fat in the liver in several ways. First, it promotes the release of free fatty acids (FFAs) from adipose tissue into the blood. Typically, adipose tissue stores lipids in the form of triglycerides, slowly releasing them into the bloodstream when insulin is low. In insulin-resistant adipose tissue, such as in people with obesity and type 2 diabetes, more triglycerides are broken down into FFAs and released into the bloodstream, promoting uptake by the liver. Second, insulin promotes the production of new FFAs in the liver via "de novo" lipogenesis; this production of liver fats continues to be stimulated by insulin, even when other tissues are insulin-resistant. These FFAs are combined back into triglycerides in the liver, forming the major constituent of the accumulated fat in the liver. The three sources of free fatty acids that contribute to liver triglyceride accumulation include FFAs circulating in the bloodstream (59%), FFAs derived from carbohydrates such as fructose and glucose (26%), and diet (14%). Despite the accumulation of triglycerides in the liver, they are not directly toxic to liver tissue. Instead, alteration of the profile of the other lipid subtypes present in the liver, such as diacylglycerols, phospholipids, ceramides, and free cholesterol, have a more significant role in the pathogenesis of NAFLD.


title: Non-alcoholic fatty liver disease

text: Once NAFLD progresses in severity to the point of NASH, this promotes further insulin resistance in the adipose tissue and liver, which results in a harmful cycle of insulin resistance, liver fat accumulation, and inflammation. Adipose tissue dysfunction also decreases secretion of the insulin-sensitizing adipokine adiponectin in people with NAFLD. Adiponectin has several properties that protect the liver. These properties include improved liver fat metabolism, decreased "de novo" lipogenesis, decreased glucose production in the liver, anti-inflammatory properties, and anti-fibrotic properties. Skeletal muscle insulin resistance may also play a role in NAFLD. Insulin-resistant skeletal muscle is not as efficient at taking up glucose from the bloodstream after a meal. This inefficient glucose uptake promotes the redistribution of consumed carbohydrates from glucose destined for use in glycogen stores in the skeletal muscles to being used as a substrate for "de novo" lipogenesis in the liver.


title: Non-alcoholic fatty liver disease

text: Disruptions in the intestinal microbiota seem to influence NAFLD risk in several ways. People with NASH can have elevated levels of blood ethanol and Pseudomonadota (which produce alcohol), with dysbiosis proposed as a mechanism for this elevation. Alterations in the composition of the intestinal microbiota may influence NAFLD risk in several ways. These changes appear to increase the permeability of intestinal tissue, thereby facilitating increased liver exposure to harmful substances (e.g., translocated bacteria, bacterial toxins, and inflammatory chemical signals). The increased transport of these harmful substances to the liver promotes liver inflammation, enhances nutrient and calorie absorption, and alters choline metabolism. Higher levels of intestinal bacteria that produce butyrate may be protective.


title: Non-alcoholic fatty liver disease

text: Excessive macronutrient intake contributes to gut inflammation and perturbation of homeostasis, and micronutrients may also be involved. In addition to reducing weight and risk factors, lifestyle changes may prompt positive changes in the gut microbiota. In particular, diet diversity may play a role that was overlooked in animal studies, since they often compare a Western high-fat, low-diversity diet against a low-fat but higher-diversity chow. The health benefits after bariatric surgery may also involve changes in the gut microbiota by increasing gut permeability.


title: Non-alcoholic fatty liver disease

text: NAFLD is defined by evidence of fatty liver without another factor that could explain the liver fat accumulation, such as excessive alcohol use (>21 standard drinks/week for men and >14 for women in the USA; >30 g daily for men and >20 g for women in UK and EU, >140 g/week for men and >70 g/week for women in Asia-Pacific and most NIH clinical studies), drug-induced steatosis, chronic hepatitis C, heredity or by deficiencies in parenteral nutrition such as choline and endocrine conditions. If any of these factors are observed, an investigation into alternative causes of fatty liver unrelated to NAFLD is recommended. A history of chronic alcohol usage is an important consideration.


title: Non-alcoholic fatty liver disease

text: NAFLD comprises two histological categories: NAFL, and the more aggressive form NASH. The presence of at least 5% fatty liver is common to both NAFL and NASH, but the features of substantial lobular inflammation and hepatocyte injuries such as ballooning or Mallory hyaline only occur in NASH. The majority of NAFL cases show minimal or no inflammation. Pericentral and perisinusoidal fibrosis occur more often in adult-onset NASH, whereas portal fibrosis is more common in children with the disorder. NASH represents a more advanced stage of NAFL and is associated with poor outcomes such as cardiovascular events, cirrhosis, or hepatocellular carcinoma. ICD-11 does not use the term NAFL as it was deemed confusing with the family of disorders NAFLD. The preferred descriptions are instead: NAFLD without NASH or simple steatosis and "NASH". Also, the modifier with or without fibrosis or cirrhosis completes the diagnostic description.


title: Non-alcoholic fatty liver disease

text: Elevated liver enzymes are common. According to National Institute for Health and Care Excellence (NICE) guidelines, it is disadvised to test enzymes levels to rule out NAFLD, as they are often within the normal range even in advanced disease.


