Progressive Familial Intrahepatic Cholestasis Research Articles

Next-generation sequencing panel test results in pediatric patients with progressive familial intrahepatic cholestasis: a single-center experience

Objective: The aim of this study is to reveal the diagnostic yield of the progressive familial intrahepatic cholestasis (PFIC) gene panel that we have used in the diagnosis of this patient group, which accounts for approximately 10% of cholestatic liver disease, and to report the clinical findings of our patients with the detected variants. Methods: In this study, we retrospectively evaluated the results of molecular genetic analysis of pediatric patients whose PFIC gene panel contained the ATP8B1, ABCB11, and ABCB4 genes. Results: In 10 patients, 12 different variants were detected that could explain the PFIC clinical picture. Three of these variants were considered novel variants. Conclusion: Our study demonstrates the usefulness of the NGS panel in diagnosing pediatric patients with PFIC findings. This diagnostic method also contributed to the variant spectrum of PFIC-related genes.

An Insight Into Neonatal Cholestasis; A Tertiary Care Hospital Experience in Rawalpindi, Pakistan

Objective: To determine the frequencies of various etiologies of neonatal cholestasis diagnosed by clinical findings and laboratory investigations at the Pak Emirates Military Hospital, Rawalpindi, Pakistan. Study Design: Cross-sectional study. Place and Duration of Study: Pediatric Department of Pak Emirates Military Hospital, Rawalpindi Pakistan, from Jan 2021 to Apr 2022. Methodology: Infants of either gender aged 14 days to six months admitted to Inpatient facility who had jaundice with direct bilirubin and more than 20% of total bilirubin were included in the study. The proforma was formulated to record the clinical features, laboratory investigations, weight, level of activity and consanguinity among the parents. Results: A total of 146 infants were included in the study. Jaundice was seen in 100% of infants, hepatomegaly in 66.4%, splenomegaly in 38.4%, followed by ascites in 25%. The most common aetiology of neonatal cholestasis was Biliary Atresia 26.7% in the extrahepatic Group, Idiopathic Neonatal Hepatitis 25.3% in the intrahepatic Group. Consanguinity was present in parents of 65% of infants. Conclusion: The most common aetiology of extrahepatic Neonatal Cholestasis was Biliary Atresia, while Idiopathic Neonatal Hepatitis and Progressive Familial Intrahepatic Cholestasis were the most common causes of intrahepatic cholestasis.

Opinion paper on the diagnosis and treatment of progressive familial intrahepatic cholestasis

Progressive familial intrahepatic cholestasis (PFIC) relates to a group of rare, debilitating, liver disorders which typically present in early childhood, but have also been reported in adults. Without early detection and effective treatment, PFIC can result in end-stage liver disease. The aim of the paper was to put forward recommendations that promote standardisation of the management of PFIC in clinical practice. A committee of six specialists came together to discuss the challenges faced by physicians in the management of PFIC. The committee agreed on two key areas where expert guidance is required to optimise care: (1) how to diagnose and treat patients with a clinical presentation of PFIC in the absence of clear genetic test results/whilst awaiting results, and (2) how to monitor disease progression and response to treatment. A systematic literature review was undertaken to contextualise and inform the recommendations. An algorithm was developed for the diagnosis and treatment of children with suspected PFIC. The algorithm recommends the use of licensed inhibitors of ileal bile acid transporters as the first-line treatment for patients with PFIC and suggests that genetic testing be used to confirm genotype whilst treatment is initiated in patients in whom PFIC is suspected. The authors recommend referring patients to an experienced centre, and ensuring that monitoring includes measurements of pruritus, serum bile acid levels, growth, and quality of life following diagnosis and during treatment. The algorithm presented within this paper offers guidance to optimise the management of paediatric PFIC. The authors hope that these recommendations will help to standardise the management of PFIC in the absence of clear clinical guidelines. This opinion paper outlines a consistent approach to the contemporaneous diagnosis, monitoring, referral and management of children with progressive familial intrahepatic cholestasis. This should assist physicians given the recent developments in genetic diagnosis and the availability of effective drug therapy. This manuscript will also help to raise awareness of current developments and educate health planners on the place for new drug therapies in progressive familial intrahepatic cholestasis.

Management and outcomes after liver transplantation for progressive familial intrahepatic cholestasis: A systematic review and meta-analysis.

Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous rare congenital cholestatic liver disease. Disease progression might necessitate liver transplantation (LT). The aim of this study was to describe the outcome of PFIC1-4 patients after LT. Electronic databases were searched to identify studies on PFIC and LT. Patients were categorized according to PFIC type, genotype, graft type, age at LT, time of follow-up, and complications and treatment during follow-up. Seventy-nine studies with 507 patients met inclusion criteria; most patients were classified as PFIC1-3. The median age at LT was 50 months. The overall 5-year patient survival was 98.5%. PFIC1 patients with diarrhea after LT were at significant risk of developing graft steatosis ( p < 0.0001). Meta-analysis showed an efficacy of 100% [95% CI: 73.9%-100%] for surgical biliary diversion to ameliorate steatosis and 94.9% [95% CI: 53.7%-100%] to improve diarrhea (n = 8). PFIC2 patients with bile salt export pump (BSEP)2 or BSEP3-genotype were at significant risk of developing antibody-induced BSEP deficiency (AIBD) ( p < 0.0001), which was reported in 16.2% of patients at a median of 36.5 months after LT. Meta-analysis showed an efficacy of 81.1% [95% CI: 47.5%-100%] for rituximab-based treatment regimens to improve AIBD (n = 18). HCC was detected in 3.6% of PFIC2 and 13.8% of PFIC4 patients at LT. Fifty percent of PFIC1 patients develop diarrhea and steatosis after LT. Biliary diversion can protect the graft from injury. PFIC2 patients with BSEP2 and BSEP3 genotypes are at significant risk of developing AIBD, and rituximab-based treatment regimens effectively improve AIBD. PFIC3 patients have no PFIC-specific complications following LT.

Outcomes of pediatric liver transplantation for progressive familial intrahepatic cholestasis.

Progressive familial intrahepatic cholestasis (PFIC) is a heterogenous group of inherited hepatocellular disorders and the clinical aspects, role of liver transplantation (LT), and its outcomes remain largely unelucidated. We present our data of LT for each type of PFIC and compare their early, and long-term outcomes, highlighting their individual differences and management strategies. Prospectively collected data over a decade (2011-2022) of children with PFIC who underwent LT was analyzed. The groups (PFIC 1-4) were compared with regard to early and long-term outcomes including attainment of catch-up growth. Of 60 children with PFIC who underwent LT, 13, 11, 31 & 5 were of PFIC 1, 2, 3 & 4, respectively. There were no significant differences in gender, PELD scores, BMI, type of grafts, cold and warm ischemia times, intraoperative blood loss, and morbidity among the groups. Post-LT chronic diarrhea was observed in 6 (46.1%) children with PFIC-I, and of them, 3 (23%) developed graft steatohepatitis. Three of these children underwent total internal biliary diversion (TIBD) and on 1-year follow-up, their graft steatosis resolved and they attained catch-up growth. Catch-up growth was significantly poorer in the PFIC1 group (44.4% vs. 88%, 90%, 100% p < .001). Overall 1- and 5-year patient survival of the four PFIC groups (1-4) were 69.2%, 81.8%, 96.8%, 100% & 69.2%, 81.8%, 96.8%, 100%, respectively. Ours is the largest to-date series of LT for PFIC illustrating their short- and long-term outcomes. While the results for the whole cohort were excellent, those after LT for PFIC1 was relatively poorer as reflected by catch-up growth, graft steatosis, and post-LT diarrhea, which can be optimized by the addition of TIBD during LT.

Liver Transplantation for Hepatocellular Carcinoma in Patients with Inherited Metabolic Liver Diseases: A Single-Center Analysis.

Liver transplantation is an acceptable treatment for some selected hepatocellular carcinoma. We report our experience of 6 patients with liver transplantation for hepatocellular carcinoma with background inherited metabolic disease. This is a single-center retrospective, descriptive study. Consecutive patients who underwent liver transplantation for hepatocellular carcinoma with background inherited metabolic disease were included in the study. The record of the patients was accessed, and the following data were extracted: sociodemographic variables, type of metabolic disease, date of liver transplantation, tumor characteristics, laboratory parameters, Model for End-Stage Liver Disease score, immediate- and long-term outcome after transplantation, disease-free survival, and overall survival. Data were analyzed using Statistical Package for the Social Sciences version 25.0. Six patients received liver transplantation for hepatocellular carcinoma with background inherited metabolic liver disease. The median age was 4.5 years. The median Model for End-Stage Liver Disease score was 29.30. The median maximum tumor diameter was 2.15 cm. Three patients had multiple tumor nodules. Half of the patients had microvascular invasion. Four of the patients had a moderately differentiated tumor. Progressive familial intrahepatic cholestasis type II is the commonest inherited metabolic disease seen in 3 patients. Median follow-up is 46.1 months. Half of the patients are currently more than 5 years post liver transplantation with no features of recurrence. The estimated survival rates at 1, 3, and 5 years are 100%, 83.3%, and 83.3%, respectively. Liver transplant for these categories of patients is associated with good disease-free and overall survival, even in the presence of some seemingly poor prognostic features.

