Benign Recurrent Intrahepatic Cholestasis Research Articles

Case Report: Intrahepatic cholestasis: a diagnostic dilemma

Cholestasis is an impairment of bile formation or bile flow. The mechanisms of cholestasis can be broadly classified into intrahepatic and extrahepatic. Most of the time, etiology can be determined with proper history, physical examination, and diagnostic testing including laboratory and imaging tests. This is a case report of a patient with severe cholestasis who underwent extensive evaluation to determine the etiology of intrahepatic cholestasis. This Case Report details a 28-year-old male who presented with seven days’ history of yellowish discoloration of eyes, the passage of dark-colored urine, generalized body itching, and the passage of clay-colored stool. The patient had no similar episode in the past. Laboratory investigations showed unconjugated hyperbilirubinemia and increased alkaline phosphatase. Magnetic resonance cholangiopancreaticography was unremarkable and liver biopsy was suggestive of cholestatic pattern and negative for acute hepatitis. The bilirubin level started decreasing after a month. The etiology of intrahepatic cholestasis remained unknown. Genotyping could not be done due to limited available resources. It may have helped to diagnose familial hepatocellular cholestasis such as benign recurrent intrahepatic cholestasis (BRIC) and progressive familial intrahepatic cholestasis. Gamma-glutamyl transferase is normal or mildly elevated in patients with BRIC. A similar picture was seen in our case as well. If the patient presents again with similar symptoms and findings, we can consider the diagnosis of BRIC.

Benign Recurrent Intrahepatic Cholestasis: Where Are We Now?

Benign recurrent intrahepatic cholestasis (BRIC) stands as a rare genetic contributor to cholestasis, aligning itself within the spectrum of inherited intrahepatic cholestasis syndromes, such as progressive familial intrahepatic cholestasis (PFIC) and intrahepatic cholestasis of pregnancy. Manifesting in infancy or early adulthood, BRIC is marked by recurrent episodes of jaundice accompanied by intense pruritus, enduring from weeks to years across the lifespan. Normal gamma-glutamyl transferase (GGT) levels are a characteristic laboratory finding. Initially considered unlikely to progress to chronic liver disease or cirrhosis, some reports suggest BRIC may evolve into a continuous and progressive form of cholestasis. Moreover, these recurrent cholestatic episodes significantly impact quality of life, and certain mutations elevate the risk of hepatobiliary malignancy. Between episodes, histological findings of centrilobular cholestasis and abnormal laboratory parameters revert to normal, potentially obviating the need for liver biopsy. This review focuses on the genetic aspects of BRIC, its pathophysiology, clinical presentation, and prognosis. Additionally, it outlines triggering factors and available treatment options.

Benign recurrent intrahepatic cholestasis – case series and literature review

Benign recurrent intrahepatic cholestasis (BRIC) is a rare form of intrahepatic cholestasis seen in patients with genetic predispositions. It is a rare disease of unknown prevalence and is transmitted as an autosomal recessive pattern of inheritance. The available literature for BRIC is limited. It is hard to formulate the true prevalence of the disorder. Often precipitated by a trigger like viral infections and drugs, this condition results in a self-limiting episode of cholestasis. We present a case series of three patients with the clinical picture of BRIC. All three cases were fully evaluated for the cause of cholestasis and thereafter treated with ursodeoxycholic acid and rifampicin, which showed complete recovery.

