Non-alcoholic fatty liver disease laboratory findings: Difference between revisions

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{{Non alcoholic fatty liver disease}}
{{Non alcoholic fatty liver disease}}
'''Editor in Chief''': Elliot Tapper, M.D., Beth Israel Deaconess Medical Center, [[User:C Michael Gibson |C. Michael Gibson, M.S., M.D.]] [mailto:charlesmichaelgibson@gmail.com]
{{CMG}}; {{AE}} {{MKK}}
==Overview==
There are no specific diagnostic laboratory findings associated with non alcoholic fatty liver disease. Laboratory findings include abnormal liver function tests but are unspecific. Other laboratory tests are generally performed  to rule out other diagnosis.
 
==Laboratory Findings==
 
*There is no specific laboratory findings diagnostic for non alcoholic fatty liver disease.<ref name="urlNonalcoholic fatty liver disease: Indications for liver biopsy and noninvasive biomarkers - Noureddin - 2012 - Clinical Liver Disease - Wiley Online Library">{{cite web |url=http://onlinelibrary.wiley.com/doi/10.1002/cld.65/pdf |title=Nonalcoholic fatty liver disease: Indications for liver biopsy and noninvasive biomarkers - Noureddin - 2012 - Clinical Liver Disease - Wiley Online Library |format= |work= |accessdate=}}</ref><ref name="urlNonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH)">{{cite web |url=https://www.uptodate.com/contents/nonalcoholic-fatty-liver-disease-nafld-including-nonalcoholic-steatohepatitis-nash-beyond-the-basics |title=Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH) |format= |work= |accessdate=}}</ref>
*Liver function tests
**Typical finding include a 2-4 fold elevation of the&nbsp;[[ALT]]&nbsp;
**An [[ALT]]/[[AST]] ratio of greater than 1.
 
* Evaluation for alternative causes of liver disease should be performed.  
** These include&nbsp;[[HCV|HCV serology]], serologies for [[autoimmune hepatitis]], and&nbsp;copper studies&nbsp;including serum [[ceruloplasmin]] and 24-hour urinary copper if [[Wilson's disease|Wilson disease]] is suspected.


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* [[Fasting plasma glucose]]&nbsp;testing following an overnight fast is important to look for [[hyperglycemia]], which is an indicator of [[insulin resistance]].
==Overview==
** Fasting [[insulin]] levels can confirm [[hyperinsulinemia]] and [[insulin resistance]]
Elevated liver function tests are common. Typically, one finds a 2-4 fold elevation of the ALT above normal limit and an ALT/AST ratio of greater than 1.<ref>Powell et al. The Natural History of Nonalcoholic Steatohepatitis: A Follow-up Study of Forty-two Patients for Up to 21 YearsHEPATOLOGY 1990; 11: 74-80</ref> This ratio is imperfect, as AST tends to rise with the degree of fibrosis.<ref>Sorbi et al. The Ratio of Aspartate Aminotransferase to Alanine Aminotransferase: Potential Value in Differentiating Nonalcoholic Steatohepatitis From Alcoholic Liver DiseaseAm J Gastroenterol 1999;94:1018–1022</ref> Furthermore, high ALT values within the reference range (less than 40 IU) are still predictive of NAFLD/NASH.<ref>Chang Y et al. Higher Concentrations of Alanine Aminotransferase within the Reference Interval Predict Nonalcoholic Fatty Liver Disease. Clinical Chemistry 2007;53(4):686–692</ref> Another blood test that can be elevated is the ferritin. Typically, and except in very advanced disease, the liver's synthetic function is intact with normal albumin and INR.
* [[Lipid]] levels (&nbsp;serum [[cholesterol]]&nbsp;and&nbsp;fasting [[triglycerides]]&nbsp;) should be evaluated
** [[Dyslipidemia]], beside being a very common finding in NAFLD, is a risk factor that can be modified by dietary and/or pharmacologic intervention.
* Iron studies&nbsp;(in particular elevated [[ferritin]] and transferring saturation) are often abnormal in NAFLD
* Some patients with NAFLD may have low titers of [[Autoimmune disease|autoimmune]] [[antibodies]].
* [[Biomarkers]]
** CK18 represents a promising [[biomarker]] for evaluation of the presence of NASH.
** A defining characteristic of NASH is [[cellular]] death, and [[serum]] CK18 levels had been shown to correlate with [[steatohepatitis]].
 
[[Non-alcoholic fatty liver disease]], especially if with cirrhosis, may be associated with [[thrombocytopenia]]<ref name="pmid34312112">{{cite journal| author=Rivera-Álvarez M, Córdova-Ramírez AC, Elías-De-La-Cruz GD, Murrieta-Álvarez I, León-Peña AA, Cantero-Fortiz Y | display-authors=etal| title=Non-alcoholic fatty liver disease and thrombocytopenia IV: its association with granulocytopenia. | journal=Hematol Transfus Cell Ther | year= 2021 | volume=  | issue=  | pages=  | pmid=34312112 | doi=10.1016/j.htct.2021.06.004 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34312112  }} </ref><ref name="pmid31575467">{{cite journal| author=Panke CL, Tovo CV, Villela-Nogueira CA, Cravo CM, Ferreira FC, Rezende GFM | display-authors=etal| title=Evaluation of thrombocytopenia in patients with non-alcoholic fatty liver disease without cirrhosis. | journal=Ann Hepatol | year= 2020 | volume= 19 | issue= 1 | pages= 88-91 | pmid=31575467 | doi=10.1016/j.aohep.2019.05.011 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31575467  }} </ref>.