title: Non-alcoholic fatty liver disease

text: Blood tests that are useful to confirm diagnosis or rule out others include erythrocyte sedimentation rate, glucose, albumin, and kidney function. Because the liver is important for making proteins used in blood clotting, coagulation-related studies are often carried out, especially the INR (international normalized ratio). In people with fatty liver with associated inflammatory injury (steatohepatitis) blood tests are usually used to rule out viral hepatitis (hepatitis A, B, C and herpesviruses such as Epstein–Barr virus or cytomegalovirus), rubella, and autoimmune diseases. Low thyroid activity is more prevalent in people with NASH, which would be detected by determining the thyroid-stimulating hormone. Some biomarker-based blood tests have been developed and may be useful for diagnosis.


title: Non-alcoholic fatty liver disease

text: Although blood tests cannot diagnose NAFLD, circulating serum biomarkers of liver fibrosis can give moderate estimates in the diagnosis of liver fibrosis and cirrhosis. The ratio of the transaminase liver enzyme aspartate aminotransferase (AST) to platelets in the blood, known as the AST/platelet ratio index (APRI score), and Fibrotest are recommended as the preferred noninvasive tests for cirrhosis by the Asian-Pacific Association for Study of the Liver (APASL). Several other scores such as FIB-4 score and NAFLD fibrosis score can also reflect the burden of the fibrosis in the liver, and previous studies have confirmed that these score can predict future development of mortality and liver cancer.


title: Non-alcoholic fatty liver disease

text: A liver ultrasound scan or magnetic resonance imaging (MRI) can diagnose steatosis, but not fibrosis and confirmation of early cirrhosis detection by ultrasound by other diagnostic methods is recommended. The European Association for the Study of the Liver (EASL) recommends screening for steatosis whenever NAFLD is suspected as this is a strong predictor of the disease evolution and predicts future type 2 diabetes, cardiovascular events, and hypertension. These non-invasive methods can be used for NAFLD screening but are not accepted as a substitute for liver biopsy in NAFLD nor NASH clinical trials, as only a liver biopsy can define liver pathology.


title: Non-alcoholic fatty liver disease

text: Ultrasound presented average sensitivity and specificity for diagnosing the disease in children, while in the adult population, sensitivity and specificity were significantly higher. Proton density fat fraction magnetic resonance imaging has been increasingly used for the diagnosis of steatosis in pediatric patients. Elastography is an effective tool for staging liver fibrosis and discriminating NASH from NAFLD in children.


title: Non-alcoholic fatty liver disease

text: CT scans and MRIs are more accurate in detecting cirrhosis than conventional ultrasound. Transient elastography is recommended for the initial assessment of liver fibrosis and cirrhosis and helps to predict complications and prognosis, but the interpretation of results is carefully weighed in the presence of limiting factors, such as steatosis, high BMI, lower degrees of hepatic fibrosis and narrow spaces between the ribs (intercostal spaces). However, transient elastography can fail for people with pre-hepatic portal hypertension. Transient elastography is not considered to be a replacement for liver biopsy.


title: Non-alcoholic fatty liver disease

text: Magnetic resonance elastography (MRE) is an emerging method that can accurately assess hepatic fibrosis and is recommended by the APASL. MRE possesses a good sensitivity to quantify hepatic fat and excellent accuracy to detect fibrosis in NAFLD regardless of BMI and inflammation and is suggested as a more reliable alternative to diagnose NAFLD and its progression to NASH compared to ultrasound and blood tests.


title: Non-alcoholic fatty liver disease

text: A liver biopsy (tissue examination) is the only test widely accepted (gold standard) as definitively diagnosing and distinguishing NAFLD (including NAFL and NASH) from other forms of liver disease and can be used to assess the severity of the inflammation and resultant fibrosis. However, since most people affected by NAFLD are likely to be asymptomatic, liver biopsy presents too high a risk for routine diagnosis, so other methods are preferred, such as liver ultrasonography or liver MRI. For young people, guidelines recommend liver ultrasonography, but biopsy remains the best evidence. Liver biopsy is also the gold standard to detect hepatic fibrosis and assess its progression. Routine liver function blood tests are not sensitive enough to detect NAFLD, and biopsy is the only procedure that can reliably differentiate NAFL from NASH.


title: Non-alcoholic fatty liver disease

text: There are several liver biopsy techniques available to obtain liver tissue. Percutaneous liver biopsy remains the most common practice. Biopsies can also be performed via the transvenous route, either during surgery or by laparoscopy, especially for people with contraindications to a percutaneous approach. The liver biopsy can also be image-guided, in real-time or not, which is recommended for some clinical situations such as people with known intra-hepatic lesions, previous intra-abdominal surgery who may have adhesions, a small liver that is difficult to percuss, obese people and people with evident ascites. Vital signs must be monitored frequently afterward (at least every 15 minutes in the hour following the biopsy).


