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 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.

scholarly journals A child with debilitating pruritus

2016 ◽  
Vol 6 (4) ◽  
Author(s):  
Nikhil Sonthalia ◽  
Sami S. Jain ◽  
Vinay B. Pawar ◽  
Vinay G. Zanwar ◽  
Ravindra G. Surude ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Alkaline Phosphatase ◽  
Bile Acid ◽  
Intrahepatic Cholestasis ◽  
Serum Alkaline Phosphatase ◽  
Gamma Glutamyl Transferase ◽  
Type I ◽  
Serum Bile Acid ◽  
Progressive Familial Intrahepatic Cholestasis ◽  
Glutamyl Transferase

We describe a case of two-year-old boy presenting with debilitating pruritus, patchy alopecia and jaundice since the age of 6 months. On evaluation he had intrahepatic cholestasis with persistently raised serum alkaline phosphatase, normal Gamma glutamyl transferase and raised serum bile acid levels. His liver biopsy showed bland cholestasis and electron microscopy showed granular bile suggestive of progressive familial intrahepatic cholestasis type I. Medical therapy with ursodeoxycholic acid, cholestyramine, rifampicin with nutritional modification was successful in alleviating the symptoms and correcting the nutritional status. To our knowledge this is only the sixth case of progressive familial intrahepatic cholestasis type I reported from India. Herein we discuss the diagnostic and therapeutic hurdles that one encounters in managing progressive familial intrahepatic cholestasis and also review the literature regarding this rare disorder.

scholarly journals Post-hoc analysis of a randomized controlled trial on the impact of pre-transplant use of probiotics on outcomes after liver transplantation

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
M. Grąt ◽  
K. Grąt ◽  
M. Krawczyk ◽  
Z. Lewandowski ◽  
M. Krasnodębski ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Graft Survival ◽  
Controlled Trial ◽  
Long Term Results ◽  
Gamma Glutamyl Transferase ◽  
Long Term Effects ◽  
Post Transplant ◽  
Glutamyl Transferase ◽  
The Impact

AbstractPerioperative use of probiotics serves as efficient prophylaxis against postoperative infections after liver transplantation, yet data on long-term effects of pre-transplant probiotic intake is lacking. The aim of this study was to assess the effects of pre-transplant probiotic administration on long-term results of liver transplantation. This was secondary analysis of a randomized trial. Patients were randomized to receive either 4-strain probiotic or placebo before liver transplantation. Five year graft survival was set as the primary end-point. Secondary end-points comprised serum bilirubin and C-reactive protein (CRP) concentration, international normalized ratio (INR), serum transaminases and gamma-glutamyl transferase (GGT) activity. Study group comprised 44 patients, of whom 21 received probiotics and 23 received placebo with 5-year graft survival of 81.0% and 87.0%, respectively (p = 0.591). Patients in the probiotic arm exhibited lower INR (p = 0.001) and CRP (p = 0.030) over the first 6 post-transplant months. In the absence of hepatitis B or C virus infection, pre-transplant administration of probiotics also reduced aspartate transaminase activity (p = 0.032). In the intervention arm, patients receiving probiotics for under and over 30 days had 5-year graft survival rates of 100% and 66.7%, respectively (p = 0.061). Duration of probiotic intake > 30 days was additionally associated with increased INR (p = 0.031), GGT (p = 0.032) and a tendency towards increased bilirubin (p = 0.074) over first 6 post-transplant months. Pre-transplant administration of probiotics has mild positive influence on 6-month allograft function, yet should not exceed 30 days due to potential negative effects on long-term outcomes. (ClinicalTrials.gov Identifier: NCT01735591).

Progressive familial intrahepatic cholestasis type 4 in an Indian child: presentation, initial course and novel compound heterozygous mutation

2020 ◽  
Vol 13 (7) ◽  
pp. e234193
Author(s):  
Nida Mirza ◽  
Ravi Bharadwaj ◽  
Smita Malhotra ◽  
Anupam Sibal
Keyword(s):  
Smooth Muscle ◽  
Intrahepatic Cholestasis ◽  
Compound Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Cholestatic Liver Disease ◽  
Gamma Glutamyl Transferase ◽  
Progressive Familial Intrahepatic Cholestasis ◽  
Smooth Muscle Antibody ◽  
Elevated Liver Enzymes ◽  
Glutamyl Transferase

A 15-year-old boy who had a history of on and off pruritus and jaundice since many years found to have a novel mutation in TJP2 gene. On examination, he had clubbing, splenomegaly, grade 3 oesophageal varices and short stature. Investigation revealed direct hyperbirubinemia with elevated liver enzymes with normal gamma-glutamyl transferase (GGT). Antinuclear antibody (ANA), smooth muscle antibody (SMA) anti-liver kidney microsomal (anti-LKM) and viral markers for hepatitis were negative. However, IgG was elevated and anti-smooth muscle antibody (ASMA) was weekly positive (1:20). He was also given a trial of steroid and azathioprine for 1 year on the basis of liver biopsy findings, raised IgG and positive ASMA but finding no improvement stopped. Genetic testing by next-generation sequencing found a novel compound heterozygous missense variation in exon 17 of the TJP2 gene confirming progressive familial intrahepatic cholestasis type 4 as the aetiology of cholestatic liver disease.