When considering NAFLD, other tests are generally performed, including those for associated conditions (e.g. glucose, hemoglobin A1C) and those to distinguish this disease from viral [[hepatitis]]. Additionally, autoimmune causes are ruled out with serology. [[Thyroid-stimulating hormone|TSH]] is warranted, as [[hypothyroidism]] is more prevalent in NASH patients.<ref>Liangpunsakul S, Chalasani N. Is hypothyroidism a risk factor for non-alcoholic steatohepatitis? ''J Clin Gastroenterol'' 2003;37:340-3. PMID 14506393</ref>
== Fibrosis score ==
A fibrosis score can be obtained via:
* Liver biopsy. Various scoring systems exist including the Ishak; however, Ishak deems cirrhosis at a score of 5 or 6<ref name="pmid7560864">{{cite journal| author=Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F | display-authors=etal| title=Histological grading and staging of chronic hepatitis. | journal=J Hepatol | year= 1995 | volume= 22 | issue= 6 | pages= 696-9 | pmid=7560864 | doi=10.1016/0168-8278(95)80226-6 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7560864  }} </ref>.
** F0. No fibrosis
** F1. Fibrous portal expansion
** F2. Few septa
** F3. Bridging fibrosis. Numerous septa
** F4. Cirrhosis
* Nonivasive serological liver fibrosis score such as AST to platelet ratio (APRI), and proprietary tests such as: FibroTest, FibroSure, Hepascore, and FibroSpect. An example is based on the "serum hyaluronic acid, procollagen type III N-terminal peptide, and tissue inhibitor of metalloproteinase 1"<ref name="pmid33185364">{{cite journal| author=Newsome PN, Buchholtz K, Cusi K, Linder M, Okanoue T, Ratziu V | display-authors=etal| title=A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. | journal=N Engl J Med | year= 2021 | volume= 384 | issue= 12 | pages= 1113-1124 | pmid=33185364 | doi=10.1056/NEJMoa2028395 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=33185364  }} </ref>.
** A score > "9.8 indicates a moderate risk of advanced fibrosis"<ref name="pmid33185364">/
** A score > "11.3 denotes a high risk of advanced fibrosis"<ref name="pmid33185364"/>
* Noninvasive imaging scores such as the Fibroscan.


==References==
==References==
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Latest revision as of 21:24, 2 February 2022

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]

Overview

There are no specific diagnostic laboratory findings associated with non alcoholic fatty liver disease. Laboratory findings include abnormal liver function tests but are unspecific. Other laboratory tests are generally performed to rule out other diagnosis.

Laboratory Findings

  • There is no specific laboratory findings diagnostic for non alcoholic fatty liver disease.[1][2]
  • Liver function tests
    • Typical finding include a 2-4 fold elevation of the ALT 
    • An ALT/AST ratio of greater than 1.

Non-alcoholic fatty liver disease, especially if with cirrhosis, may be associated with thrombocytopenia[3][4].

Fibrosis score

A fibrosis score can be obtained via:

  • Liver biopsy. Various scoring systems exist including the Ishak; however, Ishak deems cirrhosis at a score of 5 or 6[5].
    • F0. No fibrosis
    • F1. Fibrous portal expansion
    • F2. Few septa
    • F3. Bridging fibrosis. Numerous septa
    • F4. Cirrhosis
  • Nonivasive serological liver fibrosis score such as AST to platelet ratio (APRI), and proprietary tests such as: FibroTest, FibroSure, Hepascore, and FibroSpect. An example is based on the "serum hyaluronic acid, procollagen type III N-terminal peptide, and tissue inhibitor of metalloproteinase 1"[6].
    • A score > "9.8 indicates a moderate risk of advanced fibrosis"<ref name="pmid33185364">/
    • A score > "11.3 denotes a high risk of advanced fibrosis"[6]
  • Noninvasive imaging scores such as the Fibroscan.

References

  1. ↑ "Nonalcoholic fatty liver disease: Indications for liver biopsy and noninvasive biomarkers - Noureddin - 2012 - Clinical Liver Disease - Wiley Online Library".
  2. ↑ "Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH)".
  3. ↑ Rivera-Álvarez M, Córdova-Ramírez AC, Elías-De-La-Cruz GD, Murrieta-Álvarez I, León-Peña AA, Cantero-Fortiz Y; et al. (2021). "Non-alcoholic fatty liver disease and thrombocytopenia IV: its association with granulocytopenia". Hematol Transfus Cell Ther. doi:10.1016/j.htct.2021.06.004. PMID 34312112 Check |pmid= value (help).
  4. ↑ Panke CL, Tovo CV, Villela-Nogueira CA, Cravo CM, Ferreira FC, Rezende GFM; et al. (2020). "Evaluation of thrombocytopenia in patients with non-alcoholic fatty liver disease without cirrhosis". Ann Hepatol. 19 (1): 88–91. doi:10.1016/j.aohep.2019.05.011. PMID 31575467.
  5. ↑ Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F; et al. (1995). "Histological grading and staging of chronic hepatitis". J Hepatol. 22 (6): 696–9. doi:10.1016/0168-8278(95)80226-6. PMID 7560864.
  6. ↑ 6.0 6.1 Newsome PN, Buchholtz K, Cusi K, Linder M, Okanoue T, Ratziu V; et al. (2021). "A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis". N Engl J Med. 384 (12): 1113–1124. doi:10.1056/NEJMoa2028395. PMID 33185364 Check |pmid= value (help).

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