Biliary Atresia Research Articles

Combined Predictors of Long-Term Outcomes of Kasai Surgery in Infants with Biliary Atresia.

Biliary atresia (BA) is the leading cause of neonatal cholestasis (25-45%). The primary treatment is hepatic portoenterostomy (Kasai procedure), but only 20-40% provide long-term benefits. This study aimed to develop a predictive model for surgical efficacy by comparing preoperative and early postoperative indicators in infants with different outcomes. We enrolled 166 infants with BA (93 girls, 73 boys) who underwent the Kasai procedure between September 2002 and December 2021, dividing them into favorable or adverse outcome groups. Over 40 parameters were measured, and the diagnostic significance of the prognostic model was evaluated. Kasai surgery was efficacious in 69 patients (42%) and non-efficacious in 97 (58%). Our model assesses efficacy by day 14 after surgery, improving on the <34 µmol/L direct bilirubin threshold established for 3-6 months after the procedure. Including the Desmet fibrosis score refined the model. Blood cholesterol below 5.41 mmol/L, direct bilirubin below 56.3 µmol/L on postoperative days 14±3, and a low Desmet score indicate a high probability of efficacious Kasai surgery in infants with BA.

HEPATOPULMONARY SYNDROME IN PEDIATRIC PATIENTS WITH PORTAL HYPERTENSION - AN INTEGRATIVE REVIEW.

Hepatopulmonary syndrome (HPS) is characterized by the triad of abnormal arterial oxygenation caused by intrapulmonary vascular dilatations (IPVD) in the setting of advanced liver disease or portal hypertension, impacting the patient's quality of life and survival. There are still many gaps in the literature on this topic, especially in pediatrics, with practices frequently based on extrapolation of data obtained from adults. Provide a synthesis of the current knowledge about HPS in children. The research was carried out through narrative review. The databases used for the search include Medline, Embase, Elsevier, Lilacs and Scielo. The keywords used were "hepatopulmonary syndrome" AND child, children, infant, preschool, pediatric. In cirrhotic children, the prevalence of HPS can reach up to 42.5%, and it is even more common in those whose underlying condition is biliary atresia, reaching up to 63%. Screening with pulse oximetry (O2 saturation <96%), unlike in adults, has low sensitivity in the pediatric age group. Management involves supportive care with oxygen therapy; liver transplantation is the only definitive treatment to reverse the condition and HPS is considered an exceptional criterion for waitlist. The waitlist mortality is similar among children listed by HPS as a special criterion when compared to those listed for other reasons. The reported rates of complete resolution of hypo-xemia after liver transplantation are close to 100% in children. The post-liver transplantation survival is similar or slightly lower in children with HPS when compared to those without HPS. Contrary to findings from adults, no differences were found in post- liver transplantation mortality between children of different hypoxemia ranges, although longer mechanical ventilation time and hospital stay were observed in children with PaO2 <50 mmHg. HPS is not an uncommon complication of cirrhosis in children and adolescents, particularly when biliary atresia is the underlying condition. There are still many gaps to be filled regarding the condition, and this article demonstrates that not all data obtained in studies with adults reflects the disease's behavior in pediatrics, especially concerning prognosis.

Biliary atresia in children (analytical literature review and review of own observation).

Aim: to review information resources and analysis of the own experience on this problem for the provision of modern knowledge in the pathogenesis of the pathology, the latest diagnostic and treatment technologies, with consideration of the need to adhere to a single strategy in the management of patients with BA. Materials and Methods: The analysis of the data regarding the results of existing studies evaluating the clinical benefit and safety of diagnostic and treatment methods in Biliary atresia. Conclusions: BA is the leading cause of neonatal cholestasis development. Early diagnostics of BA, based on the complex evaluation of clinical-laboratory, instrumental and morphological signs of the pathology, has a significant meaning. Surgical correction during the first 2 months of life - the Kasai procedure, as well as dynamic post-surgery follow-up significantly prolong the life of children and allow postponing liver transplantation. The highest patient survival both at the first stage of treatment - conduction of the Kasai procedure and the stage of liver transplantation may be achieved by joined work of surgeons and pediatricians, which allows considering the whole row of possible problems.