Metallothionein: a game changer in histopathological diagnosis of Wilson disease.

Wilson disease (WD) is a genetic disorder of copper metabolism caused by mutations in the ATP7B gene. Toxic copper accumulation leads to hepatic, neurologic, and psychiatric disorders with variable presentation. Metallothionein (MT) immunohistochemistry was proposed as a diagnostic marker. MT immunohistochemistry was performed on liver specimens of WD patients (n = 64) and control cases (n = 160) including acute liver failure, steatotic liver disease, autoimmune hepatitis, normal liver, primary biliary cholangitis, primary and secondary sclerosing cholangitis, and progressive familial intrahepatic cholestasis. The optimal cutoff for detection of WD was determined by receiver operating characteristic (ROC) analysis. At least moderate staining in >50% of hepatocytes was observed in 81% of analysed liver specimens (n = 56/69) of WD patients, while only five control cases showed this staining pattern. The sensitivity, specificity, and accuracy for a new diagnosis of WD were 85.7%, 96.9%, and 94.9%, respectively. Sensitivity in nonfibrotic patients was 70.6% and this MT pattern was robust in small biopsies. Thehepatic copper concentration was similar between MT-positive and MT-negative liver samples (P > 0.05). Zinc treatment may induce hepatocellular MT expression. Kayser-Fleischer rings (50% versus 15%) and neurologic disorders (50% versus 13%) were significantly more prevalent in MT-negative compared to MT-positive WD patients, respectively. MT immunostaining is an excellent biomarker for histological diagnosis of WD, should be incorporated in the diagnostic work-up of patients with potential WD, and is useful in a modified Leipzig score.

Treatment of Cholestasis in Infants and Young Children.

Cholestasis is characterized by a conjugated hyperbilirubinemia secondary to impaired bile synthesis, transport, or excretion from the liver. It is always pathologic and can be indicative of an underlying hepatobiliary, genetic, or metabolic disorder, several of which require timely diagnosis to ensure proper management and optimal outcomes. This review provides an overview of the evaluation of cholestasis with a focus on current and emerging treatment strategies. Increased accessibility of next generation sequencing (NGS) allows for utilization of genetic testing early in the diagnostic process. This may alter the clinical algorithm for diagnosis of cholestatic disorders. An enhanced understanding of the underlying pathophysiology may help guide future development of targeted therapies, such as ileal bile acid transporter (IBAT) inhibitors. These were recently approved for treatment of cholestatic pruritus in patients with Alagille syndrome and Progressive Familial Intrahepatic Cholestasis. Current management of cholestasis is aimed at the biochemical consequences of impaired bile flow, including malnutrition, pruritus, and progressive fibrosis. NGS has led to an enhanced understanding of biliary pathology and may guide development of future treatment modalities based on specific gene mutations. Rapid discernment of the underlying etiology is essential as new treatment modalities emerge.

A 19-year-old Patient with Recurrent Pruritus and Jaundice

Аim: to highlight the importance of broad differential diagnosis and possibility of conversion of benign recurrent intrahepatic cholestasis type 2 into more aggressive clinical phenotype.Key points. A 19-year-old female patient was admitted to the Clinic with skin pruritus, jaundice, dark urine, clay-colored stool, and general fatigue. Past medical history was significant for recurrent aforementioned symptoms since 3 years old, that relapsed every 1–2 years and were usually ameliorated with conservative therapy. During recent years, frequency of relapses and recovery period increased, at the same time effectiveness of medical therapy decreased. Blood chemistry results revealed an elevation of total bilirubin (up to 634 μmol/L), direct bilirubin (up to 354 μmol/L), bile acids (up to 510 μmol/L) and normal gamma glutamyl transferase level. Workup was negative for viral hepatitis, autoimmune liver diseases, obstructive choledochal lesions, storage diseases, although mutation in gene ABCB11 was found. Benign recurrent intrahepatic cholestasis type 2 was diagnosed. Following conservative therapy and plasmapheresis, jaundice and skin pruritus significantly diminished, levels of bilirubin and bile acids normalized. Regular follow up, liver biopsy and measures for relapse prevention given clinical features of aggressive phenotype were recommended.Conclusion. Identification of etiology of cholestatic liver diseases requires broad differential diagnosis. Clinical course of patients with benign recurrent intrahepatic cholestasis may transform into aggressive phenotype, reminiscent of progressive familial intrahepatic cholestasis.

