2. Academic Validation
  3. Cathepsin L and B as Potential Markers for Liver Fibrosis: Insights From Patients and Experimental Models

Cathepsin L and B as Potential Markers for Liver Fibrosis: Insights From Patients and Experimental Models

  • Clin Transl Gastroenterol. 2017 Jun 15;8(6):e99. doi: 10.1038/ctg.2017.25.
Mansi Manchanda 1,  Prasenjit Das 2,  Gaurav P S Gahlot 2,  Ratnakar Singh 1,  Elke Roeb 3,  Martin Roderfeld 3,  Siddhartha Datta Gupta 2,  Anoop Saraya 4,  R M Pandey 5,  Shyam S Chauhan 1
Affiliations

Affiliations

  • 1 Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
  • 2 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
  • 3 Department of Gastroenterology, Justus-Liebig-University, Giessen, Germany.
  • 4 Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India.
  • 5 Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India.
PMID: 28617446 DOI: 10.1038/ctg.2017.25
Abstract

Objectives: Cathepsin L (CTSL) and B (CTSB) have a crucial role in extracellular matrix (ECM) degradation and tissue remodeling, which is a prominent feature of fibrogenesis. The aim of this study was to determine the role and clinical significance of these cathepsins in liver fibrosis.

Methods: Hepatic histological CTSL and CTSB expression were assessed in experimental models of liver fibrosis, patients with liver cirrhosis, chronic viral hepatitis, and controls by Real-Time PCR and immunohistochemistry. Plasma levels of CTSL and CTSB were analyzed in 51 liver cirrhosis patients (Child-Pugh stages A, B and C) and 15 controls.

Results: Significantly enhanced CTSL mRNA (P=0.02) and protein (P=0.01) levels were observed in the liver of carbon tetrachloride-treated mice compared with controls. Similarly, hepatic CTSL and CTSB mRNA levels (P=0.02) were markedly increased in Abcb4-/- (ATP-binding cassette transporter knockout) mice compared with wild-type littermates. Elevated levels of CTSL and CTSB were also found in the liver (P=0.001) and plasma (P<0.0001) of patients with hepatic cirrhosis compared with healthy controls. Furthermore, CTSL and CTSB levels correlated well with the hepatic collagen (r=0.5, P=0.007; r=0.64, P=0.0001). CTSL and CTSB levels increased with the Child-Pugh stage of liver cirrhosis and correlated with total bilirubin content (r=0.4/0.2; P≤0.05). CTSL, CTSB, and their combination had a high diagnostic accuracy (area under the curve: 0.91, 0.89 and 0.96, respectively) for distinguishing patients from controls.

Conclusions: Our data demonstrate the overexpression of CTSL and CTSB in patients and experimental mouse models, suggesting their potential as diagnostic biomarkers for chronic liver diseases.

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