RARE DISEASE
Isolated biliary atresia
Isolated biliary atresia
Isolated biliary atresia
Synonyms: Isolated atresia of bile ducts, Non-syndromic biliary atresia
Synonyms: Isolated atresia of bile ducts, Non-syndromic biliary atresia
Synonyms: Isolated atresia of bile ducts, Non-syndromic biliary atresia
Drug discovery
4
drugs
With orphan designations
Overview
Isolated biliary atresia (IBA) is a progressive neonatal cholangiopathy causing obliteration of intra-/extrahepatic bile ducts, presenting with persistent jaundice, acholic stools, and conjugated hyperbilirubinemia. Etiology involves genetic, immune, and environmental interactions, though non-hereditary. Diagnosis requires cholangiography confirmation after excluding other cholestatic causes. Kasai portoenterostomy remains first-line therapy, but 40-60% require liver transplantation by age 2 without sustained bile flow [1][3][5].
Therapies
Primary surgical: Kasai portoenterostomy (<70 days optimal), achieving native liver survival in 25-50% at 10 years [1][3][15]
Adjuvant medical: Limited efficacy of corticosteroids/IVIG; nutritional support (vitamin K, ursodiol) and infection prophylaxis [7][11]
Transplant rescue: 50% require liver transplantation by age 2, with 85% 10-year post-transplant survival [3][5]
Categories: rare abdominal surgical diseases, rare developmental anomalies during embryogenesis, rare hepatic diseases, rare transplant-related disorders
Research Papers
1,579 drug discovery papers about Isolated biliary atresia, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,579 drug discovery papers about Isolated biliary atresia, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-15 | Hepatic methionine-cycle dysregulation is associated with immune-inflammatory and fibrogenic remodeling in biliary atresia.
Biliary atresia (BA) is a progressive fibroinflammatory cholangiopathy leading to liver failure in infancy. The contribution of methionine metabolism to BA remains incompletely defined. This study investigated hepatic methionine-cycle alterations and the potential therapeutic effects of S-adenosylmethionine (SAMe). Public bulk transcriptomic and single-cell RNA sequencing datasets were analyzed to characterize methionine-cycle-related alterations in BA. Selected genes were validated in clinical liver tissues. Methionine-cycle metabolites, oxidative stress indicators, and histopathological changes were assessed in human liver samples. The effects of SAMe were examined in BA-derived liver mononuclear cells (LMNCs) and further evaluated in a rhesus rotavirus-induced BA mouse model using methionine-cycle metabolite quantification, liver transcriptomics, multiplex immunofluorescence, cytokine measurement, oxidative stress assays, and histological analysis. Methionine metabolism-related genes were dysregulated in BA, highlighting alterations in the one-carbon-methionine cycle-transsulfuration axis. Single-cell analysis localized these alterations to both hepatocyte and immune-cell compartments. Human BA liver tissues exhibited methionine-cycle imbalance, with increased methionine, S-adenosylhomocysteine, and homocysteine levels and reduced S-adenosylmethionine levels, accompanied by oxidative stress and fibrogenic responses. SAMe modulated cytokine secretion in BA-derived LMNCs. In BA mice, SAMe partially normalized methionine-cycle metabolite levels, improved hepatic redox status, reduced inflammatory immune infiltration, attenuated cytokine responses, and alleviated early fibrogenic remodeling. Hepatic methionine-cycle dysregulation is a prominent metabolic feature of BA and is associated with oxidative stress, immune-inflammatory alterations, and fibrogenic remodeling. SAMe partially alleviated these abnormalities in ex vivo and animal-model experiments, supporting further investigation of the therapeutic relevance of methionine metabolism in BA.
