Introduction
Benign recurrent intrahepatic cholestasis (BRIC) can manifest as a rare disorder occurring at any age, either inherited through an autosomal recessive pattern or can occur haphazardly. It is characterized by recurring intense episodes of itching and jaundice, which naturally subside without causing significant liver damage. While benign recurrent intrahepatic cholestasis can manifest at any age, it predominantly emerges during the first decade of life, with 80 percent of cases appearing before the age of 20. These episodes of illness can persist for weeks to months before spontaneously resolving. Importantly, patients may remain entirely symptom-free for months to years between these symptomatic periods. The definitive diagnosis of BRIC can be established only after ruling out other potential congenital or acquired causes of intrahepatic cholestasis, taking into account the recurrent nature of jaundice and the findings from hepatic biopsy.
What Is Benign Recurrent Intrahepatic Cholestasis?
Benign recurrent intrahepatic cholestasis can cause recurring episodes of cholestasis, a type of liver dysfunction. When these episodes occur, the liver cells will exhibit a reduced ability to release bile (digestive fluid). As it causes problems within the liver, it is termed intrahepatic cholestasis. The duration of cholestatic episodes can vary from a few weeks to several months, and the intervals between these episodes, characterized by the absence of symptoms, may vary from weeks to years. Benign recurrent intrahepatic cholestasis is an uncommon disorder, and its exact prevalence remains uncertain. It affects 1 in 50,000 to 1 lakh individuals globally.
Other names for this condition are:
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ABCB11-related intrahepatic cholestasis.
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Benign recurrent intrahepatic cholestasis.
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BRIC.
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ATP8B1-related intrahepatic cholestasis.
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Recurrent familial intrahepatic cholestasis.
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Low gamma-GT familial intrahepatic cholestasis.
What Are the Causes of Benign Recurrent Intrahepatic Cholestasis?
ATP8B1 gene mutations give rise to benign intrahepatic cholestasis type 1 (BRIC1), whereas ABCB11 gene mutations give rise to benign intrahepatic cholestasis type 2 (BRIC2). These genes are involved in the bile secretion. Bile helps in the digestion of fats. The ATP8B1 gene encodes a protein responsible for regulating the arrangement of specific fats known as lipids within the cell membranes of the liver. This function is thought to contribute to the maintenance of a proper equilibrium of bile acids, which are integral components of bile. This intricate process, termed bile acid homeostasis, is vital for the normal release of bile and the optimal performance of liver cells. Although the precise mechanism is not fully understood yet, mutations in the ATP8B1 gene lead to the accumulation of bile acids within liver cells. This disruption in bile acid balance results in the characteristic signs and symptoms observed in individuals with BRIC1.
The ABCB11 gene contains instructions for producing a protein known as the bile salt export pump (BSEP). This protein is primarily located in the liver and serves as its key function, which is to facilitate the removal of bile salts (a constituent of bile) from liver cells. When mutations occur in the ABCB11 gene, it results in a decrease in the functionality of BSEP. This diminished function leads to a reduction in the secretion of bile salts, ultimately giving rise to the characteristic features associated with BRIC2. The precise triggers for benign recurrent intrahepatic cholestasis episodes remain unidentified. It is worth noting that not all individuals with BRIC carry mutations in either the ATP8B1 or ABCB11 gene. In such cases, the underlying cause of the condition remains unknown.
What Are the Clinical Signs of Benign Recurrent Intrahepatic Cholestasis?
The initial episode typically manifests during an individual’s teenage or early 20s. These episodes usually commence with itching and are subsequently followed by jaundice development, typically a few weeks later. During these episodes, individuals can experience additional general symptoms such as nausea, discomfort, malaise, vomiting, and decreased appetite. A prevalent sign of BRIC is reduced fat absorption within the body, resulting in steatorrhea (excess fat in the stool). Due to impaired fat absorption and decreased appetite, those often undergo weight loss during cholestatic episodes. As it does not end up in lasting damage to the liver, it is considered a benign condition. However, at times, these liver dysfunction episodes can result in a permanent liver disease called progressive familial intrahepatic cholestasis (PFIC).
How to Manage Benign Recurrent Intrahepatic Cholestasis?
There is currently no definitive cure for benign recurrent intrahepatic cholestasis, and treatment primarily focuses on managing symptoms with medication during episodes. Medications like centrally acting opioid antagonists, bile acid sequestrants, antihistamines, and Rifampicin are employed to alleviate pruritus, which is believed to be caused by bile acid retention within the body. For instance, cholestyramine is used to reduce bile acid levels by binding with them, leading to their elimination through feces. Rifampicin helps shorten the duration of cholestasis by inhibiting the uptake of bile acids by hepatocytes. Rifampicin also helps in eliminating bile salts by inducing 6-hydroxylation of secondary bile salts. Rifampicin has proven to resolve jaundice and pruritus. In cases of cholestatic jaundice, short-term nasobiliary drainage has been found to improve pruritus. Extracorporeal albumin dialysis, as part of a Molecular adsorbent recycling system (MARS), effectively removes bile acids from the body and alleviates pruritus rapidly. Another option, partial biliary diversion, reduces pruritus by lessening the bile acid load on the ileal transport system. In rare instances of intractable pruritus, liver transplantation may be considered.
Conclusion
Benign recurrent intrahepatic cholestasis is a condition that typically resolves on its own and does not progress to chronic liver problems. It is essential to be aware of this condition as early recognition helps avoid costly diagnostic procedures, and patients can be reassured about its non-threatening nature. In adults, it is important to consider the possibility of benign recurrent intrahepatic cholestasis when dealing with patients who experience recurrent cholestatic episodes, particularly after ruling out main bile duct obstruction and other potential congenital or acquired cases of intrahepatic cholestasis.
