6 th UpDate. on Hepatology Course Bucharest Romania 2019 Title: From theory to practice in liver disease

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1 6 th UpDate on Hepatology Course Bucharest Romania 2019 Title: From theory to practice in liver disease COURSE DIRECTORS Liana GHEORGHE Anca TRIFAN Ioan SPOREA 5 th - 6 th April 2019 Bucharest Crowne Plaza Hotel roaldliver@gmail.com You can now download the dedicated application by scanning the above QR code.

2 Welcome message from the Chair Dear Colleagues, It gives us great pleasure to welcome you to the Update on Hepatology Course 2019, the popular 2 day-long interactive educational program in hepatology organized annually by the Romanian Association for Liver Diseases (RoALD), the Romanian Society of Gastroenterology and Hepatology (SRGH), Fundeni Clinical Institute and the Carol Davila University of Medicine and Pharmacy in Bucharest. Extraordinary advances in hepatology have taken place recently, advances that impact clinician s ability to diagnose and treat the most common causes of liver disease. Highly effective direct-acting antivirals for hepatitis C and B have been developed and continue to be refined. The pathophysiology of non-alcoholic fatty liver disease and fibrosis is now better understood, setting the foundation for the development of dedicated effective therapy. New approaches have emerged to manage the complications of liver cirrhosis and new innovative therapeutic concepts assist the clinician in the fight against liver cancer. New topics in the core program this year are the sessions Pregnancy and liver disease and Endo-Hepatology: optimizing endoscopy in patients with cirrhosis.hepatologyin 2019 brings together practicing hepatologists, endoscopist, oncologists,radiologists, basic scientists, liver surgeons and liver pathologists working together in a multidisciplinary team. With the theme From theory to practice in liver diseases, the meeting of this year will be focused on the integration of latest advances at the frontline 2

3 of hepatology in the daily practice. We have organized the 2019 Course in the form of 6 plenary sessions, carefully selected and structured around relevant topics for practicing hepatologist, with direct relevance to patient care.state of the art lectureswill target Hepatitis C: Persistinggaps on the road of elimination of hepatitis C and the Acute on chronic liver failure in A hands-on workshop of ultrasound elastography will be integral part of this year s program. In addition, the Satellite Symposia section will complement the scientific program offering a quick exposure to the state of research in the Industry. Over the 2-day course you will have the unique opportunity to hear a series of outstanding presentations given by renowned experts, interact and discuss informal with them during the sessions, workshops and breaks between sessions. Our educational aims remain to deliver updated knowledge, to share opinions and clinical experience, to network and develop future collaboration and to stimulate the implementation of an evidence-based approach, in order to ultimately improve the care and outcome of many people who suffer from liver diseases in Romania. Finally, we would like to thank all those contributing to the 2019 meeting the faculty, the organizing institutions, our generous corporate supporters and, last but not least, the participants, who give purpose to this educational event. We hope you will enjoy the meeting, the location the cultural, historical and scenic vibes of Bucharest in spring, we hope you will learn a lot, interact with experts and colleagues, and build further collaboration. Cordially, Course Directors: Liana Gheorghe, Anca Trifan, Ioan Sporea Scientific secretary: Speranța Maria Iacob 3

4 6 th Update on Hepatology Course Title: From theory to practice in liver disease Date: 5 th -6 th April 2019 Venue: Bucharest, Crowne Plaza Hotel Course Directors: Liana Gheorghe, Anca Trifan, Ioan Sporea International Faculty: Costică Aloman, Chicago, USA Susanne Beckebaum, Muenster, Germany Ferruccio Bonino, Pisa, Italy Vito Cicinnati, Muenster, Germany Scott Friedman, New York, USA Jeffrey Lazarus, Barcelona, Spain Mona Munteanu, Paris, France Vlad Ratziu, Paris, France Nancy Reau, Chicago, USA Erwin Santo, Tel Aviv, Israel Shiv Sarin, New Delhi, India Elsa Sola, Barcelona, Spain Cihan Yurdaydin, Ankara, Turkey National Faculty Cristina Cijevschi, Iaşi Camelia Cojocariu, Iaşi Adina Croitoru, Bucharest Mircea Diculescu, Bucharest Dan Gheonea, Craiova Liana Gheorghe, Bucharest Cristian Gheorghe, Bucharest Irina Girleanu, Iaşi Adrian Goldis, Timişoara Speranţa Iacob, Bucharest Răzvan Iacob, Bucharest Corina Pop, Bucharest Irinel Popescu, Bucharest Bogdan Procopeţ, Cluj-Napoca Zeno Spârchez, Cluj-Napoca Ioan Sporea, Timişoara Carol Stanciu, Iaşi Horia Ştefănescu, Cluj-Napoca Roxana Şirli, Timişoara Anca Trifan, Iaşi 4

5 Scientific Committee for Poster Viewing and Awards: Mircea Diculescu, Anca Trifan, Roxana Şirli Speranţa Iacob, Dan Gheonea, Bogdan Procopeţ Access during the course will be based on the badge provided to each participant at registration. Participants are kindly asked to wear their badge at all times during event. You can now download the dedicated application (compatible with ios and Android phones) by scanning the above QR code with your mobile phone, or access hepatologycourse.ro/app/ 5

6 Friday, 5 April Registration & Welcome Introduction Persisting therapeutic challenges in the management of cirrhotic patient Chair: Elsa Sola, Anca Trifan Anticoagulation therapy in liver cirrhosis Bogdan Procopeţ, Cluj-Napoca Albumin in liver cirrhosis Elsa Solà, Barcelona, Spain Non-selective beta-blockers in cirrhosis Anca Trifan, Irina Gîrleanu, Iaşi New therapeutic targets in hepatic encephalopathy Mircea Diculescu, Bucharest Coffee, herbal and dietary supplements in liver disease Cristina Cijevschi, Iaşi Coffee break and Poster Viewing Pregnancy & Liver disease Chair: Nancy Reau, Liana Gheorghe Diagnostic work up of liver test abnormalities during pregnancy Corina Pop, Bucharest Medical emergencies in pregnancy-related liver disease Liana Gheorghe, Bucharest Cholestatic pregnancy-related liver disease Speranţa Iacob, Bucharest Viral hepatitis in pregnancy Nancy Reau, Chicago, USA Satellite Symposium Abbvie Optimising the outcome of HCV patients in genotype-specific era HCV Patient Case 1 6

7 Simplifying HCV management: TIME DOES MATTER! Liana Gheorghe, Bucharest HCV Patient Case 2 Effective management on therapy: DRUG-DRUG INTERACTIONS ARE MANAGEABLE! Anca Trifan, Iaşi Lunch and Poster Viewing HCC and Liver transplantation Chair: Susanne Beckebaum, Irinel Popescu Liver transplant for hepatocellular carcinoma Irinel Popescu, Bucharest Systemic therapies for HCC: immune checkpoint and signal pathway inhibitors Adina Croitoru, Bucharest Improving screening in hepatocellular carcinoma Zeno Spârchez, Cluj-Napoca Liver transplant for alcoholic hepatitis Susanne Beckebaum, Muenster, Germany State of the Art Moderator: Corina Pop Hepatitis C: Persisting gaps on the road of elimination Jeffrey Lazarus, Barcelona, Spain Hands-on Workshop: Fibrosis assessment Coffee break will be served in the workshop area (will be held separately in 2 halls for biomarkers and US technology, respectively; participants will change from a workshop to the other after one hour) BIOMARKERS Moderators/Presenters: Mona Munteanu, Camelia Cojocariu, Iulia Simionov, Horia Ştefănescu, Iuliana Pârvulescu, Anca Leuştean US TECHNOLOGY Moderators/Presenters: Speranţa Iacob, Roxana Şirli, Horia Ştefănescu, Dan Gheonea Ruxandra Mare, Raluca Lupuşoru Dinner 7

8 Saturday, 6 April What s new in hepatitis? Chair: Ferruccio Bonino, Cihan Yurdaydin Emerging issues in hepatitis B (when to stop NUCs, renal function, risk of HCC, qhbsag, obstacle for cure) Ferruccio Bonino, Pisa, Italy New therapeutic strategies against hepatitis D Cihan Yurdaydin, Ankara, Turkey Hepatitis E an emerging issue Roxana Şirli, Timişoara Liver involvement in sarcoidosis Vito Cicinnati, Muenster, Germany Coffee Break and Poster Viewing The increasing role of molecular biology in hepatology Chair: Scott L. Friedman, Vlad Ratziu Landmark trials in NASH and fibrosis Scott L. Friedman, New York, USA Cellular immunological basis of sex differences to alcohol induced liver injury Costică Aloman, Chicago, USA Hepatocyte plasticity in vivo and in vitro the significance for regenerative therapies in liver diseases Razvan Iacob, Bucharest Understanding pathophysiology of NAFLD/NASH to identify therapeutic targets Vlad Ratziu, Paris, France Satellite Symposium Gilead Optimizing HCV treatment across all disease stages How the success looks in real life Liana Gheorghe, Bucharest Speranţa Iacob, Bucharest 8