2026-08-11 | Biliary atresia-related liver fibrosis
Biliary atresia (BA) is a devastating cholestatic disease of infancy characterized by progressive fibro-obliterative cholangiopathy, which, without timely intervention, inexorably leads to end-stage liver disease and the need for liver transplantation. Hepatic fibrosis constitutes not only the histopathological cornerstone of BA but also the principal determinant of disease trajectory, native liver survival, and long-term outcomes. This review provides a comprehensive synthesis of the current understanding and unmet clinical needs in BA-associated liver fibrosis, systematically addressing three interconnected domains: pathogenesis, diagnostic modalities, and therapeutic strategies. In the pathogenic realm, we dissect the multilayered molecular architecture-from genetic susceptibility loci (including ciliopathy-related PKD1L1, developmental regulators ADD3,GPC1, and immune-modulating polymorphisms) through aberrant cellular activation (biliary epithelial cells undergoing ductular reaction and epithelial-mesenchymal transition, hepatic stellate cells and portal fibroblasts transdifferentiating into myofibroblasts, and immune cells polarizing toward pro-fibrotic phenotypes), to the integrated signaling network of TGF-β/Smad, Wnt/β-catenin, Hippo/YAP, and Notch pathways, further sustained by epigenetic modifications involving DNA methylation, histone remodeling, and non-coding RNAs. In diagnostics, we evaluate conventional ultrasound, emerging shear wave elastography, serum matrix metalloproteinase-7 as a promising biomarker, and risk-stratification algorithms, while critically comparing their strengths and limitations. In therapeutics, we assess the enduring role of Kasai portoenterostomy (KPE), the limitations of current adjunctive therapies, and the evolving landscape of pharmacological interventions-including ileal bile acid transporter inhibitors (odevixibat), farnesoid X receptor agonists (obeticholic acid), eicosapentaenoic acid, and N-acetylcysteine-alongside ongoing clinical trials. We further highlight how single-cell and spatial transcriptomic technologies are revolutionizing our comprehension of cellular heterogeneity and intercellular crosstalk within the fibrotic niche, offering unprecedented opportunities for molecular subtyping and precision medicine. By bridging mechanistic insights with clinical translation, this review provides a conceptual framework to guide future research, improve diagnostic precision, and develop rationally targeted combination therapies for BA-associated liver fibrosis.
2026-08-07 | Ganciclovir Improves Transplant-Free Liver Survival in Children With Biliary Atresia and Concurrent Cytomegaloviral Infection: A Pilot Study.
To investigate the effect of post-operative ganciclovir therapy on transplant-free liver survival in children with biliary atresia (BA) complicated by cytomegalovirus (CMV) infection, and to propose an intervention mechanism hypothesis based on the 'CMV-hepatic stellate cell-fibrosis-long-term prognosis' pathogenic axis. This retrospective study included children diagnosed with BA complicated by CMV infection at a tertiary children's hospital between January 2017 and October 2023. Patients were divided into a treatment group and a non-treatment group based on whether ganciclovir was administered for ≥ 1 week within 3 months after Kasai portoenterostomy (KPE). All patients had follow-up of at least 2 years by 1 October 2025. Baseline characteristics and clinical outcomes (transplant-free liver survival time and 3-month post-operative jaundice clearance rate) were compared between groups. Kaplan-Meier analysis was used to generate survival curves, and differences were assessed using the Log-Rank test. Evidence from basic and clinical research was integrated to construct a mechanistic hypothesis diagram for CMV-driven hepatic fibrosis and antiviral intervention. A total of 17 children with BA were included, with 6 in the treatment group and 11 in the non-treatment group. Baseline characteristics indicated no significant differences between the two groups in terms of sex, hepatic fibrosis stage, age at surgery, preoperative DBIL and other clinical indicators, demonstrating balanced comparability (p > 0.05). Comparison of clinical outcomes and Kaplan-Meier survival curves showed that transplant-free liver survival time was significantly longer in the treatment group than in the non-treatment group: 1518 (217, 2825) versus 190 (83, 265) days, p = 0.035; the survival curve showed an improving trend (Log-Rank p = 0.087). The 3-month post-operative jaundice clearance rate did not differ significantly between groups (p > 0.05). The mechanistic hypothesis diagram suggested that CMV may activate hepatic stellate cells via multiple pathways, including CCL19/CCR7 and TGF-β, accelerating fibrosis progression, while ganciclovir may block this process. Ganciclovir antiviral therapy may be associated with improved transplant-free liver survival in CMV-positive children with BA, exerting a specific effect on long-term fibrosis progression rather than short-term bile drainage. This clinical observation aligns with the 'CMV-fibrosis-long-term prognosis' pathogenic axis hypothesis and provides preliminary evidence for clinical antiviral treatment.
