scholarly journals Intrahepatic Cholestasis Is a Clinically Significant Feature Associated with Natural History of X-Linked Myotubular Myopathy (XLMTM): A Case Series and Biopsy Report

2021 ◽  
pp. 1-10
Author(s):  
Cristina Molera ◽  
Tinatin Sarishvili ◽  
Andrés Nascimento ◽  
Irakli Rtskhiladze ◽  
Gema Muñoz Bartolo ◽  
...  
Keyword(s):  
Natural History ◽  
Intrahepatic Cholestasis ◽  
Case Series ◽  
Motor Dysfunction ◽  
Significant Feature ◽  
Gamma Glutamyl Transferase ◽  
Myotubular Myopathy ◽  
Biopsy Report ◽  
Life Threatening ◽  
Glutamyl Transferase

X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital myopathy characterized by profound skeletal muscle weakness, respiratory distress, and motor dysfunction. However, pathology is not limited to muscle and can be associated with life-threatening hepatic peliosis. Hepatobiliary disease has been reported in up to 17% of XLMTM patients but has not been extensively characterized. We report on five XLMTM patients who experienced intrahepatic cholestasis in their disease natural history, illustrating the need to further investigate these manifestations. These patients shared presentations that included pruritus, hypertransaminemia, and hyperbilirubinemia with normal gamma-glutamyl transferase, following infection or vaccination. Three patients who had genetic testing showed no evidence of genetic mutations associated with familial cholestasis. In one patient, progression to cirrhotic, decompensated liver disease occurred. Further investigations into the molecular pathomechanism underpinning these clinical observations in XLMTM patients will be important for informing patient care.

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.

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 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 Elevation of gamma-glutamyl transferase in adult: Should we think about progressive familiar intrahepatic cholestasis?

2016 ◽  
Vol 48 (2) ◽  
pp. 203-205 ◽  
Author(s):  
Hugo M. Oliveira ◽  
Cláudia Pereira ◽  
Ermelinda Santos Silva ◽  
Jorge Pinto-Basto ◽  
Helena Pessegueiro Miranda
Keyword(s):  
Intrahepatic Cholestasis ◽  
Gamma Glutamyl Transferase ◽  
Gamma Glutamyl ◽  
Glutamyl Transferase

Biallelic loss-of-function ZFYVE19 mutations are associated with congenital hepatic fibrosis, sclerosing cholangiopathy and high-GGT cholestasis

2020 ◽  
pp. jmedgenet-2019-106706
Author(s):  
Weisha Luan ◽  
Chen-Zhi Hao ◽  
Jia-Qi Li ◽  
Qing Wei ◽  
Jing-Yu Gong ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
Intrahepatic Cholestasis ◽  
Cultured Cells ◽  
High Serum ◽  
Gamma Glutamyl Transferase ◽  
Congenital Hepatic Fibrosis ◽  
Loss Of Function ◽  
Glutamyl Transferase

BackgroundFor many children with intrahepatic cholestasis and high-serum gamma-glutamyl transferase (GGT) activity, a genetic aetiology of hepatobiliary disease remains undefined. We sought to identify novel genes mutated in children with idiopathic high-GGT intrahepatic cholestasis, with clinical, histopathological and functional correlations.MethodsWe assembled a cohort of 25 children with undiagnosed high-GGT cholestasis and without clinical features of biliary-tract infection or radiological features of choledochal malformation, sclerosing cholangitis or cholelithiasis. Mutations were identified through whole-exome sequencing and targeted Sanger sequencing. We reviewed histopathological findings and assessed phenotypical effects of ZFYVE19 deficiency in cultured cells by immunofluorescence microscopy.ResultsNine Han Chinese children harboured biallelic, predictedly complete loss-of-function pathogenic mutations in ZFYVE19 (c.314C>G, p.S105X; c.379C>T, p.Q127X; c.514C>T, p.R172X; c.547C>T, p.R183X; c.226A>G, p.M76V). All had portal hypertension and, at liver biopsy, histopathological features of the ductal plate malformation (DPM)/congenital hepatic fibrosis (CHF). Four children required liver transplantation for recurrent gastrointestinal haemorrhage. DPM/CHF was confirmed at hepatectomy, with sclerosing small-duct cholangitis. Immunostaining for two primary-cilium axonemal proteins found expression that was deficient intraluminally and ectopic within cholangiocyte cytoplasm. ZFYVE19 depletion in cultured cells yielded abnormalities of centriole and axoneme.ConclusionBiallelic ZFYVE19 mutations can lead to high-GGT cholestasis and DPM/CHF in vivo. In vitro, they can lead to centriolar and axonemal abnormalities. These observations indicate that mutation in ZFYVE19 results, through as yet undefined mechanisms, in a ciliopathy.