Combination of Pirfenidone and Andrographolide Ameliorates Hepatic Stellate Cell Activation and Liver Fibrosis by Mediating TGF-β/Smad Signaling Pathway.

Biliary atresia (BA) is a devastating congenital disease characterized by inflammation and progressive liver fibrosis. Activation of hepatic stellate cells (HSCs) plays a central role in the pathogenesis of hepatic fibrosis. Our study aimed to investigate the pharmacological effect and potential mechanism of pirfenidone (PFD) and andrographolide (AGP) separately and together on liver fibrosis of BA. The bile ducts of male C57BL/6J mice were ligated or had the sham operation. The in vivo effects of PFD and/or AGP on liver fibrosis of BA were evaluated. Human hepatic stellate cells (LX-2) were also treated with PFD and/or AGP in vitro. PFD and/or AGP ameliorates liver fibrosis and inflammation in the mice model of BA, as evidenced by significant downregulated in the accumulation of collagen fibers, hepatic fibrosis markers (α-SMA, collagen I, and collagen IV), and inflammatory markers (IL-1β, IL-6, and TNF-α). Moreover, compared with monotherapy, these changes are more obvious in the combined treatment of PFD and AGP. Consistent with animal experiments, hepatic fibrosis markers (α-SMA, collagen I, and CTGF) and inflammatory markers (IL-1β, IL-6, and TNF-α) were significantly decreased in activated LX-2 cells after PFD and/or AGP treatment. In addition, PFD and/or AGP inhibited the activation of HSCs by blocking the TGF-β/Smad signaling pathway, and the combined treatment of PFD and AGP synergistically inhibited the phosphorylation of Smad2 and Smad3. The combined application of PFD and AGP exerted superior inhibitive effects on HSC activation and liver fibrosis by mediating the TGF-β/Smad signaling pathway as compared to monotherapy. Therefore, the combination of PFD and AGP may be a promising treatment strategy for liver fibrosis in BA.

Relationship between hepatic function recovery and postoperative cholangitis in neonates undergoing hepaticojejunostomy for biliary atresia.

To explore the association between hepatic function recovery and the incidence of postoperative cholangitis in neonates with biliary atresia (BA) who underwent hepaticojejunostomy. We conducted a retrospective analysis of medical records from 173 newborns diagnosed with BA and treated with hepaticojejunostomy (Kasai procedure) between February 2020 and October 2022. Participants were categorized into two cohorts: those who developed cholangitis post-surgery (cholangitis group, n=125) and those who did not (non-cholangitis group, n=48). Liver function indices pre- and post-treatment, the extent of postoperative liver function recovery, and jaundice resolution rates were compared. Risk factors for cholangitis development post-surgery were identified using univariate and multifactorial logistic regression analyses. The cholangitis group exhibited higher surgical weight (P=0.030) and elevated preoperative levels of total bilirubin (TB, P<0.001), direct bilirubin (DB, P<0.001), aspartate aminotransferase (AST, P<0.001), and gamma-glutamyl transferase (GGT, P<0.001). This group also showed better postoperative liver function recovery (P=0.002) and jaundice clearance rates (P=0.003). Logistic regression identified postoperative jaundice clearance (P=0.013), TB (P=0.004), DB (P=0.011), AST (P<0.001), and GGT (P<0.001) as independent risk factors for cholangitis. The nomogram model had a C-index of 0.930 with a goodness-of-fit test p-value of 0.873, and an AUC of 0.930. Postoperative jaundice clearance, TB, DB, AST, and GGT are independent risk factors for cholangitis. The nomogram model offers high predictive accuracy for cholangitis development, aiding early intervention and prognosis improvement in high-risk neonates.

Molecular Pathways and Animal Models of Defects in Situs.