2026-08-07 | Hepatoprotective Effects of Imeglimin Are Associated With Preserved Mitochondrial Bioenergetics and Reduced Oxidative Stress in a Murine Cholestasis Model.
Biliary atresia is a cholestatic liver disease that causes persistent inflammation and reduces the hepatic reserve. New therapeutic concepts are crucial to improve native liver survival. We investigated whether imeglimin, a mitochondria-targeting agent, has hepatoprotective effects on cholestatic liver disease using a murine bile duct ligation (BDL) model. BDL was performed in 4-5-week-old mice. After BDL, the mice received intraperitoneal imeglimin or vehicle injections. Sham-operated mice received vehicle. Blood and liver samples were collected on days 7 and 14 for biochemical and histological analysis. Mitochondrial morphology was examined by transmission electron microscopy. Quantitative PCR and immunoblotting were performed for inflammation and mitochondrial stress markers. Metabolomic profiling was conducted using capillary electrophoresis-mass spectrometry. Transcriptome was analyzed by RNA sequencing. Seahorse assays, ATP quantification, and MitoSOX staining were used to evaluate mitochondrial function and oxidative stress. Imeglimin improved survival after BDL, and reduced serum AST, ALT, and bilirubin levels. Tissue fibrosis and Col1a1 and Acta2 expression were attenuated in imeglimin-treated livers. Glycolysis, amino acid metabolism, and mitochondrial electron transport activity were enhanced. Expression of genes associated with mitochondrial function, antioxidant defense, and metabolic regulation was upregulated. Mitochondrial morphology was preserved, and mitochondrial number and size increased. Imeglimin elevated oxygen consumption, extracellular acidification rates, and ATP levels of BDL mice livers, while reducing mitochondrial superoxide and oxidative protein modification by 4-hydroxynonenal. Expression levels of Il1β, Il6, and Tnf decreased. Imeglimin exerted hepatoprotective effects on BDL-operated mice, which are associated with preserved mitochondrial bioenergetic function and reduced oxidative stress.
2026-08-07 | Outcomes of Pediatric ABO-Incompatible Living Donor Liver Transplantation: A Retrospective Single-Centre Experience from India.
ABO incompatible liver transplant (ABOi-LT) is an essential alternative to blood-group-compatible liver transplant (LT) in children, and there is limited experience with this, especially from the developing world. The current analysis focuses on our experience of ABOi-LT in children. A retrospective analysis of all children undergoing ABOi-LT at our centre from January 2011 to February 2024 was performed. Their clinical profile, desensitisation protocol, post-transplant complications, patient and graft survival were analysed. We performed 35 (5%) ABOi-LTs during the above-mentioned time period. The median (interquartile range [IQR]) age at ABOi-LT was 15 (10-72) months, and the commonest aetiology was biliary atresia in 22 (63%) patients. Nineteen (54%) patients were below 18 months of age. Pre-LT plasmapheresis was offered to 24 (64%) patients, and 24 (64%) received rituximab. In children less than 18 months of age, 8 (42%) received pre-LT rituximab. None of the patients had major infections secondary to rituximab in the pre-LT period. Post-LT plasmapheresis was offered to 20 (57%) patients and 5 (15%) required immunoadsorption for persistently high antibody titres. Acute T-cell-mediated rejection was seen in 6 (17%) and 2 (5.5%) patients developed antibody-mediated rejection (AMR). No patients had hepatic artery thrombosis, anastomotic biliary strictures or bile leaks and 1 (2.7%) had chronic portal vein thrombosis. The median (IQR) duration of hospital stay was 16 (14-19.5) days. After a median follow-up of 24 months, overall survival was 34 (97%). Two patients with AMR were successfully treated and have normal graft function on follow-up. Excellent outcomes post-ABOi-LT can be achieved in children by using effective desensitisation protocols.
