scholarly journals Case report: progressive familial intrahepatic cholestasis type 3 with compound heterozygous ABCB4 variants diagnosed 15 years after liver transplantation

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Mariam Goubran ◽  
Ayodeji Aderibigbe ◽  
Emmanuel Jacquemin ◽  
Catherine Guettier ◽  
Safwat Girgis ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Intrahepatic Cholestasis ◽  
Autoimmune Response ◽  
Compound Heterozygous ◽  
Biliary Cirrhosis ◽  
Progressive Familial Intrahepatic Cholestasis ◽  
End Stage Liver Disease ◽  
End Stage ◽  
Type 3

Abstract Background Progressive familial intrahepatic cholestasis (PFIC) type 3 is an autosomal recessive disorder arising from mutations in the ATP-binding cassette subfamily B member 4 (ABCB4) gene. This gene encodes multidrug resistance protein-3 (MDR3) that acts as a hepatocanalicular floppase that transports phosphatidylcholine from the inner to the outer canalicular membrane. In the absence of phosphatidylcholine, the detergent activity of bile salts is amplified and this leads to cholangiopathy, bile duct loss and biliary cirrhosis. Patients usually present in infancy or childhood and often progress to end-stage liver disease before adulthood. Case presentation We report a 32-year-old female who required cadaveric liver transplantation at the age of 17 for cryptogenic cirrhosis. When the patient developed chronic ductopenia in the allograft 15 years later, we hypothesized that the patient’s original disease was due to a deficiency of a biliary transport protein and the ductopenia could be explained by an autoimmune response to neoantigen that was not previously encountered by the immune system. We therefore performed genetic analyses and immunohistochemistry of the native liver, which led to a diagnosis of PFIC3. However, there was no evidence of humoral immune response to the MDR3 and therefore, we assumed that the ductopenia observed in the allograft was likely due to chronic rejection rather than autoimmune disease in the allograft. Conclusions Teenage patients referred for liver transplantation with cryptogenic liver disease should undergo work up for PFIC3. An accurate diagnosis of PFIC 3 is key for optimal management, therapeutic intervention, and avoidance of complications before the onset of end-stage liver disease.

A novel etiologic factor of highly elevated cholestanol levels: progressive familial intrahepatic cholestasis

2020 ◽  
Vol 33 (5) ◽  
pp. 665-669
Author(s):  
Aynur Küçükçongar Yavaş ◽  
Büşra Çavdarlı ◽  
Özlem Ünal Uzun ◽  
Ayşen Uncuoğlu ◽  
Mehmet Gündüz
Keyword(s):  
Primary Biliary Cirrhosis ◽  
Intrahepatic Cholestasis ◽  
Density Lipoprotein ◽  
Etiologic Factor ◽  
Compound Heterozygous ◽  
Cholestatic Liver Disease ◽  
Biliary Cirrhosis ◽  
Progressive Familial Intrahepatic Cholestasis ◽  
Turkish Patient ◽  
Type 3

AbstractBackgroundProgressive familial intrahepatic cholestasis type 3 (PFIC3) is an uncommon cholestatic liver disease caused by mutations in the ATP binding cassette subfamily B member 4 (ABCB4) gene. Although PFIC3 is frequently identified in childhood, ABCB4 disease-causing alleles have been described in adults affected by intrahepatic cholestasis of pregnancy, hormone-induced cholestasis, low-phospholipid-associated cholelithiasis syndrome or juvenile cholelithiasis, cholangiocarcinoma and in sporadic forms of primary biliary cirrhosis. Cholestanol is a biomarker which is elevated especially in cerebrotendinous xanthomatosis and rarely in primary biliary cirrhosis (PBC) and Niemann Pick type C.Case presentationHere we report a Turkish patient with compound heterozygous mutations in the ABCB4 gene, who has hepatosplenomegaly, low level of high-density lipoprotein, cholestasis and high level of cholestanol.ConclusionThis is the first PFIC3 case with a high cholestanol level described in the literature. There are very few diseases linked to increased cholestanol levels, two of which are CTX and PBC. From this case, we can conclude that a high cholestanol level might be another indicator of PFIC type 3.

