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Chronic liver diseases mainly include chronic viral liver disease, metabolic liver disease, cholestatic liver disease (CLD), autoimmune liver disease, and liver fibrosis or cirrhosis. Notably, the compound formulas of traditional Chinese medicine (TCM) is effective for chronic liver diseases in clinical trials and basic research in vivo , which provide evidence of chronic liver disease treatment with integrated TCM and traditional Western medicine. This paper aims to provide a comprehensive review of the compound formulas of TCM for treating different chronic liver diseases to elucidate the composition, main curative effects, and mechanisms of these formulas and research methods. Different keywords related to chronic liver diseases and keywords related to the compound formulas of TCM were used to search the literature. PubMed, Scopus, Web of Science, and CNKI were searched to screen out original articles about the compound formulas of TCM related to the treatment of chronic liver diseases, mainly including clinical trials and basic in vivo research related to Chinese patent drugs, classic prescriptions, proven prescriptions, and hospital preparations. We excluded review articles, meta-analysis articles, in vitro experiments, articles about TCM monomers, articles about single-medicine extracts, and articles with incomplete or uncertain description of prescription composition. Plant names were checked with MPNS (http://mpns.kew.org). In this review, the clinical efficacy and mechanism of compound formulas of TCM were summarized for the treatment of chronic viral hepatitis, nonalcoholic fatty liver disease, CLD, and liver fibrosis or cirrhosis developed from these diseases and other chronic liver diseases. For each clinical trial and basic research in vivo , this review provides a detailed record of the specific composition of the compound formulas of TCM, type of clinical research, modeling method of animal experiments, grouping methods, medication administration, main efficacy, and mechanisms. The general development process of chronic liver disease can be summarized as chronic hepatitis, liver fibrosis or cirrhosis, and hepatocellular carcinoma. The compound formulas of TCM have some applications in these stages of chronic liver diseases. Owing to the continuous progress of medical technology, the benefits of the compound formulas of TCM in the treatment of chronic liver diseases are constantly changing and developing. [Display omitted] • Review on the progress of compound formulas of TCM in the treatment of chronic liver disease from 1997 to 2023. • Focused on the compound formulas of TCM for HBV, NAFLD, CLD, hepatic fibrosis, etc. • Summarized the research scheme and results of compound formulas of TCM intervention in chronic liver disease. [ABSTRACT FROM AUTHOR]

Qingre Huashi (QRHS) formula is an empirical prescription for the treatment of Gan-Dan-Shi-Re syndrome (GDSR) syndrome in traditional Chinese medicine (TCM). GDSR is one of the typical TCM syndromes in chronic hepatitis B (CHB). However, little is known about the mechanism of the QRHS formula in treating CHB patients with GDSR. The biological basis of GDSR also remains largely unknown. Aim of the study : GDSR mostly occurs in the acute and early stages of chronic liver disease. Effectively alleviating GDSR stalls disease development and benefits patients. The purpose of this study was to explore the molecular basis of GDSR in CHB and then study the mechanism of the QRHS formula treating GDSR using transcriptomics and metabolomics. The transcriptome and metabolome of CHB patients with GDSR syndrome were detected using RNA microarray combined with ultra-high performance liquid chromatography/mass spectrometry and information mining. The potential biomarkers were identified from differentially expressed genes and metabolites, and the metabolic pathway was analyzed. We also investigated the callback of metabolic biomarkers after treatment with the QRHS formula, an empirical prescription for the treatment of GDSR syndrome. RT-PCR analysis was carried out in an independent patient cohort of CHB for validation. Four candidate genes— GPT2 , HK2 , DDIT3 , and HIF1A —and 14 candidate metabolic biomarkers, including L-alpha-aminobutyric acid, selenomethionine, and fructose 1,6-bisphosphate, were identified and validated. All four transcripts of GPT2 , HK2 , DDIT3 , and HIF1A were significantly differentially expressed between the GDSR and non-GDSR groups through independent microarray data and RT-PCR. After treatment with the QRHS formula, the clinical indexes and TCM syndrome were significantly improved, and the 14 disturbed biomarkers were obviously corrected. Three metabolic pathways were confirmed to be perturbed in CHB GDSR patients: alanine, aspartate, and glutamate metabolism, arginine biosynthesis, and aminoacyl-tRNA biosynthesis. Using integrated transcriptomic and targeted metabolomic methods, we identified the potential biomarkers and dysregulated metabolic pathways in CHB patients with GDSR syndrome, which was alleviated by the QRHS formula treatment. These results may provide the mechanism of metabolic dysregulation in GDSR syndrome as well as that underlying the curative effect of the QRHS formula. [Display omitted] [ABSTRACT FROM AUTHOR]