Journal Article

Creatinine-to-Cystatin C Ratio Combined with FIB-4 and ELF for Noninvasive Fibrosis Assessment in MASLD

Shibamoto, Akihiko, Iwai, Satoshi, Sato, Shinya, Fujinaga, Yukihisa, Mitoro, Akira, Nishimura, Norihisa, Asada, Kiyoshi, Namisaki, Tadashi, Oyama, Masafumi, Takami, Masayoshi, Kitagawa, Koh, Yoshiji, Hitoshi, Takaya, Hiroaki, Hanatani, Junichi, Inoue, Takashi, Tsuji, Yuki, Kaji, Kosuke, Masuda, Hiroyuki

2025

Overview

The creatinine-to-cystatin C ratio (CCR), a surrogate for skeletal muscle mass, may also be associated with liver fibrosis due to the strong link between sarcopenia and liver disease progression. We aimed to evaluate the utility of CCR as a noninvasive marker of liver fibrosis in metabolic-dysfunction-associated steatotic liver disease (MASLD). This retrospective study included 104 patients with biopsy-proven MASLD. CCR was calculated using serum creatinine and cystatin C levels. Liver fibrosis was staged histologically (F0–F4), and skeletal muscle mass was assessed using the skeletal muscle index (SMI) on computed tomography. Associations between CCR and liver fibrosis, SMI, and nonalcoholic fatty liver disease activity score were analyzed. ROC analysis evaluated CCR performance alone and in combination with FIB-4 and enhanced liver fibrosis (ELF) scores. CCR values were significantly lower in patients with significant fibrosis (≥F2). The AUROC of CCR for detecting ≥F2 fibrosis was 0.621 (95% CI: 0.509–0.733), with an optimal cutoff of 0.664. CCR alone yielded an AUC of 0.815 for predicting ≥F2 fibrosis. Combining CCR with FIB-4 and ELF substantially improved diagnostic accuracy, increasing the AUROC from 0.621 (CCR alone) to 0.820 for the combined model. CCR correlated positively with SMI (r = 0.451, p < 0.001). CCR is a simple, cost-effective biomarker reflecting muscle mass and liver fibrosis in MASLD. Combining CCR with established markers may enhance risk stratification and reduce the need for liver biopsy in selected cases.

• Publisher: MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
• Subject: Adult / Aged / Biomarkers - blood / Biopsy / Creatinine / Cystatin C - blood / Decision trees / Diabetes / Diagnosis / Diagnosis, Noninvasive / Disease Progression / Fatty liver / Female / Fibrosis / Health aspects / Histology / Humans / Hypertension / Inflammation / Liver - pathology / Liver cirrhosis / Liver Cirrhosis - blood / Liver Cirrhosis - diagnosis / Liver Cirrhosis - pathology / Liver diseases / Male / Measurement / Metabolic disorders / Methods / Middle Aged / Mortality / Muscle, Skeletal - diagnostic imaging / Musculoskeletal system / Non-alcoholic Fatty Liver Disease - blood / Non-alcoholic Fatty Liver Disease - complications / Non-alcoholic Fatty Liver Disease - pathology / Peptides / Physiological aspects / Retrospective Studies / Risk factors / ROC Curve / Sarcopenia / Sarcopenia - blood / Sarcopenia - diagnosis / Sarcopenia - etiology / Tomography, X-Ray Computed