Alagille syndrome and liver: an adult case report

BackgroundAlagille syndrome is a rare autosomal-dominant disorder, representing 10 to 15% of the causes of neonatal cholestasis with no gender predominance. The diagnosis is based on the association of liver, heart, eye, skeleton abnormalities, and characteristic facial appearance.Case presentationAn 18-year-old male patient, with a family history of benign recurrent intrahepatic cholestasis in a brother, was diagnosed at birth with bile duct paucity. He consulted in adulthood for cholestatic jaundice and pruritus. Physical exam found cutaneous jaundice, particular face, skeletal abnormality of fingers, posterior embryotoxon, and splenomegaly. An echocardiogram found cardiovascular abnormalities. The diagnosis of Alagille syndrome was made in front of five major criteria. A liver biopsy revealed a cirrhosis liver. Upper gastrointestinal endoscopy revealed grade II esophageal varices of portal hypertension. Laboratory tests revealed bicytopenia related to hypersplenism, hypoferritinemia, cytolysis with cholestasis, high bilirubin levels, low prothrombin time, hypoalbuminemia, decreased factor V activity, and hypocholesterolemia. The patient had vitamin K supplementation and was put on ursodeoxycholic acid, propranolol for the liver disease, a high protein hypercaloric diet for malnutrition, vitamin D supplementation and bisphosphonate for the osteoporosis, therapeutic abstention with monitoring for the asymptomatic cardiac disease. After a year of treatment, the patient had an overall health status improvement. Abdominal ultrasound found liver nodules. A biliary MRI showed a multinodular liver. The complement by CT hepatic angiography did not show any nodules while the MRI angiography revealed multiple dysplastic nodules. A liver biopsy was performed and found regenerative nodules.ConclusionThe treatment of Alagille syndrome is based on managing the cholestasis and its complications, especially pruritus because it can have a significant impact on quality of life. Due to the complexity of presentation and multi-organ involvement, management of cases with Alagille syndrome should be done by a multidisciplinary team. Liver disease is responsible for morbidity while cardiac disease is a mortality risk factor in this population.

Clinicopathologic Features, Genetics, Treatment, and Long-Term Outcomes in Japanese Children and Young Adults with Benign Recurrent Intrahepatic Cholestasis: A Multicenter Study.

Few reports of benign recurrent intrahepatic cholestasis (BRIC) have focused on East Asian patients. We describe the clinicopathologic features, genetics, treatment, and outcomes in Japanese BRIC patients. We recruited patients with BRIC type 1 (BRIC-1) or 2 (BRIC-2) treated at four pediatric centers and one adult center between April 2007 and March 2022. Demographics, clinical course, laboratory results, molecular genetic findings concerning ATP8B1 and ABCB11 genes, histopathology, and treatment response were examined retrospectively. Seven Japanese patients with BRIC were enrolled (four male, three female; four BRIC-1 and three BRIC-2). The median age at onset for BRIC-1 was 12 years; for BRIC-2, it was 1 month. Intermittent cholestatic attacks numbered from one to eight during the 11 years of median follow-up. Six patients received a mainstream education; only one patient attended special education. None developed cirrhosis. Three with BRIC-1 showed compound heterozygosity for a variant ATP8B1 gene, while one was heterozygous; two BRIC-2 patients showed compound heterozygosity in ABCB11 and one was heterozygous. Liver biopsy specimens obtained during cholestatic attacks showed fibrosis varying from none to moderate; inflammation was absent or mild. Rifampicin administered to three patients for cholestatic attacks was effective in all, as was cholestyramine in two of three. To our knowledge, this is the first East Asian multicenter study of BRIC patients. Onset age and number of cholestatic attacks varied. Rifampicin and cholestyramine were effective against attacks. No patient developed cirrhosis; most had normal growth and development. The long-term outcomes were satisfactory.

A 19-year-old Patient with Recurrent Pruritus and Jaundice

Аim: to highlight the importance of broad differential diagnosis and possibility of conversion of benign recurrent intrahepatic cholestasis type 2 into more aggressive clinical phenotype.Key points. A 19-year-old female patient was admitted to the Clinic with skin pruritus, jaundice, dark urine, clay-colored stool, and general fatigue. Past medical history was significant for recurrent aforementioned symptoms since 3 years old, that relapsed every 1–2 years and were usually ameliorated with conservative therapy. During recent years, frequency of relapses and recovery period increased, at the same time effectiveness of medical therapy decreased. Blood chemistry results revealed an elevation of total bilirubin (up to 634 μmol/L), direct bilirubin (up to 354 μmol/L), bile acids (up to 510 μmol/L) and normal gamma glutamyl transferase level. Workup was negative for viral hepatitis, autoimmune liver diseases, obstructive choledochal lesions, storage diseases, although mutation in gene ABCB11 was found. Benign recurrent intrahepatic cholestasis type 2 was diagnosed. Following conservative therapy and plasmapheresis, jaundice and skin pruritus significantly diminished, levels of bilirubin and bile acids normalized. Regular follow up, liver biopsy and measures for relapse prevention given clinical features of aggressive phenotype were recommended.Conclusion. Identification of etiology of cholestatic liver diseases requires broad differential diagnosis. Clinical course of patients with benign recurrent intrahepatic cholestasis may transform into aggressive phenotype, reminiscent of progressive familial intrahepatic cholestasis.

