Stages of progression of<unk><unk>  is defined by evidence of<unk>  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<unk>  liver unrelated to<unk>  is recommended. A history of chronic alcohol usage is an important consideration.<unk>  comprises two histological categories:<unk>  and the more aggressive form NASH. The presence of at least 5%<unk>  liver is common to both<unk> 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<unk> 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<unk> and is associated with poor outcomes such as cardiovascular events, cirrhosis, or hepatocellular carcinoma. ICD-11 does not use the term<unk> as it was deemed confusing with the family of disorders<unk> . The preferred descriptions are instead:<unk>  without NASH or simple steatosis and "NASH". Also, the modifier with or without fibrosis or cirrhosis completes the diagnostic description. Blood tests 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<unk> , as they are often within the normal range even in advanced disease. 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<unk>  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. Although blood tests cannot diagnose<unk> , 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<unk> invasive tests for cirrhosis by the Asian-Pacific Association for Study of the Liver (APASL). Several other scores such as FIB-4 score and<unk>  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. Imaging MRI of a healthy liver (top row) and one with severe steatosis (bottom row) 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<unk>  is suspected as this is a strong predictor of the disease evolution and predicts future type 2 diabetes, cardiovascular events, and hypertension. These<unk> -invasive methods can be used for<unk>  screening but are not accepted as a substitute for liver biopsy in<unk>  nor NASH clinical trials, as only a liver biopsy can define liver pathology. 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. 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<unk>  regardless of BMI and inflammation and is suggested as a more reliable alternative to diagnose<unk>  and its progression to NASH compared to ultrasound and blood tests. Liver biopsy biopsy, which is then examined under a microscope Micrograph of<unk> , demonstrating marked steatosis (fat in liver cells appears white; connective tissue, blue). Trichrome stain A liver biopsy (tissue examination) is the only test widely accepted (gold standard) as definitively diagnosing and distinguishing<unk>  (including<unk> 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<unk>  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<unk> , and biopsy is the only procedure that can reliably differentiate<unk> from NASH. 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). According to AASLD guidelines, a liver biopsy may be considered in people with<unk>  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,<unk>  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. The AASLD and ICD-11 consider that clinically useful pathology reporting distinguishes "between<unk> (steatosis),<unk> 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<unk>  Liver Inhibition of Progression (FLIP) algorithm to grade the ballooning and classify<unk> -associated liver injury, and the use of the<unk>  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<unk>  disadvises the use of NAS, as it is considered uninformative for<unk>  and inappropriate to diagnose NASH. 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.
Non-alcoholic fatty liver disease
Metabolic syndrome
Alcoholic liver disease
Alcoholic hepatitis
Fatty liver disease
Autoimmune hepatitis
Viral hepatitis
Polycystic liver disease