9 Lunch and Poster Viewing Satellite Symposium MSD Is there still a role for personalized treatment of hepatitis C in Romania? Comorbidities a key challenge in choosing DAA treatment Liana Gheorghe, Bucharest Treatment duration a key challenge in choosing DAA treatment Dan Gheonea, Craiova Endo-Hepatology: Optimizing endoscopy in patients with cirrhosis Chair: Carol Stanciu, Erwin Santo, Cristian Gheorghe Bleeding risk in cirrhotic patient who needs endoscopy and how to manage it Răzvan Iacob, Bucharest Endoscopy for gastric variceal bleeding Vito Cicinnati, Munster, Germany Special considerations of colonoscopy in cirrhotic patient Adrian Goldiş, Timişoara How to do safely ERCP in cirrhotic patient? Cristian Gheorghe, Bucharest Potential role of EUS in hepatobiliary diseases Erwin Santo, Tel Aviv, Israel State of the Art Moderator: Cristian Gheorghe Acute on Chronic Liver Failure 2019 Shiv Kumar Sarin, New Delhi, India Closing and (Poster) Awards Light dinner 9

10 Abstracts Friday, 5 April THE ROLE OF NEUTROPHIL-TO-LYMPHOCYTE RATIO IN THE PREDICTION OF OUTCOME OF PATIENTS WITH DECOMPENSATED CIRRHOSIS WITH AND WITHOUT ACUTE-ON-CHRONIC LIVER FAILURE Chiriac S.1,2; Stanciu C.2; Cojocariu C.1,2;Sfarti C.1,2;Singeap A.1,2; Girleanu I.1,2; Cuciureanu T.1,2;Stoica O.1,2; Huiban L.1; Muzica C. 1; Trifan Anca1,2 1. "Grigore T. Popa" University of Medicine and Pharmacy Iasi, Iasi, Romania. 2. Institute of Gastroenterology and Hepatology, "St. Spiridon" University Hospital, Iasi, Romania. Background: Patients with decompensated liver cirrhosis hospitalized in theintensive care unit present a high mortality rate. When acute-on-chronic liver failure (ACLF) is associated, thedeath rate is even higher. Systemic inflammation as well as an impaired response to pathogens have beenproposed as possible risk factors for ACLF. Moreover, high leucocyte count and C-reactive protein (CRP)levels have been associated with more severe ACLF grade and worse outcome. A simple method of assessingprognosis in cirrhotics is currently under evaluation, namely neutrophil-to-lymphocyte ratio (NLR). Aim: to assess the accuracy of NLR in predicting outcome in decompensated cirrhotic patients with and without ACLF. Methodology: we performed a retrospective analysis of patients diagnosed with liver cirrhosis hospitalized foracute decompensation between January 2017-June 2017 in The Intensive Care Unit of a North-eastern Romanian tertiary care center. Patients with concurrent malignancy, immunosuppressive treatment, pregnancyor immunodeficiency virus infection were excluded. Laboratory tests from venous blood obtained within 12hours of admission were retrieved. The studied outcome was 28-day mortality. Results: One hundred and eighty consecutive patients were screened and after applying exclusion criteria seventy patients were included in the study, mean age 62 ± 6.2 years, mostly men (70%). Mean Model for End-stage Liver Disease and Child-Pugh scores were ± 8.65 and ± 2.37, respectively. ACLF was diagnosed in 58 patients (82.9%). Two patients (3.4%) had ACLF grade 1, 8 patients (13.8%) had ACLF grade 2, and 48 (82.8%) had ACLF grade 3. The 28-day mortality was 75.7%, significantly higher in the ACLF group (84.5%) than in the non-aclf group (33.3%). Mean NLR value for the entire cohort was 11.7 ± 9.5, with a slightly higher value found in non-survivors, compared to survivors (12.6 ± 9.8 vs 8.6 ± 7.8, respectively). In the group with ACLF, a statistically significant difference between survivors and non-survivors was found concerning NLR (5.6 vs 12.5, P<0.05). This was not the case in the group without ACLF, where no significant differences were found. Receiver operating characteristic (ROC) analysis showed a poor accuracy for NLR in predicting outcome in patients without ACLF (Area under the ROC Curve = 0.611). However, the accuracy improved when patients with ACLF were considered (Area under the ROC Curve = 0.776). No notable differences were found in CRP and leucocyte counts between the two groups. Conclusion: NLR has shown potential in predicting short-term mortality in patients with decompensated livercirrhosis and ACLF. However, it should be noted that for patients without ACLF NLR does not presentadequate accuracy and therefore caution is required in selecting the patients that could benefit from thispredictive method. 2. FUNCTIONAL LIVER RESERVE - A PREDICTIVE FACTOR FOR THE ADVERSE EFFECTS OF ANTIVIRAL TREATMENT IN PATIENTS WITH HEPATITIS C VIRUS DECOMPENSATED LIVER CIRRHOSIS- A SINGLE CENTER EXPERIENCE Huiban L. 1,2, Stanciu C.2, Muzica C. M. 1,2, Stoica O.C. 1,2, SîngeapA. M. 1,2, Gîrleanu I. 1,2, Chiriac S. 1,2,Galatanu I. R. 2, Zenovia S. 2, Cuciureanu T.1,2, Trifan A.1,2 1. Grigore T. Popa University of Medicine and Pharmacy 2. Institute of Gastroenterology and Hepatology, Iasi, Romania Introduction: The advent of the new therapeutic strategies with direct antiviral agents in patients with hepatitis C virus liver cirrhosis (HCV- LC) required the need for correlation with clinical practice data on possible adverse effects (AE). We aimed to evaluate AE during and after antiviral treatment with Ledipasvir/Sofosbuvir ± Ribavirin (LED / SOF ± RBV) in patients with decompensated HCV-LC and their correlation with baseline liver functional status. Material and Methods: We conducted a retrospective study in a tertiary center in northeastern Romania 10

