Improving cytopenia with splenic artery embolization in a patient with paroxysmal nocturnal hemoglobinuria on eculizumab.

Paroxysmal nocturnal hemoglobinuria is a rare acquired stem cell disorder characterized by intravascular hemolysis, aplasia and an increased risk of thrombosis. We describe a patient under treatment with the anti-complement antibody eculizumab who developed pancytopenia, requiring blood transfusions, due to massive splenomegaly. The patient underwent two separate splenic embolizations, which reduced the size of the spleen and improved his blood count to the point that blood transfusions were no longer necessary. Splenic embolization was chosen over splenectomy due to the potential postoperative complications of splenectomy, especially that of thrombosis.

Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis.

We genotyped 2,861 cases of primary biliary cirrhosis (PBC) from the UK PBC Consortium and 8,514 UK population controls across 196,524 variants within 186 known autoimmune risk loci. We identified 3 loci newly associated with PBC (at P<5×10(-8)), increasing the number of known susceptibility loci to 25. The most associated variant at 19p12 is a low-frequency nonsynonymous SNP in TYK2, further implicating JAK-STAT and cytokine signaling in disease pathogenesis. An additional five loci contained nonsynonymous variants in high linkage disequilibrium (LD; r2>0.8) with the most associated variant at the locus. We found multiple independent common, low-frequency and rare variant association signals at five loci. Of the 26 independent non-human leukocyte antigen (HLA) signals tagged on the Immunochip, 15 have SNPs in B-lymphoblastoid open chromatin regions in high LD (r2>0.8) with the most associated variant. This study shows how data from dense fine-mapping arrays coupled with functional genomic data can be used to identify candidate causal variants for functional follow-up.

Budd-Chiari syndrome--a review of the diagnosis and management.

Budd-Chiari syndrome (BCS) is the liver disease resulting from hepatic venous outflow obstruction comprising a triad of abdominal discomfort, hepatomegaly and ascites. Advances in the management of this disorder over the last three decades have dramatically improved survival. We present a review of the management of BCS followed by a case which illustrates some key points in the diagnosis and treatment of this condition.

Epstein-Barr virus infection and central nervous system involvement after orthoptic liver transplant.

Epstein-Barr virus (EBV) infection presenting as encephalitis in seronegative adults in the context of solid organ transplantation is rarely reported. EBV seroconversion illnesses in the adult population after organ transplantation are quite uncommon. This report describes a case of encephalitis due to EBV infection after liver transplantation in an adult patient. The patient was seronegative for EBV pretransplant. She showed persistent viral replication indicated by high levels of EBV DNA in the serum, which raised concerns for future development of post-transplant lymphoproliferative disorder. The report discusses the management of such patients, awareness of EBV infection and earlier diagnosis by use of EBV PCR in adult immunocompromised individuals where infection may cause particular problems.

Liver transplantation following donation after cardiac death: an analysis using matched pairs.

Grafts from donation after cardiac death (DCD) donors are used to increase the number of organs available for liver transplantation. There is concern that warm ischemia may impair graft function. We compared our DCD recipients with a case-matched group of donation after brain death (DBD) recipients. Between January 2002 and April 2008, 39 DCD grafts were transplanted. These were matched with 39 DBD recipients on the basis of identified variables that had a significant impact on mortality. These were used to individually match DCD and DBD patients with similar predictive mortality. We compared patient/graft survival, primary non-function (PNF), and rates of complications. Of all liver transplants, 6.1% were DCD grafts. PNF occurred twice in the DCD group. The incidence of nonanastomotic biliary strictures (NABS; 20.5% versus 0%, P = 0.005) and hepatic artery stenosis (HAS; 12.8% versus 0%, P = 0.027) in the DCD group was higher. One-year (79.5% versus 97.4%, P = 0.029) and 3-year (63.6% versus 97.4%, P = 0.001) graft survival was lower in the DCD group. Three-year patient survival was also lower (68.2% versus 100%, P < 0.0001). Our study is the first to use case-matched patients and compare groups with similar predictive mortality. There was a higher incidence of NABS and HAS in the DCD group. NABS were likely a result of warm ischemia. HAS may have been due to ischemia or arterial injury during retrieval. The DCD group had significantly poorer outcomes, but DCD grafts remain a valuable resource. With careful donor/recipient selection, minimization of ischemia, and good postoperative care, acceptable results can be achieved.

The value of MELD and sodium in assessing potential liver transplant recipients in the United Kingdom.

As the result of the widening gap between supply and demand of organs for liver transplantation, efforts to improve allocation have become an increasingly important yet controversial subject. The MELD score has been adopted in the USA but its usefulness has rarely been examined in Europe. We carried out an intention to treat analysis of 422 patients placed on our transplant waiting list over a 5-year period. We examined multiple variables to investigate the value of MELD, sodium and other factors in predicting post-transplant outcomes. MELD at transplant was the most important indicator of post-transplant outcomes. In addition, delta-MELD and hyponatreamia were significant at predicting, which patients placed on the waiting list would not proceed to transplant. While a move to allocating solely by MELD is not justified in the UK allocation system, there is value in using MELD, delta-MELD and hyponatreamia in making decisions regarding the allocation of organs. This may subsequently help to improve overall outcomes.

Bile duct strictures after hepatobiliary surgery: assessment with MR cholangiography.

PURPOSE: To establish the accuracy of magnetic resonance (MR) cholangiography for diagnosis of postsurgical bile duct strictures. MATERIALS AND METHODS: Sixty-seven patients suspected of having bile duct strictures after liver transplantation (n = 54), cholecystectomy (n = 8), hepatic resection (n = 4), or pancreaticoduodenectomy (n = 1) underwent MR cholangiography. Thick-slab single-shot fast spin-echo (repetition time msec/echo time msec, 4,500/940) imaging was performed in the coronal through sagittal planes with rotation in 10 degrees increments, and contiguous thin-section images were obtained in the transverse and the optimal coronal oblique planes by using half-Fourier rapid acquisition with relaxation enhancement (1,900/96). Three blinded observers independently reviewed the MR images and recorded diagnostic features including presence of biliary stricture by using a five-point confidence scale. Receiver operating characteristic analysis was used to measure the accuracy of MR cholangiography. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Final diagnosis was established at surgery (n = 29) and direct cholangiography (23 of 29) or at direct cholangiography, liver biopsy, and/or serial liver function tests (n = 38). RESULTS: Thirty-three of 67 patients had strictures confirmed with the reference standard. MR cholangiography enabled correct diagnosis and depicted the site of strictures in all cases. Findings of stricture at MR cholangiography were false-positive in five patients with moderate duct dilatation and caliber change at the level of the anastomosis. Mean accuracy, sensitivity, specificity, PPV, and NPV were 94%, 97%, 74%, 86%, and 96%, respectively. CONCLUSION: MR cholangiography is as sensitive as direct cholangiography for the assessment of bile duct strictures after hepatobiliary surgery but may lead to overestimation of the importance of duct dilatation and caliber change.