The Mystery of Episodic Recurrent Jaundice in a Young Male: Cholestasis With a Normal Gamma-Glutamyl Transferase

Abstract

Benign recurrent intrahepatic cholestasis (BRIC) is a very rare autosomal recessive genetic disorder which presents with recurrent jaundice. We report the case of a young male with a history of methamphetamine use who presented with recurrent episodes of right upper quadrant abdominal pain, vomiting, dark urine, and pale stools. These symptoms always resolved within four weeks of presentation. During these episodes, the patient had a cholestatic pattern derangement of liver function tests with a normal gamma-glutamyl transferase (GGT). Workup for abnormal transaminases was unremarkable. A percutaneous liver biopsy obtained on the third visit was notable for a parenchymal lobule that exhibited slight Kupffer cell hyperplasia and subtle evidence of canalicular cholestasis. There was no evidence of cirrhosis, steatosis, hepatitis, or malignancy. Thus, a diagnosis of BRIC was made, and the patient was managed conservatively. Recognition of this rare entity is critical since its benign natural history is reassuring for the patient, and physicians can refrain from repetitive expansive and costly workups.

Benign Recurrent Intrahepatic Cholestasis: Where are we now?

“…This chronic cholestasis may lead to chronic lesions observed in liver biopsy, progressing from lobular fibrosis to cirrhosis and end-stage liver disease. Consequently, patients with PFIC1 or PFIC2 may ultimately require liver transplantation, whereas those with BRIC1 or BRIC2 experience a benign course [1][2]10]. Similar distinctions exist between BRIC2 and PFIC2, as PFIC2 carries a 15% risk of cirrhosis progressing to hepatocellular carcinoma or cholangiocarcinoma [1].…”

“…BRIC, PFIC, and Intrahepatic Cholestasis of Pregnancy (ICP) are disorders affecting similar genes and associated with intrahepatic cholestasis, collectively considered as part of intrahepatic cholestasis syndromes. However, they exhibit differences in prognosis and outcomes [1][2][3]10].…”

“…Interestingly, similar genes are implicated in BRIC 1 and PFIC1, as well as among BRIC2 and PFIC2 patients [1][2]. Despite both BRIC1 and PFIC1 stemming from mutations in ATP8B1, there is substantial differentiation in gene expression, resulting in major clinical and prognostic differences between the two entities.…”

“…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].…”

“…It was first described by Summerskill and Walshe in 1959 as a cause of jaundice [3]. Characterized by recurrent episodes of jaundice, pruritus, anorexia, nausea, vomiting, and steatorrhea, BRIC manifests symptoms that can mimic a malignant condition, leading to weight loss [1][2][3][4][5][6][7][8][9]. However, BRIC is a benign clinical entity, as between the episodes, patients experience good clinical condition with normal laboratory values and histologic findings in liver histology.…”