Case Report: Intrahepatic cholestasis: a diagnostic dilemma

Cholestasis is an impairment of bile formation or bile flow. The mechanisms of cholestasis can be broadly classified into intrahepatic and extrahepatic. Most of the time, etiology can be determined with proper history, physical examination and diagnostic testing including laboratory and imaging tests. This is a case report of a patient with severe cholestasis who underwent extensive evaluation to determine the etiology of intrahepatic cholestasis. This Case Report details a 28-year-old male who presented with seven days’ history of yellowish discoloration of eyes, passage of dark colored urine, generalized body itching, and passage of clay colored stool. Patient had no similar episode in the past. Laboratory investigations showed unconjugated hyperbilirubinemia and increased alkaline phosphatase. Magnetic resonance cholangiopancreaticography was unremarkable and liver biopsy was suggestive of cholestatic pattern and negative for acute hepatitis. The bilirubin level started decreasing after a month. The etiology of intrahepatic cholestasis remained unknown. Genotyping could not be done due to limited available resources. It may have helped to diagnose familial hepatocellular cholestasis such as benign recurrent intrahepatic cholestasis (BRIC) and progressive familial intrahepatic cholestasis. Gamma glutamyl transferase is normal or mildly elevated in patients with BRIC. A similar picture was seen in our case as well. If the patient presents again with similar symptoms and findings, we can consider the diagnosis of BRIC.

Cholestatic Liver Disease in Late Childhood: A Report of Two Rare Cases

Cholestatic liver disease in late childhood has a comprehensive list of aetiologies, requiring a multidimensional approach. Among these, the genetic aetiology can range from having a self-limiting course to being associated with morbidity and mortality, requiring liver transplantation. Progressive Familial Intrahepatic Cholestasis (PFIC) and Benign Recurrent Intrahepatic Cholestasis (BRIC) are two rare inherited autosomal recessive cholestatic disorders. Both are related to mutations in the bile formation transport system and typically manifest in infancy or early childhood. Among the PFIC types, The PFIC type 3 rapidly progresses to end-stage liver disease, while BRIC follows a benign course with intermittent asymptomatic periods. Here, authors describe two (17-year-old male, 19-year-old male) such unusual inherited autosomal recessive cholestatic disorders in late childhood: PFIC (type 3) and BRIC, which have distinct clinical presentations and liver function derangements.

Improvement of cholestatic episodes in patients with benign recurrent intrahepatic cholestasis (BRIC) treated with rifampicin. A long-term follow-up

Objective Patients with benign recurrent intrahepatic cholestasis (BRIC) suffer from recurrent episodes of cholestatic jaundice. Treatment options remain limited and are mainly symptomatic. In case reports rifampicin, plasmapheresis, and nasobiliary drainage have been reported to be effective. In this case series, we present long-term experience indicating disease-modifying effects of non-invasive treatment with rifampicin for recurrent cholestasis in BRIC type 1 (BRIC1). Materials and methods We included all adult BRIC1 patients diagnosed and followed up at a single centre in Bergen, Norway. Data regarding clinical and biochemical features during BRIC attacks with and without rifampicin treatment were retrieved from medical journals and a data registry. Results Five males with BRIC1 were included. Median age at diagnosis was 22 years (range 15–41). Together they had suffered from 65 cholestatic attacks (including four documented abortive attacks). Twenty-eight attacks were treated with rifampicin alone over the last 12 years; all cases showed symptomatic relief and reduction in the levels of bilirubin and alkaline phosphatase in blood. The attacks treated with rifampicin seemed to have shorter duration and were less likely to result in complications or hospitalization compared to attacks prior to the introduction of rifampicin. No side effects attributable to rifampicin were noted. Conclusions Episodic treatment of recurrent BRIC1 attacks with rifampicin seems to ameliorate severity and shorten the duration of attacks. Timely diagnosis and effective treatment are of major importance in BRIC, not only to decrease complications but also improving patients’ quality of life.

