K.R. Reddy

On-treatment HCV RNA in patients with varying degrees of fibrosis and cirrhosis in the SOLAR-1 trial.

BACKGROUNDnIn the Phase II SOLAR-1 study, 12 or 24 weeks of ledipasvir/sofosbuvir and ribavirin yielded high sustained virological response rates at 12 weeks (SVR12) in patients with chronic HCV infection and advanced liver disease, including untransplanted patients with decompensated cirrhosis and liver transplant recipients with all stages of liver disease.nnnMETHODSnWe performed a post hoc analysis using data from this study to investigate associations between baseline characteristics and early on-treatment HCV RNA, and to determine the utility of early virological response (week 2 and 4) to predict SVR12. Serum HCV RNA was quantified using the Roche COBAS® Ampliprep®/Cobas TaqMan HCV Test, Version 2.0 with a lower limit of quantification (LLOQ) of 15 IU/ml.nnnRESULTSnMost patients achieved HCV RNA <LLOQ by treatment week 4 and target not detected (TND) by week 6. Baseline factors significantly associated with HCV RNA <LLOQ at week 2 were low HCV RNA (<800,000 IU/ml), absence of cirrhosis, age <60 years and no prior treatment experience. At week 4, low HCV RNA, absence of cirrhosis and IL28B CC were associated with <LLOQ, TND. No baseline factors were associated with week 6 response. There was no association between early on-treatment HCV RNA and SVR12.nnnCONCLUSIONSnOn-treatment HCV RNA quantification is of limited clinical use in patients with advanced liver disease and/or liver transplantation and does not predict SVR12. ClinicalTrials.gov: NCT01938430.

P943 DIFFERENCES IN CREATININE BETWEEN GENDERS COULD DISADVANTAGE INFECTED CIRRHOTIC WOMEN: THE NACSELD EXPERIENCE

Background: Atrial fibrillation (AF) predisposes non-cirrhotic patients to ischemic stroke and requires anticoagulant therapy for prevention. Traditionally, cirrhosis is considered to be a coagulopathic state and may be associated with increased or normal coagulability. The risk of ischemic stroke amongst those with atrial fibrillation and the associated risk scores for predicting ischemic scores are not well studied. We evaluated the risk of ischemic stroke among cirrhotics relative to non-cirrhotics with atrial fibrillation in national inpatient sample (NIS). Methods: A weighted sample of NIS for the year 2008 was analyzed. The risk of stroke associated with cirrhosis, adjusted for demographic and relevant risk factors, was estimated. Using STATA software, among patients with AF, we estimated the risk of cirrhosis with ischemic stroke relative to non-cirrhotic patients using weighted multivariate analysis while adjusting for other risk factors. We also calculated the CHADVasc scores among the sample population. Covariates of interest were characterized using ICD-9 CM codes. Results: The incidence of total stroke (ischemic and hemorrhagic) was significantly lower in cirrhotics when compared to non-cirrhotics. In individuals with AF the risk of ischemic stroke matched by risk factors for stroke demonstrated a lower incidence of ischemic stroke among patients with cirrhosis than non-cirrhotic controls. Multivariate analysis revealed 75% lower risk for stroke among cirrhotic patients with AF than non-cirrhotic AF patients (Odds ratio: 0.24; 95% [CI: 0.12 0.49]). The risk of ischemic stroke was lower among cirrhotics with AF for the same CHADVasc scores amongst non-cirrhotics. However, no difference in the risk of stroke was observed in cirrhotics with AF than non-cirrhotic AF patients with respect to hemorrhagic stroke (Odds ratio: 0.24; 95% CI: 0.0.3 1.7). The detailed analysis is described in the table. Conclusions: Cirrhotics appears to have a protective effect against ischemic stroke with or without AF. The incidence of hemorrhagic stroke was found to be lower in cirrhotics in general but this effect was not seen among those with AF. The risk of stroke amongst cirrhotics with AF is lower than what is predicted by CHADSVasc. Table showing the incidence of Ischemic stroke among cirrhotic and non-cirrhotic patients with atrial fibrillation

