Case Report: A Novel Homozygous Variant Identified in a Chinese Patient With Benign Recurrent Intrahepatic Cholestasis-Type 1

Abstract

Benign recurrent intrahepatic cholestasis (BRIC) is a rare hereditary cholestatic liver disorder. Accurate diagnosis and timely interventions are important in determining outcomes. Besides clinical and pathologic diagnosis, genetic study of BRIC remains limited. Here, we report a young man enduring recurrent jaundice and severe pruritus for 15 years. The increased level of direct bilirubin was the main biochemical abnormality, and the work-up for common causes of jaundice were unremarkable. Liver biopsy showed extensive cholestasis of hepatocytes in zone 3. The novel homozygous variant including c.1817T > C and p.I606T was detected on his ATP8B1gene. The patient was finally diagnosed with BRIC-1. His symptoms were relieved, and liver function tests returned to normal after taking ursodeoxycholic acid. This case provides a different perspective to the methodology employed when dealing with cases of jaundice and helping diagnose rare diseases.

Case Report: A Rare Case of Benign Recurrent Intrahepatic Cholestasis-Type 1 With a Novel Heterozygous Pathogenic Variant of ATP8B1

“…The effects of several therapeutic strategies aimed at relieving symptoms during cholestasis attacks in patients with BRIC1, such as UDCA, corticosteroids, cholestyramine, and nasobiliary drainage, are known to be case-dependent and usually ineffective (14,15). In this report, since the patient had elevated aminotransferases, we added prednisolone to UDCA.…”

Genetic alterations and molecular mechanisms underlying hereditary intrahepatic cholestasis

“…BRIC1 is associated with heterozygous mutations in ATP8B1 , such as p. T888K ( Bing et al, 2022 ), c.1429 + 2T>G ( Mihara et al, 2022 ), c.1817T>C, and p. I606T ( Chen et al, 2021 ). These mutations are thought to affect the tubular membrane localization of ATP8B1, leading to impaired bile acid transport and cholestasis.…”

“…A heterozygous mutation of ATP8B1 can result in the abnormal localization of the tubule membrane (Chen et al, 2021;Bing et al, 2022;Mihara et al, 2022) Benign recurrent cholestasis is characterized by the gradual development of elevated serum levels of bile acids and bilirubin over several weeks to months (Bing et al, 2022) 4-PB (van der Velden et al, 2010)…”

Benign Recurrent Intrahepatic Cholestasis: Where are we now?

“…The Bile Salt Export Pump (BSEP), a member of the adenosino-triphosphate (ATP)-Binding Cassette (ABC) transporter family, utilizes ATP to transport substrates, such as taurocholate and other BS [15][16][17]. Genetic variability is present, evidenced by various mutations in in aforementioned genes [15][16][17][18][19][20][21]. New mutations in ATP8B1, ABCB11, and SLC51A genes have recently been reported [13,[15][16][17][18][19][20].…”

“…Rifampin, acting on the Pregnane X Receptor (PXR), exhibits anti-pruritic effects in cholestasis but requires vigilant liver function monitoring due to the potential for drug-induced liver injury [17,57,58]. UDCA, a dihydroxy bile acid, alters the bile acids pool to a more hydrophilic mixture, and its favorable safety profile has contributed to its increased use, even during pregnancy [2,16,20,21,28,31,59].…”