What are the other Names for this Condition? (Also known as/Synonyms)

• BRIC (Benign Recurrent Intrahepatic Cholestasis)
• Summerskill-Walshe-Tygstrup Syndrome

What is Benign Recurrent Intrahepatic Cholestasis? (Definition/Background Information)

• Benign Recurrent Intrahepatic Cholestasis (BRIC) is a rare condition that affects the liver
• There are two forms of BRIC which are classified based on the genetic cause of the condition
  • BRIC1 is caused by changes (mutations) in the ATP8B1 gene
  • And, BRIC2 is caused by mutations in the ABCB11 gene
• Both follow an autosomal recessive pattern of inheritance
• People with this condition experience episodes of cholestasis, during which the liver cells have a reduced ability to release bile (a digestive fluid). Episodes generally begin in the late teens or early twenties and may be accompanied by jaundice, severe itchiness, a vague feeling of discomfort (malaise), irritability, nausea, vomiting, and a lack of appetite
• Treatment of BRIC may include medications to manage symptoms and specialized therapies (i.e. nasobiliary drainage) to shorten episodes

(Source: Benign Recurrent Intrahepatic Cholestasis; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

Who gets Benign Recurrent Intrahepatic Cholestasis? (Age and Sex Distribution)

• Benign Recurrent Intrahepatic Cholestasis is a rare congenital disorder. The exact prevalence of this disorder is not known
• The presentation of symptoms may occur at any age; but, in most cases, symptom manifestation begins in the teenage years or early twenties of affected individuals
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Benign Recurrent Intrahepatic Cholestasis? (Predisposing Factors)

• A positive family history may be an important risk factor, since Benign Recurrent Intrahepatic Cholestasis can be inherited

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Benign Recurrent Intrahepatic Cholestasis? (Etiology)

• Benign Recurrent Intrahepatic Cholestasis type 1 is caused by mutation(s) in the ATP8B1 gene, while Benign Recurrent Intrahepatic Cholestasis type 2 is caused by mutation(s) in the ABCB11 gene
• The ATP8B1 and ABCB11 genes code for proteins that are involved in the secretion of bile, which aids in fat metabolism
• Both types of BRIC are inherited in an autosomal recessive manner

Autosomal recessive mode of inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Benign Recurrent Intrahepatic Cholestasis?

The signs and symptoms of Benign Recurrent Intrahepatic Cholestasis may vary among affected individuals in type, severity, as well as duration of episodes, and may include the following:

• Acholic stools
• Abdominal pain
• Anorexia
• Cholestatic liver disease
• Cholelithiasis
• Chronic diarrhea
• Cirrhosis
• Elevated hepatic transaminases
• Fatigue
• Hearing impairment
• Hepatocellular carcinoma
• Nausea and vomiting
• Pancreatitis
• Pruritus
• Weight loss

(Source: Benign Recurrent Intrahepatic Cholestasis; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

How is Benign Recurrent Intrahepatic Cholestasis Diagnosed?

Benign Recurrent Intrahepatic Cholestasis is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Liver function tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Benign Recurrent Intrahepatic Cholestasis?

The complications of Benign Recurrent Intrahepatic Cholestasis may include:

• Severe jaundice
• Liver damage
• Evolution into a chronic form of cholestasis, known as progressive familial intrahepatic cholestasis

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Benign Recurrent Intrahepatic Cholestasis Treated?

• There is no cure for Benign Recurrent Intrahepatic Cholestasis, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops
• A procedure known as nosobiliary drainage may be employed to provide relief from obstructed bile ducts and shorten the duration of episodes

How can Benign Recurrent Intrahepatic Cholestasis be Prevented?

Benign Recurrent Intrahepatic Cholestasis may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy), if available, may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Benign Recurrent Intrahepatic Cholestasis? (Outcomes/Resolutions)

• The prognosis of Benign Recurrent Intrahepatic Cholestasis is reported to be good. The frequency of cholestatic episodes is known to decrease with age
• However, in some, the condition may evolve into a more chronic and progressive form of familial intrahepatic cholestasis
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Benign Recurrent Intrahepatic Cholestasis:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/