Prognostic significance of growth hormone in pediatric liver transplantation

Growth hormone (GH) plays a leading role in the regulation of cell and tissue metabolism and growth. Its effects are mediated through the so-called somatomedins, among which the most important is the liver-produced insulinlike growth factor 1 (IGF-1). It has been reported that serum GH levels in liver recipients is related to the clinical transplant outcomes.Objective: to evaluate the prognostic significance of GH in pediatric liver transplantation (LT).Materials and methods. The study enrolled 148 children (61 boys) aged 2 to 60 months (median, 8) with end-stage liver disease resulting from biliary atresia (n = 86), biliary hypoplasia (n = 14), Byler disease (n = 15), Alagille syndrome (n = 12), Caroli syndrome (n = 5), and other liver diseases (n = 16, cryptogenic cirrhosis, fulminant and autoimmune hepatitis, Crigler–Najjar and Budd–Chiari syndromes, alpha-1 antitrypsin deficiency, glycogenosis and hepatoblastoma). All the patients were transplanted with the left lateral segment of the liver from a living related donor. GH concentrations were measured by enzyme immunoassay before, at one month and at one year after transplantation.Results. Median plasma GH levels in children with liver disease were 4.3 [1.6–7.2] ng/mL, significantly higher than in healthy children of the same age at 1.2 [0.3–2.4] ng/mL, p = 0.001, while mean height and body weight were lower than in healthy controls. GH levels decreased significantly after transplantation. At one month and one year later, the levels did not differ from those of healthy children (p = 0.74, p = 0.67, respectively). One month after transplantation, GH concentrations were lower in 1-year survivors than in non-survivors (p = 0.02); the diagnostically significant threshold GH level was 1.8 ng/mL. Prior to LT, plasma GH levels did not differ between 1-year survivors and non-survivors. Children with GH levels below 1.8 ng/mL post-LT were 9 times more likely to survive one year post-transplant than patients with levels above the threshold.Conclusion. GH concentrations in pediatric liver recipients is a positive prognostic indicator of pediatric LT outcomes.

Outcomes of 38 patients with PFIC3: Impact of genotype and of response to ursodeoxycholic acid therapy

Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare liver disease caused by biallelic variations in ABCB4. Data reporting on the impact of genotype and of response to ursodeoxycholic acid (UDCA) therapy on long-term outcomes are scarce. We retrospectively describe a cohort of 38 patients with PFIC3 with a median age at last follow-up of 19.5 years (range 3.8-53.8). Twenty patients presented with symptoms before 1 year of age. Thirty-one patients received ursodeoxycholic acid (UDCA) therapy resulting in serum liver test improvement in 20. Twenty-seven patients had cirrhosis at a median age of 8.1 years of whom 18 received a liver transplant at a median age of 8.5 years. Patients carrying at least one missense variation were more likely to present with positive (normal or decreased) canalicular MDR3 expression in the native liver and had prolonged native liver survival (NLS; median 12.4 years [range 3.8-53.8]). In contrast, in patients with severe genotypes (no missense variation), there was no detectable canalicular MDR3 expression, symptom onset and cirrhosis occurred earlier, and all underwent liver transplantation (at a median age of 6.7 years [range 2.3-10.3]). The latter group was refractory to UDCA treatment, whereas 87% of patients with at least one missense variation displayed an improvement in liver biochemistry in response to UDCA. Biliary phospholipid levels over 6.9% of total biliary lipid levels predicted response to UDCA. Response to UDCA predicted NLS. Patients carrying at least one missense variation, with positive canalicular expression of MDR3 and a biliary phospholipid level over 6.9% of total biliary lipid levels were more likely to respond to UDCA and to exhibit prolonged NLS. In this study, data show that genotype and response to ursodeoxycholic acid therapy predicted native liver survival in patients with PFIC3 (progressive familial intrahepatic cholestasis type 3). Patients carrying at least one missense variation, with positive (decreased or normal) immuno-staining for canalicular MDR3, and a biliary phospholipid level over 6.9% of total biliary lipids were more likely to respond to ursodeoxycholic acid therapy and to exhibit prolonged native liver survival.