Left-right patterning is among the least well understood of the three axes defining the body plan, and yet it is no less important, with left-right patterning defects causing structural birth defects with high morbidity and mortality, such as complex congenital heart disease, biliary atresia, or intestinal malrotation. The cell signaling pathways governing left-right asymmetry are highly conserved and involve multiple components of the TGF-β superfamily of cell signaling molecules. Central to left-right patterning is the differential activation of Nodal on the left, and BMP signaling on the right. In addition, a plethora of other cell signaling pathways including Shh, FGF, and Notch also contribute to the regulation of left-right patterning. In vertebrate embryos such as the mouse, frog, or zebrafish, the specification of left-right identity requires the left-right organizer (LRO) containing cells with motile and primary cilia that mediate the left-sided propagation of Nodal signaling, followed by left-sided activation of Lefty and then Pitx2, a transcription factor that specifies visceral organ asymmetry. While this overall scheme is well conserved, there are striking species differences, including the finding that motile cilia do not play a role in left-right patterning in some vertebrates. Surprisingly, the direction of heart looping, one of the first signs of organ left-right asymmetry, was recently shown to be specified by intrinsic cell chirality, not Nodal signaling, possibly a reflection of the early origin of Nodal signaling in radially symmetric organisms. How this intrinsic chirality interacts with downstream molecular pathways regulating visceral organ asymmetry will need to be further investigated to elucidate how disturbance in left-right patterning may contribute to complex CHD.

Protein biomarkers GDF15 and FGF21 to differentiate mitochondrial hepatopathies from other pediatric liver diseases.

Mitochondrial hepatopathies (MHs) are primary mitochondrial genetic disorders that can present as childhood liver disease. No recognized biomarkers discriminate MH from other childhood liver diseases. The protein biomarkers growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21) differentiate mitochondrial myopathies from other myopathies. We evaluated these biomarkers to determine if they discriminate MH from other liver diseases in children. Serum biomarkers were measured in 36 children with MH (17 had a genetic diagnosis); 38 each with biliary atresia, α1-antitrypsin deficiency, and Alagille syndrome; 20 with NASH; and 186 controls. GDF15 levels compared to controls were mildly elevated in patients with α1-antitrypsin deficiency, Alagille syndrome, and biliary atresia-young subgroup, but markedly elevated in MH (p<0.001). FGF21 levels were mildly elevated in NASH and markedly elevated in MH (p<0.001). Both biomarkers were higher in patients with MH with a known genetic cause but were similar in acute and chronic presentations. Both markers had a strong performance to identify MH with a molecular diagnosis with the AUC for GDF15 0.93±0.04 and for FGF21 0.90±0.06. Simultaneous elevation of both markers >98th percentile of controls identified genetically confirmed MH with a sensitivity of 88% and specificity of 96%. In MH, independent predictors of survival without requiring liver transplantation were international normalized ratio and either GDF15 or FGF21 levels, with levels <2000 ng/L predicting survival without liver transplantation (p<0.01). GDF15 and FGF21 are significantly higher in children with MH compared to other childhood liver diseases and controls and, when combined, were predictive of MH and had prognostic implications.

Effect of Kasai procedure on liver transplantation in children with biliary atresia: a systematic review and updated meta-analysis.

