Biliary transporter gene mutations in severe intrahepatic cholestasis of pregnancy: Diagnostic and management implications.

BACKGROUND AND AIMS: Clinical syndromes associated with biallelic mutations of bile acid (BA) transporters usually present in childhood. Subtle mutations may underlie intrahepatic cholestasis of pregnancy (ICP) and oral contraceptive steroid (OCS) induced cholestasis. In five women with identified genetic mutations of such transporters, with eight observed pregnancies complicated by ICP, we examined relationships between transporter mutations, clinical phenotypes, and treatment outcomes. METHODS: Gene mutation analysis for BA transporter deficiencies was performed using Next Generation/Sanger sequencing, with analysis for gene deletions/duplications. RESULTS: Intrahepatic cholestasis of pregnancy was early-onset (9-32 weeks gestation) and severe (peak BA 74-370 µmol/L), with premature delivery (28+1 -370 weeks gestation) in 7/8 pregnancies, in utero passage of meconium in 4/8, but overall good perinatal outcomes, with no stillbirths. There was generally no response to ursodeoxycholic acid and variable responses to rifampicin and chelation therapies; naso-biliary drainage appeared effective in 2/2 episodes persisting post-partum in each of the two sisters. Episodic jaundice occurring spontaneously or provoked by non-specific infections, and OCS-induced cholestasis, had previously occurred in 3/5 women. Two cases showed biallelic heterozygosity for several ABCB11 mutations, one was homozygous for an ABCB4 mutation and a fourth case was heterozygous for another ABCB4 mutation. CONCLUSIONS: Early-onset or recurrent ICP, especially with previous spontaneous or OCS-induced episodes of cholestasis and/or familial cholestasis, may be attributable to transporter mutations, including biallelic mutations of one or more transporters. Response to standard therapies for ICP is often incomplete; BA sequestering therapy or naso-biliary drainage may be effective. Optimized management can produce good outcomes despite premature birth and evidence of fetal compromise.

Non-Surgical Management of Bile Leakage After Hepatectomy: A Single-Center Study.

BACKGROUND: Bile leakage after hepatectomy is a common complication. The purpose of the present study was to retrospectively evaluate the usefulness of non-surgical management of bile leakage after hepatectomy, using 12-year data from a single center study. METHODS: Data from 15 patients (13 men, two women; mean age 67.1 ± 7.0 years) who had undergone non-surgical management for bile leakage between January 2005 and November 2017 were retrospectively reviewed. RESULTS: We categorized bile leakage as central (n = 5) or peripheral (n = 10) leakage based on communication with the biliary tree. Percutaneous bile leakage drainage and/or endoscopic naso-biliary drainage (ENBD) (n = 2) or the rendezvous technique (n = 3) was successfully performed in five central-type cases, while all peripheral-type cases were treated with drainage alone; only one case required additional ethanol ablation. Bacterial bile cultures were positive in 11 cases and negative in four cases. The drainage catheters were removed after complete resolution in 13 cases (86.7%), while two patients with cases of peripheral-type leakage died due to cancer progression while the drain was in place. No case needed conversion to reoperation. The mean duration of drainage therapy in all cases was 210.1 ± 163.0 days (range 17-531 days), with 316.8 ± 180.8 days in the central type and 156.7 ± 131.5 days in the peripheral type; this duration was not significantly different (P = 0.129). CONCLUSION: Non-surgical treatment is a minimally invasive and effective management strategy for postoperative bile leakage and the modality used depends on the type of bile leakage encountered.

Endoscopic Treatment for Severe Acute Biliary Pancreatitis / 中国微创外科杂志

Objective To evaluate the value of endoscopic treatment for severe acute biliary pancreatitis (SABP). Methods A total of 36 patients with SABP, who received emergency operation were enrolled into this study. Among the patients, 16 received endoscopic naso-biliary drainage (ENBD) because of acute cholecystitis or cholecystolithiasis; 11 underwent endoscopic sphincterotomy (EST) and ENBD due to stenotic papillitis or choledocholithiasis; 4 were treated with EST using needle knife and ENBD due to difficulties in inserting bow knife and cannula catheter into the common bile duct; and 2 experienced the guide wire entering into the wirsung’s duct for over 3 times, when the cannula catheter was inserted into the common bile duct. Thus, the sphincter of Oddi was incised by bow knife to expose the opening of the cystic duct, and then ENBD was performed. Open surgery was performed in 3 cases because of failure of ENBD. In all the patients, systemic medical treatment was carried out after the operations.Results ENBD was completed in 33 cases, among which 29 (81%) patients were cured and 4 (11%) patients died. The operation failed in 3 cases. After the operation, 3 patients developed peripancreatic infection. No hemorrhage of the duodenum papilla, duodenal perforation, or cholangitis occurred in this series. The mean hospital stay was 22 d (15-75 d). 26 of the cured patients were followed up for 12-36 months (mean, 18 months), no recurrence of the symptoms of pancreatitis was found. Conclusions Endoscopic treatment combined with systemic medical therapy may reduce the course of disease and increase the cure rate for patients with SABP.