11 between May 2017 and February 2019, which included patients with decompensated HCV-LC treated with LED / SOF ± RBV. The frequency of AE and correlation with baseline liver functional status, as estimated by the MELD and Child-Pugh score (CPS), were assessed. Results: The study included 88 patients (52 women %, 36 men %), with an average of 56 ± 0.28 years. Overall, 27 (30%) of AE were recorded in 18 patients, of which 10 (56%) had major AE and 8 (44%) patients with minor AE. There were 14 (52%) types of major AE (3 (21.4%) cases of upper gastrointestinal bleeding due to acute esophageal variceal bleeding, 4 (28.5%) clinically significant hepatoportal encephalopathy, 4 (28.5%) with refractory ascites, 1 (7.1%) with portal thrombosis, 1 (7.1%) with severe thrombocytopenia, 1 (7.1%) inaugural epileptic seizures) and 13 (48%) of minor AE (4 (30.76%) with insomnia, 7 (53.84%) with marked physical asthenia and 2 (15.38%) cases involving nausea and vomiting). In the group of 82 patients with CPS class B, AE were recorded in 15 (18.3%) compared with 3 (50%) patients with AE in 6 patients with CPS class C. Those with CPS class C presented a higher risk for the development of significant AE [OR = 7.7, 95% CI ( ), P = 0.19]. There were 68 patients with MELD <15 and 20 with MELD> 15. AE in patients with MELD <15 were found in a proportion of 19.1% compared to 25% in patients with MELD 15. The comparative analysis showed significant differences between patients, those with CPS class C and MELD 15 had a higher risk of AE. Conclusions: Pre-existing liver dysfunction predisposes to significant AE, justifying a rational and prudent recommendation for antiviral treatment in patients with advanced decompensated LC. 3. THROMBOTIC EVENTS IN PATIENTS WITH HEPATITIS C VIRUS LIVER CIRRHOSIS TREATED WITH DIRECT ACTING ANTIVIRALS AND SUSTAINED VIROLOGICAL RESPONSE- A REAL LIFE STUDY Huiban L. 1,2, Stanciu C. 2, Muzica C.M. 1,2, Stoica O.C.1,2, Sîngeap A. M.1,2, Gîrleanu I. 1,2, Chiriac S. 1,2, Galatanu I. R. 2, Zenovia S. 2, Cuciureanu T. 1,2, Trifan A.1,2 1. Grigore T. Popa University of Medicine and Pharmacy 2. Institute of Gastroenterology and Hepatology, Iasi, Romania Keywords: direct antivirals, sustained virologic response, thrombosis Introduction: The advent of direct-acting antivirals (DAAs) is a major breakthrough in hepatology representing the therapeutical standard of care in patients with chronic hepatitis C virus infection over the past few years. Despite high rates of sustained virological response (SVR), DAAs therapy doesn t eliminate the risk of thrombotic events. Aim: In our study we aimed to assess the occurrence of thrombotic events and clinical presentation in patients treated with DAAs and sustained virological response. Material and Methods: We retrospectively analyzed a cohort of patients with HCV-related liver cirrhosis treated with paritaprevir/ritonavir, ombitasvir and dasabuvir (PrOD) ± ribavirin and ledipasvir/sofosbuvir (LED/SOF) ± ribavirin for 12/24 weeks, in a tertiary gastroenterology referral center from North-Eastern Romania, between January 1st 2016 and July 1st2018. All patients with presumption of thrombosis were evaluated by vascular Doppler, abdominal ultrasound and confirmed by CT scan. Results: The study included 473 HCV-infected cirrhotic patients treated with PrOD or LED/SOF, with documented SVR, mean age 69,7 ± 5,5 years, predominantly female (59%). Of the total number, 284 (60.04%) received PrOD and 189 (39.95%) patients were treated with LED/SOF. Mean period from SVR and the occurrence of thrombotic events was 230±103 days. Thrombotic complications were reported in 23 (4.86%) patients: 3 (13.04%) with deep vein thrombosis, 14 (60.86%) with portal vein thrombosis (PVT), 6 (26.08%) with malignant PVT. All patients had associated cardiovascular ( %) and metabolic comorbidities ( %). The main clinical manifestations at diagnosis were: swelling, edema, erythema and lower limb pain in 3 patients, upper digestive haemorrhage in 8 patients, asciticdecompensation in 4 patient, abdominal pain in 5 patients and 3 patients were asymptomatic. Biologically there was no significant change in prothrombin serum levels (baseline values in patients treated with PrOD was ± 0.91 versus ± 0.83 at SVR, p=0.993, respectively 11.5 ± 0.84 sec at baseline versus 11.4 ± 0.68 at SVR, p=0.715 in patients treated with LED/SOF±RBV) and platelet count ( ( ) vs ( ), p= in patients treated with PrOD, respectively ± 32 vs ± 35, p= 0.853, in patients treated with LED/SOF+RBV). Conclusions: We conclude that thrombotic events in patients with HCV-related liver cirrhosis treated with DAAs are not influenced by the variations of coagulation parameters, rather correspond to the hypercoagulability status and the natural evolution of the cirrhotic patient. 11

12 4. Psoas muscle area independent predictor of mortality in patients with cirrhosisincluded on the waiting list for liver transplantation Iacob S., Stanescu C., Iacob R., Vadan R., Gheorghe C., Lupescu I., Gheorghe L. Fundeni Clinical Institute, Bucharest, Romania Background: Malnutrition and sarcopenia are frequent complications in cirrhosis and contribute to increased risk of sepsis-related mortality, poor quality of life, post-lt adverse outcomes. Sarcopenia is defined by cross-sectional imaging-based muscular assessment, however computed tomography (CT) scan determinations vary as well as cutoff values. AIM: To study the independent risk factors for occurrence of infections and death before LT. Methods: All cirrhotic patients admitted on the waiting list for liver transplantation in our Hepatology Unit between years underwent anthropometric assessments and abdominal CTscan including L3 and umbilical levels for measuring transverse psoas muscle thickness. Multiple regression was used to determine independent risk factors for occurrence of infections and death before LT. Results: One hundred thirty two patients with liver cirrhosis (% with alcoholic cirrhosis)were included. The average age was 53.9 ± 10.7 years, and 66% of patients were men. Child C class was encountered in 29.3% of patients and associated hepatocellular carcinoma was present in 17.8%. Large ascites (8-10 litres) was present in 27.7%. There is a moderate correlation between right psoas muscle area and adjusted BMI without ascites(r=0.26, p=0.007), arm circumference (r=0.39, p=0.0001), right hand grip (r=0.45, p<0.0001) and a very good correlation with the left psoas muscle (r=0.85, p<0.0001). There was no correlation between right psoas muscle area and skin fold.patients with sarcopenia (defined as arm circumference <22mm and hand-grip <45dyne) and Child Pugh Class C cirrhosis had a significantly lower right psoas muscle area compared to patients with Child Pugh class A/B cirrhosis (624cm3 vs 931.3cm3, p=0.04). Right psoas muscle area was identified by multiple regression as independent risk factor for both infections and death while on the waiting list for LT (p=0.03 for each). The value of the AUROC right psoas muscle area for predicting 1-yr mortality was 0.73 for a cut-off value of 608cm3. Conclusions: Transverse right psoas muscle area was an independent predictor of mortality in cirrhotic patients. Psoas muscle area can be used as another negative prognostic factor in Child Pugh C cirrhosis. 5. The risk of variceal bleeding after stopping beta blockers in cirrhotic patients with refractory ascites Girleanu I., Trifan A., Teodorescu A., Cojocariu C, Petrea O. C, Singeap A. M., Sfarti C., Chiriac S., Huiban L., Nemteanu R., Cuciureanu T., Stanciu C. Grigore T. Popa University of Medicine and Pharmacy, St. Spiridon University Hospital, Institute of Gastroenterology and Hepatology, Iași, Romania Introduction The non selective beta-blockant (NSBB) treatment in cirrhotic patients has several limitations regarding side effects, as arterial hypotension or bradicardia. Caution should be taken in cirrhotic patients with refractory ascites, hyponatremia or arterial hypotension, as NSBB could precipitated the development of the acute kidney injury. The aim of this study was to evaluate the risk of variceal bleeding after the NSBB treatment is stopped in patients with refractory ascites. Material and methods: All consecutive patients with liver cirrhosis and refractory ascites admitted to the Institute of Gastroenterology and Hepatology from January 2017 to December 2017 were included in this study. The diagnosis of refractory ascites was established according to the current guidelines. Results During the study period a total of 57 patients were diagnosed with refractory ascites. In more than half of them, 29 patients (50.8%), the NSBB treatment was stopped, the main cause of stopping the treatment being systolic blood pressure less than 90 mmhg. The majority of the patients were receiving propranolol (86.2%), and only 4 patients (3.8%) received carvedilol. Out of the 29 patients that stopped the treatment, 21 (72.4%) were Child-Pugh class C, and 5 patients (17.2%) developed variceal bleeding. The risk of variceal bleeding was not increased in cirrhotic patients with refractory ascites that stopped the NSBB treatment ( OR 1.207, CI , p=0.796). Conclusion Stopping the NSBB treatment in patients with refractory ascites is not associated with an increased risk of variceal bleedin, despite the severity of liver disease. 12