226 LONG-TERM ANTIBIOTIC AND PROTON-PUMP INHIBITOR USE ARE STRONG PREDICTORS OF RECURRENT INFECTIONS IN CIRRHOSIS: A PROSPECTIVE MULTI-CENTER STUDY FROM NACSELD

(type V collagen), C6M (type VI collagen), BGM (Biglycan), ELM (Elastin), and CRPM (CRP)), and ECM formation markers (P3NP (type III collagen) and P4NP7S (type IV collagen)) were measured. Results: The markers measured in hepatic venous blood correlated to the level measured in arterial blood (R=0.89–0.98; p < 0.0001). In hepatic venous blood, all markers correlated directly to Child Score and MELD, and inversely to ICG clearance and serum albumin, strongest with P3NP (R=0.46, 0.48, −0.53, and −0.46; respectively, p < 0.0001). All markers except ELM were inversely correlated to hematocrit and to hemoglobin, especially C4M and C1M showed strongest correlations (R = −0.31; −0.40; respectively, p = 0.001p < 0.0001). In both arterial and hepatic venous blood all markers except CRPM correlated to HVPG (e.g. P3NP for both sites R =0.47, p < 0.0001). A multiple regression analysis including P3NP, C6M and MELD improved the correlation (R =0.62, p < 0.0001). P3NP could clearly separate controls from HVPG levels <10mmHg (p < 0.01) and those with HVPG<10mmHg from those with HVPG levels ≥10mmHg (p < 0.0001). C4M, C5M, and ELM were all significantly higher in patients with HVPG levels ≥12mmHg compared to lower HVPG levels (p < 0.01–0.0001). Conclusion: The Protein Fingerprint markers reflect liver function and stage of disease. A strong correlation between the markers measured in hepatic venous and arterial blood was observed. A multimarker model in combination with clinical scores predicted HVPG and separated clinical relevant HVPG thresholds noninvasively. Therefore these markers and their models are suitable for non-invasive evaluation of portal hypertension in cirrhosis.

P0199 : Acute kidney injury in cirrhosis: Baseline serum creatinine predicts patient outcomes

Background & Aims Intrahepatic and splanchnic angiogenesis plays an important role in Portal Hypertension (PHT) caused by cirrhosis. Krupple-like factor 2 (KLF2), a critical angiogenic protective factor, can maintain endothelial cellular phenotype by negatively regulating angiogenesis. Our research is to study whether KLF2 play a role in cirrhosisinduced PHT and its possible mechanism. Methods Human serum samples were collected from 41 PHT patients and 20 healthy subjects, and portal vessel tissue were obtained from 6 PHT patients and 6 cholecystitis controls during their surgeries. Rat models of portal vein ligation (PVL) and CCL4 were also used for our study. The expression of KLF2 and relevant angiogenic factors such asHIF-1α and VEGFwere evaluated. Additionally, human endothelial cells were used for vitro study. Lentivirus was transfected to overexpress KLF2. Tube formation and activation of cells were examined while KLF2 target protein expression were determined. Results We observed a remarkable upregluation of KLF2 in portal vein of PHT patients and angiogenic duodenum of PVL rats compared with controls, accompanied by a significant increasement of some relevant angiogenic factors such as VEGF and HIF-1α in PHT human and rat model. In addition, our vitro experiment observed that stimulated by hypoxia andinflammatory factor, KLF2-overexpressed endothelial cells showed decreased proliferation,migration and vessel tube formation.We also found that, in KLF2-overexpressed cells, KLF2 downstream angiogenic factors such as Ang-2 and NF-κB level were inhibited while eNOS upregulated. Conclusion KLF2 level and angiogenesis were elevated in portal hypertension caused by cirrhosis. KLF2 may suppress the progress of angiogenesis via inhibiting the endothelial cells activation and modulating Ang-2 and NF-κB pathway.