M. Priest

The efficacy and safety of treating hepatitis C in patients with a diagnosis of schizophrenia

Treating chronic hepatitis C with pegylated interferon alpha may induce or exacerbate psychiatric illness including depression, mania and aggressive behaviour. There is limited data regarding treatment in the context of chronic schizophrenia. We sought to establish the safety and efficacy of treating patients with schizophrenia. Patient and treatment data, prospectively collected on the Scottish hepatitis C database, were analysed according to the presence or absence of a diagnosis of schizophrenia. Time from referral to treatment, and the proportion of patients commencing treatment in each group, was calculated. Outcomes including sustained viral response rates, reasons for treatment termination and adverse events were compared. Of 5497 patients, 64 (1.2%) had a diagnosis of schizophrenia. Patients with schizophrenia (PWS) were as likely to receive treatment as those without [28/61(46%) vs 1639/4415 (37%) P = 0.19]. Sustained viral response (SVR) rates were higher in PWS [21/25 (84%) vs 788/1453 (54%) P < 0.01]. SVR rates by genotype were similar [4/8 (50%) vs 239/684 (35%) Genotype 1 (P = 0.56), 17/17 (100%) vs 599/742 (81%) non‐Genotype 1 (P = 0.09)]. Adverse events leading to cessation of treatment were comparable [2/25(8%) vs 189/1453 (13%) P: 0.66]. Patients with schizophrenia are good candidates for hepatitis C treatment, with equivalent SVR and treatment discontinuation rates to patients without schizophrenia.

OC-115 The use of sofosbuvir based regimens amongst treatment naive and experienced patients with advanced fibrosis/cirrhosis: real world results from a difficult to treat cohort

Introduction Patients with cirrhosis account for 17–23% of subjects in Phase 3 trials of Sofosbuvir, however strict inclusion/exclusion criteria may make outcomes less reproducible in routine practice. Data is lacking for GT1 treatment experienced (TE) patients, and data for treating GT3 patients with interferon based regimens limited. We sought to establish the tolerability and effectiveness of Sofosbuvir based regimens in such patients with advanced fibrosis/cirrhosis in routine care. Method We analysed the Scottish HCV Database to identify patients with a liver stiffness measurement (LSM) ≥9.5 kPa, starting a Sof based regimen in Glasgow treatment centres between June and October 2014 inclusive. Data were obtained on demographics, LSM, cirrhosis status, treatment status, baseline labs, Child’s score, drug and alcohol use. Data were compared with trial inclusion/exclusion criteria. Baseline viral load, week 4 PCR, EOTR, SVR12 and premature discontinuations were recorded. Results 123 patients, were treated with either Sof/IFN/Rib (n = 108) or Sof/Rib (n = 15). Baseline characteristics are summarised in Table 1. 97 (78.9%) patients were cirrhotic (median LSM 20.8 (IQR 14.8–35.5)). The majority were GT3 (68, 55.3%) or GT1 (47, 38.2%). Half (61, 49.6%) were TE, including 9 PI failures. 65 (52.8%) would have failed at least one trial inclusion/exclusion criteria (37 (30.1%) due to baseline labs, 30 (24.4%) recent drug/ alcohol misuse, schizophrenia (1, (0.8%)). At week 4 38/121 (31.4%) patients were undetectable (RealTime HCV, Abbott), 49 (40.5%) detectable <12 IU/ml, and 32 (26.4%) quantifiable (median 23 IU/ml, IQR 15–56). On an ITT basis, 103/114 (90.3%) patients achieved EOTR. 5 discontinued prematurely (including one due to an AE and one death unrelated to treatment), 5 were lost to follow up. 1 patient was detectable (<12 iu/ml) at end of treatment. Per protocol 37/44 (84%) of patients have to date achieved an SVR12. SVR data for the remaining cohort will be presented.Abstract OC-115 Table 1 Conclusion Patients with advanced fibrosis/cirrhosis and unfavourable baseline characteristics can be treated effectively with Sofosbuvir based regimens. High rates of detectable HCV RNA at week 4, did not appear to impact on end of treatment response. Initial SVR12 results are encouraging. Disclosure of interest D. Sutherland: None Declared, E. Forrest: None Declared, M. Heydtmann: None Declared, M. Priest: None Declared, P. Mills: None Declared, J. Morris: None Declared, A. Stanley: None Declared, R. Fox Consultant for: Gilead, Janssen, BMS, Abbvie, Speaker Bureau of: Gilead, Janssen, BMS, Abbvie, S. Barclay Consultant for: Gilead, Janssen, BMS, Abbvie, Speaker Bureau of: Gilead, Janssen.