Kasai procedure and liver transplantation are effective ways to save the life of children with biliary atresia (BA). However, with the gradual development of liver transplantation technology, scholars have questioned the necessity of the Kasai procedure. Therefore, we conducted a meta-analysis to evaluate the effect of previous Kasai procedures on liver transplantation in children with BA. Seven databases were searched and screened from the establishment of the database to May 3, 2023. The data in the included literature were extracted for meta-analysis to compare the differences between the Kasai group and the non-Kasai group. Finally, a publication bias test, sensitivity analysis, subgroup analysis, and systematic review were performed. A total of 26 studies were included in which 6,522 children with BA underwent liver transplantation, including 4,989 in the Kasai group. Compared with the non-Kasai group, the Kasai group had older age [standardized mean difference (SMD) =0.64; 95% confidence interval (CI): 0.46, 0.82; P<0.001] (I2=78.6%), heavier weight (SMD =0.41; 95% CI: 0.33, 0.48; P<0.001) (after sensitivity analysis, I2=0.0%), lower pediatric end-stage liver disease (PELD) (SMD =-0.41; 95% CI: -0.48, -0.35; P<0.001) (I2=20.1%), longer operation time (SMD =0.33; 95% CI: 0.01, 0.65; P<0.001) (I2=83.2%), more intraoperative blood loss (SMD =0.26; 95% CI: 0.06, 0.46; P=0.012) (I2=19.1%), shorter intensive care unit (ICU) stay (SMD =-0.09; 95% CI: -0.34, 0.15; P=0.027) (I2=68.6%) and higher incidence of intestinal perforation [odds ratio (OR) =1.96; 95% CI: 1.20, 3.18; P=0.007] (I2=7.4%) and biliary complications (OR =1.41; 95% CI: 1.05, 1.89; P=0.024) (I2=31.4%). In the "Asia" subgroup, the Kasai group was older (SMD =0.68; 95% CI: 0.52, 0.84; P<0.001) (I2=28.2%). In the "Cases since 2000" subgroup, there was no significant difference in operation time between the two groups (I2=28.5%). In the "Other" and the "non-Asia" subgroup, there was no significant difference in length of intensive care unit (ICU) stay between the two groups (I2=0.0%). However, there were no significant differences in other postoperative complications and prognostic indicators between the two groups. For children with BA undergoing liver transplantation, although previous Kasai procedure may increase the risk of intraoperative bleeding, biliary complications, and intestinal perforation, it does not affect the main clinical outcomes, and can even delay the timing of liver transplantation and improve the preoperative status of children. Therefore, when BA children have no obvious contraindications to Kasai procedure, the sequential treatment of Kasai procedure-liver transplantation should be supported first.

Diversity of Diseases-Causing Neonatal Jaundice - Experience of Pediatric Surgery Unit in Saidu Group of Teaching Hospital, Swat

Background: Rapidly establishing the cause of neonatal jaundice is very important. Delaying an exact diagnosis can have lifelong consequences. Timely treatment, if possible, is a universal solution. Objectives: This study aimed to report on the prevalence &amp; diagnostic approach of the myriad disorders causing persistent neonatal jaundice in patients presenting to the pediatric surgery unit of Saidu Group of Teaching Hospital (SGTH), Swat. Materials and Methods: Clinical chemistry and cause of disease were retrospectively analyzed in 40 infants (male n=21, 52.5%) that had presented with neonatal jaundice to SGTH, from January 2020 to December 2021. Results: The most common cause of persistent neonatal jaundice was biliary atresia (52 %) followed by idiopathic causes (15%) and Progressive familial intrahepatic cholestasis (10%). Conclusion: Although in the last 2 decades, new causes such as the progressive familial intrahepatic cholestasis followed by idiopathic cases have been identified biliary atresia still represents the major cause of persistent neonatal jaundice.

Study of Intrahepatic Biliary Architecture in Patients Operated for Extrahepatic Biliary Atresia using Magnetic Resonance Cholangiopancreatography.

