benign recurrent intrahepatic cholestasis ( bric ) is an autosomal - recessive cholestatic disorder   which was first described by summerskill and walshe in 1959 in two patients with recurring cholestasis [ 2 , 3 ] .
ten years later , tygstrup and jensen   formulated the defining criteria as : ( 1 ) several episodes of pronounced jaundice with severe pruritus separated by symptom - free intervals lasting several months or years , ( 2 ) absence of a factor known to produce intrahepatic cholestasis ( e.g. drug intake , pregnancy , intoxication ) , ( 3 ) biomechanical signs of obstructive jaundice but with normal intrahepatic and extrahepatic bile ducts ( visualized by cholangiography ) , and finally ( 4 ) bile plugs within ducts in histological specimens [ 1 , 2 , 4 , 5 ] .
previously , summerskill - walshe - tygstrup syndrome has been regarded as an idiopathic disease [ 1 , 2 ] .
meanwhile it is known that bric displays a genetic heterogeneity and is associated with mutations in the atp8b1 ( bric 1 ) and abcb11 ( bric 2 ) genes and belongs to the  canalicular transport defects .
as it typically does not lead to liver cirrhosis , it is considered as a benign liver disease .
for the right diagnosis , both clinical and pathological features are pivotal [ 5 , 6 ] .
therapeutically , in moderate cases , conservative treatment with cholestyramine , rifampicin [ 6 , 7 , 8 ] , steroids , phenobarbital , ursodeoxycholic acid or 5-adenosylmethionine   may be applied . in more severe cases , a nasobiliary drainage tube can be inserted , or surgical interventions such as partial biliary diversion or ileal bypass may be performed to relieve the patient 's suffering . despite these various possibilities , in some patients symptoms  mostly pruritus  may still be resistant [ 5 , 9 ] . for such severe cases ,
new therapeutic approaches are required to avoid liver transplantation as the ultimate required therapy . in 1988 , several attempts succeeded in lowering bile acids by plasmapheresis [ 10 , 11 ] .
additionally , since 2001 , albumin dialysis ( molecular adsorbent recirculation system , mars ) has been successfully applied to improve these patients medical condition and to significantly reduce serum bilirubin and bile acid levels [ 8 , 12 , 13 ] . in the case of our patient , the extracorporeal liver assist device prometheus ( fresenius medical care , bad homburg , germany ) , which is frequently used in patients with severe
cholestasis or liver failure as a bridging procedure to transplantation [ 14 , 15 ] , has been applied to resolve therapy - resistant pruritus .
we report a 45-year - old caucasian woman with summerskill - walshe - tygstrup syndrome which was first diagnosed in 1998 . despite extensive conservative therapy with prednisolone ( 510 mg / day ) , ursodeoxycholic acid ( 3  500 mg / day ) and cholestyramine ( 3  4 g / day )
, she suffered from intermittent attacks of cholestatic jaundice , severe pruritus and anxious nervousness . on clinical examination
usually , serum bile acids were elevated at 22.5  2.7 mol / l ( normal
< 6 mol / l ) , while transaminases as well as -glutamyltransferase ( -gt ) and alkaline phosphatase ( ap ) remained at approximately normal values ( < 35
e , cmv , ebv and hsv ) and immunological serology ( ana , ama , anca , sma , sla , lkm , -globulin and igg / igm ) were all negative .
however , both the patient 's grandmother and mother suffered from cholecystolithiasis . in march 2008
ultrasound examination revealed normal liver morphology without signs of obstructive cholestasis ( diameter of the common bile duct 3 mm ) .
additionally , a liver biopsy was performed which demonstrated normal hepatocyte architecture without inflammatory cells or bile plugs within the canaliculi ( fig .
the first 3 dialysis cycles were performed in april 2008 , followed by another 5 cycles in june 2008 , leading to complete recovery and decreasing laboratory parameters . in the following years
, bile acids were lowered significantly by 78% from an average of 22.5  2.7 to 7.3  1.7 mol / l ( p = 0.003 ) . due to cicatrization of the dialysis catheter , a cimino - brescia fistula was finally applied in january 2011 .
we here report a patient with characteristic features of bric , occurring frequently with insistent symptoms . she suffered from intermitting severe pruritus as well as infrequent jaundice .
