Abstract

Zheng is the basic theory and essence of traditional Chinese medicine (TCM) in diagnosing diseases. However, there are no biological evidences to support TCM Zheng differentiation. In this study we elucidated the biological alteration of cirrhosis with TCM “Liver-Kidney Yin Deficiency (YX)” or “Dampness-Heat Internal Smoldering (SR)” Zheng and the potential of urine metabonomics in TCM Zheng differentiation. Differential metabolites contributing to the intergroup variation between healthy controls and liver cirrhosis patients were investigated, respectively, and mainly participated in energy metabolism, gut microbiota metabolism, oxidative stress, and bile acid metabolism. Three metabolites, aconitate, citrate, and 2-pentendioate, altered significantly in YX Zheng only, representing the abnormal energy metabolism. Contrarily, hippurate and 4-pyridinecarboxylate altered significantly in SR Zheng only, representing the abnormalities of gut microbiota metabolism. Moreover, there were significant differences between two TCM Zhengs in three metabolites, glycoursodeoxycholate, cortolone-3-glucuronide, and L-aspartyl-4-phosphate, among all differential metabolites. Metabonomic profiling, as a powerful approach, provides support to the understanding of biological mechanisms of TCM Zheng stratification. The altered urinary metabolites constitute a panel of reliable biological evidence for TCM Zheng differentiation in patients with posthepatitis B cirrhosis and may be used for the potential biomarkers of TCM Zheng stratification.

Highlights

  • Cirrhosis is scarring of the liver and is the final stage of many chronic liver diseases, leading to portal hypertension and end-stage liver disease [1]

  • Our results further proved the correlation between intestinal flora, enterohepatic circulation, and liver damage in the posthepatitis B cirrhosis patients

  • Our results suggest that a panel of unique urinary metabolite markers is of clinical potential for the disease diagnosis and patient stratification for liver cirrhosis

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Summary

Introduction

Cirrhosis is scarring of the liver and is the final stage of many chronic liver diseases, leading to portal hypertension and end-stage liver disease [1]. Child-Pugh (CP) scores classification is a widespread method to grade the liver function levels in cirrhotic patients [13, 14]. It can reasonably predict survival in many chronic liver conditions and the likelihood of major complications such as bleeding from varices and spontaneous bacterial peritonitis and is still considered to be a cornerstone in prognostic evaluation of cirrhosis [15, 16]. The CP score does not provide direct evidence of the pathological stage or state of cirrhosis [2]. It has some drawbacks such as the limited discriminatory ability as well as the fact that it depends greatly on the clinician’s experience [3, 4]

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