Non-alcoholic fatty liver disease

non-alcoholic steatohepatitisnonalcoholic fatty liver diseasenonalcoholic steatohepatitisNAFLDNASHnon-alcoholic fatty liver disease (NAFLD)Liver fat metabolismfatty liver diseasenon alcoholic steatohepatitisnon-alcoholic
Non-alcoholic fatty liver disease (NAFLD) is excessive fat build-up in the liver with insulin resistance due to causes other than alcohol use.wikipedia
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Hepatitis

chronic hepatitisliver inflammationacute hepatitis
There are two types; non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), with the latter also including liver inflammation.
Other causes include heavy alcohol use, certain medications, toxins, other infections, autoimmune diseases, and non-alcoholic steatohepatitis (NASH).

Cirrhosis

cirrhosis of the liverliver cirrhosisliver fibrosis
It may lead to complications such as cirrhosis, liver cancer, liver failure, or cardiovascular disease.
Cirrhosis is most commonly caused by alcohol, hepatitis B, hepatitis C, and non-alcoholic fatty liver disease.

Hepatocellular carcinoma

liver cancerhepatocarcinomahepatic cancer
It may lead to complications such as cirrhosis, liver cancer, liver failure, or cardiovascular disease.
Metabolic syndrome and NASH are also increasingly recognized as risk factors for HCC.

Metabolic syndrome

syndrome XMetabolic syndrome XCardio metabolic risk
Other risks include metabolic syndromes (diabetes, obesity, high blood pressure), a diet high in fructose, and older age.
Associated conditions include hyperuricemia; fatty liver (especially in concurrent obesity) progressing to nonalcoholic fatty liver disease; polycystic ovarian syndrome in women and erectile dysfunction in men; and acanthosis nigricans.

Obesity

obesemorbidly obeseoverweight
Other risks include metabolic syndromes (diabetes, obesity, high blood pressure), a diet high in fructose, and older age.
Health consequences fall into two broad categories: those attributable to the effects of increased fat mass (such as osteoarthritis, obstructive sleep apnea, social stigmatization) and those due to the increased number of fat cells (diabetes, cancer, cardiovascular disease, non-alcoholic fatty liver disease).

Insulin resistance

insulin sensitivityresistantinsulin resistant
Non-alcoholic fatty liver disease (NAFLD) is excessive fat build-up in the liver with insulin resistance due to causes other than alcohol use.
Polycystic ovary syndrome and non-alcoholic fatty liver disease (NAFLD) are associated with insulin resistance.

Steatohepatitis

Fatty changes to the liverliver inflammation from the excess fat in the liverSteato-hepatitis
NAFLD is a continuum of liver abnormalities, from non-alcoholic fatty liver (NAFL, simple steatosis) to non-alcoholic steatohepatitis (NASH).
There are two main types of fatty liver disease: alcohol-related fatty liver disease and non-alcoholic fatty liver disease (NAFLD).

Choline

choline salicylateanticholinergicCholine bitartrate
Choline deficiency can lead to the development of NAFLD.
Symptomatic choline deficiency – rare in humans – causes nonalcoholic fatty liver disease and muscle damage.

Fatty liver disease

fatty liverhepatic steatosisAlcoholic fatty liver
NAFLD and alcoholic liver disease are types of fatty liver disease.
There are two types of fatty liver disease non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease.

Chronic liver disease

end-stage liver disease
NAFLD is the leading cause of chronic liver disease, and the second most common reason for liver transplantation in USA and Europe as of 2017.

Liver failure

hepatic failureliverhepatic
It may lead to complications such as cirrhosis, liver cancer, liver failure, or cardiovascular disease.
Chronic liver failure usually occurs in the context of cirrhosis, itself potentially the result of many possible causes, such as excessive alcohol intake, hepatitis B or C, autoimmune, hereditary and metabolic causes (such as iron or copper overload, steatohepatitis or non-alcoholic fatty liver disease).

Liver function tests

liver enzymeliver function testliver enzymes
NAFLD can be diagnosed by performing a liver biopsy, and is often incidentally diagnosed following abnormal liver function tests during routine blood tests or after a hepatic steatosis is detected by biopsy.
Alcoholic liver disease, Non-alcoholic fatty liver disease (NAFLD), fat accumulation in liver during childhood obesity, steatohepatitis (inflammation of fatty liver disease) are associated with a rise in ALT.