scholarly journals Etiology and outcome of neonatal cholestasis: an experience in a tertiary center of Bangladesh

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Salavhuddin Mahmud ◽  
Jahida Gulshan ◽  
Mashud Parvez ◽  
Farhana Tasneem ◽  
Syed Shafi Ahmed
Keyword(s):  
Intrahepatic Cholestasis ◽  
Age Of Onset ◽  
Intrahepatic Bile Duct ◽  
Gamma Glutamyl Transferase ◽  
Neonatal Cholestasis ◽  
Common Cause ◽  
Young Infants ◽  
Tertiary Center ◽  
Glutamyl Transferase

Abstract Background Neonatal cholestasis (NC) is a major cause of morbidity and mortality in young infants. This study examines the etiology of NC and its outcome during 2 years of follow-up at a tertiary referral center in Bangladesh. Results Out of 80 cholestatic infants, 60% had intrahepatic cholestasis with a mean age of onset of 12.4±2.8 days and a mean age of admission of 82.4±29.0 days. The remaining 40% were extrahepatic with a mean age of onset of 6.7±2.3 days and a mean age of admission of 94.6±50.4 days. Biliary atresia (BA), idiopathic neonatal hepatitis (INH), and TORCH (Toxoplasma, rubella, cytomegalovirus, and herpes simplex) infection except rubella were the most common causes. After receiving treatment, 46.2% of the cases improved, 23.8% deteriorated with morbidity, and 30% died. The majority of the children with INH, TORCH, choledochal cyst, hypothyroidism, galactosemia, and urinary tract infection (UTI) with sepsis were improved. Significant mortality was found in BA (56.6%), intrahepatic bile duct paucity (PIBD) (100%), and progressive familial intrahepatic cholestasis (PFIC) (100%) whereas the rest of BA (43.4%) live with persistent morbidity. Significant clinical improvement was observed in 37 (46.2%) cases of cholestasis evidenced by decreasing jaundice, change of color of urine from dark to normal color, change of stool color from pale to yellow, and gradual decrease in liver size from hepatomegaly state. In addition, decreasing median total bilirubin, direct bilirubin, alanine transaminase, gamma-glutamyl transferase, and alkaline phosphatase showed biochemical improvement at 2 years follow-up. The age of admission, etiology, and presence of ascites are the predictors of outcomes. Conclusion BA was the most common cause of extrahepatic while INH and TORCH infection were the most common cause of intrahepatic cholestasis. Majority of children with intrahepatic cholestasis improved but deteriorated with BA and genetic causes. Prompt referral and early diagnosis as well as the etiology of NC were the main determinants of the favorable outcome.

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 Case Report: Viral Pneumonia Could Prompt the Advancement of Immune-Mediated Liver Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Qian Li ◽  
Jun Wang ◽  
Xueshi Zhou ◽  
Hongzhou Lu ◽  
Mengji Lu ◽  
...  
Keyword(s):  
Liver Injury ◽  
Autoimmune Hepatitis ◽  
Influenza A ◽  
Case Series ◽  
Unknown Origin ◽  
Gamma Glutamyl Transferase ◽  
Influenza A H1n1 ◽  
Infection Patient ◽  
Glutamyl Transferase ◽  
The Impact

Background: The impact of the influenza A (H1N1) and SARS-CoV-2 virus on the development of autoimmune hepatitis has not been described previously.Methods: In this case series, we evaluated the dynamic changes in liver function of three patients with autoimmune hepatitis who presented with viral infection (two with the H1N1 and one with the SARS-CoV-2 virus) during the recent COVID-19 outbreak.Result: Patient 1 was a 68-year-old woman with a history of hepatitis of unknown origin before being infected with the H1N1 virus. Autoimmune hepatitis with an exacerbation of liver injury was diagnosed during the infection. Patient 2 was a 48-year-old woman with pre-existing autoimmune hepatitis. Despite being on immunosuppressant therapy (using glucocorticoids), liver injury recurred with elevated total bilirubin and gamma-glutamyl transferase levels post H1N1 infection. Patient 3 was a 61-year-old woman with probable autoimmune hepatitis. Liver injury recurred with a flare in alanine transaminase/aspartate transaminase levels post SARS-CoV-2 infection, in spite of the patient being on liver protection therapy (using ursodeoxycholic acid).Conclusion: The case series raises the possibility that COVID-19 or influenza induced pneumonia triggers the progression of autoimmune hepatitis.

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