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

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.