Steatosis

fatty changefat in the liverfatty degeneration
These diseases begin with fatty accumulation in the liver (hepatic steatosis).
In Bristol University's study Children of the 90s, 2.5% of 4,000 people born in 1991 and 1992 were found by ultrasound scanning at the age of 18 to have non-alcoholic fatty liver disease; five years later transient elastography (fibroscan) found over 20% to have the fatty deposits on the liver of steatosis, indicating non-alcoholic fatty liver disease; half of those were classified as severe.

Fibrosis

fibroticscarringfibrogenic
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 a non-alcoholic steatohepatitis (NASH), a state in which steatosis is combined with inflammation and sometimes fibrosis (steatohepatitis).
In Bristol University's study Children of the 90s, 2.5% of 4,000 people born in 1991 and 1992 were found by ultrasound scanning at the age of 18 to have non-alcoholic fatty liver disease; five years later transient elastography (fibroscan) found over 20% to have the fatty deposits on the liver of steatosis, indicating non-alcoholic fatty liver disease; half of those were classified as severe.

Vitamin E

EHypervitaminosis EVitamins E
There is tentative evidence for pioglitazone and vitamin E.
alpha-Tocopherol can be used in the treatment of nonalcoholic fatty liver disease (NAFLD) and the more extreme subset known as nonalcoholic steatohepatitis (NASH).

Polycystic ovary syndrome

PCOSPolycystic Ovarian Syndromepolycystic ovaries
It is also associated with hormonal disorders (panhypopituitarism, hypothyroidism, hypogonadism, polycystic ovary syndrome), persistently elevated transaminases, increasing age and BMI and hypoxia caused by obstructive sleep apnea, with some of them predicting disease progression.

Liver cancer

liverliver tumourcancer of the liver
The AASLD further recommends for people with a cirrhotic NASH to be systematically screened for gastroesophageal varices and liver cancer.
Other causes include aflatoxin, non-alcoholic fatty liver disease and liver flukes.

Human gastrointestinal microbiota

gut floragut microbiotaintestinal flora
Links between dysbiosis of the gut microbiota and liver diseases, in particular NAFLD, have been documented.
Dysbiosis in the gut flora has been linked with the development of cirrhosis and non-alcoholic fatty liver disease.

TM6SF2

Two genetic mutations for NAFLD susceptibility have been identified and validated in large cohorts: the non-synonymous single-nucleotide polymorphisms (SNPs) in PNPLA3 and TM6SF2, as they have been shown to correlate with NAFLD presence and severity, but their roles for diagnosis remain unclear.
A variant TM6SF2 gene causes susceptibility to nonalcoholic fatty liver disease due to impaired very low density lipoprotein (VLDL) production14.

Ballooning degeneration

ballooning
NAFLD can include either a steatosis alone; a steatosis concurrent with lobular or portal inflammation without ballooning; or a steatosis with ballooning but without inflammation.

Cenicriviroc

, clinical trials are underway for cenicriviroc, elafibranor, obeticholic acid and selonsertib in phase 3, and several others in phase 2.
Cenicriviroc (INN, code names TAK-652, TBR-652) is an experimental drug candidate for the treatment of HIV infection and in combination with Tropifexor for non-alcoholic steatohepatitis.

Hepatomegaly

enlarged liverliver enlargementliver
Other symptoms might be present, such as right upper quadrant pain or acanthosis nigricans, the latter being frequently observed in children with NASH, or hepatomegaly found in 30–40% of children with NAFLD.

Thiazolidinedione

thiazolidinediones(Thiazolidinedionethiazolide
Insulin sensitizers (metformin and thiazolidinediones, such as pioglitazone) and liraglutide are not specially recommended for NAFLD as they do not directly improve the liver condition, but they can be indicated for diabetic individuals, after a careful assessment of risks, to reduce insulin resistance and risks of complications.
Experimental investigations on TZDs have been carried out since 2005 in polycystic ovary syndrome (PCOS), non-alcoholic steatohepatitis (NASH), psoriasis, autism, ovarian hyperstimulation syndrome (by VEGF inhibition in granulosa cells), lichen planopilaris, and other conditions.

Elafibranor

GFT505
Obeticholic acid and elafibranor might improve NASH but are not recommended by the AASLD nor the Asia-Pacific Work Group until phase 3 trials are completed as they produce inconsistent results and adverse effects.
Elafibranor (INN, code name GFT505) is an experimental medication that is being studied and developed by Genfit for the treatment of cardiometabolic diseases including diabetes, insulin resistance, dyslipidemia, and non-alcoholic fatty liver disease (NAFLD).