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Mutations in the ABCB4 gene are associated with failure of bile acid emulsification leading to cholestatic liver disease. Presentations range from progressive familial intrahepatic cholestasis type 3 (PFIC3) in childhood, to milder forms seen in adulthood.We sought to characterize adult disease with particular reference to histology which has been hitherto poorly defined.Four unrelated adults (three female, mean age 39 years) and three sisters presenting with cholestatic liver disease in adulthood, associated with variants in the ABCB4 gene, were identified. Clinical review and detailed blinded histopathological analysis were performed.Two novel pathogenic ABCB4 variants were identified: c.620 T G, p.(Ile207Arg) and c.2301dupT, p.(Thr768TyrfsTer26). Sub-phenotypes observed included low-phospholipid-associated cholelithiasis syndrome (LPAC), intrahepatic cholestasis of pregnancy (ICP), drug-induced cholestasis, idiopathic adulthood ductopenia, and adult PFIC3. Of note, 5/7 had presented with gallstone complications (4 meeting LPAC definition) and 4/6 females had a history of ICP. Considerable overlap was observed phenotypically and liver transplantation was required in 3/7 of patients. Histologically, cases generally demonstrated ductopenia of the smaller tracts, mild non-ductocentric portal inflammation, bilirubinostasis, significant copper-associated protein deposition, and varying degrees of fibrosis.Adults with ABCB4 mutations may harbor a spectrum of cholestatic disease phenotypes and can progress to liver transplantation. We observed a distinct histological pattern which differs from classical biliary disease and describe two novel pathogenic ABCB4 variants. ABCB4 sequencing should be considered in patients with relevant cholestatic phenotypes and/or suggestive histology; accurate diagnosis can guide potential interventions to delay progression and inform family screening.

Hepatitis delta (HDV) infection is either acquired simultaneously with, or as a superinfection to, existing Hepatitis B (HBV). It leads to a serious form of chronic viral hepatitis and accelerated liver-related morbidity and mortality including hepatocellular carcinoma. Current treatment regimes propose Pegylated interferon-alpha for 48 weeks however sustained virological response (SVR) rates remain low. We report a patient who initially responded to Pegylated interferon treatment for HBV-HDV co-infection. Although initial improvement in viraemia from both virsues was seen, SVR was not achieved with ongoing progression of liver injury biochemically. However, the summative effect of a second course of Pegylated interferon 2 years later led to HDV cure (SVR 12 months post-treatment), very low level HBV carrier status (with persistently undetectable viral load) and ongoing biochemical normalization. This case illustrates a successful treatment strategy for persistent HBV-HDV co-infection where proposed treatment regimes elicit an initial response but SVR is not achieved.

Introduction Anastomotic biliary strictures (ABS) have been reported in approximately 13% of patients undergoing orthotopic liver transplantation (OLT). Without treatment these can lead to progressive graft failure. Endoscopic management of these strictures with temporary fully covered self-expanding metal stents (SEMS) offers a non-surgical option for their management. This retrospective case series describes the outcomes of ABS managed using SEMS at our centre. Unit standard practice is to reserve endoscopic management for early ABS and undertake a biliary sphincterotomy to reduce pancreatitis risk. Methods The electronic records of all patients who underwent both OLT and endoscopic retrograde cholangiopancreatography (ERCP) between January 2013 and March 2020 were reviewed. Patients were selected from this group if they were found to have an ABS as diagnosed by biochemical liver function test derangement and corresponding characteristic radiological findings. Demographic data, technical aspects of the procedure, success rate, and complications were recorded. Results A total of 36 transplant recipients were diagnosed with ABS. This group underwent a total of 45 ERCP procedures. The median time from transplant to ABS diagnosis was 6 months (interquartile range (IQR) 2 – 22 months). There was a balloon dilatation prior to stent placement in 13 procedures (29%). There was a sphincterotomy either at the time of stent placement or during a preceding procedure in 33 cases (92%). There were ten cases of pancreatitis (22%), four cases of cholangitis (9%) and two of bile leak (4%). There were eight cases of pancreatitis in the group of 33 who had undergone sphincterotomy (24%) and two cases of pancreatitis in the group of three who had not (67%). There was one case of bleeding following sphincterotomy (3%) that occurred immediately and did not require transfusion. The median time to stent removal was 105 days (IQR 67 – 125). Only one case (3%) required surgical biliary reconstruction. The avoidance of the need for biliary reconstruction was regarded as the key outcome for successful endoscopic management of ABS and this was achieved in 35 cases (97%). Conclusion Early ABS following OLT were effectively managed using endoscopically placed biliary stents in the majority of cases. The rate of pancreatitis was lower in the sphincterotomy group. These data support the practice of temporary SEMS placement for early ABS and sphincterotomy to reduce pancreatitis risk.