S2933 BRIC Type 3? A Case of Benign Recurrent Intrahepatic Cholestasis Unlinked to ATP8B1 and ABCB11

Introduction: Benign Recurrent Intrahepatic Cholestasis (BRIC) is a genetic disorder with two common subtypes: BRIC I (mutated ATP8B1 gene), and BRIC II (mutated ABCB11 gene). Diagnosis requires high degree of suspicion and is confirmed by genetic testing. There are rare cases where patients lack both of the typical mutations. We present a patient with clinical, lab and histological evidence of BRIC without the usual mutations. Case Description/Methods: A 17-year-old male with no medical history presented with yellow eyes, pruritus, and acholic stools for six weeks, without triggering illness or stress. He denied fatigue, fevers, rash, dizziness, nausea, vomiting, diarrhea, constipation, arthralgias, melena, hematochezia, or hematemesis. He had no tattoos, blood transfusions, or allergies. He denied medications, alcohol, smoking, and drug use. On exam, he was icteric, with normal abdominal exam, and Alkaline Phosphatase 370 U/L, ALT 96 U/L, AST 66 U/L, and conjugated bilirubin of 6.7 mg/dL. Serological tests were normal, including antibodies for hepatitis A/B/C, CMV, EBV, HIV; alpha-1 antitrypsin; ceruloplasmin; iron, transferrin, C28Y/H63D mutations; TSH; antinuclear, anti-smooth muscle, anti-liver kidney microsomal, anti-mitochondrial antibodies; serum tissue transglutaminase; urine chlamydia and gonorrhea. Liver ultrasound had no biliary dilation. Genetic testing revealed negative ATP8B1 and ABCB11. Nonfocal liver biopsy showed bland cholestasis with coarse granular material in dilated bile canaliculi, compatible with a disorder of intrahepatic cholestasis, with morphologically similarities to biopsies seen in BRIC. He received ursodiol and symptoms improved. He stopped ursodiol after discharge and presented six months later with similar lab abnormalities. Repeat serological workup was normal. He received ursodiol and symptoms resolved again (Figure). Discussion: Diagnostic criteria for BRIC include episodes of jaundice separated by a symptom-free interval of at least six months, lab and histological evidence of non-inflammatory cholestasis, non-dilated biliary ducts, and no other explanatory causes. Our patient satisfied these diagnostic criteria. Some evidence indicates the presence of additional disease loci for low γ-GT BRIC, explaining why some patients diagnosed with BRIC on clinical and histopathologic evidence lack usual mutations in ATP8B1 or ABCB11. This disorder is informally termed “BRIC 3”; it is unclear which genes are implicated in this form and further research is needed.Figure 1.: Histopathologic appearance of the liver biopsy. Bland centrilobular cholestasis with coarse granular biliary material within dilated bile canaliculi, without any significant inflammation, bile duct damage, or ductular reaction.

S3274 A Rare Case of Benign Recurrent Intrahepatic Cholestasis (BRIC) Presenting as an Unexplained Cholestatic Jaundice

Introduction: Benign Recurrent Intrahepatic Cholestasis (BRIC) is a very rare autosomal recessive disorder characterized by episodes of recurrent cholestatic jaundice followed by complete resolution. BRIC is associated with a mutation in both alleles of ATP8B1 (BRIC 1) or ABCB11 (BRIC2). It causes cholestasis by impairing the function of the bile salt export pump. Recognition of BRIC is important as it can lead to delayed or no diagnosis, also it is underrecognized and challenging diagnosis. Case Description/Methods: A 19-year-old South Asian male presented with nausea, vomiting, deep jaundice and pruritus of 10 days duration. Family history was negative for jaundice. He was not consuming alcohol or any drugs. Past medical records revealed three past episodes of undiagnosed cholestatic jaundice lasting for three to four weeks with complete recovery at the age of 8, 11 and 14 years respectively. Physical examination revealed stable vitals, deep icterus, cutaneous scratch marks and mild tender hepatomegaly. No stigmata of acute or chronic liver disease were identified. PT was prolonged with an INR of 1.8. AST and ALT were initially raised on admission which gradually trended down while serum total bilirubin, direct bilirubin and alkaline phosphatase continued to raise over 8 weeks. GGT remained within normal limits (Table 1). Viral markers for hepatitis A, B, C, E; HIV 1&2; EBV and CMV were negative. Workups for autoimmune hepatitis and Wilson's disease were negative. Ultrasound of the abdomen and MRCP were unremarkable. A liver biopsy was performed which showed intrahepatic and canalicular cholestasis predominantly involving zone 3 suggestive of BRIC (Figure A). He was treated with intravenous fluids, antiemetics, cholestyramine and antihistamines for symptomatic relief. Because of severe pruritus, Rifampicin was added later on for 14 days resulting in significant improvement. Liver function tests returned to baseline after 3 months. The patient was followed up for 6 months and remained asymptomatic. Discussion: Till date very few cases of BRIC have been reported, which may be due to the rarity of the condition compounded by under-recognition by clinicians. Despite being a genetic disease, most cases are sporadic. Diagnosis in our case was based on the past episodes of jaundice, present clinical features, laboratory parameters and liver biopsy findings as proposed by Luketic and Shiffman for the diagnosis of BRIC. This is a self-limiting disease with no residual damage and treatment is symptomatic.Figure 1.: A. Liver Histology (H&E × 400): Intrahepatic cholestasis (black arrow) with preserved liver architecture. Table 1. - Laboratory results T. Bilirubin (mg/dl) D. Bilirubin (mg/dl) ALP (U/L) GGT (U/L) ALT (U/L) AST (U/L) Day – 1 8.2 6.1 388 15.2 415 205 Day – 7 12.4 9.8 421 15.4 354 106 Day – 14 14.6 12.2 510 14.8 156 88 Day – 21 18.0 16.5 615 14.5 80 60 Day – 31 21.5 18.3 830 12 48 32 Day – 45 24.32 22.45 950 11.3 38 22 Day – 60 26.82 24.13 1152 10.1 36 20 Day – 75 11.24 9.12 353 9.2 32 18 Day – 90 1.6 0.8 86 9 28 15