2026-08-15 | Hepatic methionine-cycle dysregulation is associated with immune-inflammatory and fibrogenic remodeling in biliary atresia.
Biliary atresia (BA) is a progressive fibroinflammatory cholangiopathy leading to liver failure in infancy. The contribution of methionine metabolism to BA remains incompletely defined. This study investigated hepatic methionine-cycle alterations and the potential therapeutic effects of S-adenosylmethionine (SAMe). Public bulk transcriptomic and single-cell RNA sequencing datasets were analyzed to characterize methionine-cycle-related alterations in BA. Selected genes were validated in clinical liver tissues. Methionine-cycle metabolites, oxidative stress indicators, and histopathological changes were assessed in human liver samples. The effects of SAMe were examined in BA-derived liver mononuclear cells (LMNCs) and further evaluated in a rhesus rotavirus-induced BA mouse model using methionine-cycle metabolite quantification, liver transcriptomics, multiplex immunofluorescence, cytokine measurement, oxidative stress assays, and histological analysis. Methionine metabolism-related genes were dysregulated in BA, highlighting alterations in the one-carbon-methionine cycle-transsulfuration axis. Single-cell analysis localized these alterations to both hepatocyte and immune-cell compartments. Human BA liver tissues exhibited methionine-cycle imbalance, with increased methionine, S-adenosylhomocysteine, and homocysteine levels and reduced S-adenosylmethionine levels, accompanied by oxidative stress and fibrogenic responses. SAMe modulated cytokine secretion in BA-derived LMNCs. In BA mice, SAMe partially normalized methionine-cycle metabolite levels, improved hepatic redox status, reduced inflammatory immune infiltration, attenuated cytokine responses, and alleviated early fibrogenic remodeling. Hepatic methionine-cycle dysregulation is a prominent metabolic feature of BA and is associated with oxidative stress, immune-inflammatory alterations, and fibrogenic remodeling. SAMe partially alleviated these abnormalities in ex vivo and animal-model experiments, supporting further investigation of the therapeutic relevance of methionine metabolism in BA.
2026-08-11 | Biliary atresia-related liver fibrosis
Biliary atresia (BA) is a devastating cholestatic disease of infancy characterized by progressive fibro-obliterative cholangiopathy, which, without timely intervention, inexorably leads to end-stage liver disease and the need for liver transplantation. Hepatic fibrosis constitutes not only the histopathological cornerstone of BA but also the principal determinant of disease trajectory, native liver survival, and long-term outcomes. This review provides a comprehensive synthesis of the current understanding and unmet clinical needs in BA-associated liver fibrosis, systematically addressing three interconnected domains: pathogenesis, diagnostic modalities, and therapeutic strategies. In the pathogenic realm, we dissect the multilayered molecular architecture-from genetic susceptibility loci (including ciliopathy-related PKD1L1, developmental regulators ADD3,GPC1, and immune-modulating polymorphisms) through aberrant cellular activation (biliary epithelial cells undergoing ductular reaction and epithelial-mesenchymal transition, hepatic stellate cells and portal fibroblasts transdifferentiating into myofibroblasts, and immune cells polarizing toward pro-fibrotic phenotypes), to the integrated signaling network of TGF-β/Smad, Wnt/β-catenin, Hippo/YAP, and Notch pathways, further sustained by epigenetic modifications involving DNA methylation, histone remodeling, and non-coding RNAs. In diagnostics, we evaluate conventional ultrasound, emerging shear wave elastography, serum matrix metalloproteinase-7 as a promising biomarker, and risk-stratification algorithms, while critically comparing their strengths and limitations. In therapeutics, we assess the enduring role of Kasai portoenterostomy (KPE), the limitations of current adjunctive therapies, and the evolving landscape of pharmacological interventions-including ileal bile acid transporter inhibitors (odevixibat), farnesoid X receptor agonists (obeticholic acid), eicosapentaenoic acid, and N-acetylcysteine-alongside ongoing clinical trials. We further highlight how single-cell and spatial transcriptomic technologies are revolutionizing our comprehension of cellular heterogeneity and intercellular crosstalk within the fibrotic niche, offering unprecedented opportunities for molecular subtyping and precision medicine. By bridging mechanistic insights with clinical translation, this review provides a conceptual framework to guide future research, improve diagnostic precision, and develop rationally targeted combination therapies for BA-associated liver fibrosis.