scholarly journals Liver Transplantation in Progressive Familial Intrahepatic Cholestasis With Normal Gamma-Glutamyl Transferase: Evaluation of Post-Transplant Steatosis and Steatohepatitis

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Mohammad Hossein Anbardar ◽  
Seyed Mohsen Dehghani ◽  
Maryam Poostkar ◽  
Seyed Ali Malek-Hosseini
Keyword(s):  
Liver Transplantation ◽  
Growth Retardation ◽  
Intrahepatic Cholestasis ◽  
Clinical Manifestations ◽  
Gamma Glutamyl Transferase ◽  
Progressive Familial Intrahepatic Cholestasis ◽  
Post Transplant ◽  
End Stage Liver Disease ◽  
Glutamyl Transferase ◽  
End Stage

Background: Progressive familial intrahepatic cholestasis is a disease presenting with severe cholestasis and progressing to the end-stage liver disease later. Liver transplantation is a treatment modality available for progressive familial intrahepatic cholestasis, especially in patients with end-stage liver disease or those who are unsuitable for or have failed biliary diversion. Objectives: To evaluate clinical and pathological characteristics of progressive familial intrahepatic cholestasis patients who had undergone liver transplantation and to determine post-transplant steatosis and steatohepatitis. Methods: We evaluated 111 progressive familial intrahepatic cholestasis patients with normal gamma-glutamyl transferase that performed liver transplantation in Shiraz Transplant Center in Iran between March 2000 and March 2017. Results: The most common clinical manifestations were jaundice and pruritus. Growth retardation and diarrhea were detected in 76.6% and 42.5% of the patients. After transplantation, growth retardation was seen in 31.5% of the patients, and diarrhea in 36.9% of them. Besides, 29.1% of the patients died post-transplant. Post-transplant liver biopsies were taken from 50 patients, and 15 (30%) patients had steatosis or steatohepatitis, five of whom (10%) had macro-vesicular steatosis alone, and 10 (20%) had steatohepatitis. Only one patient showed moderate bridging fibrosis (stage III), and none of them showed severe fibrosis. Conclusions: Liver transplantation is the final treatment option for these patients, and it can relieve most clinical manifestations. However, post-transplant mortality rate was relatively high in our center. Diarrhea, growth retardation, and steatosis are unique post-transplant complications in these patients. The rate of post-transplant steatosis and steatohepatitis in patients with liver biopsy in our study was 30%, with a significant difference from previous studies.

scholarly journals A Novel Compound Heterozygous Mutation in ABCB4 Gene Leading to Cholelithiasis, Progressive Familial Intrahepatic Cholestasis (Type 3), and Cirrhosis in a Child

2020 ◽  
Vol 10 (01) ◽  
pp. e134-e136
Author(s):  
Nida Mirza ◽  
Smita Malhotra ◽  
Anupam Sibal
Keyword(s):  
Intrahepatic Cholestasis ◽  
Gall Stone ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Initial Symptom ◽  
Progressive Familial Intrahepatic Cholestasis ◽  
Presenting Symptoms ◽  
Abcb4 Gene ◽  
Type 3

AbstractProgressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive disorders of childhood which presents with intermittent or progressive episodes of cholestasis, with jaundice and pruritus as most common presenting symptoms. PFIC type 3 occurs due to mutations in the ABCB4 gene, mutation in this gene has wide spectrum of features which include intrahepatic stones, cholelithiasis, PFIC type 3, and intrahepatic cholestasis of pregnancy. Here, we are reporting a peculiar case of young male adolescent with novel variant compound heterozygote missense mutation in ABCB4 gene who had gall stone as initial symptom, followed by symptoms of PFIC and eventually decompensated chronic liver disease.

Low psoas muscle index as an unfavorable factor in children with end‐stage liver disease undergoing liver transplantation

2021 ◽  
Author(s):  
Settapong Jitwongwai ◽  
Chatmanee Lertudomphonwanit ◽  
Thitiporn Junhasavasdikul ◽  
Praman Fuangfa ◽  
Pornthep Tanpowpong ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Psoas Muscle ◽  
End Stage Liver Disease ◽  
End Stage

scholarly journals RIPK3-Mediated Necroptosis and Neutrophil Infiltration Are Associated with Poor Prognosis in Patients with Alcoholic Cirrhosis