S1935 A Unique Case of Small Duct Primary Sclerosing Cholangitis Leading to Recurrent Cholestatic Hepatitis

Introduction: Small Duct Primary Sclerosing Cholangitis (sdPSC) is the narrowing of intrahepatic bile ducts which often leads to cholestasis and cirrhosis. We present a patient diagnosed with sdPSC which is an uncommon form of PSC. Case Description/Methods: A 42-year-old male patient, with a history of hypertension and gunshot wound with bowel resection presented for abdominal pain associated with recurrent cholangitis. Previous history also included bouts of abdominal pain, jaundice and hyperbilirubinemia that occurred roughly three times a year. A liver biopsy was taken during admission and revealed mild portal inflammation and cholestasis, bridging fibrosis, and intracytoplasmic iron granules. One month later a colonoscopy showed patchy erythema with biopsies demonstrating mild acute proctitis. Given cholestatic pattern, + ANA 1:320, recurrent admissions with sepsis, and recent colonoscopy showing evidence of proctitis (biopsy proven), the patient was diagnosed with sdPSC with overlap of autoimmune cholangiopathy. The sdPSC was treated with a cadaveric liver transplant, and upon explant, the patient’s liver showed chronic obstructive cholangiopathy. His postoperative course was notable for persistently elevated bilirubin of which half was indirect. Upon ERCP, the liver showed a mild anastomotic stricture and tortuous duct which was treated with a stent. However, the stent was removed because of lack of frank stricture. The patient was started on a prednisone taper with tacrolimus. The patient is currently doing well post-transplant on low dose tacrolimus and mycophenolate. Discussion: Clinical presentation of sdPSC often consists of pruritis, jaundice, and acute cholangitis from cholestasis, and fatigue, liver failure and hepatosplenomegaly from liver cirrhosis. Notably, the patient presented with hepatomegaly, and jaundice. With this presentation, PSC, sdPSC, and benign recurrent intrahepatic cholestasis (BRIC) were all possible diagnoses. Unremarkable MRCP imaging highlighted the unlikeliness of PSC, and liver biopsy showed bridging fibrosis which excluded BRIC. Clinical diagnosis of sdPSC is difficult and a high degree of clinical suspicion is needed. The cause for Small Duct Primary Sclerosing Cholangitis is unknown, but there is an association with irritable bowel disease, presence of HLA-B8 and HLA-DR3 and autoimmune disease like hyper IgM.