Optimal liver transplant procedure in progressive familial intrahepatic cholestasis type 1 treated with biliary diversion or intestinal transplantation: Lessons learned from three cases treated with different approaches.

Progressive familial intrahepatic cholestasis type 1 (PFIC1) is an autosomal recessive cholestatic liver disorder caused by ATP8B1 gene mutations. Although liver transplantation (LT) is indicated for progressive liver disease, postoperative complications, including severe diarrhea and graft steatohepatitis leading to graft loss, have been reported. The first patient had jaundice, pruritus, diarrhea, and growth retardation (weight z-score: -2.5; height z-score: -3.7). She underwent LT with total internal biliary diversion (TIBD) to the colon at 2 years of age. Graft biopsy at the 7-year follow-up examination revealed microvesicular steatosis (60%). Her diarrhea improved, and her growth failure was recovering (weight z-score: -1.0; height z-score: -1.7). The second patient underwent sequential intestine-liver transplantation at 8 years of age due to end-stage liver disease (ESLD) and short bowel syndrome caused by massive bowel resection for internal hernia after partial external biliary diversion (PEBD) at 21 months of age. She developed severe pancreatitis induced by steroid-bolus therapy for rejection after transplantation. She died 1.7 years after intestinal transplantation due to an uncontrollable pancreatic abscess and acute respiratory distress syndrome. The third patient underwent PEBD at 15 months of age and received LT with TEBD at 15 years of age due to ESLD with hepatic encephalopathy. Throughout the perioperative period, she showed no abdominal symptoms, including diarrhea and pancreatitis. Graft biopsy at the 2-year follow-up examination revealed macrovesicular steatosis (60%) with inflammation. The patients showed different outcomes. Effective therapeutic options to mitigate post-LT complications in patients with PFIC1 must be considered individually.

Oral findings in children with congenital cholestatic disease: A systematic review of case reports and case series

Multiple causes of congenital neonatal cholestasis have been identified, and are classified as extrahepatic or intrahepatic. Biliary atresia (BA), Alagille syndrome (AGS), and progressive familial intrahepatic cholestasis (PFIC) are the most common of these. Many factors associated with cholestatic diseases are known to degrade the oral health of these children. What are the oral manifestations associated with these diseases in the pediatric population? The aim of this article was to evaluate the impact of congenital cholestasis on oral health in pediatric patients.A systematic review of case reports and case series was carried out in PubMed, the Cochrane Library, and the Web of Science to identify relevant articles in French and English published up to April 2022.The review included 19 studies, 16 case reports, and three case series. Only studies dealing with BA and AGS were found. These studies showed an impact on jaw morphology, dental structure, and periodontal health. The facial dysmorphism observed in AGS was specific. Exposure to high levels of bilirubin during the period of dental calcification led to particular coloration. Regarding periodontal status, gingival inflammation was common in these patients, probably resulting from the use of certain treatment-associated drugs and poor oral hygiene. Cohort studies are needed to confirm the classification of these children as being at high individual risk of caries.Many major oral manifestations are found in children with AGS and BA, confirming the need to include a dentist in the care team of patients with congenital cholestatic disease as early as possible. It appears necessary to carry out individual prospective studies of each phenotype in order to confirm and better describe the oral impact of these cholestatic diseases and provide adequate medical care.

Diagnostic yield and novel candidate genes by next generation sequencing in 166 children with intrahepatic cholestasis.

