Red cell distribution width/platelet ratio predicts decompensation of metabolic dysfunction-associated steatotic liver disease-related compensated advanced chronic liver disease

Table 1 Red cell distribution width/platelet ratio in non-hepatic conditions

Ref.	Method	Findings	Conclusion
Acute conditions
Cetinkaya et al[43], 2014	Totally 102 patients with AP were recruited	RPR with a cutoff value of 0.000067 presented an area under the receiver operating characteristic curve of 0.783 (95%CI: 0.688-0.878) and predicted the mortality of approximately 80% of the patients	RPR is a valuable biomarker of mortality in AP
Pusuroglu et al[44], 2015	Totally 470 consecutive patients with STEMI submitted for primary PCI were prospectively enrolled	At LRA, high RPR was an independent predictor of one-year cardiovascular mortality (P = 0.003, OR = 3.106, 95%CI: 1.456-6.623)	RPR is an inexpensive and readily available biomarker which offers additional risk stratification in predicting long-term MACE and cardiovascular mortality in STEMI
Celık et al[42], 2015	Totally 580 STEMI patients were divided into two groups according to thrombolysis in myocardial infarction flow grades after primary PCI	At LRA, RPR was among the independent predictors of no-reflow after primary PCI. In its turn, being in the no-reflow group compared to the reflow patients was associated with higher odds of in-hospital MACE, and cardiovascular mortality	RPR is among the independent predictors of no-reflow and in-hospital MACE among patients with STEMI undergoing primary PCI
Karabulut and Arcagok[45], 2020	RPR was compared to C-reactive protein and procalcitonin to investigate the potential to predict EOS in newborns	RPR and other biomarkers had higher values in proven EOS than in the controls	RPR may be used in the diagnosis of EOS among newborns as a good alternative to other tools
Lehmann et al[46], 2021	Totally 102 subjects with deep-seated ICH were included	At LRA elevated RPR ≥ 0.06 was among the independent predictors of 90-day mortality	RPR, as a biomarker of inflammation, might serve for prognostic assessment in deep-seated ICH
Jiang et al[47], 2022	Totally 47 individuals with MSA, 125 subjects with Parkinson’s disease, and 124 healthy controls were enrolled	At LRA, RPR was associated with the risk of MSA	Patients with MSA probably have peripheral inflammatory reaction
Liu et al[48], 2022	Totally 3367 patients with sepsis were enrolled	After adjustment for confounders, high RPR was significantly associated with increased mortality both for categorical and continuous variables (adjusted HR = 1.210, 95%CI: 1.045–1.400; and adjusted HR = 2.826, 95%CI: 2.025–3.944, respectively)	Elevated RPR values predict 28-day mortality in patients with sepsis
Wang et al[49], 2022	Totally 45 newborns were included in each of three groups of different severity; mild, moderate, and severe conditions based on SNAPE-II	A positive correlation was found between the SNAPE-II scores and RPR among newborns in NICU	Further to the SNAPE-II, also RPR can be used as a supplementary predictor biomarker for the assessment of neonatal morbidity and mortality in NICU
Liang et al[50], 2023	Retrospective cohort study of 2823 adults with ICH	After adjustment for confounding factors, the 3rd tertile of RPR values, compared to the 1st tertile, was associated with increased odds of 30-day death in patients with ICH (HR = 1.37, 95%CI: 1.15–1.64)	Among subjects with ICH, elevated RPR levels predict 30-day mortality
Kasirer et al[51], 2024	Totally 69 infants with NEC and 78 controls were enrolled	RPR was significantly associated with both NEC diagnosis (P < 0.0001) and mortality (P = 0.01). However, at LRA only variations of platelet count from birth to diagnosis remained significant	The often-elusive attempts to definitively diagnose NEC among preterm newborns may benefit from largely available, cheap, and easily calculated platelet indices
Chronic and acute-on chronic conditions
Özer Bekmez et al[52], 2018	A cohort of 112 infants with medically treated hsPDA and 96 controls were recruited	At LRA analysis, high RPR (OR = 3.3, 95%CI: 1.438-5.872, P < 0.05) was one of the independent risk factors for hsPDA	RPR is a promising biomarker for the diagnosis of hsPDA
Bilgin et al[53], 2019	Totally 312 CRC patients were enrolled	Among subjects with right-sided advanced cancer, OS was statistically significantly better for those with RPR ≥ 0.05 compared to those with RPR < 0.05 (median OS; RPR ≥ 0.05: 24.8 months vs < 0.05: 13.9 months; P = 0.035)	After validation, RPR can be used as a prognostic marker in CRC
Dagistan and Cosgun[54], 2019	Retrospective survey of 1342 subjects submitted to cranial MRI	A statistically significant difference was found in RPR values among the various study groups (Fazekas 0 to Fazekas 3) (P < 0.001)	Increased RPR values may suggest higher Fazekas's score and dementia in cranial MRI studies
Guler Kazanci et al[55], 2019	Totally 481 infants were recruited (169 with hsPDA and 312 controls)	RPR was significantly higher in the hsPDA group (P < 0.05). At LRA RPR > 0.070 (risk ratio = 5.33; 95%CI: 3.28-8.65; P < 0.001) was among the independent predictors of hsPDA	High RPR values in the first hours of life are a risk factor for hsPDA (and hsPDA refractive to ibuprofen treatment) in preterm infants
Chen et al[56], 2023	Totally 1922 AECOPD adults participating in the MIMIC-III and MIMIC-IV; and 1738 AECOPD patients from Emergency Intensive Care Unit Collaborative Research Database were recruited	After adjusting for confounders, Log (RPR×1000) was associated with elevated risk of in-hospital mortality of AECOPD patients (OR = 1.36, 95%CI: 1.01–1.84)	Among AECOPD patients RPR was associated with in-hospital mortality

