Role of osteoprotegerin/receptor activator of nuclear factor kappa B/receptor activator of nuclear factor kappa B ligand axis in nonalcoholic fatty liver disease

Table 1 Studies assessing the association between osteoprotegerin and nonalcoholic fatty liver disease

Ref.	Study design	Population	Findings
Yilmaz et al[75], 2010	Cross-sectional study	56 adult patients with histological-proven definite NASH; 26 with borderline NASH; 17 with simple fatty liver; and 58 healthy controls without evidence of liver disease (normal results on liver function tests and normal liver ultrasound).	OPG levels were significantly decreased in patients with definite NASH and borderline NASH than in controls. No significant differences were found between patients with simple fatty liver and controls.
Ayaz et al[79], 2014	Case-control study	60 adult patients with ultrasound-proven NAFLD and 30 control subjects.	OPG levels were significantly increased in patients with NAFLD compared to control subjects.
Yang et al[76], 2015	Cross-sectional study	179 patients with biopsy-proven NAFLD (training group) and 91 age- and gender-matched healthy subjects. 63 other NAFLD patients were separately collected as validation group.	Serum levels of OPG decreased in a stepwise fashion in controls, non-NASH NAFLD patients and NASH patients.
Monseu et al[80], 2016	Cross-sectional study	314 adult subjects with at least one criterion for metabolic syndrome.	OPG levels were positively associated with both liver markers (such as alanine aminotransferase, gamma-glutamyl transferase and ferritin levels) and increased liver fat content as assessed by magnetic resonance imaging.
Niu et al[77], 2016	Case-control study	746 adult patients with type 2 diabetes, of whom 367 with ultrasound-proven NAFLD.	OPG levels were significantly decreased in patients with NAFLD compared to those without NAFLD.
			Participants in the lowest OPG quartile had a significantly increased risk for NAFLD (OR = 3.49, 95%CI: 1.86-6.94).
Erol et al[78], 2016	Cross-sectional study	107 children with obesity of whom 62 had ultrasound-proven NAFLD and 37 control subjects.	OPG levels in the obese group were significantly lower than in controls. Among obese youths, those with high fasting insulin and high HOMA-IR values had significantly lower OPG levels. Patients with hepatic steatosis had lower OPG concentrations than those without liver involvement, although they did not reach statistical significance.

NASH: Non-alcoholic steatohepatitis; OPG: Osteoprotegerin; NAFLD: Nonalcoholic fatty liver disease; HOMA-IR: Homeostasis model assessment for insulin resistance.