Cholestatic liver disease is a leading referral to pediatric liver transplant centers. Inherited disorders are the second most frequent cause of cholestasis in the first month of life. We retrospectively characterized the genotype and phenotype of 166 participants with intrahepatic cholestasis, and re-analyzed phenotype and whole-exome sequencing (WES) data from patients with previously undetermined genetic etiology for newly published genes and novel candidates. Functional validations of selected variants were conducted in cultured cells. Overall, we identified disease-causing variants in 31% (52/166) of our study participants. Of the 52 individuals, 18 (35%) had metabolic liver diseases, 9 (17%) had syndromic cholestasis, 9 (17%) had progressive familial intrahepatic cholestasis, 3 (6%) had bile acid synthesis defects, 3(6%) had infantile liver failure and 10 (19%) had a phenocopy of intrahepatic cholestasis. By reverse phenotyping, we identified a de novo variant c.1883G > A in FAM111B of a case with high glutamyl transpeptidase (GGT) cholestasis. By re-analyzing WES data, two patients were newly solved, who had compound heterozygous variants in recently published genes KIF12 and USP53, respectively. Our additional search for novel candidates in unsolved WES families revealed four potential novel candidate genes (NCOA6, CCDC88B, USP24 and ATP11C), among which the patients with variants in NCOA6 and ATP11C recapitulate the cholestasis phenotype in mice models. In a single-center pediatric cohort, we identified monogenic variants in 22 known human intrahepatic cholestasis or phenocopy genes, explaining up to 31% of the intrahepatic cholestasis patients. Our findings suggest that re-evaluating existing WES data from well-phenotyped patients on a regular basis can increase the diagnostic yield for cholestatic liver disease in children.

Progressive familial intrahepatic cholestasis-outcome and time to transplant after biliary diversion according to genetic subtypes.

Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous disease characterized by progressive cholestasis in early childhood. Surgical therapy aims at preventing bile absorption either by external or internal biliary diversion (BD). Several different genetic subtypes encode for defects in bile transport proteins, and new subtypes are being discovered ongoingly. Overall, the literature is scarce, however, accumulating evidence points to PFIC 2 having a more aggressive course and to respond less favorable to BD. With this knowledge, we aimed to retrospectively analyze the long-term outcome of PFIC 2 compared to PFIC 1 following BD in children at our center. Clinical data and laboratory findings of all children with PFIC, who were treated and managed in our hospital between 1993 and 2022, were analyzed retrospectively. Overall, we treated 40 children with PFIC 1 (n = 10), PFIC 2 (n = 20) and PFIC 3 (n = 10). Biliary diversion was performed in 13 children (PFIC 1, n = 6 and 2, n = 7). Following BD, bile acids (BA) (p = 0.0002), cholesterol (p < 0.0001) and triglyceride (p < 0.0001) levels significantly decreased only in children with PFIC 1 but not in PFIC 2. Three out of 6 children (50%) with PFIC 1 and 4 out of 7 children (57%) with PFIC 2 required liver transplantation despite undergoing BD. On an individual case basis, BA reduction following BD predicted this outcome. Of the 10 children who had PFIC 3, none had biliary diversion and 7 (70%) required liver transplantation. In our cohort, biliary diversion was effective in decreasing bile acids, cholesterol levels as well as triglycerides in the serum only in children with PFIC 1 but not PFIC 2. On an individual case level, a decrease in BA following BD predicted the need for liver transplantation.

Progressive familial intrahepatic cholestasis type 2 on the example of one family. Liver transplantation as an effective treatment method. Case report

The article presents the structure of diseases that led to the need for liver sector transplantation in children living in the Novosibirsk region. The paper provides a detailed description of progressive familial intrahepatic cholestasis, principles of modern diagnosis and treatment. A description of the medical history of family members and, in particular, a clinical case in a young child with type 2 PFIC (Byler's syndrome) is given.

WED-282 - Analysis of safety in maralixibat-treated participants with progressive familial intrahepatic cholestasis: data from MARCH-PFIC

WED-282 - Analysis of safety in maralixibat-treated participants with progressive familial intrahepatic cholestasis: data from MARCH-PFIC

OS-072 - Maralixibat leads to significant reductions in bilirubin for patients with progressive familial intrahepatic cholestasis: data from MARCH-PFIC

OS-072 - Maralixibat leads to significant reductions in bilirubin for patients with progressive familial intrahepatic cholestasis: data from MARCH-PFIC

LBP-35 - Long-term maintenance of response and improved liver health with maralixibat in patients with progressive familial intrahepatic cholestasis (PFIC): data from the MARCH-ON study

LBP-35 - Long-term maintenance of response and improved liver health with maralixibat in patients with progressive familial intrahepatic cholestasis (PFIC): data from the MARCH-ON study

TOP-057 - Long-term efficacy and safety of odevixibat in patients with progressive familial intrahepatic cholestasis: results with 96 weeks or more of treatment

TOP-057 - Long-term efficacy and safety of odevixibat in patients with progressive familial intrahepatic cholestasis: results with 96 weeks or more of treatment