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

Oliveira, Hugo M.; Pereira, Carlos; Silva, Ermelinda Santos; Pinto‐Basto, Jorge; Miranda, Helena Pessegueiro

doi:10.1016/j.dld.2015.11.002

Cited by 6 publications

(6 citation statements)

References 9 publications

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“…Cholestasis and biliary tract injury present in PBC patients, and these conditions worsen as the disease progresses 9 , 19 . Furthermore, elevated GGT is a valuable indicator of bile duct obstruction 20 – 22 , which often manifests in PBC patients. We tested whether ALP or GGT levels correlated with serum or salivary AMA-M2.…”

Section: Resultsmentioning

confidence: 99%

Detection of AMA-M2 in human saliva: Potentials in diagnosis and monitoring of primary biliary cholangitis

Hou

et al. 2017

Sci Rep

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Serum anti-mitochondrial antibody type 2 (AMA-M2) is considered as a pivotal biomarker for the diagnosis of primary biliary cholangitis (PBC). However, serological tests have many limitations, including inconvenience, invasiveness, and infection risks. Thus, a less invasive approach to detect AMA-M2 titer is desirable. We examined salivary AMA-M2 of potential PBC patients and found that AMA-M2 could be detected only in saliva of serum AMA-M2-positive PBC patients, but not in saliva of serum AMA-M2-negative PBC patients, oral lichen planus patients (OLP) patients, or healthy controls. Furthermore, the concentration of salivary AMA-M2 was positively correlated with the amount of serum AMA-M2 in patients. The salivary inflammatory cytokines were increased in the PBC, consistent with the results of serum test. These findings indicated that saliva might be a less invasive and cost-effective medium to accurately test for AMA-M2 levels and this is a promising development for the diagnosis and monitoring of PBC.

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Section: Resultsmentioning

confidence: 99%

Detection of AMA-M2 in human saliva: Potentials in diagnosis and monitoring of primary biliary cholangitis

Hou

et al. 2017

Sci Rep

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“…[ 13 ] A prospective multicenter study assessed the efficacy and safety of the serotonin reuptake inhibitor sertraline, for the treatment of children with refractory cholestatic pruritus. [ 14 ] Oliveira et al [ 15 ] thought that the genetic defect in PFIC-3 appears to explains the pathogenesis of intrahepatic cholestasis in pregnancy; their understanding may might provide insights into for developing new therapeutics therapies. After analyzing >150 BSEP mutations, Dröge et al [ 16 ] demonstrated that the extent of exon skipping depends on the genomic and cellular contexts, and that regulation of splicing may have therapeutic potential for PFIC-2.…”

Section: Discussionmentioning

confidence: 99%

Liver transplantation for decompensated liver cirrhosis caused by progressive familial intrahepatic cholestasis type 3

Ding¹,

Wang

et al. 2017

Medicine

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Rationale:Progressive familial intrahepatic cholestasis (PFIC) type 3, characterized by high gamma glutamyl transferase (GGT), is an autosomal recessive genetic disease. It often occurs in patients’ first years of age. However, high GGT type PFIC is still rare.Patient concerns:The present study reports a case of liver transplantation for decompensated liver cirrhosis caused by PFIC type 3. An 18-year-old male presented with a history of abdominal distension and jaundice for 2 months. He had abdominal tenderness but no rebounding pain. Moreover, his dullness was felt over the liver and the spleen was palpable 8 cm below the ribs.Diagnoses:Computed tomography and magnetic resonance cholangiopancreato graphy of the upper abdomen revealed cirrhosis, portal hypertension, collateral circulation formation, large spleen, and ascites. Blood biochemistry showed high alanine transaminase, aspartate transaminase, and GGT. The diagnosis of decompensated liver cirrhosis caused by PFIC-3 was finally confirmed by plasma gene detecting.Interventions:The patient received an open surgery named allogeneic liver transplantation after successful matching of immune types between the recipient and donor. Peritoneal puncture and catheter drainage under B-ultrasound was performed when an encapsulated effusion between the liver and stomach arose.Outcomes:The patient was discharged without specific discomfort and was almost free of fluid accumulation 51 days after the surgery. At the 6-month follow-up, he had no discomfort and the blood routine, liver functions showed no abnormalities.Lessons:We found a new mutant fragment of ABCB4 gene in the process of diagnosis. Liver transplantation remains the most definitive treatment for PFIC. Current medical therapies and surgical interventions such as biliary diversion have potentially created a synergistic outcome.

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“…The association between PSC and variants in ABCB4 remains controversial although several case reports in adults allude to a possible association. [28][29][30] A study looking at the role of heterozygous variants in ABCB4 in 76 PBC and 46 PSC adult patients did not demonstrate any haplotype distribution and linkage disequilibrium in patients against healthy controls. 31 However, in a study of 32 adults with histologic evidence of cholestatic liver disease of unknown etiology 34% were found to have a heterozygous variant in ABCB4.…”

Section: The Possible Clinical Consequencesmentioning

confidence: 99%

Clinical outcomes of ABCB4 heterozygosity in infants and children with cholestatic liver disease

Hegarty,

Gurra,

Tarawally

et al. 2023

J. pediatr. gastroenterol. nutr.

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ObjectivesBiallelic variants in the adenosine triphosphate binding cassette subfamily B member 4 (ABCB4) gene which encodes the multidrug resistance 3 protein (MDR3) leads to progressive familiar intrahepatic cholestasis type 3. However, monoallelic variants are increasingly recognized as contributing to liver disease in adults. Our aim was to describe the clinical characteristics of MDR3 heterozygous variants in a large cohort of infants and children with cholestatic liver disease.MethodsThe clinical and genotypic data on pediatric patients seen at King's College Hospital, London, between 2004 and 2022 and found to harbour heterozygous variants in ABCB4 were reviewed.ResultsNinety‐two patients amongst 1568 tested were identified with a monoallelic variant (5.9%). The most common presenting problem was conjugated hyperbilirubinemia (n = 46; 50%) followed by cholelithiasis (n = 12; 13%) and cholestatic hepatitis (n = 10; 11%). The median values of liver biochemistry at presentation were: GGT 105 IU/L and total bilirubin 86 µmol/L. Thirty‐two genetic variants were identified including 22 missense (69%), 4 deletions (13%), 5 splice site (16%) and 1 termination (3%). At a median follow up of 1 year there was resolution of liver disease.ConclusionsRare variants in ABCB4 were found amongst infants and children with cholestatic liver disease. The presenting problems were variable and abnormalities tended to normalize over time. Those with severe mutations could develop liver disease later in life when exposed to further insult and should be counseled appropriately.

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

Abstract: Disease and mechanisms that determine cholestasis are complex and their understanding may provide new therapeutics.

Cited by 6 publications

References 9 publications

Detection of AMA-M2 in human saliva: Potentials in diagnosis and monitoring of primary biliary cholangitis

Detection of AMA-M2 in human saliva: Potentials in diagnosis and monitoring of primary biliary cholangitis

Liver transplantation for decompensated liver cirrhosis caused by progressive familial intrahepatic cholestasis type 3

Clinical outcomes of ABCB4 heterozygosity in infants and children with cholestatic liver disease

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