title: Non-alcoholic fatty liver disease

text: According to AASLD guidelines, a liver biopsy may be considered in people with NAFLD who are at increased risk of having steatohepatitis with or without advanced fibrosis, but only when all other competing chronic liver diseases are excluded (such as alcoholic liver disease). The presence of metabolic syndrome, NAFLD Fibrosis Score (FIB-4), or liver stiffness (as measured by Vibration-controlled transient elastography or MRE) can identify the individuals who are at higher risk of steatohepatitis or advanced fibrosis.


title: Non-alcoholic fatty liver disease

text: The AASLD and ICD-11 consider that clinically useful pathology reporting distinguishes "between NAFL (steatosis), NAFL with inflammation and NASH (steatosis with lobular and portal inflammation and hepatocellular ballooning)" with the presence or absence of fibrosis being described and optionally comment on severity. The EASL recommends the Fatty Liver Inhibition of Progression (FLIP) algorithm to grade the ballooning and classify NAFLD-associated liver injury, and the use of the NAFLD Activity Score (NAS) to grade the severity of NASH rather than for its diagnosis. They also consider the steatosis, activity, and fibrosis (SAF) score to be an accurate and reproducible scoring system. The AASLD recommends the use of the NAS scoring system with or without the SAF score if deemed appropriate. The Asia-Pacific Working Group on NAFLD disadvises the use of NAS, as it is considered uninformative for NAFLD and inappropriate to diagnose NASH.


title: Non-alcoholic fatty liver disease

text: For liver fibrosis assessment, percutaneous liver biopsy, with or without image guidance, is contraindicated in uncooperative people. Transjugular liver biopsy is indicated for any person with diffuse liver disease who needs a biopsy but has a contraindication to percutaneous biopsy or needs a hemodynamic evaluation for diagnostic purposes. A transvenous liver biopsy is recommended instead of a percutaneous approach in people with clinically evident ascites, although percutaneous biopsy is an acceptable alternative approach after the removal of ascites.


title: Non-alcoholic fatty liver disease

text: NAFLD warrants treatment regardless of whether the affected person is overweight or not. NAFLD is a preventable cause of death. Guidelines are available from the American Association for the Study of Liver Diseases (AASLD), American Association of Clinical Endocrinologists (AACE) National Institute for Health and Care Excellence (NICE), the European Association for the Study of the Liver (EASL), and the Asia-Pacific Working Party on NAFLD.


title: Non-alcoholic fatty liver disease

text: Weight loss is the most effective treatment for NAFLD. A loss of 4% to 10% body weight is recommended, with 10% to 40% weight loss completely reversing NASH without cirrhosis. A structured weight loss program helps people with NAFLD lose more weight compared with advice alone. This type of program also leads to improvements in NAFLD measured using blood tests, ultrasound, imaging, or liver biopsies. Although fibrosis improves with lifestyle interventions and weight loss, there is limited evidence for cirrhosis improvement.


title: Non-alcoholic fatty liver disease

text: A combination of improved diet and exercise, rather than either alone, appears to best help manage NAFLD and reduce insulin resistance. Motivational support, such as with cognitive behavioral therapy, is helpful, as most people with NAFLD do not perceive their condition as a disease, and thus have a low motivation to change.


title: Non-alcoholic fatty liver disease

text: Higher-intensity behavioral weight loss therapies (diet and exercise combined) may produce more weight loss than lower-intensity ones. Weight loss is associated with improvements in biomarkers, NAFLD grade, and reduced chances of NASH, but their impact on long-term health is yet unknown. A 2019 systematic review thus suggests a change of guidelines to recommend these therapies for NAFLD management.


title: Non-alcoholic fatty liver disease

text: As of 2021, there is limited evidence to indicate that lifestyle modifications and nutritional supplementation have an effect on mortality, liver cirrhosis, liver decompensation, liver transplantation, and hepatocellular carcinoma in people with nonalcohol-related fatty liver disease.


title: Non-alcoholic fatty liver disease

text: Treatment of NAFLD typically involves counseling to improve nutrition and calorie restriction. People with NAFLD can benefit from a moderate to low-carbohydrate diet and a low-fat diet. The Mediterranean diet also showed promising results in a 6-week study with a reduction of NASH induced inflammation and fibrosis, independently from weight loss. Tentative evidence supports dietary interventions in individuals with fatty liver who are not overweight.


title: Non-alcoholic fatty liver disease

text: The EASL recommends energy restriction of 500–1000 kcal per week less than the normal daily diet, a target of 7–10% weight loss for obese/overweight NAFLD, a low- to moderate-fat, and moderate- to high-carbohydrate diet, or a low-carbohydrate ketogenic or high-protein diet such as the Mediterranean diet, and avoiding all beverages and food containing fructose.


title: Non-alcoholic fatty liver disease

text: Alcohol is an aggravating factor, and the AASLD recommends that people with NAFLD or NASH avoid alcohol consumption. The EASL allows alcohol consumption below 30g/day for men and 20g/day for women. The role of coffee consumption for NAFLD treatment is unclear though some studies indicate that regular coffee consumption may have protective effects.