13 6. Brain MRI findings in liver cirrhosis patients with subclinical hepatic encephalopathy Lupescu I.C. 1, Iacob S. 2,4, Lupescu I.G. 3,4, Gheorghe L. 2,4 1 Neurology Department, Fundeni Clinical Institute, Bucharest, Romania 2 Gastroenterology Department, Fundeni Clinical Institute, Bucharest, Romania 3 Medical Imaging Department, Fundeni Clinical Institute, Bucharest, Romania 4 Carol Davila University of Medicine and Pharmacy, Bucharest, Romania Background: Brain MRI abnormalities in cirrhotic patients are well recognized and include mainly bilateral symmetric hyperintensities of the globus pallidus and substantia nigra. However, no correlation has been found between the severity of liver dysfunction and the degree of MRI abnormalities. Aim: To correlate brain MRI findings with the presence of minimal hepatic encephalopathy (MHE). Material and methods: 30 adult cirrhotic patients were assessed for MHE using EncephalApp Stroop test on electronic tablet computers. MHE was defined based on currently approved cut-offs of 145 seconds (for patients <45 years-old) and >190 seconds (for patients 45 years-old). For this study we did MR brain imaging on a 1.5 Tesla scanner using a standardized protocol for all patients. Results: For our group the mean age was 50.2±9.9 years-old (range years-old), out of which 76.6% males (n=23). Mean Stroop result (Off+On) was ± 26.1 seconds. Mean MELD score was 15±5 points. Mean Child-Pugh score was 8±2 points. Bilateral hyperintensities involving the globus pallidus were noted in 83.3% of patients (n=25), with extension to cerebral peduncles in 13.3% (n=4). No MRI abnormalities were found in 16.6% of patients (n=5). All patients < 45 years of age scored 145 seconds and all had brain MRI abnormalities. For the patients 45 years of age, 17.4% scored >190 seconds (n=4), all of which presented brain MRI abnormalities. Conclusions: 36.6% of our patients presented MHE based on Stroop test assessment. Brain MRI abnormalities were more frequent (83.3%). Based on Fischer exact test, no correlation was found between presence of brain MRI findings and presence of MHE (p=0.12). 7. INCIDENCE OF CLOSTRIDIUM DIFFICILE INFECTION IN PATIENTS WITH LIVER CIRRHOSIS Petrea O. C1,2, Stanciu C. 2, Girleanu I. 1,2, Singeap A. M.1,2, Cojocariu C. 1,2, Huiban L. 1, Muzica C. 1,2, Chiriac S. 1,2, Trifan A.1,2 1 Grigore T. Popa University of Medicine and Pharmacy, Iasi 2 St. Spiridon University Hospital, Institute of Gastroenterology and Hepatology, Iasi Introduction: Clostridium difficile infection (CDI) remains the leading cause of healthcare- associated diarrhoea worldwide. Despite multiple efforts to prevent this infection, CDI has increased over past years both in incidence and severity.traditionally, CDI was more frequentlydiagnosed in elderly patients with recent antibiotic exposure, prolongedhospitalizations, immunodeficiency or prior gastrointestinal surgery. Despite the setraditionalrisk factors, CDI incidence became more constant in other several subpopulations of patients like those withliver cirrhosis. Aim: The aim of this study was to assess the incidence of CDI in patients admitted at a tertiaryreferral center fromnortheast Romania, focusing on patients diagnosed with livercirrhosis. Methods: We performed a retrospective analysis of all cases of CDI admitted to our institute between January 2012 and December CDI was defined as the presence of toxin A or B (or both) ina diarrhoeal specimenstool, and classified as community-associatedor healthcare-associated. Results: Over the study period, there was a significant increase in the overall incidence rates of CDI, with almost 3.9 cases/1000 admissions in 2012 and 21.3 cases/1000 admissions in 2018.The same ascending trend was observed in patients with livercirrhosis. The overall incidence rate in this category of patients was0.88 cases/1000 admissions in 2012 with an increase of 12.8 cases/1000 admissions in Conclusion: CDI incidence is increasing over time with livercirrhosisbeingone of the most susceptible risk category. 13

14 8. Phenotypic assessment of liver-derived cell cultures during in-vitro cell population expansion protocol Iacob R. 1,2,3, Herlea V. 1,2,4*,Matei I.V.1,4, Florea I. R. 1,4, Ilie V.M. 1,4, Irit Meivar-Levy 4,5,6, Lixandru D.1,3, Dima S. O.1,2,4, Albulescu R.4, Tanase C.4, Popescu I. 1,2,4 and Ferber S.4,5,6 1 Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest 2 Center for Digestive Diseases and Liver Transplantation, Fundeni Clinical Institute, Bucharest 3 Carol Davila University of Medicine and Pharmacy Bucharest 4 Dia-Cure, Acad. NicolaeCajal Institute of Medical Scientific Research, TituMaiorescu University Bucharest 5 The Sheba Regenerative Medicine, Stem Cell and Tissue Engineering Center, Sheba Medical Center, Tel- Hashomer 6 Orgenesis Inc. Israel Background: Hepatocytes represent an attractive cell source for regenerative medicine. Hepatocytes can be easily obtained even by liver biopsy and can be substantially expanded in vitro, to reach the numbers needed for therapy purpose. The aim of our study was to characterize liver-derived cell cultures during in-vitro expansion protocol, by comparing gene expression as well as protein expression, in four different liver cell cultures, at low passage (6-8) in comparison to high passage (10-12). Methods: Liver cells have been isolated and expanded as previously described (Sapir T et al. PNAS 2005.). Relative gene expression using normal liver tissue as reference was compared between the two time points (low vs high). There have been used two cell line controls for reference: HepG2 and F46 human primary fibroblasts. At specified time points, 3 x 106 cells have been harvested and processed according to the Cell block cytology technique in order to generate paraffin blocks and subsequent immunohistochemistry staining. The expression of a large subset of significant genes (transcription factors, functional proteins, cytoskeleton/cell junction proteins, cell surface markers) have been analyzed at mrna and protein level. Results: During in-vitro cell population expansion protocol, liver cells have lost liver specific gene expression (liver enriched transcription factors and functional proteins expression) but still have preserved the endoderm origin memory by maintaining the expression of endoderm transcription factors GATA4 and GATA6. The conversion to a proliferative cell phenotype is supported by an epithelial to mesenchymal transition promoted by the up-regulation of SLUG, Twist1 and Twist2 transcription factors. The loss of e-cadherin expression and increase in vimentin and SMA expression, further supports this process. There was no overexpression of reprogramming transcription factors Sox2 and Nanog or htert detected. The mesenchymal stem cell markers CD44, CD90, CD105, CD73 were positive by flow cytometry in >90% of cells. There was no statistically significant difference in gene expression between the two analyzed time points, suggesting a stable cell phenotype during the expansion protocol. Conclusions: During the in-vitro expansion protocol, liver-derived cell cultures rapidly loose liver specific gene expression and adopt a proliferative mesenchymal phenotype through an EMT process. Cells could be substantially expanded to high passages, showing a conserved gene expression pattern with minimal variability between cell lines. According to our study, the cell phenotype pattern, that is consistent between the analyzed liver-derived cell lines, could be defined as Vim +, Sma +, E-cadh -, Des-, CK18+/-, CK19+/-, CD44+, CD90+, CD105+, CD OPTIMISING THE TREATMENT OF ACUTE HEPATIC ENCEPHALOPATHY IN PATIENTS WITH LIVER CIRRHOSIS Sahawneh D.1, Hordila A.1, Asaftei M.1, Girleanu I1,2, Petrea O.1,2, Stanciu C. 1, Trifan A.1,2, Cojocariu C. 1,2 Institute of Gastroenterology and Hepatology, St. Spiridon Emergency Clinical Hospital1, Grigore T. Popa University of Medicine and Pharmacy2, Iasi, Romania; Introduction:epatic encephalopathy (HE) is a potentially reversible functional disorder of the brain with neurological and psychiatric symptoms. HE occurs in more than 70% of patients with advanced liver disease and the most frequent precipitating factors are gastrointestinal bleeding, infections, medications, etc. An important aim of treatment of HE is the reduction of the ammonia level by lowering the amount of ammonia produced and increasing its detoxification. Enteric production of ammonia can be decreased by non-absorbable disaccharides such as lactulose and antibiotics such as rifaximin. L-ornithine -L-aspartate (LOLA), the salt of the natural amino acids ornithine and aspartate acts through the mechanism of substrate activation to detoxify ammonia. 14