PWE-127 Microbiological assessment of ascitic fluid in liver disease: culture techniques, sensitivities and interpretation

Introduction Diagnostic paracentesis is a routine procedure for the assessment ascitic patients and the diagnosis of spontaneous bacterial peritonitis (SBP). It is recommended that samples are sent in blood culture bottles (BC) as well as universal containers (UC) for the best culture yield. However there is uncertainty regarding the significance of bacterascites (BA). We aimed to determine the culture yield of paired BC and UC samples and to assess outcome relative to the presence of SBP, BA or culture negative neutrocytic ascites (CNNA). Method This was a retrospective review of all the ascitic fluid samples sent for microbiology analysis in North Glasgow between November 2010 and December 2013. Measured white cell count (WCC) and bacterial cultures were noted. Positive samples were defined as follows: BApositive culture with WCC <250; CNNAWCC >250 but negative culture; SBPwas positive culture with WCC >250. Samples were classified on the basis of the initial sample or if >3 months since the previous sample. Results A total of 4131 samples were received from patients with liver disease. Of these there were 1520 BC and UC paired cultures in 503 individual patients; the majority having alcoholic liver disease (74%). Pathogens were cultured in 118 paired samples: 47% only in BC; 34% in both BC and UC; 19% only in UC. Commensals were more common in UC: 72% compared with BC, 34%. 90 positive samples had had previous negative samples: 24 had negative samples less than 1 week prior to positive sample. 69% of pathogens cultured were sensitive to co-amoxiclav. BA and SBP were associated with a worse outcome compared with negative samples: HR 3.46 (2.0, 5.98); p < 0.0001 and HR 0.082 (0.039, 0.175); p < 0.0001 respectively. Culture of any pathogen was associated with a reduced 90 day survival compared with negative samples: HR 0.244 (0.159, 0.374); p < 0.0001.Abstract PWE-127 Figure 1 Conclusion Both BC and UC samples yield relevant pathogen cultures and both should be requested for the best chance of a positive culture. BA is not a benign finding. Direct culture of any pathogen irrespective of WCC is associated with a worse 90 day outcome. Disclosure of interest None Declared.

PWE-139 Tace In The Management Of Hcc In A Regional Centre: 5 Year Analysis And Assessment Of Predictors Of Outcome

Introduction Transarterial chemoembolisation (TACE) is a useful treatment for selected patients unsuitable for surgical management of hepatocellular carcinoma (HCC). The Hepatoma Arterial-embolization Prognostic (HAP) score has been proposed to be a a better predictor of post-TACE outcome than the Child-Pugh or BCLC (Barcelona clinic liver cancer) scores.1 Methods Patients diagnosed with HCC from January 2008 until December 2012 were identified from a prospectively compiled regional MDT database. Patients were risk stratified by Child Pugh grade, BCLC and HAP scores. Response to treatment was assessed by the mRECIST criteria (modified response evaluation criteria in solid tumours).2 Relationship between risk scores and outcomes were assessed using Log-Rank tests and median survivals. Results 282 patients were diagnosed with HCC during the study period. 101 of these patients (81 male, 20 female) mean age 66.0 (SD 10.1 years, range 37 to 85) were treated locally with TACE. Aetiology was alcoholic liver disease in 30%, unknown in 21%, non alcoholic liver disease 15%, viral hepatitis 12%, haemochromatosis 8%, other and mixed aetiology 14%. Baseline Child-Pugh grades A, B and C were 76, 21 and 3% respectively. BCLC Staging was A, B, C and D in 25, 58, 13 and 4% respectively. HAP Scores A, B, C and D were 14, 39, 37 and 11% respectively. A total of 228 TACE procedures were performed (mean 2.3 per patient; range 1–6). In 10 (10 %) of patients, TACE was used in combination with radiofrequency ablation and in two (2%) cases it was successfully used as a bridge to transplant. 88% of patients had TACE as sole therapy. Radiological follow-up post TACE was performed in 208 occasions with 18% having a mRECIST complete response, 43% a partial response, 26% static disease and 14% progressive disease. Analysis of the HCC risk stratification scores demonstrates the HAP Score predicted post-TACE survival (p = 0.002), but the Child Pugh (p = 0.192) and BCLC scores (p = 0.210) did not. There was a 3 fold increase in median survival in patients in the HAP A group when compared to those in the HAP D group (36.6 vs. 12.3 months). Abstract PWE-139 Figure 1 Conclusion We report patient survival following TACE for treatment of HCC which compares favourably with published studies.1 The HAP score for TACE appears promising in our population and superior to existing scores. Reference Kadalayil et al. A simple prognostic scoring systems for patients receiving transarterial embolisation for hepatocellular cancer. Annals of Oncology 2013;24:2565–2570 Disclosure of Interest None Declared.

