D. Patch

Long-term follow-up of hepatitis C infection in a large cohort of patients with inherited bleeding disorders

BACKGROUND & AIMS Patients with inherited bleeding disorders are an interesting group to study the long-term course of chronic hepatitis C virus (HCV) infection, because of their uniform mode of infection and reliable follow-up. Our aim was to assess the long-term occurrence of adverse liver-related events in these patients. METHODS The occurrence and determinants of end-stage liver disease (ESLD) were assessed using retrospective data of 863 HCV infected patients with inherited bleeding disorders from the Netherlands and the UK. RESULTS Median follow-up since HCV infection was 31 years, while 30% of patients had >35 follow-up years. Nineteen percent of patients spontaneously cleared the virus and 81% developed chronic HCV infection. Of the 700 patients with chronic HCV, 90 (13%) developed ESLD. Hepatocellular carcinoma (HCC) was diagnosed in 3% of patients with chronic HCV, 41% of which occurred in the last six years. Determinants of ESLD development were age at infection (hazard ratio (HR) 1.09 per year increase), HIV co-infection (HR 10.85), history of alcohol abuse (HR 4.34) and successful antiviral treatment (HR 0.14). Of the 487 patients who were still alive at the end of follow-up, 49% did not undergo optimal conventional antiviral treatment. CONCLUSIONS After over 30 years of HCV infection, ESLD occurred in a significant proportion of patients with inherited bleeding disorders. HCC appears to be an increasing problem. There is a significant potential for both conventional and new antiviral treatment regimens to try and limit ESLD occurrence in the future.

Calreticulin mutations and their importance in splanchnic vein thrombosis

We have read the recent publications on Calreticulin (CALR) gene mutated splanchnic vein thrombosis (SVT) with great interest (Castro et al, 2015; Haslam & Langabeer, 2015; Roques et al, 2015). Between 25% and 40% of patients with SVT have overt or occult myeloproliferative neoplasms (MPNs), which are usually associated with JAK2 mutations (Smalberg et al, 2012; Sekhar et al, 2013). CALR mutated MPNs are typically associated with a lower incidence of thrombosis than their JAK2 mutated counterparts (Andrikovics et al, 2014). We have summarized the data from five recent reports that have been published regarding this group of patients (Table I). We wish to highlight data on our patients with CALR related SVT. Between 2006 and 2014, 24 of 83 patients (29%) with SVT in whom local pathology had been ruled outwere found to have a JAK2 V617F mutation and two patients (2 4%) were found to have CALR mutations (Table II). Both of these patients had significant disease burden related to SVT, ascites and portal hypertension (PHT). Given previous reports of therapy with alpha interferon in CALR mutated essential thrombocythaemia (Cassinat et al, 2014) and with a view to improving the underlying myeloproliferative state, splenomegaly and PHT, both patients were treated with Ruxolitinib. Ruxolitinib treatment at doses of 20–40 mg/d resulted in improvement in some but not all disease characteristics (Table II). We agree with the conclusion reached by some of authors (Plompen et al, 2015; Roques et al, 2015; Turon et al, 2015) that the diagnostic algorithm for SVT should include CALR mutation analysis when looking for an underlying myeloproliferative disorder, as this can be done when screening for the presence of JAK2 mutation. CALR mutations have been reported in 0–2% of MPN-SVT patients; our cohort of 83 patients confirm this, as 2 4% of our patients had CALR mutations. However, the burden of disease is significant in all of the affected individuals listed in Table I, with four patients requiring TIPPS procedures and two patients dying of gastrointestinal haemorrhage. In conclusion, we have presented here the CALR mutation data from our cohort of 83 SVT patients; in particular the long-term clinical follow-up of two patients with MPN-SVT in whom the data demonstrate the severity of thrombosis in the context of CALR mutated MPN. In addition, we present the long-term follow-up of treatment (12 and 9 months) with Ruxolitinib in these patients. These patients demonstrate that (i) CALR mutated MPN can be associated with

Characteristics of Epstein-Barr viraemia in adult liver transplant patients: a retrospective cohort study.

