Background and Aims Previous studies have found a close association between intrahepatic immune regulation and the development of liver fibrosis. However, the key genes associated with immune cells in liver fibrosis are still unclear. Therefore, this study aimed to investigate the correlation between key genes in liver fibrosis, disease progression, and the distribution of intrahepatic immune cells.Methods Differential gene expression analysis was performed on RNA sequencing data (RNA-seq) from liver tissues with different degrees of liver fibrosis obtained from public databases (GSE162694 and GSE49541), using normal liver samples as controls. The relative expression order (REO) algorithm was used to identify relative reversal stabile pairs. Key genes associated with liver fibrosis were analyzed. A CCl₄-induced mouse model of liver fibrosis was established, and histopathological changes were identified using Masson staining. The mRNA and protein expression of key genes were detected using qRT-PCR and Western blot methods, respectively. The relationship between key genes and immune cells as well as the progression of liver fibrosis was analyzed using the xCell tool.Results Analysis of the sequencing data identified two overlapping reverse gene pairs associated with liver fibrosis (THBS2>RHDE and LBH>LRRC19). Both THBS2 and LBH were upregulated in liver fibrosis tissues, and the expression of LBH was significantly correlated with fibrosis stage, histological score, and inflammation score (all P<0.05). Compared to the control group, the mRNA and protein levels of LBH in the liver of the model mice were significantly upregulated (both P<0.05). Based on the median expression value of LBH, the samples from the liver fibrosis datasets GSE162694 and GSE49541 were divided into the LBH high-expression group and the LBH low-expression group. The xCell analysis revealed that CD4⁺ memory T cells, central memory CD8⁺ T cells, dendritic cells, aDC, cDC, and other immune cells were enriched and immune cell scores were significantly upregulated in the high LBH expression group (all P<0.05).Conclusion The transcriptional co-factor LBH may regulate the distribution of intrahepatic immune cells and promote the progression of liver fibrosis.