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Zhenzhen Zhang ◽  
Guomin Xie ◽  
Li Liang ◽  
Hui Liu ◽  
Jing Pan ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Poor Prognosis ◽  
Alcoholic Cirrhosis ◽  
Normal Liver ◽  
Neutrophil Infiltration ◽  
Meld Score ◽  
End Stage Liver Disease ◽  
Cirrhotic Patients ◽  
End Stage

Alcoholic cirrhosis is an end-stage liver disease with impaired survival and often requires liver transplantation. Recent data suggests that receptor-interacting protein kinase-3- (RIPK3-) mediated necroptosis plays an important role in alcoholic cirrhosis. Additionally, neutrophil infiltration is the most characteristic pathologic hallmark of alcoholic hepatitis. Whether RIPK3 level is correlated with neutrophil infiltration or poor prognosis in alcoholic cirrhotic patients is still unknown. We aimed to determine the correlation of RIPK3 and neutrophil infiltration with the prognosis in the end-stage alcoholic cirrhotic patients. A total of 20 alcoholic cirrhotic patients subjected to liver transplantation and 5 normal liver samples from control patients were retrospectively enrolled in this study. Neutrophil infiltration and necroptosis were assessed by immunohistochemical staining for myeloperoxidase (MPO) and RIPK3, respectively. The noninvasive score system (model for end-stage liver disease (MELD)) and histological score systems (Ishak, Knodell, and ALD grading and ALD stage) were used to evaluate the prognosis. Neutrophil infiltration was aggravated in patients with a high MELD score (≥32) in the liver. The MPO and RIPK3 levels in the liver were positively related to the Ishak score. The RIPK3 was also significantly and positively related to the Knodell score. In conclusion, RIPK3-mediated necroptosis and neutrophil-mediated alcoholic liver inflammatory response are highly correlated with poor prognosis in patients with end-stage alcoholic cirrhosis. RIPK3 and MPO might serve as potential predictors for poor prognosis in alcoholic cirrhotic patients.

Diastolic Dysfunction in Patients with End-Stage Liver Disease Is Associated with Development of Heart Failure Early after Liver Transplantation

2011 ◽  
Vol 17 (8) ◽  
pp. S19
Author(s):  
Taylor F. Dowsley ◽  
David B. Bayne ◽  
Alan N. Langnas ◽  
Ioana Dumitru ◽  
John R. Windle ◽  
...  
Keyword(s):  
Heart Failure ◽  
Liver Transplantation ◽  
Liver Disease ◽  
Diastolic Dysfunction ◽  
End Stage Liver Disease ◽  
End Stage

Liver Transplantation for the Gastroenterologist

2015 ◽  
Author(s):  
Andreea M. Catana ◽  
Michael P. Curry
Keyword(s):  
United States ◽  
Liver Transplantation ◽  
Liver Disease ◽  
Organ Procurement ◽  
The United States ◽  
Waiting Lists ◽  
Liver Graft ◽  
Term Survival ◽  
End Stage Liver Disease ◽  
End Stage

The first liver transplantation (LT) was performed in 1963, and currently more than 65,000 people in the United States are living with a transplanted liver. In 2012, the number of adults who registered on the LT waiting list decreased for the first time since 2002; 10,143 candidates were added compared with 10,359 in 2011. LT offers long-term survival for complications of end-stage liver disease and prolongs life in properly selected patients, but problems such as donor deficit, geographic disparities, and long waiting lists remain. This overview of LT for the gastroenterologist details the indications for LT and patient selection, evaluation, liver organ allocation, prioritization for transplantation, transplantation benefit by the Model for End-Stage Liver Disease (MELD), MELD limitations, sources of liver graft, strategies employed to decrease the donor deficit, complications, and outcomes. Figures include indications for LT in Europe and the United States, Organ Procurement and Transplantation Network regions in the United States, the number of transplants and size of active waiting lists, mortality by MELD, regional disparity, patient survival rates with and without hepatitis C virus, and unadjusted patient and graft survival. Tables list LT milestones, indications for LT, contraindications for LT, minimal listing criteria for LT, criteria for LT in acute liver failure, LT evaluation process, adult recipient listing status 1A, and early posttransplantation complications. This review contains 7 highly rendered figures, 8 tables, and 46 references. 

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