Background Obtaining a CCT (Certificate of Completion of Training) in Hepatology requires 24 months of dedicated Hepatology training. The non-academic pathway includes an advanced training program (ATP) year which is nationally competitive (17 posts) and often geographically challenging. Shape of Training will enforce a reduction in Gastroenterology training to 4 years requiring trainees to make earlier and more restrictive career decisions (e.g. dropping colonoscopy), and demands training program designers to provide sufficient timely training opportunities while meeting workforce requirements. Of note, the number of Hepatologists nationally is insufficient. With respect to Hepatology training, we sought to gauge the opinions of ST3/4 Gastroenterology trainees to help inform program design. Methodology Quantitative and qualitative data was collected using anonymised questionnaires which were completed by trainees attending the BSG-led ‘Introduction to Gastroenterology Day 2019’ with subsequent framework analysis of qualitative data. Results 44 trainees completed the questionnaire and 32 (73%) are considering a career in Hepatology (5 ‘definitely’, 17 ‘probably’, 10 ‘maybe’). Reasons include: positive clinical experiences, Hepatology patients and disease pathogenesis, and personal circumstances (mainly geographical). 5/32 (16%) aim to work in a Level 3 centre, 15/32 (47%) in a level 2 centre, 3/32 (9%) in a district general hospital (DGH) with the remainder undecided. Of note (considering the whole dataset), 5/44 (11%) are unsure if there is a transplant centre in their deanery. 10/32 (31%) would be able to move and 7/32 (22%) would want to move for an ATP. 16/32 (50%) trainees considering Hepatology favour current national allocation, regarding it as a fair process. The remaining 16/32 (50%) favour local allocation largely due to availability of level 2/3 centres in their deanery. Of the 22 trainees who are ‘probably’ or ‘definitely’ considering Hepatology, 12/22 (55%) are willing to drop colonoscopy training (including 4/5 (80%) who are ‘definitely’ considering Hepatology). Discussion Our results suggest that a significant proportion of early trainees are interested in a career in Hepatology providing reassurance regarding any potential increase in ATPs. Furthermore, outcomes regarding dropping colonoscopy (as necessitated by a shorter training program) are reassuring. Trainees are less interested in DGH Hepatology which is concerning as this is where the need is (Lancet Commission 2019). National ATP allocation is generally supported but would benefit from greater post coverage geographically. Providing trainees with salient information early- ideally prior to commencing specialty training- will facilitate decision making (including choosing or moving deaneries) to permit successful career planning.

Background Venesection is the standard treatment for hereditary haemochromatosis (HH) preventing morbidity and mortality, but therapeutic venesection may not be clinically beneficial in all patients. Furthermore, serum ferritin may not accurately reflect the true extent of iron overload. To inform practice we correlated magnetic resonance (MR) iron quantification data in a cohort investigated for HH. Methods A cross-sectional study of 93 hyperferritinaemic subjects without known liver or haematological disease was undertaken. All subjects underwent HFE genotyping and MR imaging with hepatic iron quantification. Serum ferritin and transferrin saturation values were time-matched with MR liver iron concentration (LIC). For those patients undergoing venesection, volume of blood removed was calculated as a measure of iron overload. Results The cohort comprised 45 C282Y homozygotes, 23 compound heterozygotes (C282Y/H63D) and 25 who were either C282Y heterozygotes or wild-type for HFE. Of 45 C282Y homozygotes (20 females, 25 males, mean age 60), serum ferritin ranged 184–4523 mcg/l (mean 1027 mcg/l), transferrin saturation 43–100% (mean 81%), and LIC 1.27–9.97 mg/g (mean 5.06 mg/g). Removing the two homozygotes with ferritin >3000 mcg/l, there was a moderately positive correlation between ferritin and LIC in homozygotes (r=0.48). Of 23 compound heterozygotes (5 females, 18 males, mean age 55), serum ferritin ranged 418–3016 mcg/l (mean 1033 mcg/l), transferrin saturation 29%-100% (mean 51%) and LIC 1.36–4.58 mg/g (mean 2.43 mg/g). Serum ferritin of >1000 mcg/l had 92% sensitivity and 50% specificity for the detection of significant iron overload (LIC >2.5 mg/g). In the remaining group (3 females, 22 males, average age 65), serum ferritin ranged 351–1957 mcg/l (mean 1113 mcg/l), transferrin saturation 21%-96% (mean 46%) and LIC 1.41–4.23 mg/g (mean 2.11 mg/g). Those with liver risk factors (including alcohol and high BMI) had higher serum ferritin (1254 vs 901 mcg/l, p LIC was significantly higher in homozygotes compared with other groups for any given ferritin concentration. Of the 93 patients, 20 homozygotes and 4 compound heterozygotes were venesected to serum ferritin Conclusion MR LIC correlates well with iron overload in HH as calculated by volume of blood removed; LIC is therefore likely to be discriminatory in non-homozygotes where additional risk factors contribute to hyperferritinaemia. Compound heterozygotes are more likely to benefit from venesection when serum ferritin is >1000 mcg/l.

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