A Complex Case of Cholestasis in a Patient with ABCB4 and ABCB11 Mutations

Cardoso, Mariana Ferreira; Branco, Joana C.; Anapaz, Vera; Rodrigues, Catarina; Carvalho, Rita; Horta, David; Martins, Alexandra; Reis, Jorge

doi:10.1159/000484612

Cited by 5 publications

(4 citation statements)

References 26 publications

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“…There are only a few reports of such combined mutations in the literature. A similar digenic variation has been reported earlier by Cardoso et al ( 9 ) in a 39-year-old Caucasian male with choledocholithiasis, hepatolithiasis, and persistent conjugated hyperbilirubinemia after retrieval of stones. The patient fulfilled the criteria for LPAC syndrome and responded to UDCA therapy.…”

Section: Discussionsupporting

confidence: 88%

Combined Mutations of Canalicular Transporter Proteins Causing Low Phospholipid-Associated Cholelithiasis and Transient Neonatal Cholestasis in an Infant

2021

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Low phospholipid-associated cholelithiasis syndrome is characterized by the development of cholelithiasis in early adulthood (<40 years of age) but is rarely diagnosed in childhood. It is associated with gene sequence variants in the ABCB4 gene encoding the multidrug resistance protein 3 which are mostly heterozygous. Transient neonatal cholestasis has been reported with heterozygous mutations in both ABCB4 and ABCB11 (Bile Salt Exporter Protein). We report a 3-month-old male with cholelithiasis and transient neonatal cholestasis in the setting of combined pathogenic heterozygous mutations in the genes ABCB4 and ABCB11. Initiation of ursodeoxycholic acid therapy led to a resolution of the cholestasis and gall stones. Our case highlights the complex nature of the genetics of cholestatic disorders.

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Section: Discussionsupporting

confidence: 88%

Combined Mutations of Canalicular Transporter Proteins Causing Low Phospholipid-Associated Cholelithiasis and Transient Neonatal Cholestasis in an Infant

2021

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“…Furthermore, isolated cases of patients with hepatitis delta have shown that AIH is also observed after treatment with pegylated interferon[ 18 ]. In contrast, a case of HDV-RNA flare has been reported in a previously negative patient who received immunosuppressive treatment for AIH[ 5 ].…”

Section: Aih Induced By Hdvmentioning

confidence: 99%

“…Many clinical studies have shown that HDV infection most often causes progressive liver disease more rapidly than other viral hepatitis, leading to liver cirrhosis in 70% of cases within 5 to 10 years[ 3 ]. Furthermore, HDV is independently associated with an increased risk of hepatocellular carcinoma (HCC) than hepatitis B virus (HBV) monoinfection[ 4 ] and has been associated with the development of autoimmune hepatitis (AIH), as in the serum of HBV/HDV co-infected patients, positive autoantibodies have been detected, and autoimmune features have been reported[ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Management of autoimmune hepatitis induced by hepatitis delta virus

Gigi,

Lagopoulos,

Liakos

2024

World J Gastroenterol

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Approximately 12-72 million people worldwide are co-infected with hepatitis B virus (HBV) and hepatitis delta virus (HDV). This concurrent infection can lead to several severe outcomes with hepatic disease, such as cirrhosis, fulminant hepatitis, and hepatocellular carcinoma, being the most common. Over the past few decades, a correlation between viral hepatitis and autoimmune diseases has been reported. Furthermore, autoantibodies have been detected in the serum of patients co-infected with HBV/HDV, and autoimmune features have been reported. However, to date, very few cases of clinically significant autoimmune hepatitis (AIH) have been reported in patients with HDV infection, mainly in those who have received treatment with pegylated interferon. Interestingly, there are some patients with HBV infection and AIH in whom HDV infection is unearthed after receiving treatment with immunosuppressants. Consequently, several questions remain unanswered with the challenge to distinguish whether it is autoimmune or “autoimmune-like” hepatitis being the most crucial. Second, it remains uncertain whether autoimmunity is induced by HBV or delta virus. Finally, we investigated whether the cause of AIH lies in the previous treatment of HDV with pegylated interferon. These pressing issues should be elucidated to clarify whether new antiviral treatments for HDV, such as Bulevirtide or immu-nosuppressive drugs, are more appropriate for the management of patients with HDV and AIH.

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“…A case of DIC during ciprofloxacin therapy was described in a subject with LPAC, carrier of ABCB4 -related c.1954A>G (p.R652G), a homozygous missense mutation, already described in PFIC3 and ICP, combined to p.V444A in the ABCB11 gene in a heterozygous state [ 101 ].…”

Section: Canalicular Efflux Transport Proteins and Compounds Involved...mentioning

confidence: 99%

Molecular and Clinical Links between Drug-Induced Cholestasis and Familial Intrahepatic Cholestasis

Vitale

Mattiaccio

Conti

et al. 2023

IJMS

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Idiosyncratic Drug-Induced Liver Injury (iDILI) represents an actual health challenge, accounting for more than 40% of hepatitis cases in adults over 50 years and more than 50% of acute fulminant hepatic failure cases. In addition, approximately 30% of iDILI are cholestatic (drug-induced cholestasis (DIC)). The liver’s metabolism and clearance of lipophilic drugs depend on their emission into the bile. Therefore, many medications cause cholestasis through their interaction with hepatic transporters. The main canalicular efflux transport proteins include: 1. the bile salt export pump (BSEP) protein (ABCB11); 2. the multidrug resistance protein-2 (MRP2, ABCC2) regulating the bile salts’ independent flow by excretion of glutathione; 3. the multidrug resistance-1 protein (MDR1, ABCB1) that transports organic cations; 4. the multidrug resistance-3 protein (MDR3, ABCB4). Two of the most known proteins involved in bile acids’ (BAs) metabolism and transport are BSEP and MDR3. BSEP inhibition by drugs leads to reduced BAs’ secretion and their retention within hepatocytes, exiting in cholestasis, while mutations in the ABCB4 gene expose the biliary epithelium to the injurious detergent actions of BAs, thus increasing susceptibility to DIC. Herein, we review the leading molecular pathways behind the DIC, the links with the other clinical forms of familial intrahepatic cholestasis, and, finally, the main cholestasis-inducing drugs.

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A Complex Case of Cholestasis in a Patient with ABCB4 and ABCB11 Mutations

Cited by 5 publications

References 26 publications

Combined Mutations of Canalicular Transporter Proteins Causing Low Phospholipid-Associated Cholelithiasis and Transient Neonatal Cholestasis in an Infant

Combined Mutations of Canalicular Transporter Proteins Causing Low Phospholipid-Associated Cholelithiasis and Transient Neonatal Cholestasis in an Infant

Management of autoimmune hepatitis induced by hepatitis delta virus

Molecular and Clinical Links between Drug-Induced Cholestasis and Familial Intrahepatic Cholestasis

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