Liver transplant and autoimmune liver diseases: An up-to-date review

Table 1 Emerging therapies for autoimmune hepatitis

Disease	Emerging therapies	Mechanism/target	Current evidence	Ref.
Autoimmune hepatitis	Rituximab	anti-CD20 monoclonal antibody → B-cell depletion	Positive results in refractory cases; clinical and biochemical improvement	Than et al[56], 2019
				Multicenter retrospective series, n = 22
	Zetomipzomib	Selective immunoproteasome inhibitor	Approximately 36% complete biochemical response in phase 2a trial	PORTOLA Trial (Kezar Life Sciences), 2025
				Phase 2a, n = 24
	JKB-122	TLR4 antagonist	Biochemical and histological improvement in animal model; potentiates corticosteroid effect	Hsu et al[57], 2017
				Preclinical study (murine model)

TLR4: Toll-like receptor 4.

Table 2 Emerging therapies for primary biliary cholangitis

Disease	Emerging therapies	Mechanism/target	Current evidence	Ref.
Primary biliary cholangitis	Obeticholic acid	FXR agonist; increases bile flow, has immunomodulatory and anti-inflammatory effects	Improves biochemical markers and is associated with longer transplant-free survival	Hirschfield et al[76], 2015
				Phase 3, n = 217
	Bezafibrate/fenofibrate	PPARα agonists	Off-label use has been shown to improve liver biochemistry and transplant-free survival	Khakoo et al[80], 2023
				Meta-analysis, n = 1107 (8 RCTs)
	Seladelpar, Elafibranor, or Saroglitazar	PPARδ or PPAR pan-agonists	Clinical trials show promising biochemical improvement	Hirschfield et al[76], 2015
				(Seladelpar phase 3, n = 193)
	Setanaxib	NOX inhibitor; reduces oxidative stress and fibrosis	Ongoing studies are promising with anti-fibrotic effect	GS-02 trial, University of Miami, 2025
				Phase 2, n ≈ 111

FXR: Farnesoid X receptor; PPAR: Peroxisome proliferator-activated receptor; RCTs: Randomized controlled trials; NOX: Nicotinamide adenine dinucleotide phosphate oxidase.

Table 3 Emerging therapies for primary sclerosing cholangitis

Disease	Emerging therapies	Mechanism/target	Current evidence	Ref.
Primary sclerosing cholangitis	NorUDCA	Modified bile acid; anti-fibrotic, anti-inflammatory effect	Clinical trials in progress	Karlsen et al[14], 2017
				Phase 2, n ≈ 161
	FXR agonists	Regulates bile acid metabolism and has anti-inflammatory properties	Preliminary positive results	Hov and Karlsen[14], 2023
				Review and translational data
	anti-TNF anti-integrin agents	Target immune-mediated inflammation	Early experimental and clinical studies	Karlsen et al[16] 2017
				Translational/pilot data
	Autologous hematopoietic stem cell transplantation	Immune reconstitution and graft protection	Pilot study showing promising results for recurrent PSC after transplantation	Chruscinski et al[95], 2022
				Pilot, n = 6

NorUDCA: 24-nor-ursodeoxycholic acid; FXR: Farnesoid X receptor; TNF: Tumor necrosis factor; PSC: Primary sclerosing cholangitis.

Table 4 Recurrence after liver transplantation in autoimmune liver diseases

Disease	Estimated recurrence rate and main risk factors	Post-transplant surveillance and management considerations	Ref.
AIH	Recurrence in 10%-35% of recipients; risk increases with younger age, high pre-LT inflammatory activity, rapid corticosteroid withdrawal, and use of tacrolimus-based regimens (evidence moderate)	Monitor AST, ALT, IgG levels every 3 months in first year; consider protocol biopsy at 12 months in high-risk cases; maintain low-dose corticosteroid or azathioprine in selected patients to reduce recurrence	[97,101]
PBC	Recurrence in 15%-25% of cases; higher risk with female sex, younger age, persistent cholestasis, and shorter duration of UDCA therapy pre-LT (evidence moderate)	Routine monitoring of ALP and GGT; early recognition of cholestasis patterns; UDCA prophylaxis may be considered in centers with historically higher recurrence or in patients with biochemical cholestasis - not mandatory per EASL/AASLD guidelines	[71,73,74]
PSC	Recurrence in 20%-30% of recipients; increased risk with active IBD, male sex, younger age, and biliary anastomotic strictures (evidence moderate-high)	Surveillance with MRCP or ultrasound every 6-12 months and liver biochemistry every 3 months; aggressive management of IBD activity; prompt treatment of biliary strictures or infections to prevent graft injury	[17,95,99]

AIH: Autoimmune hepatitis; PBC: Primary biliary cholangitis; PSC: Primary sclerosing cholangitis; IBD: Inflammatory bowel disease; LT: Liver transplantation; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; UDCA: Ursodeoxycholic acid; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transferase; EASL: European Association for the Study of the Liver; AASLD: American Association for the Study of Liver Diseases; MRCP: Magnetic resonance cholangiopancreatography.