2026-08-07 | Ganciclovir Improves Transplant-Free Liver Survival in Children With Biliary Atresia and Concurrent Cytomegaloviral Infection: A Pilot Study.
To investigate the effect of post-operative ganciclovir therapy on transplant-free liver survival in children with biliary atresia (BA) complicated by cytomegalovirus (CMV) infection, and to propose an intervention mechanism hypothesis based on the 'CMV-hepatic stellate cell-fibrosis-long-term prognosis' pathogenic axis. This retrospective study included children diagnosed with BA complicated by CMV infection at a tertiary children's hospital between January 2017 and October 2023. Patients were divided into a treatment group and a non-treatment group based on whether ganciclovir was administered for ≥ 1 week within 3 months after Kasai portoenterostomy (KPE). All patients had follow-up of at least 2 years by 1 October 2025. Baseline characteristics and clinical outcomes (transplant-free liver survival time and 3-month post-operative jaundice clearance rate) were compared between groups. Kaplan-Meier analysis was used to generate survival curves, and differences were assessed using the Log-Rank test. Evidence from basic and clinical research was integrated to construct a mechanistic hypothesis diagram for CMV-driven hepatic fibrosis and antiviral intervention. A total of 17 children with BA were included, with 6 in the treatment group and 11 in the non-treatment group. Baseline characteristics indicated no significant differences between the two groups in terms of sex, hepatic fibrosis stage, age at surgery, preoperative DBIL and other clinical indicators, demonstrating balanced comparability (p > 0.05). Comparison of clinical outcomes and Kaplan-Meier survival curves showed that transplant-free liver survival time was significantly longer in the treatment group than in the non-treatment group: 1518 (217, 2825) versus 190 (83, 265) days, p = 0.035; the survival curve showed an improving trend (Log-Rank p = 0.087). The 3-month post-operative jaundice clearance rate did not differ significantly between groups (p > 0.05). The mechanistic hypothesis diagram suggested that CMV may activate hepatic stellate cells via multiple pathways, including CCL19/CCR7 and TGF-β, accelerating fibrosis progression, while ganciclovir may block this process. Ganciclovir antiviral therapy may be associated with improved transplant-free liver survival in CMV-positive children with BA, exerting a specific effect on long-term fibrosis progression rather than short-term bile drainage. This clinical observation aligns with the 'CMV-fibrosis-long-term prognosis' pathogenic axis hypothesis and provides preliminary evidence for clinical antiviral treatment.
2026-08-07 | Hepatoprotective Effects of Imeglimin Are Associated With Preserved Mitochondrial Bioenergetics and Reduced Oxidative Stress in a Murine Cholestasis Model.