Identification of low gamma-glutamyl transferase familial intrahepatic cholestasis - benign recurrent intrahepatic cholestasis in a 22-year-old woman: A case report and literature review

Introduction: Benign recurrent intrahepatic cholestasis (BRIC) is a rare genetic disorder characterized by recurrent episodes of cholestatic jaundice that may last days to months. It can start at any age, but often in a first decade of life. The syndrome does not lead to progressive liver dysfunction and cirrhosis. Between cholestatic episodes patients have no symptoms and laboratory levels are within the norms. The exact mechanism of cholestasis in BRIC and many other cholestatic conditions is poorly understood. Syndrome the first time was described in 1959r., in 2004 was proposed the following diagnostic criteria. The report presents a 22-year-old woman with the diagnosis of jaundice with an accompanying severe pruritus (first episode of BRIC).
 The aim: This article describes clinical presentation, laboratory abnormalities, and proposed etiologic factors responsible for BRIC. We intend to report this case due to rarity of this disease in Poland.
 Clinical case: Described as a clinical case course features of the BRIC. Knowledge of this entity is important issue as an early recognition that might prevent performance of expensive diagnostic algorithm. The laboratory tests and the whole clinical picture had conclusive results. Moreover, despite negative genetic test, the authors were sure that it is BRIC.
 Conclusion: BRIC is a disease not leading to progressive liver dysfunction and cirrhosis. It should be remembered the characteristic symptoms of BRIC, a very low level of GGT accompanied by jaundice and itching. It has a great diagnostic importance (by shortening the procedure algorithm), allowing for a quick diagnosis.

Progressive familial intrahepatic cholestasis-2 and concomitant cytomegalovirus infection in an infant: a case report

Conjugated hyperbilirubinemia (CH) in infancy can have anatomic, infectious, auto-immune and metabolic causes. We reported a case of CH presented at 2 months and 20 days, with clinical jaundice and evidence of acute on chronic liver failure. Significant history of elder sibling death at the age of 5 months due to hepatic failure and intracranial bleed was present. Investigations revealed a normal gamma glutamyl transpeptidase (GGT) levels. Toxoplasmosis, rubella, cytomegalovirus and herpes simplex (TORCH) panel showed cytomegalovirus (CMV) immunoglobulin M (IgM), immunoglobulin G (IgG) and deoxyribonucleic acid polymerase chain reaction (DNA PCR) positive with mother’s serum CMV IgG, so she was started on oral valganciclovir in addition to other treatment for cholestasis. A clinical exome panel was also sent which showed homozygous two base-pair deletion in exon 27 of the ABCB11 gene [c.3659 3660del (p.Ser1220Ter)] suggestive of benign recurrent intrahepatic cholestasis (BRIC)/progressive familial intrahepatic cholestasis-2 (PFIC-2). The child responded initially to treatment showing reduced serum conjugated bilirubin level and near normalization of INR. However, she was re-admitted with deranged coagulation profile and rising conjugated bilirubin levels after 30 days of discharge and expired due to fulminant hepatic failure with encephalopathy at 6 months of age while she was being prepared for live donor (father) liver transplantation. We presented this case because we found evidence of CMV infection in a child with PFIC-2. The relative contribution of either aetiology needs to be ascertained in view of early recurrence of CH despite standard management protocol including oral valgancyclovir for CMV infection.

Benign Recurrent Intrahepatic cholestasis- A case series

Background and Aim: Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive inherited disorder characterised by repeated self-limiting episode complex of cholestatic jaundice with intense pruritus, weight loss, lasting several weeks to months with normal asymptomatic phases in between episodes. Due to rarity of disease, no guideline is available for treatment of BRIC. We compared various aspects of three adult patients who were diagnosed as BRIC, including demographics, clinical signs and symptoms, investigations, treatment and outcome. Methods:Three cases of young adults presented to a tertiary care hospital in last one year with progressive cholestatic jaundice with intense pruritus. In all three cases the diagnosis of BRIC was made by a combination of clinical features, laboratory findings and typical histopathological features on liver biopsy and exclusion of other causes of cholestasis. Results: The case series includes three male patients, mean age 23.3 years with conjugated hyperbilirubinemia, high ALP levels, with normal GGTP. Two of the three patients had at least two such attacks with normal asymptomatic period between episodes. One patient had single such episode but all other causes of cholestatic hepatitis were ruled out and diagnosis was made based on liver biopsy in all patients. Genetic study was done in one patient with pending report. All of them were treated with rifampicin, UDCA, tapering steroids, anti-histamines and cholestyramine. Episodes resolved within 2-3 months. Conclusions: BRIC presents around first two decades of life with male preponderance. The diagnosis can be made by exclusion of other causes, histopathology and confirmation by generic testing. Resolution is usually slow, and treatment remains largely symptomatic. As a non-invasive treatment, rifampicin may be the first choice.