title: Non-alcoholic fatty liver disease

text: Herbal compounds such as silymarin (a milk thistle seed extract), curcumin, a turmeric extract, and green tea appear to improve NAFLD biomarkers and reduce the grade of NAFLD. Studies suggest an association between microscopic organisms that inhabit the gut (microbiota) and NAFLD. Reviews reported the use of probiotics and synbiotics (combinations of probiotics and prebiotics) were associated with improvement in liver-specific markers of hepatic inflammation, measurements of liver stiffness, and steatosis in persons with NAFLD.


title: Non-alcoholic fatty liver disease

text: Vitamin E does not improve established liver fibrosis in those with NAFLD but seems to improve certain markers of liver function and reduces inflammation and fattiness of the liver in some people with NAFLD. The Asia-Pacific Work Group advises that Vitamin E may improve liver condition and aminotransferase levels, but only in adults without diabetes or cirrhosis who have NASH. The NICE guidelines recommend Vitamin E as an option for children and adults with NAFLD with advanced liver fibrosis, regardless of whether the person has diabetes mellitus.


title: Non-alcoholic fatty liver disease

text: The genum of mold Aspergillus and/or Monascus are used in the fabrication of Red yeast rice to stimulate the production of lovastatin, where lovastatin and other statins inhibit the total cholesterol and LDL cholesterol synthesis by blocking action of the enzyme HMG-CoA reductase.


title: Non-alcoholic fatty liver disease

text: The safety of red yeast rice has not yet been established as studies found that some commercial supplements contain high levels of toxin citrinin.


title: Non-alcoholic fatty liver disease

text: There are reports in the literature of muscle myopathy and liver damage resulting from red yeast rice usage.


title: Non-alcoholic fatty liver disease

text: Research shows that essential phospholipids from soy lecithin (Latin: phospholipida sojae praeparata), polyenylphosphatidylcholine being the active component, has a well-established mode of action, therapeutic effectiveness, and lack of toxicity, which ensures clinically relevant efficacy-to-safety ratio. It influences membrane- dependent cellular functions and shows anti-inflammatory, antioxidant, antifibrogenic, anti apoptotic, membrane-protective, and lipid-regulating effects. Due to its positive effects on membrane composition and functions, it accelerates the improvement or normalization of subjective symptoms; pathological, clinical, and biochemical findings; hepatic imaging; and liver histology. It is justified to administer EPL together with other therapeutic measurements in the liver.


title: Non-alcoholic fatty liver disease

text: The usual dosage for adults and children older than 12 years of age (and of at least 43 kg of weight) is 600 mg three times a day.


title: Non-alcoholic fatty liver disease

text: Weight loss may improve NAFLD and is recommended particularly for obese or overweight people; similar physical activities and diets are advisable for overweight people with NAFLD as for other obese and overweight people. Although physical activity is less important for weight loss than dietary adaptations (to reduce caloric intake), the NICE advises physical activity to reduce liver fat even if there is no overall bodyweight reduction. Weight loss, through exercise or diet, is the most effective way to reduce liver fat and help NASH and fibrosis remission. Exercise alone can prevent or reduce hepatic steatosis, but it remains unknown whether it can improve all other aspects of the liver; hence a combined approach with diet and exercise is advised. Aerobic exercise may be more effective than resistance training, although there are contradictory results. Vigorous training is preferable to moderate training, as only the high-intensity exercise reduced the chances of NAFLD developing into NASH or advanced fibrosis. The EASL recommends between 150 and 200 min/week in 3 to 5 sessions of moderate-intensity aerobic physical activity or resistance training. Since both effectively reduce liver fat, a pragmatic approach to the choice of physical activity that accounts for the individual's preferences for what they can maintain in the long-term is preferred. Any engagement in physical activity or increase over previous levels is better than remaining sedentary.


title: Non-alcoholic fatty liver disease

text: Treatment with medications is primarily aimed at improving liver disease and is generally limited to those with biopsy-proven NASH and fibrosis.


title: Non-alcoholic fatty liver disease

text: No medicines specifically for NAFLD or NASH had received approval, , although anti-diabetic medications may help in liver fat loss. While many treatments appear to improve biochemical markers such as alanine transaminase levels, most do not reverse histological abnormalities or improve outcomes.


title: Non-alcoholic fatty liver disease

text: Insulin sensitizers (metformin and thiazolidinediones, such as pioglitazone) and liraglutide are not specifically recommended for NAFLD as they do not directly improve the liver condition. They can be indicated for diabetic individuals, after a careful assessment of risks, to reduce insulin resistance and risks of complications. Indeed, the side effects associated with thiazolidinedione medications, which include osteopenia, increased fracture risk, fluid retention, congestive heart failure, bladder cancer, and long-term weight gain, have limited their adoption. Due to these side effects, the AASLD recommends the use of pioglitazone only for individuals with biopsy-proven NASH, and the Asia-Pacific Work Group recommends them only for individuals with NAFLD with known diabetic issues. However, the AASLD advises against the use of metformin as studies were inconclusive about the improvement of the liver's histological condition. Although there was an improvement in insulin resistance and serum aminotransferases, this did not translate into NASH improvements. The NICE provides similar guidelines to the AASLD regarding pioglitazone and recommends it be administered in secondary care to adults with advanced liver fibrosis irrespective of whether or not they have diabetes.


