Magnetic Resonance Liver Iron Concentration Can Guide Venesection Decision-Making in Hyperferritinemia.

BACKGROUND: The clinical benefit of venesection in suspected iron overload can be unclear and serum ferritin may overestimate the degree of iron overload. AIMS: To help inform practice, we examined magnetic resonance liver iron concentration (MRLIC) in a cohort investigated for haemochromatosis. METHODS: One hundred and six subjects with suspected haemochromatosis underwent HFE genotyping and MRLIC with time-matched serum ferritin and transferrin saturation values. For those treated with venesection, volume of blood removed was calculated as a measure of iron overload. RESULTS: Forty-seven C282Y homozygotes had median ferritin 937 µg/l and MRLIC 4.83 mg/g; MRLIC was significantly higher vs non-homozygotes for any given ferritin concentration. No significant difference in MRLIC was observed between homozygotes with and without additional risk factors for hyperferritinemia. Thirty-three compound heterozygotes (C282Y/H63D) had median ferritin 767 µg/l and MRLIC 2.58 mg/g; ferritin < 750 µg/l showed 100% specificity for lack of significant iron overload (< 3.2 mg/g). 79% of C282Y/H63D had additional risk factors-mean MRLIC was significantly lower in this sub-group (2.4 mg/g vs 3.23 mg/g). 26 C282Y heterozygous or wild-type had median ferritin 1226 µg/l and MRLIC 2.13 mg/g; 69% with additional risk factors had significantly higher ferritin concentrations (with comparable MRLIC) and ferritin < 1000 µg/l showed 100% specificity for lack of significant iron overload. In 31 patients (26 homozygotes, 5 C282Y/H63D) venesected to ferritin < 100 µg/l, MRLIC and total venesection volume correlated strongly (r = 0.749), unlike MRLIC and serum ferritin. CONCLUSION: MRLIC is an accurate marker of iron overload in haemochromatosis. We propose serum ferritin thresholds in non-homozygotes which, if validated, could tailor cost-effective use of MRLIC in venesection decision-making.

ABCB4 Mutations in Adults Cause a Spectrum Cholestatic Disorder Histologically Distinct from Other Biliary Disease.

BACKGROUND: 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. AIMS: We sought to characterize adult disease with particular reference to histology which has been hitherto poorly defined. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

'Double-hit' pegylated interferon-alpha successfully treats Hepatitis B and Hepatitis D co-infection.

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.

Early clinical experience of the safety and efficacy of EndoClot in the management of non-variceal upper gastrointestinal bleeding.

BACKGROUND AND STUDY AIMS: EndoClot is a novel topical hemostatic powder approved for use in non-variceal upper gastrointestinal bleeding. This study examines its impact as rescue therapy in the management of gastrointestinal bleeding for which standard endoscopic therapy failed to achieve hemostasis. METHODS: This observational study covered a 24-month period. Data were collated from patients treated with EndoClot for comparison with a cohort of patients managed with standard endoscopic therapy. End points of this study included immediate hemostasis, 30-day rebleed rate, 30-day mortality rate, and adverse events. RESULTS: Between April 1, 2012, and March 31, 2014, gastroscopic procedures were performed in 1009 patients, of whom 173 required endoscopic therapy. EndoClot was used in 21 patients, with immediate hemostasis achieved in all cases, a 30-day rebleed rate of 4.8 % (95 % confidence interval [95 %CI] - 4.34 % to 3.94 %), and a 30-day mortality rate of 19.0 % (95 %CI 2.29 % - 35.91 %). Despite higher risk bleeds in this cohort of patients, Fisher's exact test demonstrated no significant difference between their 30-day mortality rate (P = 0.51) and rebleed rate (P = 0.31) and those of the patients treated with standard endoscopic hemostatic techniques. CONCLUSIONS: This study demonstrates that EndoClot can be used both safely and effectively in the management of non-variceal upper gastrointestinal bleeding.