PWE-149 The Efficacy and Safety of Treating Hepatitis C in Patients with a Diagnosis of Schizophrenia

Introduction Treating hepatitis C with pegylated interferon alpha may induce or exacerbate psychiatric illness including depression, mania and aggressive behaviour. There is limited data regarding treatment in the context of chronic schizophrenia. We sought to establish the safety and efficacy of treatment of patients with a diagnosis of schizophrenia amongst patients attending treatment centres in Greater Glasgow Abstract PWE-149 Figure Methods Patient and treatment data collected on the Scottish hepatitis C database were retrospectively analysed according to the presence or absence of a diagnosis of schizophrenia. Combination antiviral therapy was defined as Interferon (pegylated or standard) and Ribavirin. Treatment outcomes including sustained viral response (SVR) rates, reasons for treatment termination and adverse events were documented Results 5497 patients were recorded on the database, of whom 64 (1.2%) had a diagnosis of schizophrenia. Patients with and without schizophrenia were of similar age at diagnosis [median 34 (IQR 31–40) vs 36 (IQR 29–41) years, p = 0.85]. Patients with schizophrenia had higher rates of current or previous intravenous drug use [50/64 (78.1%) vs 3015/5433 (55.5%), p < 0.01] and prior alcohol excess > 21 units/week [25/64 (39%) vs 1211/5433 (22.2%), p = 0.02)]. More patients with schizophrenia had a diagnosis of cirrhosis [13/64 (20.3%) vs 589/5419 (10.86%), p = 0.02]. Of those patients who had attended at least one clinic appointment 1639/4415 (37.1%) of patients without schizophrenia commenced treatment versus 26/61 (42.6%) of patients with schizophrenia (p = 0.21). Patients with schizophrenia took almost three times as long to commence treatment after initial referral [median 1123 (IQR 531–2130) vs 421 (IQR 209–1086) days, p < 0.01], despite similar times from referral to first attendance [median 65 (IQR 36–141) vs 62 (IQR 35–130) days, p = 0.92] The treatment outcomes were as follows: Conclusion Patients with stable schizophrenia are good candidates for hepatitis C treatment Disclosure of Interest None Declared.

PMO-183 Role of IL28B polymorphism in prediction of response to therapy in patients with genotype 1 chronic hepatitis c infection

Introduction Patients with chronic hepatitis C virus (HCV) infection have a variable response to antiviral therapy with pegylated interferon and ribavirin. Influences include age, gender, viral genotype, viral load, severity of liver disease and coinfection. Around 45% of patients with viral genotype 1(G1) infection respond compared with 70%–80% with genotype 2/3. Recently a human IL28B polymorphism has been found to predict response in patients with G1 infection. There is little data on this from Europe and a study of IL28B polymorphisms in patients with G1 infection treated in Glasgow was conducted. Methods Sequential Caucasian patients with G1 chronic HCV who had been treated with combination antiviral therapy were studied. Responses were classified as sustained viral response (SVR), relapse (R) or non-responder (NR). None had coinfection. Data on age, gender, viral load, duration of therapy and severity of liver disease (Ishak fibrosis stage <4 or ≥4) were collected. Individuals were genotyped for IL28B polymorphism rs12979860 using TaqMan®, Drug Metabolism Genotyping Assays and reported as CC, CT or TT. Results 63 patients were classified (number, mean age, females, advanced fibrosis) by treatment response as SVR (18, 44, 4, 1), R (20, 46, 8, 8) and NR (25, 46.4, 4, 10). Mean pre-treatment viral load was similar in the three groups (5.2, 5.4, 5.8 log10 IU/ml) and mean duration of therapy shorter for NR (46.2, 47.2, 8.4 weeks) who often fulfilled an early stopping rule. The IL28B genotype was highly predictive of response (Abstract PMO-183 table 1). CC individuals have a much greater likelihood (p<0.002) of being in the SVR group than CT or TT individuals. Poorer response was also seen in patients with advanced fibrosis.Abstract PMO-183 Table 1 Total CC CT TT SVR 18 12 4 2 Relapse 20 9 10 1 Non-responder 25 2 16 7Abstract PMO-183 Figure 1 Characteristics of study subjects Conclusion The IL28B polymorphism is a useful and cheap assay allowing some prediction of response to antiviral therapy in patients with G1 chronic HCV infection. Competing interests None declared.