title: Non-alcoholic fatty liver disease

text: Statin medications appear to improve liver histology and markers of liver biochemistry in people with NAFLD. Since people with NAFLD are at a higher risk of cardiovascular disease, statin treatment is indicated. People with NAFLD are not at higher risk for serious liver injury from statins, according to AASLD and EASL. However, even if statins are safe to use in people with NASH cirrhosis, the AASLD suggests avoiding them in people with decompensated cirrhosis. Guidelines recommend statins to treat dyslipidemia for people with NAFLD. According to NICE guidelines, statins can continue unless liver enzyme levels double within three months of starting statins. Treatment with pentoxifylline is not recommended.


title: Non-alcoholic fatty liver disease

text: As of 2018, neither the AASLD nor the Asia-Pacific Working Group recommends obeticholic acid or elafibranor due to inconsistent results for NASH treatment and concerns about safety.


title: Non-alcoholic fatty liver disease

text: Omega-3 fatty acids may reduce liver fat and improve blood lipid profile but do not seem to improve liver histology (fibrosis, cirrhosis, cancer). The NICE does not recommend omega-3 fatty acid supplementation since randomized trials were inconclusive. Previous systematic reviews found that omega-3 fatty acid supplementation in those with NAFLD/NASH using doses of one  gram daily or more (median dose four  grams/day with median treatment duration six  months) has been associated with improvements in liver fat. According to AASLD guidelines, "omega-3 fatty acids should not be used as a specific treatment of NAFLD or NASH, but they may be considered to treat hypertriglyceridemia for patients with NAFLD".


title: Non-alcoholic fatty liver disease

text: Bariatric surgery is an effective method for obese and diabetic individuals with NAFLD to induce weight loss and reduce or resolve NASH inflammation, including fibrosis, and improve longevity. For the AASLD, bariatric surgery can be considered only for NASH on a case-by-case basis by an experienced bariatric surgery program. Indeed, some individuals might develop new or worsened features of NAFLD.


title: Non-alcoholic fatty liver disease

text: About 92% of people with NAFLD saw an improvement in steatosis and 70% a complete resolution after bariatric surgery.


title: Non-alcoholic fatty liver disease

text: A preoperative diet such as a low-calorie diet or a very-low-calorie diet is usually recommended to reduce liver volume by 16–20%. Preoperative weight loss is the only factor associated with postoperative weight loss. Preoperative weight loss can reduce operative time and hospital stay, although there is insufficient evidence whether preoperative weight loss reduces long-term morbidity or complications. Weight loss and decreases in liver size may be independent of the amount of calorie restriction.


title: Non-alcoholic fatty liver disease

text: The APWG on NAFLD recommends bariatric surgery as a treatment option for those with class II obesity (BMI >32.5 kg/m for Asians, 35 kg/m for Caucasians). They consider its effects on improving liver-related complications as unproven yet, but it effectively increases longevity by improving cardiovascular factors.


title: Non-alcoholic fatty liver disease

text: Surgery carries more risks for individuals with NASH cirrhosis, with a review estimating overall morbidity to be 21%. For people with NAFLD who have undifferentiated cirrhosis, the APWG recommends an investigation to determine the cause of the cirrhosis as well as the person's liver function and whether they have portal hypertension.


title: Non-alcoholic fatty liver disease

text: Cardiovascular system screening is considered mandatory by the EASL, as NAFLD outcomes often result in cardiovascular complications, which can manifest as subclinical atherosclerosis, the cause of the majority of NAFLD-related deaths. People with NAFLD are at high risk for cardiovascular morbidity and mortality, and "aggressive modification of cardiovascular disease risk factors is warranted in all patients with NAFLD," according to AASLD.


title: Non-alcoholic fatty liver disease

text: The AASLD further recommends for people with a cirrhotic NASH to be systematically screened for gastric and esophageal varices and liver cancer. They do not recommend routine liver biopsies and screening for liver cancer for non-cirrhotic people with NASH, but such screening sometimes occurs on a case-by-case basis.


title: Non-alcoholic fatty liver disease

text: Also, people with NAFLD may be considered for screening for hepatocellular carcinoma (liver cancer) and gastroesophageal varices. The NICE advises regular screening of NAFLD for advanced liver fibrosis every three years to adults and every two years for children using the enhanced liver fibrosis (ELF) blood test. Follow-up is recommended for people with obesity and insulin resistance using the homeostasis model assessment of insulin resistance (HOMA-IR). People with NASH with fibrosis and hypertension merit closer monitoring as there is a higher risk of disease progression.


title: Non-alcoholic fatty liver disease

text: NAFLD is the second most common indication for liver transplantation in the US and Europe as of 2017. NAFLD/NASH is expected to become the leading cause of liver transplantation by 2020.


title: Non-alcoholic fatty liver disease

text: For people with NASH and end-stage liver disease, liver failure, or liver cancer, liver transplantation is an accepted procedure according to the EASL. People with NASH cirrhosis NASH who are being considered for a liver transplant warrant systematic evaluation for cardiovascular diseases (whether the symptoms are apparent or not).


