Bile acid metabolic disorders and their role in hepatic encephalopathy of cirrhosis

Table 1 Serum bile acid profiles and key metabolic alterations in liver diseases of different etiologies

Etiology	Serum BA characteristics	Key metabolic enzyme/transporter alterations
MASLD	Total BAs elevated with fibrosis progression; conjugated primary BAs increased[77]. Cytotoxic DCA, LCA, and CDCA elevated, associated with advanced fibrosis[59,60,78]	CYP7A1 upregulated, FGF19 decreased, NTCP upregulated, BSEP unchanged[58]. CYP8B1 downregulated, HSD3B7 unchanged[61]
HBV-related	Total BAs elevated; increased ratio of glycine/taurine-conjugated BAs[65]. Lithocholate-3-O-glucuronide decreased in early stage[64]. GCA, GCDCA, TCA, TCDCA, and TUDCA progressively elevated (TCDCA most significant)[66,79]	HBV preS1 competitively binds to NTCP; NTCP downregulated in severe liver injury, reduced FXR activation relieves CYP7A1 inhibition[62,63,80]
HCV-related	Total BAs elevated, independently correlated with fibrosis severity[67]. TCA, GCA, GUDCA, TCDCA, and GCDCA elevated[68]	HSD3B7 and CYP8B1 characteristically downregulated, CA synthesis reduced; restored post-treatment with compensatory CYP27A1 upregulation[61,81]
Alcoholic-related	Total BAs significantly elevated[72]. Increased secondary BAs proportion with abnormal conjugated secondary BAs in duodenum[69,73]	CGH upregulation enhances deconjugation, disrupting gut-liver axis and driving CYP7A1 overexpression[70]. FXR inactivation via acetylation[71]. FGF19 elevated, correlated with MELD score[82]
PBC	Total BAs significantly elevated, TCA and GCA markedly elevated[71,74,83]. Taurine-conjugated BAs proportion significantly elevated[83]. GCDCA and TDCA levels elevated with Child-Pugh grade, correlating with disease severity[84]	Reduced BAs entering intestine, impaired BSH activity[74,75]. Weakened intestinal FXR-FGF19 negative feedback, CYP7A1 overexpression[76]

MASLD: Metabolic dysfunction-associated steatotic liver disease; BAs: Bile acids; DCA: Deoxycholic acid; LCA: Lithocholic acid; CDCA: Chenodeoxycholic acid; CYP7A1: Cholesterol 7α-hydroxylase; FGF19: Fibroblast growth factor 19; NTCP: Sodium taurocholate cotransporting polypeptide; BSEP: Bile salt export pump; CYP8B1: Sterol 12α-hydroxylase; HSD3B7: 3β-hydroxysteroid dehydrogenase type 7; HBV: Hepatitis B virus; GCA: Glycocholic acid; GCDCA: Glycochenodeoxycholic acid; TCA: Taurocholic acid; TCDCA: Taurochenodeoxycholic acid; TUDCA: Tauroursodeoxycholic acid; FXR: Farnesoid X receptor; HCV: Hepatitis C virus; GUDCA: Glycoursodeoxycholic acid; CGH: Choloylglycine hydrolase; MELD: Model for end-stage liver disease; PBC: Primary biliary cholangitis; BSH: Bile salt hydrolase; TDCA: Taurodeoxycholic acid; CYP27A1: Sterol 27-hydroxylase.