The aim is to study intrahepatic biliary architecture in patients following Kasai's portoenterostomy for extrahepatic biliary atresia using magnetic resonance cholangiopancreatography (MRCP). It is a prospective observational study in a cohort of patients who have survived with a complete jaundice-free period for at least 1 year. MRCP was done to look for various intrahepatic architectural changes during their last visit. Findings were correlated with liver functions and growth and development. Twenty-one patients were included in the study. The male-to-female sex ratio was 1.6:1, the median age at surgery was 75 days (18-140 days), and the median age at magnetic resonance imaging (MRI) was 4 years (18 months-18 years). More than 2 years of follow-up was in seven patients. Left lobe hypertrophy was observed in six patients, right lobe hypertrophy was in three patients, intrahepatic biliary tract dilatation was in five patients, and altered signal intensity between intrahepatic ducts was seen in five patients. In addition, hypointense foci in the spleen were seen in one patient. Twelve children had normal weight for their age, ten children had the normal height for their age, and gamma-glutamyl transferase was elevated in all children. Only four children had a history of fever and jaundice. The patients who survive after successful surgical intervention have near-normal liver gross architecture as on MRI/MRCP. Occasional findings of dilatation and lobar atrophy/hypertrophy are possible, especially in those with a history of cholangitis. The survivors also have acceptable growth parameters and normal liver functions.

Indocyanine green faecal excretion holds potential for diagnosis of neonatal biliary atresia

Indocyanine green faecal excretion holds potential for diagnosis of neonatal biliary atresia

Perinatally Detected Subhepatic Cysts: Choledochal Cyst? or Cystic Biliary Atresia?

Perinatally Detected Subhepatic Cysts: Choledochal Cyst? or Cystic Biliary Atresia?

Explant pathology in Biliary Atresia post Kasai procedure: a tale of two livers

Explant pathology in Biliary Atresia post Kasai procedure: a tale of two livers

Factors associated with biliary atresia in children with cholestasis in Surabaya

Introduction. Biliary atresia (BA) represents a progressive and obstructive fibrotic cholangiopathy, serving as a leading cause of liver failure and pediatric liver transplantation worldwide. Identifying risk factors associated with BA incidence is crucial for expediting diagnosis; however, limited research has been conducted in Indonesia. This study aims to investigate the characteristics and analyze the factors associated with the occurrence of BA. Methods. A retrospective observational analysis of medical records encompassing 523 cholestatic patients at the Pediatric Hepatology Outpatient Department and Pediatric Ward of Dr. Soetomo General Academic Hospital, Surabaya, from 2011 to 2022 was conducted. The data was segregated into BA and non-BA groups, and diagnostic chi-square tests were employed to determine interrelationships among variables. Subsequently, logistic regression analysis was performed to identify the most impactful variable. Results. Notably, age at first time visiting specialist (p = 0.003), gestational age (p &lt;0.001), birth weight (p = 0.039), and domicile (p = 0.028) exhibited substantial associations with BA. Moreover, gestational age emerged as the most influential factor (p = 0.004). Infants with normal birth weight (≥2,500 grams) exhibited strongest factor associated factor of BA cholestasis. Conclusion. Initial specialist consultations were predominantly observed within the 0-6 months age range, while term infant and normal birth weight were linked to a higher likelihood of BA cholestasis. Residence in rural areas exhibited a significant correlation with BA incidence.

TORCH serological marker on cholestasis with the occurrence of biliary atresia and its clinical manifestations

Background and objectives. Biliary atresia occurs due to multifactorial etiology, and it was recently suggested that perinatal infection with TORCH, especially Cytomegalovirus (CMV), triggers inflammation of the bile ducts. This study aims to evaluate the TORCH infection on cholestasis with the occurrence of biliary atresia and its clinical manifestations. Materials and methods. A prospective single-center study was performed on 113 cholestatic infants and classified into two groups based on their positivity of immunoglobulin M and G (IgM and IgG). They were tested for CMV, Rubella, and Toxoplasmosis by a Gold Standard Diagnostics ELISA kit in our laboratory. Clinical conditions, laboratory tests (Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), and liver histopathology between the two groups were analyzed with p &lt;0.05 was considered significant. Results. Out of 113 infants of cholestasis, 94.7% (n = 107) were CMV IgG-positive, followed by Rubella IgG-positive (47.8%, n=54). Rubella and toxoplasma IgM antibodies were least commonly found in cholestasis (8% and 7.1%, respectively). CMV IgG-positive status was noted to be older at the onset of jaundice. Infants with Rubella IgG-positive had less incidence of extrahepatic cholestasis (37.7% vs 62.3%) and liver fibrosis (39% vs 61%) (p&lt;0.05). There was no difference in sex, birth weight, gestational age, AST, ALT, GGT, coagulation hemostasis, and abdominal USG abnormality based on torch serological markers (p&gt;0.05). Conclusion: CMV infection mostly occurs in infants with cholestasis, followed by rubella infection. TORCH infection screening may be necessary in all infants with cholestasis.