Therapeutic immunosuppression following solid organ transplantation increases the risk of Epstein–Barr (EBV) viraemia, which is implicated in post‐transplant lymphoproliferative disease (PTLD). We retrospectively analysed the incidence of EBV viraemia and clinical outcomes in 98 liver transplant recipients. Patients underwent EBV DNA monitoring by whole‐blood PCR: EBV levels were correlated with clinical parameters and outcomes for a median of 249 days. 67% patients developed EBV viraemia (EBV DNA ≥100 copies/ml) and 30% had sustained viraemia. There was a trend towards higher hazard ratios for viraemia with exposure to aciclovir (HR 1.57, P = 0.12) or in recipients of a poorly HLA‐matched graft (HR 1.62, P = 0.10). These associations became significant in the subgroup with >90 days surveillance; HR 2.54 (P = 0.0015) for aciclovir and HR 1.99 (P = 0.03) for poorly matched grafts. The converse was true with ganciclovir (HR 0.56 P = 0.13). Viraemia was more prolonged in men (median duration 7 days vs 1; P = 0.01) and in those with lower UKELD scores (11 days vs 1 day; P = 0.001) but shortened with ganciclovir exposure (P = 0.06). Younger patients were more likely to have high peak viral loads (P = 0.07). No clinical signs or symptoms or adverse outcomes were associated with EBV reactivation.

P1302 THE OPTIMAL IMMUNOSUPPRESSION REGIMEN FOR DELAYING FIBROSIS PROGRESSION IN HCV AFTER LIVER TRANSPLANTATION

of 73% (56/77). No deaths occurred; no clinically meaningful differences were observed in frequencies of serious adverse events (AEs), AEs leading to discontinuation, or grade 3/4 AST/ALT elevations in patients with or without cirrhosis. Conclusions: All-oral DCV+ASV treatment exhibited similarly high SVR rates and no clinically relevant differences in safety/tolerability in cirrhotic and non-cirrhotic patients with HCV genotype 1b infection.

197 TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNTS FOLLOWING LIVER TRANSPLANTATION CAN BE ASSOCIATED WITH A GOOD PROGNOSIS: A SINGLE CENTRE EXPERIENCE

Introduction Transjugular intrahepatic portosystemic shunt (TIPS) is indicated in the management of portal vein thrombosis or stenosis, portal hypertension and for veno-occlusive disease in post-liver transplant (LT) patients. Previous series have reported 1-year mortality rates of 14%–67%. A MELD score >15 at the time of insertion may indicate a poor long term prognosis. We aimed to evaluate the safety of TIPS after LT at a UK tertiary referral centre. Methods We retrospectively analysed data from the Royal Free Hospital TIPS database between 1st January 1991 and the 31st January 2011. All patients who had undergone TIPS following LT were included. Results During the period studied 629 patients received a TIPS. In the same period 1192 liver transplant operations were performed. 10 TIPS were inserted into patients following LT for recurrent cirrhosis with refractory ascites (4), veno-occlusive disease (3) and portal vein thrombosis (3). The original indications for transplantation were PSC (3), PBC (3), Hepatitis C (1), Autoimmune (1), Primary Oxalosis (1) and Acute Liver Failure (1). We noted a median survival of 38 months. Survival at 1 and 5 years was 100% and 60% respectively. The median MELD at the time of TIPS insertion was 12 (range 7–19). No correlation between the MELD score at the time of TIPS insertion and survival was demonstrated (p=0.62). Conclusion These results suggest that TIPS can be performed safely after LT and that survival rates better than those previously reported can be achieved. We suggest TIPS should be used in carefully selected candidates following LT as a definitive treatment for patients not suitable for re-transplant or as a bridge to re-transplantation. The alternative of re-transplantation should always be considered prior to TIPS insertion where indicated. Competing interests None declared. References 1. Saad WEA , et al. Transjugular intrahepatic portosystemic shunts in liver transplant recipients for management of refractory ascites: clinical outcome. J Vasc Interv Radiol 2010; 21 :218–23. 2. Kim JJ , et al. Transjugular intrahepatic portosystemic shunts in liver transplant recipients. Liver Int 2008; 28 :240–8. 3. Feyssa E , et al. MELD score less than 15 predicts prolonged survival after transjugular intrahepatic portosystemic shunt for refractory ascites after liver transplantation. Transplantation 2011; 91 :786–92.