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Fig. 3 | BMC Medicine

Fig. 3

From: Non-alcoholic fatty liver disease (NAFLD) as a neglected metabolic companion of psychiatric disorders: common pathways and future approaches

Fig. 3

Diagnostic algorithm for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in psychiatric populations.

† Elevated AST/ALT levels should be considered from 1.5 times the upper limit of normal values. However, normal levels do not preclude a diagnosis of NAFLD.

‡ The diagnosis of NAFLD requires the exclusion of alcohol abuse. However, alcohol use is the most common cause of induced hepatic fibrosis and cirrhosis and it should be considered particularly in psychiatric populations. In the case of high alcohol intake, non-invasive assessments for liver fibrosis (commonly an ultrasound elastography) should be performed.

§ Ultra-sound misses around 20% of steatosis diagnoses. Steatosis may be detected on non-contrast CT, but due to similarity to or lower sensitivity than ultrasound, exposure to radiation, and potential for misdiagnosis, it is less useful than ultrasound as a screening test. Magnetic resonance imaging (MRI) is the most sensitive modality for the evaluation of hepatic steatosis (with 92%-100% sensitivity, 92%-97% specificity, and the ability to reliably detect as little as 3% steatosis) but is significantly more costly than ultrasound. None of these imaging modalities can differentiate NAFLD from NASH, and they have limited ability to discern those patients with advanced fibrosis.

¶ The distinction of NASH from simple steatosis is key. Steatosis due to secondary causes, such as viruses, autoimmune responses, metabolic or hereditary factors, and drugs or toxins, should be ruled out (Table 1). However, the rising prevalence of NAFLD makes its coexistence with other chronic liver diseases quite possible. Therefore, a positive diagnosis rather that a diagnosis based on exclusion of concomitant diseases has been proposed10. Over the last years, the ability to identify NAFLD and to estimate steatofibrosis with ultrasound-based techniques (semi-quantitative, quantitative, elastographic, and contrast-enhanced) has undergone tremendous progress. However, it is still difficult to capture the inflammatory component of NASH with ultrasound-assisted techniques112.

* The FIB-4 index is a simple formula based on age, ALT, AST, and platelet count that predicts fibrosis and has been validated in NAFLD and NASH. However, patients in the indeterminate cut-off values require additional testing to exclude fibrosis.

** Non-invasive imaging–based evaluation for fibrosis primarily relies on measuring elastic shear wave propagation through the liver parenchyma, with stiffer fibrotic tissue propagating waves faster. The best-validated methods are transient elastography using ultrasound, such as FibroScan, which has a sensitivity of 85% for detecting advanced fibrosis and 92% for detecting cirrhosis, and magnetic resonance, which provides a quantitative estimation of liver fat, but it is comparatively expensive, has limited availability, is time-consuming, and requires special software.

*** Liver biopsy, although typically well tolerated, can be painful and can carry morbidity such as bleeding, infection, bile leak, damage to other organs, and rare mortality risk (<0.01%).

Abbreviations: DM: diabetes mellitus; FIB-4: fibrosis 4 index; MRE: Magnetic Resonance Elastography; MetS: metabolic syndrome; NAFLD: nonalcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis.

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