Utilization of older deceased donors for pediatric liver transplant may negatively impact long-term survival.

Multiple adult studies have investigated the role of older donors (ODs) in expanding the donor pool. However, the impact of donor age on pediatric liver transplantation (LT)has not been fully elucidated. UNOS database was used to identify pediatric (≤18 years) LTs performed in the United States during 2002-22. Donors ≥40 years at donation were classified as older donors (ODs). Propensity analysis was performed with 1:1 matching for potentially confounding variables. A total of 10,024 pediatric liver transplantation (PLT) patients met inclusion criteria; 669 received liver grafts from ODs. Candidates receiving OD liver grafts were more likely to be transplanted for acute liver failure, have higher Model End-Stage Liver Disease/Pediatric End-Stage Liver Disease (MELD/PELD) scores at LT, listed as Status 1/1A at LT, and be in the intensive care unit(ICU) at time of LT (all p < 0.001). Kaplan-Meier (KM) analyses showed that recipients of OD grafts had worse patient and graft survival (p < 0.001)compared to recipients of younger donor (YD)grafts. KM analyses performed on candidates matched for acuity at LT revealed inferior patient and graft survival in recipients of deceased donor grafts (p < 0.001), but not living donor grafts (p > 0.1)from ODs. Cox regression analysis demonstrated that living donor LT, diagnosis of biliary atresia and first liver transplant were favorable predictors of recipient outcomes, whereas ICU stay before LT and transplantation during 2002-12 were unfavorable. Livers from ODs were used for candidates with higher acuity. Pediatric recipients of livers from ODs had worse outcome compared to YDs; however, living donor LT from ODs had the least negative impact on recipient outcomes.

Accurate prediction of biliary atresia with an integrated model using MMP-7 levels and bile acids.

Biliary atresia (BA) is a rare fatal liver disease in children, and the aim of this study was to develop a method to diagnose BA early. We determined serum levels of matrix metalloproteinase-7 (MMP-7), the results of 13 liver tests, and the levels of 20 bile acids, and integrated computational models were constructed to diagnose BA. Our findings demonstrated that MMP-7 expression levels, as well as the results of four liver tests and levels of ten bile acids, were significantly different between 86 BA and 59 non-BA patients (P < 0.05). The computational prediction model revealed that MMP-7 levels alone had a higher predictive accuracy [area under the receiver operating characteristic curve (AUC) = 0.966, 95% confidence interval (CI): 0.942, 0.989] than liver test results and bile acid levels. The AUC was 0.890 (95% CI 0.837, 0.943) for liver test results and 0.825 (95% CI 0.758, 0.892) for bile acid levels. Furthermore, bile levels had a higher contribution to enhancing the predictive accuracy of MMP-7 levels (AUC = 0.976, 95% CI 0.953, 1.000) than liver test results. The AUC was 0.983 (95% CI 0.962, 1.000) for MMP-7 levels combined with liver test results and bile acid levels. In addition, we found that MMP-7 levels were highly correlated with gamma-glutamyl transferase levels and the liver fibrosis score. The innovative integrated models based on a large number of indicators provide a noninvasive and cost-effective approach for accurately diagnosing BA in children. Video Abstract (MP4 142103 KB).