title: Non-alcoholic fatty liver disease

text: The overall survival is comparable to transplantation following other diseases. People with NASH cirrhosis who undergo liver transplantation are more likely to die post-transplant because of cardiovascular disease or chronic kidney disease. These people with NASH are often older and are thus more prone to these complications. For these reasons and others, individuals with morbid obesity (BMI ≥ 40 kg/m) and NASH with cirrhosis may be considered unfit for liver transplantation until they follow lifestyle modifications to reduce bodyweight. Diabetic people with poor glycemic control are at similar risks, and optimal glycemic control is essential before attempting transplantation.


title: Non-alcoholic fatty liver disease

text: The Asia Pacific Working Group guidelines recommend healthcare providers discuss lifestyle modifications before and after transplantation to reduce potential surgery risks and to assist with NAFLD management after the transplant.


title: Non-alcoholic fatty liver disease

text: Simultaneous bariatric surgery and liver transplantation were performed in exceptional circumstances.


title: Non-alcoholic fatty liver disease

text: After transplantation, liver biopsy is the best method to monitor the evolution of post-transplant fibrosis, with significant fibrosis or portal hypertension one year after transplantation predicting rapid progression and graft loss and indicating the need for urgent intervention.


title: Non-alcoholic fatty liver disease

text: There is no special treatment for liver cancer associated with NAFLD/NASH and are treated according to general guidelines on liver cancers.


title: Non-alcoholic fatty liver disease

text: The average progression rate from one stage of liver fibrosis to the next in humans with NASH is estimated to be seven years, compared to 14 years with NAFLD. The course of progression varies with different clinical manifestations among individuals. Fibrosis in humans with NASH progressed more rapidly than in humans with NAFLD. Obesity predicts a worse long-term outcome than for lean individuals. In the Asia-Pacific region, about 25% of NAFLD cases progress to NASH under three years, but only a low proportion (3.7%) develop advanced liver fibrosis. An international study showed that people with NAFLD had a 10-year survival rate of 81.5%.


title: Non-alcoholic fatty liver disease

text: NAFLD is a risk factor for fibrosis, hypertension, chronic kidney disease, atrial fibrillation, myocardial infarction, ischemic stroke, and death from cardiovascular causes based on very-low to low-quality evidence from observational studies. Although NAFLD can cause cirrhosis and liver failure and liver cancer, most deaths among people with NAFLD are attributable to cardiovascular disease. According to a meta-analysis of 34,000 people with NAFLD over seven years, these individuals have a 65% increased risk of developing fatal or nonfatal cardiovascular events when compared to those without NAFLD.


title: Non-alcoholic fatty liver disease

text: NAFLD and NASH increase the risk of liver cancer. Cirrhosis and liver cancer induced by NAFLD were the second cause of liver transplantation in the US in 2017. Liver cancer develops in NASH in the absence of cirrhosis in 45% in the cases, and people with NASH cirrhosis have an increased risk of liver cancer. The rate of liver cancer associated with NASH increased fourfold between 2002 and 2012 in the US, which is more than any other cause of liver cancer. NAFLD constitutes the third most common risk factor for liver cancer. NAFLD and NASH were found to worsen with cirrhosis in respectively 2–3% and 15–20% of the people over a 10–20 year period. Cirrhosis is found in only about 50% of people with NAFLD and with liver cancer, so that liver cancer and cirrhosis are not always linked.


title: Non-alcoholic fatty liver disease

text: NAFLD may be a precursor of metabolic syndrome, although a bidirectional influence is possible. The presence and stage of fibrosis are the strongest prognostic factors for liver-related events and mortality, in particular for NAFLD.


title: Non-alcoholic fatty liver disease

text: NAFLD incidence is rapidly rising, along with obesity and diabetes, and has become the most common cause of liver disease in developed countries, for adults, teenagers, and children. The percentage of people with NAFLD ranges from 9 to 36.9% in different parts of the world. Approximately 20% of the United States and 25% of the Asia-Pacific populations have non-alcoholic fatty liver. Similar prevalence can be found in Europe, although less data is available. NAFLD is the most common in the Middle East (32%) and South America (30%), while Africa has the lowest rates (13%). Compared to the 2000s, NAFL and NASH respectively increased 2-fold and 2.5-fold in the 2010s in the USA.


title: Non-alcoholic fatty liver disease

text: NAFLD and NASH are more prevalent in Hispanics - which can be attributed to high rates of obesity and type 2 diabetes in Hispanic populations, intermediate in Whites, and lowest in Blacks. NAFLD was observed to be twice as prevalent in men as women. For severely obese individuals, the prevalence of NAFLD rises over 90%, and for those with diabetes, over 60%, and up to 20% for normal-weight people. NAFLD is present in 65% to 90% of people that had bariatric surgery, and up to 75% of them have NASH. Ultrasonography and proton NMR spectroscopy studies suggest about 25% of the population seems to be affected by NAFLD or NASH.


