Table 2.

Published studies on role of red blood cell distribution width in liver disorders

Ref.	No. of subjects	Study period	Liver pathology	Outcome measures	RDW value (%)	Statistics	Other laboratory studies	Main findings
Lou et al[35], 2012	16 AHB	August 1st, 2010	AHB, CHB, CHB-severe	RDW association with HBV related liver disease states and mortality	14.38 ± 1.72 (AHB)	P < 0.05	ALT, total bilirubin, total protein, albumin, WBC, Hb, MCV, INR, Creatinine, BUN, HBsAg HBeAg, HBcAb IgM, HBV DNA	RDW is significantly increased in HBV infected patients compared to controls, and RDW is an independent predicting factor for the 3 mo mortality rate in HBV infected patients.
	61 CHB	August 1st, 2011	MELD score		16.37 ± 2.43 (CHB)	P < 0.001
	46 CHB-severe				18.3 ± 3.11 (CHB-severe)	P < 0.001
	48 healthy controls				13.03 ± 1.33 healthy controls
			NASH (Brunt’s criteria)			P < 0.01	Liver biopsy,	Patients with NASH had higher RDW relative to simple steatosis and healthy control groups.
Cengiz et al[32], 2013	62 NASH	Jan-10	Advanced fibrosis (2-4 points)	RDW association with NASH and fibrosis	NASH 14.28 ± 0.25	P < 0.01	Hb, platelets, MPV, WBC, lymphocytes,	RDW was higher in patients with advanced fibrosis compared to mild
	32 simple steatosis	May-13	Mild fibrosis (0-1)		Simple steatosis 13.37 ± 0.12		ALT, AST, GGT Albumin, BUN, Creatinine, alkaline phosphatase
	30 healthy controls				Healthy controls 12.96 ± 0.14
					Advanced fibrosis 15.86 ± 0.4
					Mild fibrosis 13.63 ± 0.67
Yang et al[38], 2013	1637 normal control	Individuals were initially enrolled during 2010	NAFLD criteria presence of definite hepatic steatosis on US scan (grade 3), and exclusion of secondary hepatic steatosis.	RDW in NAFLD patients	12.96 ± 1.08 (control)	P = 0.000	Total cholesterol, TG, Fasting glucose, Hb	RDW was increased in NAFLD patients
	619 NALFD				13.23 ± 1.01 (NAFLD)
Kim et al[55], 2013	24547 NAFLD patients	Individuals were enrolled in 2010 (January 1st to December 30th)	NAFLD diagnosis by US and questionnaires about alcohol consumption. Degree of liver fibrosis by BARD and FIB-4 scores	RDW and the level of fibrosis in NAFLD	12.59±0.62 BARD score (0,1)	P < 0.001	Hb, MCV, LDL, TG, HDL, HbA1C, high sensitivity CRP, ferritin, Platelet	Increased RDW is independently associated with advanced fibrosis in NAFLD
					12.99 ± 0.85 (BARD score 2-4)	P < 0.001
					12.61±0.77 (FIB-4 score < 1.3)
					12.89 ± 0.71(FIB-4 score ≥ 1.3)
Karagoz et al[42], 2014	229 biopsy proven naïve chronic hepatitis B (CHB) patients	January 2010 and November 2013	Fibrosis in CHB (Ishak score)	Relationship of RDW and MPV with the severity of fibrosis in CHB patients	12.6 (cut off)	91.50%	Liver biopsy, WBC, Hb, Ht, platelets, MPV, PDW, AST, ALT, total bilirubin, albumin,	RDW and MPV are significantly higher in HBV infected patients with severe fibrosis
						Sensitivity
						42.50%
						Specificity
Huang et al[36], 2014	69 CHB	January 2011 and October 2013	HBV related liver cirrhosis	Correlation of RDW with HBV cirrhosis, CHB; Child-Pugh and MELD scores	16.07 ± 2.41 (HBV cirrhosis)	P < 0.01	AST, ALT, total bilirubin, albumin, WBC, Hb, platelets, INR, Creatinine, BUN. HBeAg, HBV DNA	RDW was elevated in HBV related cirrhosis and CHB relative to control, and was positively correlated with severity of HBV related cirrhosis
	61 HBV liver cirrhosis		Child-Pugh and MELD scores		13.29 ± 1.09 (CHB)
	41 controls				12.75 ± 0.7 (controls)
Dogan et al[39], 2015	54 NASH	Dec-10	NASH (NAFLD activity score)	Inflammation in NASH	13.3 (cut off)	79.50%	Liver biopsy,	RDW is a specific and sensitive method to assess inflammation in NASH patients
	39 controls	Mar-12	Fibrosis, 0 not significant (F0-F1); 1 significant (F2-F4)			Sensitivity	Ht, MCV platelets, ALT, AST, GGT LDL, HDL, TG, Fasting glucose, insulin,
			Steatosis, 0 mild (grade 1); 1 moderate to severe (grade 2-3)			73.30%	Alkaline phosphatase
			0 lobular inflammation (0-1);			Specificity
			1 moderate-severe (2-3)
Xu et al[34], 2015	446 HBV infected patients who underwent liver biopsy	January 2010 and December 2011	Liver fibrosis (no significant S0-S2, fibrosis vs advanced, S3-S4)	RDW in liver fibrosis and inflammation	13.3 (S0-S2)	P = 0.01	Liver biopsy, AST, ALT, total bilirubin, albumin, WBC, Hb, platelets, MCV, MPV, HBeAg, HBV DNA	RDW, together with other serum markers, could be useful in predicting liver fibrosis and necroinflammation in HBV infected patients
			Inflammation (no significant (G0-G2) vs significant (G3-G4)		13.6 (S3-S4)	P < 0.001
					13.2 (G0-G2)
					13.7 (G3-G4)
Wang et al[37], 2016	116 CHB	January 2010 to January 2015	Liver fibrosis and inflammation: absent-mild (S0-S1, G0-G1) vs moderate-severe (S2-S4, G2-G4)	RDW association with liver fibrosis and inflammation in chronic hepatitis	13.4 (S0-S1)	P < 0.001	AST, ALT, alkaline phosphatase, GGT, globulin, total bilirubin, total bilirubin acid, total protein, albumin, WBC, RBC, Hb, MCV, platelets	RDW and globulin could be useful predictors of liver fibrosis and inflammation in chronic hepatitis patients, respectively.
	65 PBC				14.5 (S2-S4)
	37 AIH				13.0 (G0-G1)
					14.2 (G2-G4)

RDW: Red blood cell distribution width; Hb: Hemoglobin; HbA1C: Hemoglobin A1C; Ht: Hematocrit; CRP: C reactive protein, AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; WBC: White blood cell; RBC: Red blood cell; MCV: Mean corpuscular volume; PDW: Platelet distribution width; MPV: Mean platelet volume; GGT: Gamma-glutamyl transpeptidase; HBV: Hepatitis B virus; HbeAg: Hepatitis B e antigen; HbsAg: Hepatitis B s antigen; HbcAb: Hepatitis B core antibody; NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitits; TG: Triglyceride; LDL: Low-density lipoprotein; HDL: High-density lipoprotein; BUN: Blood urea nitrogen; INR: International normalized ratio; AHB: Acute hepatitis B; HBVDNA: Hepatitis B virus DNA; PBC: Primary biliary cirrhosis; AIH: Autoimmune hepatitis.