Carriers of ABCB4 gene variants show a mild clinical course, but impaired quality of life and limited risk for cholangiocarcinoma

Background and aims: ABCB4 deficiency may lead to progressive familial intrahepatic cholestasis type 3 (PFIC3), biliary cirrhosis, low-phospholipid-associated cholelithiasis (LPAC), intrahepatic cholestasis of pregnancy (ICP), oral contraceptive-induced cholestasis (CIC) or may remain asymptomatic. The long-term course, quality of life and histology were investigated in ABCB4 deficiency.

Methods: Adult carriers of ABCB4 gene variants from two regional academic centers were analyzed by history taking, electronic patient files, physical examination, blood analysis, abdominal ultrasound (US) and liver elastography. Patients completed a 36-Item-Short-Form-Health-Survey (SF-36) for quality of life and a Visual Analogue Scale (VAS) for pruritus. Available liver specimens were re-classified according to the Nakanuma scoring system, so far validated for primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) only. Quality-of-life-data were compared to published data of patients with PBC, PSC and the general population.

Results: Sixty-seven patients were identified, 64 (96%) were alive at time of analysis, 62 (93%) were (at some time) treated with ursodeoxycholic acid. Two patients died of cholangio-carcinoma, one of decompensated biliary cirrhosis. Three additional deaths of cholangiocarcinoma were reported in first degree relatives. Transplant-free survival was 91% (median follow-up 14 years). Liver stiffness was normal (<6.3 kPa) in 75%, intrahepatic stones were detected at US in 33% and micro-calcifications in 22% of cases. Quality of life (n=48) was lower than in the general population particularly in energy/fatigue and general health domains and comparable to that in PSC. Staging according to Nakanuma in 15 specimens reflected the clinical course.

Conclusions: ABCB4 deficiency has a mild clinical course, but impaired quality of life and limited risk of cholangiocarcinoma. The Nakanuma scoring system appears feasible for histological evaluation in ABCB4 deficiency.

Keywords: ABCB4 deficiency; intrahepatic cholestasis of pregnancy (ICP); low phospholipid-associated cholelithiasis (LPAC); persistent hepatocellular secretory failure (PHSF); quality of life.