Prognostic significance of red blood cell distribution width in gastrointestinal disorders

Table 1 Published studies on role of red blood cell distribution width in inflammatory bowel disease

Ref.	No. of subjects	Study period	Activity index	Outcome measures	RDW Value	Statistics		Other laboratory studies	Main findings
						Sensitivity (%)	Specificity (%)
Clarke et al[21], 2008	156 CD	January 1st 2004 to December 31st 2005		Differential diagnosis CD vs UC	CD 14.9 UC 14.3	P = 0.027			RDW value was significantly higher in CD relative to ulcerative colitis patients
	128 UC
Cakal et al[23], 2009	74 UC, 22 CD, and 20 age/sex-matched controls		CDAI					CRP, ESR, Fibrinogen, PLT, WBC, Hb	RDW and CRP were the most significant indicators of active UC and active CD, respectively
			> 150 = active	Active UC or CD	UC 14	88	71
			Truelove-Witts scale for UC moderate and severe = active		CD 14.1	78	63
Oustamanolakis et al[28], 2011	51 CD		CDAI	Anemia (IDA/ACD)	14 (cut off)	93	81	Ferritin, Tsat, sTfR	High RDW and low RSF values were the best markers for the diagnosis of IDA
	49 UC		> 150 active	IDA				RDWR-C, RSF, IRF,
	102 age matched controls		< 150 inactive					Hb, ESR
			Simple Clinical					CRP
			Colitis Activity Index for UC
			Active ≥ 3
Yeşil et al[24], 2011	56 CD		CDAI	Active UC/CD	14 (cut off )	79 (CD)	93 (CD)	CRP, ESR, PLT, Hb	RDW was elevated in IBD and markedly increased in active disease. RDW may be a marker of active CD, whereas ESR is for active UC
	61 UC		> 150 = active			17 (UC)	84 (UC)
	44 age/sex matched controls		Truelove-Witts scale for UC
Song et al[26], 2012	101 CD	January 2003 and December 2010	CDAI	Active UC/CD	14.1 CD without anemia (cut off)	82 (CD)	83 (CD)	CRP, ESR, PLT, WBC, Hb,	RDW was associated with active CD/UC in patients with or without anemia
	120 UC		remission < 150, mild 150-220, moderate to severe ≥ 220; Mayo score for UC		13.8 UC without anemia (cut off )
			remission < 3, mild 3-6, moderate to severe ≥ 6			76 (UC)	86 (UC)
Ipek et al[25], 2015	206 active UC	January 2009 to December 2011	Endoscopic Rachmilewitz activity index > 4 = Active UC		Active UC 16.8			CRP, ESR, PLT, WBC, Hb	RDW can be used as a marker for disease activity in ulcerative colitis, but not in the non-anemic group
	104 remission UC			Active UC vs remission	Remission UC 15.5	P < 0.001
Oliveira et al[27], 2016	20 Active CD	January 1st and September 30th 2013	CDAI	RDW association with Active CD	16 (Cut off )	30	88	CRP, ESR, PLT, WBC, Hb, MCV	RDW was associated with the severity of CD. The RDW cutoff 16% showed possible clinical applicability
	99 remission CD		≥ 150 = active CD

CD: Crohn’s disease; UC: Ulcerative colitis; CDAI: Crohn’s disease activity index; CRP: C-reactive protein; ESR: Erythrocyte Sedimentation Rate; PLT: Platelets; WBC: White blood cells; Tsat: Transferrin saturation; sTfR: Soluble transferrin receptor; RSF: Red blood cell size factor; IRF: Immature reticulocyte fraction; RDWR-CV: Reticulocyte distribution width-coefficient of variation; IDA: Iron deficiency anemia; ACD: Anemia of chronic disease.

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.