AECOPD: Acute exacerbations of chronic obstructive pulmonary disease; AP: Acute pancreatitis; CRC: Colorectal cancer; EOS: Early onset sepsis; HR: Hazard ratio; ICH: Intracerebral hemorrhage; HsPDA: Hemodynamically significant patent ductus arteriosus; LRA: Logistic regression analysis; MACE: Major adverse cardiovascular events; MIMIC: Medical Information Mart for Intensive Care; MSA: Multiple system atrophy; MRI: Magnetic resonance imaging; NEC: Necrotizing enterocolitis; NICU: Neonatal intensive care units; OR: Odds ratio; OS: Overall survival; PCI: Percutaneous coronary intervention; RPR: Red cell distribution width/platelet ratio; SNAPE-II: Score for neonatal acute physiology and perinatal extension II; STEMI: ST-segment elevation myocardial infarction.

Table 2 Red cell distribution width/platelet ratio in liver disease

Ref.	Method	Findings	Conclusion
Taefi et al[60], 2015	Totally 152 subjects with native livers and 70 with transplanted livers were recruited	In the native liver group RPR showed the strongest correlation with the degree of fibrosis (P < 0.001), AUC for cirrhosis = 0.684. However, in the transplanted liver group, none of the variables was significantly correlated with the stages of fibrosis nor did it predict cirrhosis	While it can be a strong predictor of the stage of fibrosis and cirrhosis in patients with CHB hepatitis and native liver, the use of RPR is limited among those with transplanted livers
Cengiz and Ozenirler[61], 2015	Totally 123 consecutive individuals with biopsy-proven NAFLD were analyzed	AUROC of the RPR was 0.69 in predicting significant fibrosis (≥ F2), 0.81 in advanced fibrosis (≥ F3), and 0.85 in F4, and all were statistically significant (P < 0.001). RPR was correlated with fibrosis (r = 0.37, 95%CI: 0.21-0.52, P < 0.001). At LRA, RPR independently predicted both significant and advanced fibrosis (P < 0.05)	The finding that RPR predicted liver fibrosis may be useful to reduce liver biopsy burden in NAFLD
Koksal et al[62], 2016	Totally 228 individuals with biopsy-proven CHB were enrolled	Statistically significant increases in all scores, including RPR, and decrease in platelet count were observed as the fibrosis level increased. However, RPR (and platelet count) were best in demonstrating advanced fibrosis	While they cannot replace liver biopsy for diagnosis, noninvasive scores such as APRI score can be used for monitoring the response to treatment with entecavir and tenefovir
Karagöz et al[63], 2016	Totally 98 biopsy-proven treatment-naïve CHC patients were recruited	The AUC of RPR (cut-off = 0.07 Fl) for predicting significant fibrosis was 0.705, which was superior to other non-invasive indices of fibrosis	RPR values, being significantly higher in patients with CHC, and associated with the severity of fibrosis, can be used to predict advanced liver histology, thereby decreasing the need of liver biopsy
Huang et al[64], 2017	Totally 256 CHB subjects were recruited	The diagnostic performance of GPR was not significantly different from APRI, FIB-4, and RPR in identifying significant fibrosis, advanced fibrosis, and cirrhosis, but it was significantly superior to area at risk and neutrophil-to-lymphocyte ratio in both HBeAg positive CHB and HBeAg negative CHB	GPR does not show any advantages over APRI, FIB-4, and RPR in identifying significant liver fibrosis, advanced liver fibrosis, and liver cirrhosis among Chinese subjects with HBeAg positive CHB or HBeAg negative CHB
Ferdous et al[65], 2018	Totally 40 subjects with CHB were enrolled	RPR was positively correlated with stages of hepatic fibrosis (Spearman's correlation coefficient = 0.749, P < 0.001)	Among CHB patients RPR values are strongly associated with stages of increasing severity of hepatic fibrosis
Liu et al[66], 2019	Totally 123 individuals with CHB were enrolled	The AUC values for RPR for the diagnoses of substantial fibrosis, severe fibrosis, and cirrhosis were 0.692, 0.732, and 0.808, respectively	Among CHB patients two-dimensional shear wave elastography is significantly more accurate than other non-invasive indices, including RPR, in the diagnosis of substantial fibrosis, severe fibrosis, and cirrhosis (P < 0.05)