title: Non-alcoholic fatty liver disease

text: Although the disease is commonly associated with obesity, a significant proportion of those affected are normal weight or lean. Lean NAFLD affects between 10 and 20% of Americans and Europeans, and approximately 25% of the Asians, although some countries have a higher incidence (e.g., India has a very high proportion of lean NAFLD and almost no obese NAFLD). PNPLA3 may be relevant for the progression of NAFLD in lean people. Thus, people with NAFLD deserve consideration for treatment regardless of the presence or absence of obesity.


title: Non-alcoholic fatty liver disease

text: In children ages 1 to 19, the prevalence was found to be approximately 8% in the general population up to 34% in studies with data from child obesity clinics.


title: Non-alcoholic fatty liver disease

text: The majority of cryptogenic cirrhosis is believed to be due to NASH. NAFLD prevalence is expected to increase steadily, from 25% in 2018 to a projected 33.5% of people with NAFLD globally in 2030, and from 20% to a projected 27% of those with NAFLD will progress to NASH.


title: Non-alcoholic fatty liver disease

text: The first acknowledged case of obesity-related non-alcoholic fatty liver was observed in 1952 by Samuel Zelman. Zelman started investigating after observing a fatty liver in a hospital employee who drank more than twenty bottles of Coca-Cola a day. He then went on to design a trial for a year and a half on 20 obese people who were not alcoholic, finding that about half of them had substantially fatty livers. Fatty liver was, however, linked to diabetes since at least 1784 — an observation picked up again in the 1930s. Studies in experimental animals implicated choline inadequacy in the 1920s and excess sugar consumption in 1949.


title: Non-alcoholic fatty liver disease

text: The name "non-alcoholic steatohepatitis" (NASH) was later defined in 1980 by Jurgen Ludwig and his colleagues from the Mayo Clinic to raise awareness of the existence of this pathology, as similar reports previously were dismissed as "patients' lies". This paper was mostly ignored at the time but eventually came to be seen as a landmark paper, and starting in the mid-1990s, the condition began to be intensively studied, with a series of international meetings being held on the topic since 1998. The broader NAFLD term started to be used around 2002. Diagnostic criteria began to be worked out, and in 2005 the Pathology Committee of the NIH NASH Clinical Research Network proposed the NAS scoring system.


title: Non-alcoholic fatty liver disease

text: EASL recommends Europe's public health authorities to "restrict advertising and marketing of sugar-sweetened beverages and industrially processed foods high in saturated fat, sugar, and salt", as well as "fiscal measures to discourage the consumption of sugar-sweetened beverages and legislation to ensure that the food industry improves labeling and the composition of processed foods", as well as "public awareness campaigns on liver disease, highlighting that it is not only linked to excessive consumption of alcohol".


title: Non-alcoholic fatty liver disease

text: In France, the French syndicate of non-alcoholic beverages "Boissons Rafraîchissantes de France" (that included soft drink producers such as Coca-Cola France, Orangina, PepsiCo France) was denounced by the French journal "" for misleading consumers using a communication on their website titled "Better understanding the NASH pathology", explaining that "NASH pathology is sometimes called the soda illness by language abuse or an unfortunate semantic shortcut, as it is not directly linked to the consumption of non-alcoholic beverages". This page and others on the same website, such as one titled "Say no to disinformation," were since then removed.


title: Non-alcoholic fatty liver disease

text: Pediatric NAFLD was first reported in 1983. It is the most common chronic liver disease among children and adolescents since at least 2007, affecting 10 to 20% of them in the US in 2016. NAFLD is associated with metabolic syndrome, which is a cluster of risk factors that contribute to the development of cardiovascular disease and type 2 diabetes mellitus. Studies have demonstrated that abdominal obesity and insulin resistance, in particular, are significant contributors to the development of NAFLD. Coexisting liver diseases, such as hepatitis C and cardiovascular diseases such as atherosclerosis, are also associated with an increased risk of NAFLD. Some children were diagnosed as early as two years old, with a mean age of diagnosis between 11 and 13 years old. The mean age is usually above 10 years, as children can also report non-specific symptoms and are thus difficult to diagnose for NAFLD.


title: Non-alcoholic fatty liver disease

text: Boys are more likely to be diagnosed with NAFLD than girls. Overweight, or even weight gain, in childhood and adolescence, is associated with an increased risk of NAFLD later in life, with adult NAFLD predicted in a 31-year follow-up study by risk factors during childhood including BMI, plasma insulin levels, male sex, genetic background (PNPLA3 and TM6SF2 variants) and low birth weight, an emerging risk factor for adulthood NAFLD. In a study, simple steatosis was present in up to 45% in children with a clinical suspicion of NAFLD. Children with simple steatosis have a worse prognosis than adults, with significantly more of them progressing from NAFLD to NASH compared to adults. Indeed, 17-25% of children with NAFLD develop a NASH in general, and up to 83% for children with severe obesity (versus 29% for adults), further suggesting that hepatic fibrosis seems to follow a more aggressive clinical course in children compared to adults.


title: Non-alcoholic fatty liver disease

text: Early diagnosis of NAFLD in children may help prevent the development of liver disease during adulthood. This is challenging as most children with NAFLD are asymptomatic, with only 42-59% showing abdominal pain. Other symptoms might be present, such as right upper quadrant pain or acanthosis nigricans, the latter of which is often present in children with NASH. An enlarged liver occurs in 30–40% of children with NAFLD.