ABO Incompatible Living Donor Liver Transplantation in Children: A Single Centre Experience from India

BackgroundIn recent years, pediatric ABO incompatible (ABOi) living donor liver transplant (LT) has shown promising outcomes and can potentially eliminate organ shortage. This study aims to report pediatric ABOi LT experience including short- and long-term outcomes. MethodsIt is a single-centre retrospective study. Out of 108 LTs, 20 were done in children. We compared the outcomes between ABOi (n=20) and non-ABOi (n=220) pediatric living donor liver transplantation (LDLT) performed during the study period. All the children received pre-LT desensitization therapy comprising rituximab and plasmapheresis targeting pre-LT isohemagglutinin (IHA) titres of ≤1:16. ResultsOut of 239 pediatric LDLT from 2017-2022, 19 children (11 females) underwent 20 ABOi LT (including one retransplant with ABOi domino allograft) at a median age of 12(12,51) months with majority being biliary atresia (60%). The median change in CD19 cell%, CD20 cell%, and IHA titres after rituximab from day -14 to day -1 (before LT) was satisfactory. In the first 3 months following LT, acute cellular rejection, culture proven sepsis, biliary and vascular complications were seen in 10%, 20%, 20%, and 15% respectively. None of the ABOi LT recipients developed antibody mediated rejection. ABOi LT recipients as compared to non ABOi LT had higher incidence of bile leak and prolonged hospital stay with rest of the complications including biliary strictures and long-term outcome being comparable. At a median follow up of 21(14,33) months, 4 children expired (21%). ConclusionABOi LT in children shows excellent outcomes and can be performed safely with prior desensitization when compatible liver is unavailable.

Diagnostic and prognostic value of the gut microbiota and its metabolite butyrate in children with biliary atresia.

To determine the prevalent microbiological profile of biliary atresia (BA) patients at the time of its occurrence by studying their intestinal flora. A total of 118 gut microbiota samples from three groups of 43 BA patients, 33 disease controls (DC) with other cholestatic diseases and 42 healthy controls (HC), were analyzed by deep mining of public data. Subsequently, a total of 23 fecal samples from three groups of clinically collected patients (11 BA, 6 DC and 6 HC) were sequenced for 16S rRNA gene amplification and analyzed for serum butyrate (BU) level by liquid chromatography. Taxonomic analysis revealed significant differences in the composition of the intestinal microbiota between BA patients and controls, with a reduction in diversity and a higher abundance of Proteobacteria, Streptococcus and Lactobacillus in the BA group. Database and clinical data analyses concluded that Streptococcus/Bacteroides (AUC = 0.9035, 95% CI 0.8347-0.9722, P < 0.0001) or Streptococcus/Eggerthella (AUC = 0.8333, 95% CI 0.6340-1.000, P = 0.027) was the best microbiota to differentiate between BA and DC. Serum butyrate levels were low in the BA and DC groups and differed from the HC group (P = 0.01, P = 0.04). Butyrate levels in BA were negatively correlated with jaundice clearance and cholangitis, but not statistically significant. Our study reveals changes in the composition of the gut microbiota in BA, especially the butyrate-producing microbiota, and suggests the potential for using gut microbiota as a noninvasive diagnostic benefit for BA. Low levels of serum butyrate in BA may indicate a poor prognosis.

Unraveling the complexities of fibrosis and ductular reaction in liver disease: pathogenesis, mechanisms, and therapeutic insights.

Ductular reaction and fibrosis are hallmarks of many liver diseases including primary sclerosing cholangitis, primary biliary cholangitis, biliary atresia, alcoholic liver disease, and metabolic dysfunction-associated steatotic liver disease/metabolic dysfunction-associated steatohepatitis. Liver fibrosis is the accumulation of extracellular matrix often caused by excess collagen deposition by myofibroblasts. Ductular reaction is the proliferation of bile ducts (which are composed of cholangiocytes) during liver injury. Many other cells including hepatic stellate cells, hepatocytes, hepatic progenitor cells, mesenchymal stem cells, and immune cells contribute to ductular reaction and fibrosis by either directly or indirectly interacting with myofibroblasts and cholangiocytes. This review summarizes the recent findings in cellular links between ductular reaction and fibrosis in numerous liver diseases.