this disease is remarkable for its discrepancy between a rise in serum bile acids at the onset of each attack and a later rise in total serum bilirubin levels . due to conservative treatment with prednisolone ( 510 mg / day ) , ursodeoxycholic acid ( 3  500 mg / day ) and cholestyramine ( 3  4 g / day ) ,
in contrast , conservative treatment did not have any positive effects on agonizing pruritus . during this stage
, laboratory parameters revealed the typical periodic elevation of total serum bilirubin and bile acids .
however , transaminases , ap and -gt were less affected ( < 35 u / l ) . whenever intractable pruritus appeared , liver dialysis using the prometheus system was performed .
the first cycle was set after worsening of the patient 's condition when a 7 fr nasobiliary drainage tube dislocated in march 2008 . in the following years
, 3 up to 5 cycles of liver dialysis per session were necessary to normalize laboratory parameters and relieve the patient 's suffering .
this range for dialysis sessions is in accordance with other studies describing the application of prometheus in patients with insistent pruritus [ 16 , 17 , 18 ] .
the pathogenesis of cholestatic pruritus is not completely clear . besides bile acids , which apparently seem to play a major role as pruritogens , elevated levels of endogenous opioids and amphiphilic lysophosphatidic acid ( lpa )
in contrast to bile acids , lpa and autotaxin ( the enzyme responsible for the transformation of lysophosphatidylcholine into lpa ) plasma levels were demonstrated to correlate significantly with the severity of patients pruritus .
conservative treatment is based upon this knowledge as e.g. the bile acid sequestrate cholestyramine is recommended as the first - line treatment by easl and aasld .
involvement of the opioid system furthermore allows the application of opioid antagonists   such as naltrexone to resolve pruritus . reported positive effects of the serotonin re - uptake inhibitor sertraline
actually indicate an involvement of the serotonin system . despite these numerous mechanisms by which the pathogenesis of pruritus can already be affected therapeutically to relieve the majority of patients from pruritus , some of them remain resistant to these therapies . as severe pruritus
may lead to reduced quality of life and even to suicide [ 16 , 17 ] , the necessity for an effective therapy becomes obvious .
in these patients , e.g. with primary biliary cirrhosis , liver transplantation may become the ultimate therapeutic option . until now
, several studies have provided evidence for extracorporeal liver support systems , first for mars and later for prometheus , to be an effective and safe therapeutic alternative for patients with cholestatic pruritus [ 8 , 12 , 13 , 16 , 17 ] . with regard to the elimination of albumin - bound molecules such as bilirubin ( strongly albumin - bound ) or bile acids ( less tightly albumin - bound ) , there are slight differences between these two methods .
krisper and stauber   characterized the dialysis performance of prometheus as less selective to albumin - bound molecules and more efficient at the same time as compared to mars . concerning bile acid removal , stadlbauer et al
.   found similar efficiency for both prometheus and mars , while a change in the particular bile acid profile towards hydrophobic bile acids was observed only under prometheus treatment .
besides changes in white blood cell count , no adverse effects have been reported so far [ 18 , 22 ] .
because of its rareness summerskill - walshe - tygstrup syndrome is first considered in the differential diagnosis of cholestasis after many years of extensive investigations .
however , in some cases , prometheus liver dialysis appears to be a beneficial alternative for patients with bric - related symptoms  mainly intractable pruritus 
 summerskill - walshe - tygstrup syndrome is a rare benign chronic liver disease characterized by recurring cholestasis with jaundice and severe pruritus . due to insufficient conservative treatment , liver dialysis by prometheus 
 was applied to a 45-year - old female patient with resistant pruritus . 
 initially , other possible liver diseases were excluded and the patient was treated symptomatically since the diagnosis of summerskill - walshe - tygstrup was stated in 1998 . as conservative and endoscopic methods progressively failed to relieve the patient 's suffering , prometheus liver dialysis was performed regularly since 2006 at 3-month intervals and successfully led to a decrease in the patient 's symptoms . 
 cholestatic liver enzymes and also serum bile acids could be lowered significantly from an average of 22.5  2.7 to 7.3  1.7 mol / l . 
 consequently , prometheus liver dialysis may be a beneficial option for patients with benign recurrent intrahepatic cholestasis suffering from therapy - resistant symptoms and may be used as well as other extracorporeal liver support devices which have already been reported to improve cholestatic pruritus . 