15 Aim: To determine the efficacy of LOLA in addition to therapy with lactulose and rifaximin for the treatment of HE. Methods: We have examined 66 patients with liver cirrhosis (LC) admitted in St. Spiridon Emergency Hospital Iasi for HE during Subjects were divided into two equal groups (n = 33) with similar age, gender and characteristics of liver disease (ethiology, Child-Pugh score). Group 1 received lactulose and rifaximin and Group 2 lactulose, rifaximin and LOLA. Results: Among our study group, of which stage B by Child-Pugh in 9 (13.63%); stage C in 57 (86.36%), all patients had chronic liver cirrhosis and hepatic encephalopathy (HE) I III degrees according to West Haven criteria. All patients were divided into two groups (n=33) depending on the therapeutic approach: I - lactulose 20 ml x2/day + rifaximin 1200 mg/day; II LOLA 15 g/day + lactulose 20 mlx2/day + rifaximin 1200 mg/day. There were no significant differences regarding age, sex and cirrhosis etiology between the two groups. The patients that received LOLA had a lower readmission rate in compare with those without LOLA treatment (33.36% vs 54.54%, p=0,002). The mortality rate was similar in both groups. After 10 days of treatment, the ammonia concentration in the blood on the therapy background decreases maximum in patients of group II 59.3% versus 30.5% in group I (p=0,01). Conclusion: In clinical trials, LOLA has shown a statistically significant effect to reduce HE grade, in reduction of blood ammonia concentration and positive effects on psychomotor function in patients of cirrhosis with minimal HE and overt chronic Grade I HE, as compared to placebo. However, there is lack of data on the efficacy of LOLA in patients with overt acute hepatic encephalopathy which is one of the major causes of hospital admissions and resource utilization in decompensated cirrhosis. The combined therapy of HE with Rifaximin, LOLA and basic therapy proved to be the most effective. 10. Multidisciplinary team approach to hepatocellular carcinoma management in a liver transplant center from Romania Cerban R.1, Iacob S.1, Croitoru A.1, Popescu I.3, Dumitru R.2, Grasu M.2, Ester C.1, Pietrăreanu C. 1, Ghioca M.1, Gheorghe C.1 and Gheorghe L.1 1 Department of Gastroenterology and Hepatology, Fundeni Clinical Institute, Bucharest Romania 2 Radiology Department, Fundeni Clinical Institute, Bucharest Romania 3 Dan Setlacec Centre of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania. Introduction: Optimal care of the patient with hepatocellular carcinoma (HCC) requires the involvement of multiple specialists. The aim of our study is to evaluate the outcome following the decision taken in a Multidisciplinary Liver Tumour Board for the treatment of HCC. Methods: In this prospective study from January 2015 to October 2017 we included 255 treatment naive patients, diagnosed with HCC. All patients were discussed in the Tumour Board and the therapeutic decisions were: resection 11 patients(4.3%), liver transplantation: 48 patients(18.8%); intraoperative radiofrequency ablation (RFA): 14 patients(5.4%), percutaneus RFA: 10 patients(3.9%), transarterial chemoembolization (TACE): 90 patients(39,2%), Sorafenib treatment: 45 patients(17.6%) and best supportive care (BSC): 50 patients(19.6%). Results: All patients (M=160, F=95) with an average age of 62 years (±8.1) that were included had cirrhosis (HCV-related in 55.9%). Short-term mortality rate (3 months) was 17.6% (45 patients), 77.8% of those patients being in the BSC group and the rest (10 patients) died on the transplant list due to complications of cirrhosis. The success rate was nearly equal in RFA (79.3%) and surgery (81.9%), whereas the success rate was 63.9% in TACE. In 62 patients (68%) a classic lipiodol TACE was performed, while 31% of patients had a drug eluting microsphere procedure. 34 patients had complete tumor response after one TACE. There was a significant transient decrease in the mean platelet level after TACE (p=0.006). Liver transplantation was performed in 20 patients (7.8%). The median follow-up period was 18 months. Overall patient survival at 1 year for surgery group, TACE and BSC was 96.1, 95.7% and 6% respectively. Conclusion: Therapeutic interventions should be decided on a case by case analysis. Surgery has comparable outcome to RFA but is more invasive. TACE was the most frequent procedure performed on HCC patients in our centre, and was shown to be a safe and effective therapy. 15

16 11. Metabolic syndrome in liver transplant recipients The role of genetic testing and blood based biomarkers Ester C.1,3, Cerban R.1,3,, Iacob R.1,3, Iacob S.1,3, Sorop A.4, Savu L.6, Lita M.1, Constantin G.2, Paslaru L.2,3, Grancea C.5, Ruta S.3,5, Popescu I.4, Gheorghe L.1,3 1. Department of Hepatology and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania 2. Department of Biochemistry Liver Transplant Unit, Fundeni Clinical Institute, Bucharest, Romania 3. Carol Davila University of Medicine and Pharmacy, Bucharest, Romania 4. Department of General Sugery and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania 5. Stefan Nicolau Virology National Institute, Bucharest, Romania 6. Genetic Lab, Bucharest, Romania Aim: Liver transplant recipients are more likely to develop de-novo or recurrent non-alcoholic fatty liver disease (NAFLD), most of them fulfilling the criteria for metabolic syndrome. Our aim was to assess the impact of single nucleotide polymorphyisms of PNPLA3 rs ( C>G) and TM6SF2 ( C>T) and novel blood biomarkers (CXCL-10 and CXCL-12) on the presence of steatosis, fibrosis progression and metabolic syndrome. Methods: We assessed61 liver transplant recipients for clinical and biological features and genetic polymorphism in the PNPLA3 and TM6SF2 genes using the automated TaqMan pre-designed SNP genotyping assay. All patients performed abdominal ultrasound, Fibroscan with CAP module and non-invasive scores for liver fibrosis (APRI, FIB-4, NAFLD). Results: HCV cirrhosis wasthe main indication for liver transplantation (69% of patients), 62.3% were males and the mean age at evaluation was 56 years. The incidence of metabolic syndrome was 53.33% in the studied population. The heterozygous SNP polymorphisms of PNPLA3 (CG) was the most frequent in the studied population (52,83%), and the homozygous mutation was found in 13,21% (7 patients). Regarding the TM6SF2 polymorphism the heterozygous type was found in 11,32% of patients and no patients presented the homozygous form. The univariate logistic regression for the predictors of the metabolic syndrome identified PNPLA3 SNP that a genotype other than CC for PNPLA3 is associated with a lower risk for metabolic syndrome : for CG variant OR = 0.35 but the evidence is inconclusive (p = 0.131), and for GG variant OR = 0.12 with p < No significant statistical difference was found for the TM6SF2 SNP (OR=0,39, p=0,571). For the PNPLA3 SNP rs we can observe a progressive decrease in the mean serum total cholesterol values when the mutation is present (from 176 mg/dl in CC SNP, to 170 mg/dl in CG SNP to 165 mg/dl in GG SNP) and a slight increase in the median triglycerides serum levels from 106 mg/dl with the CC SNP towards 126 mg/dl with the GG SNP. The multivariate logistic regression results identified.pnpla3 variants and CXCL10 > 350 ng/ml as independent risk factors for fibrosis, although for CG variant of PNPLA3 the evidence is inconclusive (p = 0.062). Conclusion: PNPLA3 polymorphism impacts on the key elements of metabolic syndrome like the increase in serum tryglicerides and fibrosis progression. The observed result of lower serum cholesterol in patients with heterozygous and even more in patients with homozygous polymorphism of PNPLA3 gene could be closely correlated with the increase in intrahepatic cholesterol deposits, but this should be confirmed by larger histology-based studies. PNPLA3 polymorphism and CXCL-10 have been identified as the mai predictors for advanced fibrosis in liver transplant recipients. Saturday, 6 April Hepatitis B virus status in patients with chronic hepatitis C Cojocariu C.1,2, Huiban L.2, Girleanu I.1,2, Singeap A.M.1,2, Sahawneh D.1, Hordila A.1, Stanciu C.1, Trifan A.1,2 Institute of Gastroenterology and Hepatology, St. Spiridon Emergency Clinical Hospital1, University of Medicine and Pharmacy Grigore T. Popa 2, Iasi, Romania Introduction: The risk of hepatitis B virus (HBV) reactivation among hepatitis C virus (HCV)-infected patients receiving IFN free therapy raises questions about how many HCV-infected patients have active, past, or latent/occult HBV co-infection. Aim: to evaluate the status of hepatitis B [hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti HBs), total hepatitis B core antibody (anti-hbc)] infection in patients with hepatitis C antibody positive. Material and method: we performed a prospective study in which we included all patients with hepatitis C antibody positive who were admitted in a tertiary referral center from North-Eastern Romania and were evaluated for IFN free treatment between June 1st, 2018 and March 1st, All patients included in the 16