A case of benign recurrent intrahepatic cholestasis unlinked to ATP8B1 and ABCB11

Benign Recurrent Intrahepatic Cholestasis (BRIC) is a rare genetic disorder characterized by recurring episodes of jaundice. Two subtypes of BRIC have been well-characterized in the literature: BRIC I, caused by mutations in ATP8B1 gene, and BRIC II, triggered by mutations in ABCB11 gene. There are exceedingly rare cases of BRIC in which individuals do not have mutations in either of the associated genes, suggesting the possibility additional loci implicated in this disorder. Herein, we present a case of BRIC in a 21-year-old male who demonstrated clinical, biochemical and histological evidence of disease but lacked both of the associated mutations in ATP8B1 and ABCB11.

S2678 Benign Recurrent Intrahepatic Cholestasis Type 2 Presenting With Worse Outcome During Pregnancy

S2678 Benign Recurrent Intrahepatic Cholestasis Type 2 Presenting With Worse Outcome During Pregnancy

ПРОГРЕССИРУЮЩИЙ СЕМЕЙНЫЙ ВНУТРИПЕЧЁНОЧНЫЙ ХОЛЕСТАЗ: ДИАГНОСТИКА, ЛЕЧЕНИЕ (КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ)

Jaundice is a manifestation of many diseases both benign and malignant. Genetic progress allowed to distinguish the group of unknown earlier rare cholestatic jaundices, which are resulted from gene mutations. There are no described algorithms of their diagnosis or treatment. In this article case report of the patient with benign recurrent intrahepatic cholestasis type 1 is presented. There is also literature analysis of this theme.

Triggers of benign recurrent intrahepatic cholestasis and its pathophysiology: a review of literature.

Benign recurrent intrahepatic cholestasis (BRIC) is a rare genetic disorder that is characterized by episodes of cholestasis followed by complete resolution. The episodic nature of BRIC raises concerns about its possible trigger factors. Indeed, case reports of this orphan disease have associated BRIC to some triggers. In the absence of any reviews, we reviewed BRIC trigger factors and its pathophysiology. The study consisted of a systematic search for case reports using PubMed. Articles describing a clear case of BRIC associated with a trigger were included resulting in 22 articles that describe 35 patients. Infection was responsible for 54.3% of triggered episodes, followed by hormonal, drugs, and miscellaneous causes reporting as 30%, 10%, and 5.7% respectively. Females predominated with 62.9%. The longest episode ranged between 3 months to 2 years with a mean of 32.37 weeks. The mean age of the first episode was 14.28 ranging between 3 months to 48 years. Winter and autumn were the major seasons during which episodes happened. Hence, BRIC is potentially triggered by infection, which is most commonly a viral infection, hormonal disturbances as seen in oral contraceptive pills and pregnancy state, and less commonly by certain drugs and other causes. The appearance of cholestasis during the first two trimesters of pregnancy compared to intrahepatic cholestasis of pregnancy could help to differentiate between the two conditions. The possible mechanism of BRIC induction implicates a role of BSEP and ATP8B1. While estrogen, drugs, and cytokines are known to affect BSEP, less is known about their action on ATP8B1.

Case Report: A Novel Single Variant TJP2 Mutation in a Case of Benign Recurrent Intrahepatic Cholestasis

Benign recurrent intrahepatic cholestasis (BRIC) is a disease on the spectrum of familial intrahepatic cholestasis caused by homozygous ABCB11 or ATP8B1 mutations. In recent years, genetic testing has allowed for discovery of a variety of homozygous or compound heterozygous TJP2 mutations associated with progressive familial intrahepatic cholestasis and intrahepatic cholestasis of pregnancy. To our knowledge, no cases of BRIC caused by a single variant mutation of TJP2 have been reported. We describe a 15-year-old female presenting with recurrent episodes of jaundice, vomiting, with intense pruritus, anorexia, and weight loss. Blood work revealed elevated serum conjugated bilirubin and liver enzymes but normal gamma-glutamyl transferase, consistent with BRIC. A genetic panel identified a not previously described single allele mutation in TJP2 of unknown functional significance. This is the first reported case of a clinical entity resembling BRIC with a heterozygous mutation in TJP2, without associated mutations in other cholestasis-related genes.