Reversal of Minimal Hepatic Encephalopathy aftera Probiotic Administration. A Prospective, Randomized, Placebo-Controlled, Double-Blind Study

ORAL PRESENTATIONS (number connection test, NCT) and neurophysiological (brainstem auditory evoked potentials, BAEP) modalities. MHE was defined by abnormality on at least one test modality. Seventy eight (55%) patients diagnosed with MHE and 72 of them were equally randomized into Lactobacillus plantarum 299v at a dose of 1010 units per sachet (Lp299v) or identical placebo, given twice a day for a period of 12 weeks. All tests were repeated on the 12-week visit. Results: Seventy two patients (62 men, mean (SD) age: 59 (10)) were randomized to receive Lp299v (n = 37) or placebo (n = 35). Alcohol was the cause of cirrhosis in 58%, mean (SD) Child-Pugh score was 6.4 (1.6), 46% were Child-Pugh A and the mean (SD) MELD score was 11.9 (3.6). At baseline, there were no significant differences between the groups in demographics, liver function tests, serum fasting NH3 levels or performance of psychometric and neurophysiological tests. After 12 weeks, MHE was reversed in 21 patients (57%) of the probiotic group but in only 3 patients (8.6%) who received placebo and the difference was statistically significant ( p < 0.001). Moreover, the performance of the NCT test significantly improved in the treatment group ( p = 0.02) as well as the performance of the BAEP ( p = 0.03). Serum fasting NH3 levels significantly decreased in the treatment group ( p = 0.015) while no changes were found in the placebo group. Six patients in the placebo group versus none in the Lp299v group developed overt HE during the 12-week trial. Two patients in the Lp299v group and one patient in the placebo group stopped study due to side-effects. The adherence was excellent (>80%). Conclusions: We found that the administration of a probiotic (Lp299v) achieved a significant rate of MHE reversal compared to placebo in patients with cirrhosis and it might be considered as a valuable alternative for the treatment of MHE.

are achieved only in a minority of patients. We hypothesize that immunological parameters detectable before NUC discontinuation can be used to predict whether therapy can be safely interrupted. Methods: Nineteen CHB patients were followed prior to and after NUC discontinuation for 1–2 years and their PBMCs were collected at 4-weekly intervals. HBV-specific T cell responses were assessed by IFN-γ ELISPOT after in vitro expansion in the presence of HBV peptides spanning the entire viral proteome. T cell phenotype and functionality were studied longitudinally by analyzing the expression of >35 markers involved in cell activation, differentiation and exhaustion, by cytometry time of flight (CyTOF), a novel mass cytometry technology. Results: Following NUC discontinuation, patients differentiated into 2 groups based on the presence/absence of HF. Using CyTOF, patients without HF could be distinguished, prior to NUC discontinuation, by significantly higher frequencies of global CD4+ and CD8+ memory T cell populations (central & effector memory; CD45RA- and CCR7+/− respectively) compared to those patients developing HF. Patients without HF also show increased functionality of CD8+ memory T cells, marked by expression of CD40L, IL-2 and TNFα. Notably, the increased global T cell memory population present in non-flare patients is associated with the detection of T cells targeting HBV polymerase. Conclusions: Our data suggest that the frequency of global memory and HBV-polymerase specific T cells may represent a potential biomarker to identify patients who will control HBV, without the development of HF after NUC discontinuation.

Cirrhosis 2

PS058 THE NON-STEROIDAL FXR AGONIST GS-9674 REDUCES LIVER FIBROSIS AND AMELIORATES PORTAL HYPERTENSION IN A RAT NASH MODEL P. Schwabl1, E. Hambruch2, P. Supper1, M. Burnet3, M. PeckRadosavljevic1, T. Reiberger1, C. Kremoser2, M. Trauner1. 1Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; 2Phenex Pharmaceuticals AG, Heidelberg; 3Synovo GmbH, Tübingen, Germany E-mail: [email protected]

PS057 REVERSAL OF MINIMAL HEPATIC ENCEPHALOPATHY AFTER A PROBIOTIC ADMINISTRATION. A PROSPECTIVE, RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND STUDY J. Vlachogiannakos1, P. Vasianopoulou2, N. Viazis2, M. Chroni3, D. Karamanolis2, S.D. Ladas1. 1Academic Department of Gastroenterology, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens; 2Department of Gastroenterology; 3 Otolaryngology, Evangelismos General Hospital, Athens, Greece E-mail: [email protected]

Background and Aims: FXR agonists exert beneficial effects in patients with cholestatic liver diseases and NASH as well as in rat models of cirrhosis and portal hypertension. We assessed therapeutic effects of the novel non-steroidal FXR agonist GS-9674 on liver fibrosis and hemodynamics in a rat model of advanced NASH. Methods: Male Wistar rats were fed a choline-deficient high fat diet (CDHFD) and given repeated NaNO2 injections (25 mg/kg i.p., 2x/ week) for 10 weeks. GS-9674 (10 mg/kg or 30 mg/kg) was gavaged daily from weeks 4–10. Fibrosis was assessed by Sirius Red area (%SR) and hepatic hydroxyproline (HP) content. Hepatic and ileal gene expression were measured by real-time PCR. In another set of NASH rats systemic hemodynamics, portal pressure (PP) and superior mesenteric blood flow (SMABF) were measured after chronic (6

Background and Aims: Minimal hepatic encephalopathy (MHE) is considered the mildest form in the spectrum of hepatic encephalopathy (HE) and represents patients with cirrhosis without clinical symptoms of brain dysfunction who perform worse on psychometric tests compared with healthy subjects. This disorder may impair daily functioning and quality of life of cirrhotic patients. In this prospective study, we investigated the potential role of a probiotic in the treatment of MHE, in cirrhotic patients. Methods: We screened for MHE 142 consecutive cirrhotics who attended the out-patient liver clinic using both, psychometric Table: (abstract: PS058). CONTROL

−1

Heart rate [bpm ] Mean arterial pressure [mmHg] Portal pressure [mmHg] Splanchnic blood flow [ml/min/100g]

CHRONIC

ACUTE

CO-VEH

NASH-VEH

NASH GS-9674

NASH - PROP

NASH - GS-9674 +PROP

NASH GS-9674

NASH - PROP

NASH - GS-9674 +PROP

362±55 137±7*

345±56 116±23

343±78 127±31

203±36* 81±16*

218±56* 89±20*

375±26 129±12

230±54* 82±23*

214±41* 83±44*

7.37±1.52*

11.92±2.07

8.96±2.16*

10.88±2.78

9.45±2.40*

12.63±1.81

9.01±1.41*

8.35±2.55*

9.85±1.55*

14.18±3.27

15.65±1.36

9.45±3.54*

10.48±3.74*

12.41±4.43

9.88±2.71*

8.84±1.61*

* p<0.05 vs. NASH-VEH Journal of Hepatology 2016 vol. 64 | S159–S182

S165