17 study performed the quantitative determination of HCV RNA, HBsAg, anti HBs, anti-hbc; HBV DNA was determinate only in HBsAg positive patients. Results: we evaluated 473 patients with hepatitis C antibody positive; mean age was 54.6±5.2 years and the most patients were female ( %). Among all patients only four of them (female) were positive for HBsAg (0.85%); the HVB DNA was undetectable in two patients and detectable but less than 1000 UI/ml. 12.5% of patients had antibodies anti HBs, but most of them with unprotected levels of antibodies anti HBs (non of these patients have record of any HBV vaccination). However, 24.5% of patients were anti-hbc positive. During the IFN free treatment and the follow-up period we do not observed any reactivation of hepatitis B virus (based on no flare of aminotransferase that could suggest that). Conclusion: although in HCV patients a small proportion (0.85%) is positive for HBsAg, almost 25% have evidence of past HBV infection (anti-hbc positive). The immunity to HBV evidenced by anti-hbs is quite low, only 12.5% of patients, explained probable by the mean age of our patients and HVB vaccination missing. 13. METABOLIC CHANGES AFTER VIRAL ERADICATION IN PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION Cuciureanu T.1,2, Huiban L.1,2, Chiriac S.1,2 Muzica C.M. 1,2 Singeap A.M.1,2, Stanciu C.2, Trifan A.1,2 1. Grigore T Popa University of Medicine and Pharmacy 2. Institute of Gastroenterology and Hepatology, Iasi, Romania Introduction: Chronic hepatitis C infection is a systemic disease, and it is to be considerednowadays a new cardiovascular risk factor due to its metabolic changes and its effect on the vascular endothelium. Aim: The purpose of our study was to evaluate the metabolic changes after viral eradication, in order to observe if the cardiovascular riskremains the sameor increases after antiviral treatment. Methodology: We conducted a prospective study between May 2017 and December 2018 in which we included patients with chronic hepatitis C (CHCV) hospitalized in the department of Gastroenterology and Hepatology at Saint Spiridon Hospital, Iasi. The patients received treatment with direct acting antivirals. All patients included in the study were completely evaluatedbefore and after the treatment and 6 months later. We analyzed the lipid profile, serum glucose and body mass index before and after antiviral treatment with direct acting antivirals. Results: 100 patients included out of which 58 men and 42 women, mean age years (34-80 years). At the baseline before receiving antiviral treatment, the study group registered higher values of LDL cholesterol in 32% of patients and blood glucose in 28 % in absence of known diabetes. At first evaluation, 52 patients had the body mass index (BMI) above 25kg/m², out of which 22 had obesity type I, 28 patients were overweight. After obtaining sustained viral response (SVR) in 49 % patients with CHCV is seen an improvement in lipid profile and blood glucose value. At 6 months evaluation from the SVR, an increase of the BMI is seen in 25 % of the patients, LDL cholesterol increases in 28% of the cases, with no improvement of HDL cholesterol in the study group. Conclusion: Our study shows an improvement in glucose and lipid profile after SVR in a short term reducing overall cardiac risk, but after a period more than 6 months a small percentage of patients experience weight problems and worsening of the lipid profile due to causes that need further studies. KEYWORDS: VIRUS C, METABOLISM, ANTIVIRAL 14. De novo occurrence of non-hodgkin s lymphoma after SVR with direct acting antivirals for HCV infection Ghioca M.1,4, Iacob S.1,4, Ester C.1,4, Cerban R.1,4, Bardas A. 2, Coriu D.2,4, Lupescu I.3,4, Becheanu G.1, Dobrea C.4, Gheorghe C.1,4, Gheorghe L.1,4 1 Department of Gastroenterology and Hepatology, Fundeni Clinical Institute, Bucharest, Romania 2 Department of Hematology, Fundeni Clinical Institute, Bucharest, Romania 3 Department of Radiology, Fundeni Clinical Institute, Bucharest, Romania 4 Carol Davila University of Medicine and Pharmacy, Bucharest, Romania Background and aims: Hepatitis C virus (HCV) is known to be a lymphotropic virus, triggering B-cells and promoting B lymphocyte proliferation. It is associated with various lymphoproliferative disorders. Antiviral therapy for HCV, including direct acting antivirals (DAA s) has proven to be effective in the treatment of HCV- 17

18 related lymphomas. There are reported only a few cases of lymphoma after viral eradication. Methods: We report a series of 3 cases with HCV- related liver cirrhosis, two of them with sustained virological response (SVR) after DAA therapy for HCV infection and one with SVR after interferon + Ribavirin therapy, that were diagnosed with large B cell non-hodgkin s lymphoma. Results: The first two cases are those of a 65 years-old woman and a 51 years-old male, diagnosed with HCV-related liver cirrhosis in 2014, respectively in 2017, based on high HVC- RNA level, with compensated disease, that were treated during 12 weeks with Ombitasvir-Paritaprevir/ Ritonavir + Dasabuvir in 2015, and respectively with Ledispasvir + Sofosbuvir in They obtained SVR after DAA s and did not present any complications during the follow-up period. The first patient presented 2 years after HCV eradication with large laterocervical adenopathies and the second one presented in July 2018 with diffuse abdominal pain. The last case is a 67 years-old woman, diagnosed with HCV-related liver cirrhosis in 2007, treated with interferon + Ribavirin in 2006, with SVR, that in August 2018 presented with diffuse abdominal pain and weight loss. The diagnosis was established trough a close collaboration between the hematologist, radiologist and the anatomopathologist in all 3 cases, using imaging techniques (computed tomography scan) and a CT guided lymph node biopsy, respectively liver biopsy were performed and the histopathological diagnosis was large B-cell non-hodgkin s lymphoma. Conclusions: Direct acting antivirals are the strategy to mainly prevent the occurrence of hepatic manifestations, and also extrahepatic, including lymphoma, but in some rare cases, HCV eradication is not the end point. 15. FACTORS ASSOCIATED WITH INTRATUMORAL ELASTOGRAPHIC MEASUREMENTS VARIABILITY Ghiuchici AM. 1, Danila M. 1, Popescu A. 1, Sirli R. 1, Burciu C. 1, Topan M. 1, Sporea I. 1 1 Victor Babeş University of Medicine and Pharmacy, Timişoara, Romania Objectives: Several studies showed that elastography can bring additional information regarding the stiffness of focal liver lesion, in order to predict their nature. However, there is a great amount of heterogeneity shown in the studies published to date. This study aimed to evaluate the factors that influence intratumoral elastographic variability. Methods: This prospective study included 106 patients, presenting to our tertiary department with focal liver lesions (FLLs) diagnosed on conventional ultrasound: 60 men (56.6%) and 46 women (43.4%), mean age 64.3± 12.3 years. A total of 116 FLLs were examined. The final FLL diagnosis was established by an imaging method (contrast enhanced CT or MRI) or biopsy. Elastographic measurements (EM) were obtained in 116 FLLs using VTQ (Siemens). We performed 10 EM in the liver parenchyma and 10 EM in each focal liver lesion. Medians and interquartile ranges (IQRs) were calculated (m/s). We used the interclass correlation coefficient (ICC) with 95%b lower and upper limits of agreement (LOA) to assess the intraobserver reproducibility of VTQ. We analyzed the correlation between intralesional elastographic variability and tumor size, depth, tumor heterogeneity. Results: A total of 116 lesions were evaluated. The lesions were: 88/116(75.9%) hepatocellular carcinomas, 11/116(9.5%) hemangiomas, 12/116(10.3%) metastases, 3/116(2.6%) focal nodular hyperplasia and 2/116(1.7%) adenoma. The total mean values obtained were: 2.2 m/s in HCCs, 1.9 m/s in hemangiomas, 2.9 m/s in metastases, 2.4 m/s in FNH and 2.35 m/s in adenoma. We did not find significant differences between the first five and the last five EM, the intraobserver reproducibility was excellent ICC: (95% CI: ). However, the tumor size, heterogeneity and depth correlated with higher variability in intralesional stiffness (p<.0001). Conclusions: Overall intraobserver reproducibility was excellent ICC: (95% CI: ). Tumor size, depth and tumor heterogenity correlated with higher intralesional stiffness variability (p<.0001). 18

19 16. SPONTANEOUS SEROREVERSION OF ANTI-HEPATITIS C VIRUS DURING THE NATURAL COURSE OF HEPATITIS C VIRUS INFECTION IN THE PATIENTS EVALUATED FOR TREATMENT - A SINGLE CENTER EXPERIENCE Cojocariu C. 1,2, Huiban L.1,2, Stanciu C.2, Muzica C.M. 1,2, Stoica O. 1,2, Girleanu I.1,2, Singeap A. M.1,2, Cuciureanu T. 1,2, Chiriac S. 1,2, Trifan A.1,2 1. Grigore T Popa University of Medicine and Pharmacy 2. Institute of Gastroenterology and Hepatology, Iasi, Romania Keywords: hepatitis C virus infection, spontaneous seroreversion, direct antivirals Introduction: Hepatitis C virus (HCV) infection is common worldwide but there are different prevalence rates in different countries. Spontaneous viral clearance occurs in 10 25% of infected individuals after acute infectionyet controversy exists regarding the frequency of spontaneous clearance during the natural course of HCV infection in the general population. Aim: In our study we aimed to evaluateundetectable ARN HCV prevalence inantibodies HCV population evaluated for IFN free treatment. Material and Methods: We performed a prospective study in which we included all patients with positive anti -HCV antibodies who were admitted in a tertiary referral center from North-Eastern Romania and were evaluated for IFN free treatmentbetween June 1st 2018 and March 1st All patients included in the study performed the quantitative determination ofhcvviraemia. The patients with sustained virological response tointerferon (IFN) therapy were excluded from the study. Results: The study included 473personswith positive anti -HCV antibodies; mean age was 54.6±5.2 years, predominantly female( %).among all patients with positive anti-hcv antibodies, in 45 (9.51%) cases we found undetectable HCV viraemia. Seroreversion occurred in individuals with a median age of 58 years (range 45 66). Of the patients with undetectable HCV viraemia, 28.8% had elevated transaminases. Conclusions: The frequency of spontaneousviral clearance in a homogeneous population of immunocompetent subjects not related to treatment with IFN was low (9.51%). These data are consistent with the literature where viral spontaneous clearance was 2-10% in a cohort of HCV infection. 17. Upper gastrointestinal bleeding in hepatocellular carcinoma: role of portal vein thrombosis Gîrleanu I., Trifan A., Teodorescu A, Cojocariu C., Petrea O. C., Sîngeap A.M., Sfarti C., Chiriac S., Huiban L., Cuciureanu T., Stanciu C. Grigore T. Popa University of Medicine and Pharmacy, St. Spiridon University Hospital, Institute of Gastroenterology and Hepatology, Iași, Romania Introduction: Hepatocellular carcinoma (HCC) is one of the most severe complication of liver cirrhosis. The leading causes of death in HCC are hepatic failure and GI bleeding (GIB). Although, variceal bleeding is mostly due to cirrhosis induced portal hypertension (PH), portal vein thrombosis (PVT) induced PH may play a role. HCC is a leading cause of PVT by tumor invasion of the PV. Therefore the aim of this study was to assess the role of PVT development in cirrhotic patients diagnosed with HCC. Material and methods: A prospective analysis was performed on 56 cirrhotic patients diagnosed with HCC who were admitted in a tertiary center from January 2016 to December After resuscitation, emergency upper GI endoscopy was performed searching for the source of bleeding. Appropriate endoscopic therapy was applied to control bleeding whenever indicated. A full lab and imaging studies were done for all patients. Results: Out of the 56 cirrhotic patients diagnosed with HCC, 41 patients (73.2%) were males of relatively younger age (mean 53.5 years). HCV was detected in 42.8 % of our HCC patients, while HBV was detected in 19.6 %. All our bleeding HCC patients were cirrhotics with 51 (91.1 %) of them were Child s class B or C. PVT was detected in 46.4 % of bleeding HCC patients with 50 % of them Child s class C. Varices is the most common cause of UGIB in our HCC patients (96.1 %), while non-variceal sources were detected in only 4 patients (7.1 %). Most of the patients (89.2 %) presented with 1st bleeding episode, while 6 (10.7 %) presented with recurrent bleeding. PVT was diagnosed in 23 patients (41.07%). Out of the 23 patients diagnosed with PVT, 9 patients died during hospitalization and in 18 patients we failed to control bleeding. Conclusions: Variceal bleeding is the most common cause of UGIB among HCC patients. PVT plays an im- 19

