The purpose of the study is to improve the prognosis of inhereditary cholestasis caused by ABCB11 gene mutations by using BSEP function rescue drugs
Bile acids function as detergents to aid digestion and as signaling molecules to regulate gene expression and metabolism. They are synthesized from cholesterol in the liver, secreted into bile and re -turned from chyme to liver in portal- vein blood 6-10 times per day (enterohepatic circulation. Enterohepatic circulation of bile acids involves more than 20 transporters among which bile salt export pump (BSEP), encoded by ABCB11 plays a key role. BSEP medi-ates the secretion of bile acids across the canalicular membrane of hepatocytes into bile to provide the osmotic pressure for bile flow. Mutations in ABCB11 can cause absence or dysfunction of BSEP leading to cholestasis. Bile acid accumulation in hepatocytes caused by BSEP dysfunction is associated with a range of liver dis-eases, ranging from transient neonatal cholestasis to fatal progressive familial intrahepatic cholestasis (PFIC), with jaundice, growth retardation, cirrhosis, liver failure and death. Our current indicates that more than 70% patents with ABCB11 mutations need liver-transplantation or dead during follow-up. In recent years, some targeted drugs including 4-phenylbutyrate(for patients with BSEP trafficking abnormal), ivacaftor(for patients with abnormal BSEP transport function), and gentamicin (for patients with none sense mutations) have emerged make it possible for individual targeted therapy possible.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
4-phenylbutyrate therapy will be started at a daily dose of 200 mg kg/d divided in 2 oral doses of sodium phenylbutyrate (AMMONAPS, Swedish Orphan Inter AB). In order to get the best effect, the dose will be increased up to a maximum of 500 mg kg/d.
Native liver survive time
Time of patient survived with native liver will be accessed.
Time frame: During follow-up (about 3 years）
ALT(Alanine Aminotransferase)
It is a repeated measurement variable. ALT would be measured.
Time frame: at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080
DB(direct bilirubin) levels
It is a repeated measurement variable. DB would be measured.
Time frame: at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080
TB(total bilirubin)
It is a repeated measurement variable. TB would be measured.
Time frame: at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080
AST(Aspartate Aminotransferase)
It is a repeated measurement variable. AST would be measured.
Time frame: at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080
Weight
It is a repeated measurement variable. The weight of the patients.
Time frame: at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080
Length
It is a repeated measurement variable. The length of the patients
Time frame: at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080
Itching relief
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It is a repeated measurement variable.The itching score level will be accessed using a score ranged from 0 to 10.
Time frame: at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080
Liver pathological staging
It is a repeated measurement variable.Liver pathological staging will be accessed using the Batts-Ludwig system.
Time frame: day 90, 180
Coagulation function
It is a repeated measurement variable.The INR(international normalized ratio)/PT(prothrombin time) levels will be followed if with coagulation function abnormal.
Time frame: at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080
Hypoglycemia
It is a repeated measurement variable.The glucose wil be followed.
Time frame: at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080
Hypo25-hydroxyvitamin Demia
It is a repeated measurement variable. Hypo25-hydroxyvitamin D levels will be followed.
Time frame: at day 0, 90, 120, 180, 240, 300, 360, 540, 720 and 1080
The bile acid profiling
It is a repeated measurement variable. The bile acid profiling will be checked during follow-up.
Time frame: at day 30, 60, 90, 180, 360, 720 and 1080
Hypoproteinemia
It is a repeated measurement variable. The albumin wil be followed.
Time frame: at day 0, 7, 14, 28, 56, 90, 120, 180, 240, 300, 360, 540, 720 and 1080
Adverse events
It is a binary variable(1/0). If any adverse events including bleeding, fractures, tumors, and hepatic encephalopathy happended during the follow-up, the variable would be setted into "1". The incidence of each adverse events will also be calculated.
Time frame: During follow-up (about 3 years）