title: Non-alcoholic fatty liver disease

text: The AASLD recommends a diagnostic liver biopsy in children when the diagnosis is unclear or before starting a potentially hepatotoxic medical therapy. The EASL suggests using fibrosis tests such as elastography, acoustic radiation force impulse imaging, and serum biomarkers to reduce the number of biopsies. In follow up, NICE guidelines recommend that healthcare providers offer children regular NAFLD screening for advanced liver fibrosis every two years using the enhanced liver fibrosis (ELF) blood test. Several studies also suggest magnetic resonance elastography as an alternative to the less reliable ultrasonography.


title: Non-alcoholic fatty liver disease

text: Intensive lifestyle modifications, including physical activity and dietary changes, are the first line of treatment according to AASLD and EASL as it improves the liver histology and aminotransferase levels. In terms of pharmacological treatment, the AASLD and EASL do not recommend metformin, but vitamin E may improve liver health for some children. The NICE advises the use of vitamin E for children with advanced liver fibrosis, whether they have diabetes or not. The only treatment shown to be effective in childhood NAFLD is weight loss.


title: Non-alcoholic fatty liver disease

text: Some evidence indicates that maternal undernutrition or overnutrition increases a child's susceptibility to NASH and hastens its progression.


title: Non-alcoholic fatty liver disease

text: Since a NAFLD diagnosis based on a liver biopsy is invasive and makes it difficult to estimate epidemiology, it is a high research priority to find accurate, inexpensive, and noninvasive methods of diagnosing and monitoring NAFLD disease and its progression. The search for these biomarkers of NAFLD, NAFL, and NASH involves lipidomics, medical imaging, proteomics, blood tests, and scoring systems.


title: Non-alcoholic fatty liver disease

text: According to a review, proton density fat fraction estimation by magnetic resonance imaging (MRI-PDFF) may be considered the most accurate and even gold standard test to quantify hepatic steatosis. They recommend ultrasound-based transient elastography to accurately diagnose both fibrosis and cirrhosis in a routine clinical setting, with more objectivity than ultrasonography but with lower accuracy than magnetic resonance elastography; and plasma cytokeratin 18 (CK18) fragment levels to be a moderately accurate biomarker of steatohepatitis. However, transient elastography can fail for people with pre-hepatic portal hypertension.


title: Non-alcoholic fatty liver disease

text: Medication development for NASH is very active and advancing rapidly. New medications are being designed to target various intrahepatic sites, from regulating lipids and glucose homeostasis to oxidant stress and mitochondrial targets in hepatocytes, inflammatory signals on hepatocytes, and intracellular targets related to hepatic stellate cell activation and fibrogenesis. , pivotal trials are underway for obeticholic acid (FXR agonist), Resmetirom (THRβ agonist), belapectin (Galectin-3 inhibitor), and Aramchol (SCD1 inhibitor).


title: Identity matrix

text: In linear algebra, the identity matrix of size formula_1 is the formula_2 square matrix with ones on the main diagonal and zeros elsewhere.


title: Identity matrix

text: The identity matrix is often denoted by formula_3, or simply by formula_4 if the size is immaterial or can be trivially determined by the context.


title: Identity matrix

text: The term unit matrix has also been widely used, but the term "identity matrix" is now standard. The term "unit matrix" is ambiguous, because it is also used for a matrix of ones and for any unit of the ring of all formula_2 matrices.


title: Identity matrix

text: In some fields, such as group theory or quantum mechanics, the identity matrix is sometimes denoted by a boldface one, formula_7, or called "id" (short for identity). Less frequently, some mathematics books use formula_8 or formula_9 to represent the identity matrix, standing for "unit matrix" and the German word respectively.


title: Identity matrix

text: In terms of a notation that is sometimes used to concisely describe diagonal matrices, the identity matrix can be written as


title: Identity matrix

text: In particular, the identity matrix serves as the multiplicative identity of the matrix ring of all formula_2 matrices, and as the identity element of the general linear group formula_16, which consists of all invertible formula_2 matrices under the matrix multiplication operation. In particular, the identity matrix is invertible. It is an involutory matrix, equal to its own inverse. In this group, two square matrices have the identity matrix as their product exactly when they are the inverses of each other.


title: Identity matrix

text: When formula_2 matrices are used to represent linear transformations from an formula_1-dimensional vector space to itself, the identity matrix formula_3 represents the identity function, for whatever basis was used in this representation.


title: Identity matrix

text: The formula_21th column of an identity matrix is the unit vector formula_22, a vector whose formula_21th entry is 1 and 0 elsewhere. The determinant of the identity matrix is 1, and its trace is formula_1.


title: Identity matrix

text: The identity matrix is the only idempotent matrix with non-zero determinant. That is, it is the only matrix such that:


title: Identity matrix

text: The principal square root of an identity matrix is itself, and this is its only positive-definite square root. However, every identity matrix with at least two rows and columns has an infinitude of symmetric square roots.