20 portant role both in the initiation as well as recurrence of variceal bleeding in HCC patients and negatively influences the patient prognosis. 18. Interferon-free treatment risk factor for the portal vein thrombosis? Lazăr R.¹, Confederat L. ¹, Gîrleanu I. 1,² ¹ Grigore T. Popa University of Medicine and Pharmacy, Faculty of Medicine- Iași, Romania ² Institute of Gastroenterology and Hepatology Iași, Romania Background: Interferon-free treatment, with-acting antiviral agents (DAA), represented a key-point regarding the cure of chronic hepatitis C and the prevention of hepatocellular carcinoma. Interferon-free treatment regimens have many advantages including an increase of sustained virological response rate (SVR), a therapeutic option for patients with low SVR or contraindications for (peg)-inf, as well as a favorable profile of side effects. Side effects of interferon-free treatment, evidenced through phase 2 and 3 of clinical studies, include asthenia, fatigability, nausea, insomnia, pruritus adding increased values of AST and bilirubin and a decrease of the hemoglobin level. Material and method: We present a case report concerning a female patient, 58 years old, diagnosed with hepatic cirrhosis due to hepatic C virus infection (Fibromax-Fibro test score = 0.88, F4), who underwent the following interferon-free treatment regimen: Dasabuvir 250 mg 1 tablet twice daily, Ombitasvir/ Paritaprevir/ Ritonavir 12.5 mg/75 mg/50 mg 2 tablets daily for 3 months with the achievement of sustained virological response. The patient also presents a double mechanical valvular prosthesis which requires permanent oral anticoagulation. Results and discussions: 1 year following the end of the treatment and the achievement of SVR, the patient returns to the Gastroenterology department, where portal vein thrombosis is detected and in addition hepatocellular carcinoma. Conclusions: The particularity of this case is the fact that the portal vein thrombosis was developed at INR values between 4 and 5, under anticoagulation, which raises the question: could the interferon-free treatment be involved per se in the development of portal vein thrombosis or the hepatocellular carcinoma favored it through the pro-coagulant status induced by neoplasm with its paraneoplastic syndrome? The question is propped by the fact that the results of the possible drug interactions between oral anticoagulants and DAA could be the risk of bleeding, not the thrombosis. 19. EVALUATION OF LIVER FIBROSIS AND STEATOSIS IN PATIENTS WITH METABOLIC SYNDROME- PRELIMI- NARY DATA Mare R., Nistorescu S., Sporea I., Popescu A., Tomescu M, Șirli R. Dept. of Gastroenterology and Hepatology, Victor Babeș University of Medicine and Pharmacy Timișoara, Romania Patient with metabolic syndrome have in many cases liver steatosis (NAFLD) and sometimes this can be followed by significant liver fibrosis. The aim of the present study was to determine the severity of liver steatosis and fibrosis in a cohort of metabolic syndrome patients, using non-invasive methods: Transient Elastography (TE) with Controlled Attenuation Parameter (CAP) and ultrasound. Material and methods: 55 patients were prospectively recruited in the study. Evaluation of liver fibrosis and steatosis was made using Transient Elastography (FibroScan) with Controlled Attenuation Parameter (CAP), performed in fasting conditions, using both probes.reliable liver stiffness measurements (LSM) were defined as the median value of 10 LSM with an IQR/median <30%.Besides this, steatosis was evaluated by means of ultrasound and graded in mild, moderate and severe. A semi-quantitative scale was used, according to the subjective assessment of the brightness ofthe liver as compared to the renal parenchyma and the intensity of posterior attenuation.when the evaluation of steatosis was performed by CAPwe used the following cut-off values proposed by the manufacter: S1 (mild) <230, S2(moderate): db/m, S3(severe) > 300 db/m.on the other hand, a cut-off value of 8.5 kpa[1] was used to define clinically relevant fibrosis (F 2). 20 Results: Reliable liver stiffness measurements were obtained with FibroScanin 94.6% (52/55). The mean age value was 59.4± 10.5, the majority of them were males 60% and the BMI was35.1± 5.02kg/m2. Moderate and severe steatosis by means of CAP was found in 7.7% and 75% cases, respectively. Clinically relevant fibrosis was detected by means of TE (LSM 8.5 kpa) in 25% (13/52) of subjects, all subjects concomitantly had CAP values 300db/m, suggesting severe steatosis. The correlation between CAP and ultrasound assess

21 ment of steatosis was high (r=0.90, p<0.0001). Conclusions: In our group, 82.7% of metabolic syndrome patients had moderate and severe steatosis by CAP and 25% of them had clinically relevant fibrosis by TE. Standard ultrasound of the liver showed good correlation with CAP for the evaluation of steatosis. References:1. Petta S et al. Improved Noninvasive prediction of Liver Stiffness Measurement in Patients with Nonalcoholic Fatty Liver Disease Accounting for Controlled Attenuation Parameter Values. Hepatology Doi: /hep Wilson s disease: clinical presentation, biochemical profile and outcome- a 5-year experience of a tertiary referral centre Nemteanu R.1,2, Plesa A.1,2, Ciortescu I.1,2, Girleanu I1,2, Stanciu C. 2, Trifan A.1,2 1. University of Medicine and Pharmacy Grigore T. Popa, Faculty of Medicine, Iasi, Romania 2. St. Spiridon Hospital, Institute of Gastroenterology and Hepatology, Iasi, Romania Background: Wilson's disease (WD) is a rare genetic disorder related to copper storage, leading to liver cirrhosis and neuropsychological deterioration. Epidemiological and clinical data are limited in the northeastern part of Romania owing to low disease frequency. Objective and methods: We performed a retrospective five-year analysis (1st January, st December, 2018) of medical records of all adult patients diagnosed with WD, examined at the Institute of Gastroenterology and Hepatology, Iasi, Romania. Clinical manifestations, biochemical, and histological profiles were assessed for each patient to determine presentation, diagnostic course and long term outcome. Results: A total of 22 patients, 16(72.7%) female, mean age 29.78±11.23 years were included. Diagnostic criteria for non-ceruloplasmin bound serum copper, serum ceruloplasmin, 24 h urinary copper excretion, liver copper content were researched in all patients evaluated, and the presence of Kayser Fleischer rings and histological signs of chronic liver damage were reached in 12 (54.5%) and 3 (13.6%) of patients, respectively. Patients with neurological symptoms were significantly older at the onset of symptoms than patients with hepatic symptoms (29.1 versus 22.5 years of age, p=0.06), and the neurological symptoms were associated with a significantly longer time from onset to diagnosis than hepatic symptoms (53.4 versus12.8 months, p<0.05). Most patients stabilized or improved on chelation therapy (77.2%), but 18% deteriorated; 2 cases required liver transplant, and 9% died within the observation period. Cirrhosis at diagnosis was the best predictor of death (OR 7.9; 95% CI, ; P =.023). After initiating treatment, 81% of the patients had a stable or improved course of the disease. Disease progression under treatment was more likely for neuropsychiatric than for hepatic symptoms. Conclusion: WD patients had an overall good long-term prognosis. Early diagnosis, at a precirrhotic stage, might increase survival times and reduce the need for a liver transplant. 21. Liver involvement among adult patients with celiac disease Nemteanu R. 1,2, Plesa A.1,2, Ciortescu I.1,2, Girleanu I.1,2, Gorincioi C.2, Stanciu C2, Trifan A.1,2 1. University of Medicine and Pharmacy Grigore T. Popa, Faculty of Medicine, Iasi, Romania 2. St. Spiridon Emergency Hospital, Institute of Gastroenterology and Hepatology, Iasi, Romania Introduction: Celiac disease (CD) in multifaced autoimmune disorder with several extraintestinal manifestations. The aim of the present study was to determine the proportion of adult patients CD who had idiopathic hypertransaminasemia at diagnosis and at follow up, after initiation of a gluten free diet (GFD). Material and methods: The study included only adult patients with biopsy proven CD evaluated in the Institute of Gastroenterology and Hepatology, a tertiary referral center between October, October, 2018, identified through computerized biopsy reports from the Department of Pathology. Electronic or paper patient records were systematically collected and general information and information about presenting symptoms, serology, laboratory parameters, and histological assessment of biopsy samples were obtained manually and stored into one data base. Alanine transaminase (ALT) and aspartate transaminase (AST) values at diagnosis and after initiation of a gluten-free diet (GFD) were assessed. Results: The study group included 102 patients, 80 (78.4%) females, and the mean age was 40.36±12.31 years (range 20-73years). When assessing the serological parameters, IgA-tTG levels (61.45± u/ml vs 21