Milas et al[67], 2019	Meta-analysis of 18 published studies totaling approximately 1800 patients for each outcome	Sensitivity, specificity, and AUC were as follows: (1) Significant fibrosis: 0.635, 0.769, and 0.747; (2) Advanced fibrosis: 0.607, 0.783, and 0.773; and (3) Cirrhosis: 0.739, 0.768, and 0.818. Similar findings, in all outcomes, were registered for CHB. Subgroup analysis indicated a high specificity for advanced fibrosis detection in PBC. For patients with advanced fibrosis, studies outside of China showed a higher sensitivity than investigations performed in China	With AUC > 0.7 for all outcomes and AUC > 0.8 for cirrhosis, RPR is a good biomarker of fibrosis, particularly among the most advanced forms of CLD
Jiang et al[68], 2020	Totally 118 biopsy-proven PBC subjects were recruited	The AUROC of RPR for predicting advanced fibrosis was 0.517	The AUROC of the total bile acid to platelet ratio in diagnosing fibrosis among PBC subjects was higher than that of other non-invasive serological models, including RPR
Gozdas and Ince[69], 2020	Totally 81 subjects with HCV chronic infection were enrolled	RPR values of those with severe fibrosis were significantly higher than those of the mild fibrosis group (P < 0.05). However, MPV/P had the biggest AUROC in the prediction of advanced fibrosis	MPV/P is an easy and practical biomarker to gain a preliminary insight into advanced fibrosis among subjects with chronic HCV infection
O’Hara et al[70], 2020	Cross-sectional survey of 8099 individuals in South-Western Uganda	In this study, RPR scores were excluded from further statistical analysis given that only few individuals had an elevated score	This population-based cohort study did not have statistical power sufficient to detect any factors associated with abnormal RPR scores given that only few subjects had an elevated RPR score
Chen et al[71], 2020	Retrospective analysis of 1005 CHB patients submitted to liver biopsies and laboratory profiling	Stepwise applying RPR, GPR, and easy liver fibrosis test would accurately discriminate 60% of patients as having either cirrhosis or no cirrhosis	Stepwise applying routine tests could be a strategy for cirrhosis detection in resource-limited settings
Ramzy et al[72], 2021	Cross-sectional analysis of 197 Egyptians with CHC	RPR values were significantly different among subjects with various fibrosis stages (P < 0.01) and RPR cut-off values of 0.007 and 0.008 were reliable predictors of significant and advanced fibrosis, respectively. However, at LRA, RPR was not an independent predictor of fibrosis	While having fair sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy for predicting significant fibrosis in patients with CHC, RPR was not an independent predictor of fibrosis at LRA
Zhang et al[59], 2023	Totally 168 HBVDC patients were enrolled	AT LRA, RPR (together with MELD score) was an independent predictor of mortality at 30 days. RPR and MELD score had similar predictive value and the combination of the two indexes further improved their predictive value for mortality	RPR is a reliable biomarker for the prediction of mortality at 30 days among HBVDC subjects
Nawalerspanya et al[73], 2024	Retrospective cross-sectional study of 139 individuals with biopsy-proven AIH or AIH-PBC overlap syndrome	With an AUROC of 0.742, RPR distinguishes cirrhosis from non-cirrhosis stages of CLD better than FIB-4 and APRI	In distinguishing cirrhotic from non-cirrhotic CLD among individuals with either AIH or AIH-PBC, RPR is more accurate than other non-invasive biomarkers of fibrosis

AIH: Autoimmune hepatitis; APRI: Aspartate aminotransferase/platelet ratio index; AUC: Area under the curve; AUROC: Area under the receiver operating characteristic curves; CHB: Chronic hepatitis B; CHC: Chronic hepatitis C; CLD: Chronic liver disease; GPR: Glutamyl transpeptidase to platelet ratio; FIB-4: Fibrosis 4; HbeAg: Hepatitis e antigen; HBVDC: Hepatitis B virus-associated decompensated cirrhosis; HCV: Hepatitis C virus; LRA: Logistic regression analysis; MELD: Model for end-stage liver disease; MPV/P: Mean platelet volume to platelet ratio; NAFLD: Nonalcoholic fatty liver disease; PBC: Primary biliary cholangitis; RPR: Red cell distribution width/platelet ratio.