scholarly journals Clinical and Para Clinical Findings in Children with Progressive Familial Intrahepatic Cholestasis in Iran; A Referral Center Report

2020 ◽  
Author(s):  
Mohammad Zarenezhad ◽  
Seyed Mohsen Dehghani ◽  
Fardad Ejtehadi ◽  
Mohammad Reza Fattahi ◽  
Reza Kaboodkhani ◽  
...  
Keyword(s):  
Intrahepatic Cholestasis ◽  
Clinical Manifestations ◽  
Clinical Findings ◽  
Nodule Formation ◽  
Progressive Familial Intrahepatic Cholestasis ◽  
Referral Center ◽  
Elevated Liver Enzymes ◽  
Clinicopathological Findings ◽  
Histopathologic Evaluation ◽  
End Stage

Abstract BackgroundProgressive Familial Intrahepatic Cholestasis (PFIC) is a heterogeneous group of disorders with various clinical and para-clinical manifestations. We report clinical and para-clinical findings in children with progressive familial intrahepatic cholestasis in Southern Iran.MethodsMedical records of 102 patients aged ≤18 years old diagnosed with PFIC who referred to our referral center were evaluated from 2008 to 2012. Baseline and clinical characteristics, outcomes and survival of these patients were recorded. ResultsThe study included 61 boys and 41 girls. Most common complaints were jaundice in 53 (51.96 %), pruritus and jaundice in 15 (14.70 %) and jaundice+elevated liver enzymes in 11 (10.78%) children. Main clinical findings in children were jaundice (51.96%), ascites (28.43%), pruritus (19.60%), fever (16.66%) and encephalopathy (14.70%). Inhomogeneous echogenicity (31.37%), splenomegaly (26.47%), hepatomegaly (17.64%), cirrhosis (9.80%) and ascites (6.86%) were the most common sonography findings among children with PFIC, respectively. Histopathologic evaluation showed cirrhosis (34.31%), followed by fibrosis (18.62%), cholestasis (10.78%), inflammation of liver tissue (4.90%), nodule formation (2.94%), and destruction of lobular and vascular architecture (1.96%). Liver transplantation, medical therapy and biliary diversion had been performed for 67%, 13% and 11% of the patients, respectively. Mean (SD) PELD and MELD scores among children with PFIC were 7.14±14.63 and 15.75±7.21, respectively. Three month mortality rate for PFIC patients with end stage liver disease was 13.1%.ConclusionInhere we reported invaluable clinicopathological findings among a large series of patients with PFIC.

Recovery from LCDD-associated Severe Liver Cholestasis: a Case Report and Literature Review

2016 ◽  
Vol 25 (1) ◽  
pp. 99-103 ◽  
Author(s):  
Benoit Brilland ◽  
Johnny Sayegh ◽  
Anne Croue ◽  
Frank Bridoux ◽  
Jean-François Subra ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Intrahepatic Cholestasis ◽  
Relevant Literature ◽  
Gamma Glutamyl Transferase ◽  
Light Chain Deposition Disease ◽  
Deposition Disease ◽  
Uncommon Presentation ◽  
Light Chain Deposition ◽  
Glutamyl Transferase

Light chain deposition disease (LCDD) is a rare multisystemic disorder associated with plasma cell proliferation. It mainly affects the kidney, but liver and heart involvement may occur, sometimes mimicking the picture of systemic amyloidosis. Liver disease in LCDD is usually asymptomatic and exceptionally manifests with severe cholestatic hepatitis. We report the case of a 66-year-old female with κ-LCDD and cast nephropathy in the setting of symptomatic multiple myeloma who, after a first cycle of bortezomib-dexamethasone chemotherapy, developed severe and rapidly worsening intrahepatic cholestasis secondary to liver κ-light chain deposition. Intrahepatic cholestasis was attributed to LCDD on the basis of the liver histology and exclusion of possible diagnoses. Chemotherapy was maintained and resulted in progressive resolution of cholestasis. We report here an uncommon presentation of LCDD, with prominent liver involvement that fully recovered with bortezomib-based chemotherapy, and briefly review the relevant literature. Abbreviations: AKI: Acute kidney injury; ALP: alkaline phosphatase; ALT: alanine aminotransferase; AST: aspartate aminotransferase; CMV: Cytomegalovirus; EBV: Epstein–Barr virus; GGT: gamma-glutamyl transferase; HSV: Herpes simplex virus; LC: light chain; LCDD: Light chain deposition disease; MIDD: Monoclonal immunoglobulin deposition disease; MM: Multiple myeloma.

Sign in / Sign up

Export Citation Format

Share Document