Biliary atresia is a cholestatic liver disease that causes persistent inflammation and reduces the hepatic reserve. New therapeutic concepts are crucial to improve native liver survival. We investigated whether imeglimin, a mitochondria-targeting agent, has hepatoprotective effects on cholestatic liver disease using a murine bile duct ligation (BDL) model. BDL was performed in 4-5-week-old mice. After BDL, the mice received intraperitoneal imeglimin or vehicle injections. Sham-operated mice received vehicle. Blood and liver samples were collected on days 7 and 14 for biochemical and histological analysis. Mitochondrial morphology was examined by transmission electron microscopy. Quantitative PCR and immunoblotting were performed for inflammation and mitochondrial stress markers. Metabolomic profiling was conducted using capillary electrophoresis-mass spectrometry. Transcriptome was analyzed by RNA sequencing. Seahorse assays, ATP quantification, and MitoSOX staining were used to evaluate mitochondrial function and oxidative stress. Imeglimin improved survival after BDL, and reduced serum AST, ALT, and bilirubin levels. Tissue fibrosis and Col1a1 and Acta2 expression were attenuated in imeglimin-treated livers. Glycolysis, amino acid metabolism, and mitochondrial electron transport activity were enhanced. Expression of genes associated with mitochondrial function, antioxidant defense, and metabolic regulation was upregulated. Mitochondrial morphology was preserved, and mitochondrial number and size increased. Imeglimin elevated oxygen consumption, extracellular acidification rates, and ATP levels of BDL mice livers, while reducing mitochondrial superoxide and oxidative protein modification by 4-hydroxynonenal. Expression levels of Il1β, Il6, and Tnf decreased. Imeglimin exerted hepatoprotective effects on BDL-operated mice, which are associated with preserved mitochondrial bioenergetic function and reduced oxidative stress.
2026-08-07 | Outcomes of Pediatric ABO-Incompatible Living Donor Liver Transplantation: A Retrospective Single-Centre Experience from India.
ABO incompatible liver transplant (ABOi-LT) is an essential alternative to blood-group-compatible liver transplant (LT) in children, and there is limited experience with this, especially from the developing world. The current analysis focuses on our experience of ABOi-LT in children. A retrospective analysis of all children undergoing ABOi-LT at our centre from January 2011 to February 2024 was performed. Their clinical profile, desensitisation protocol, post-transplant complications, patient and graft survival were analysed. We performed 35 (5%) ABOi-LTs during the above-mentioned time period. The median (interquartile range [IQR]) age at ABOi-LT was 15 (10-72) months, and the commonest aetiology was biliary atresia in 22 (63%) patients. Nineteen (54%) patients were below 18 months of age. Pre-LT plasmapheresis was offered to 24 (64%) patients, and 24 (64%) received rituximab. In children less than 18 months of age, 8 (42%) received pre-LT rituximab. None of the patients had major infections secondary to rituximab in the pre-LT period. Post-LT plasmapheresis was offered to 20 (57%) patients and 5 (15%) required immunoadsorption for persistently high antibody titres. Acute T-cell-mediated rejection was seen in 6 (17%) and 2 (5.5%) patients developed antibody-mediated rejection (AMR). No patients had hepatic artery thrombosis, anastomotic biliary strictures or bile leaks and 1 (2.7%) had chronic portal vein thrombosis. The median (IQR) duration of hospital stay was 16 (14-19.5) days. After a median follow-up of 24 months, overall survival was 34 (97%). Two patients with AMR were successfully treated and have normal graft function on follow-up. Excellent outcomes post-ABOi-LT can be achieved in children by using effective desensitisation protocols.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
4 orphan drug designations for Isolated biliary atresia.
4 orphan drug designations for Isolated biliary atresia.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
maralixibat | small molecules | FDA | 2020-10-21 | — | Mirum Pharmaceuticals, Inc. |
Maralixibat chloride | small molecules | EMA | 2020-07-27 | — | Mirum Pharmaceuticals International B.V. |
odevixibat | small molecules | FDA | 2019-01-16 | — | Ipsen Biopharmaceuticals, Inc. |
(2S)-2-{[(2R)-2-[({[3,3-dibutyl-7-(methylthio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydro-1,2,5-benzothiadiazepin-8-yl]oxy}acetyl)amino]-2-(4-hydroxyphenyl)acetyl]amino}butanoic acid | small molecules | EMA | 2018-12-14 | — | Ipsen Pharma |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI's forecasts to outperform average preclinical success rates. Whether you're expanding your R&D pipeline, evaluating a partnership, or simply have a question — we'd love to hear from you.