22 162.02± u/ml, P=0.001) correlated with intestinal villous atrophy (Marsh 1-2 vs Marsh 3a-c) in CD patients, with a sensitivity of % and a specificity of %. A total of 48 (47%) had idiopathic hypertransaminasemia at the time of diagnosis. Of the 48 patients with hypertransaminasemia at diagnosis who had repeat laboratory test results after starting the GFD, 32(66.6%) normalized whereas 16 (33.3%) remained elevated. Those with hypertransaminasemia were younger than those with normal levels (P < ). Gender, symptoms at diagnosis, and body mass index were not predictive of elevated transaminases. Conclusions: Hypertransaminasemia is present at diagnosis in a considerable proportion of patients with CD. Younger patients are more likely to have an elevation in transaminases. Abnormal transaminases normalize in the majority of patients after initiation of a GFD. 22. BODY MASS INDEX A NOTICEABLE FEATURE IN THE CLINICAL PROFILE OF AUTOIMMUNE HEPATITIS Sîngeap A. M. 1,2, Girleanu I. 1,2, Petrea O.1,2, Huiban L. 1,2, Stanciu C.2, Trifan A.1,2 1 Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania 2 Sf. Spiridon Emergency Hospital, Institute of Gastroenterology and Hepatology, Iasi, Romania Introduction: Autoimmune hepatitis (AIH) is rare. Viral, alcoholic and non-alcoholic steatohepatitis(nash) are more frequent and thus are firstly sought in the differential etiological diagnosis of chronic liver disease. In the clinical practice, early recognition of AIH is of upmost importance, due to its potentially severe natural course, exposing the patients to the risk of cirrhosis and its complications. Higher awareness and specific clinical profiles could help early identifying AIH. Aim: Establishing if body weight and overweight correlate with autoimmune cause of chronic hepatitis, so that they could be a confounding risk factor for AIH and NASH. Material and methods: Our study retrospectively analysedall the cases of AIH diagnosed in our tertiary referral care centre, in a three-year period. Patient s body mass index (BMI) were assessed. Proportions of normoponderal, overweight and obese patients were compared to a similar group of patients (matched for age, sex and height) with viral chronic hepatitis. The cases of cirrhosis were excluded from the analysis, from both groups. Results: Between January 2016 and December 2018, 40 patients (31 female, 9 male) were diagnosed with AIHwith no signs of liver cirrhosis. According to BMI, three (7.5%) patients were underweight, 19 (47.5%) patients were normoponderal, 15 (37.5%) patients were overweight and 3 (7.5%) patients had obesity. Body weight (72.5 +/ kg) and BMI (26.8 +/- 1.9 kg/m2) in patients with AIH were higher than in patients with viral chronic hepatitis (65 +/- 9.2 kg, and /- 5.8 kg/m2, respectively). Proportion of overweight and obese patients was significantly higher in the group of AIH patients compared to the patients with viral hepatitis (45% vs 20%, respectively, p<0.05). Conclusion: Overweight appears to be frequent among patients with AIH. As this clinical feature might primarily evoke non-alcoholic steatohepatitisin front of a non-viral and non-alcoholic chronic liver disease, attention must be drawn to careful extension of etiological work-up, to exclude AIH. 23. Hepatobiliary manifestations and complications in Inflammatory Bowel Disease- A Retrospective Study from a Tertiary Center in Romania Gîlcă-Blanariu G. E. 1,2, Petrea O.C.1,2, Ciocoiu M. 1, Timofte O. 1,2, Ștefănescu G.1,2 1 Grigore T Popa University of Medicine and Pharmacy, Iasi, Romania 2 Gastroenterology Department, Sf Spiridon County Clinical Emergency Hospital, Iași, Romania Introduction: Liver and biliary tract related manifestations and complications are considered common in inflammatory bowel disease (IBD) patients, potentially arising at any moment during disease evolution. Aim: to evaluate the hepatobiliary manifestations and complications arising in IBD patients hospitalized In the 2nd Gastroenterology Department of a tertiary center in North-Eastern Romania during a 24 months period. Material and methods: We conducted a descriptive retrospective study with data collected from all patients with IBD, admitted in the 2nd Gastroenterology Department from the Sf Spiridon County Clinical Emergency Hospital, Iasi, from January, 2017 to February, Demographic data, clinical characteristics and biochemical parameters were reviewed. Results:The study population included 364 IBD patients(mean age 48.19±14.71 years), predominantly male patients (58.9%). A total of 256(70.32%) were diagnosed with ulcerative colitis(uc) and 108(29.67%) with Crohn s disease(cd). The study group consisted predominantly of left-sided colitis(52.7%) and colonic CD cases(34.5%); 76% of patients were following 5-ASAtreatment. Among the study group, 29.12%(106)patients 22

23 presented hepatobiliary manifestations and/or complications. Liver steatosis was found in 98 patients(26,92%), being more prevalent among UC patients compared to CD patients(68,48% vs.31,52); 3 patients(0,82%) had associated primary sclerosing cholangitis, all of themwith UC. No viral hepatitis reactivation or persistent hepatocytolisis syndrome was reported as being associated duringibd treatment. Discussions: The hepatobiliary manifestations were more prevalent in UC patients; the most frequent hepatic manifestation in the studied group was liver steatosis; the identified prevalence of otherhepatobiliary manifestations in IBD patients from our center was inferior to literature reports, especially regarding primary sclerosing cholangitis.lacking identification of viral hepatitis reactivation and persistant hepatocytolisis syndrome during IBD therapy may be related to the predominant use of 5ASA therapy, and less biological therapy and thiopurines, but could moreover reside in underreporting of these complications associated with IBD treatment. Conclusion: Hepatobiliary manifestations and complications in IBD patients are common and need better surveillance. It is important to raise awareness into better monitoring of liver function and early identifying potential associated hepatobiliary involvement in this patient category, both regarding the potential involvement during disease course and also eventual side effects of therapy. 23

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28 Platinum Endorsed by EASL Gold Silver Sponsors Media Partners DATE: 5 th - 6 h April 2019 LOCATION: Crowne Plaza Hotel, Bucharest, Romania ORGANIZING SOCIETIES/INSTITUTIONS: Romanian Association for Liver Deseases (ROALD) Romanian Society of Gastroenterology & Hepatology (SRGH) Fundeni Clinical Institute, Bucharest University of Medicine and Pharmacy Carol Davila Bucharest COURSE DIRECTORS: Liana GHEORGHE, Anca TRIFAN, Ioan SPOREA ORGANIZING SCIENTIFIC COMMITTEE: Mircea DICULESCU, Anca TRIFAN, Roxana ŞIRLI Speranţa Iacob, Dan Gheonea, Bogdan Procopeţ OFFICIAL LANGUAGE: The official language of the course is English. From theory to practice in liver disease 11 CME for the two days course You can now download the dedicated application by scanning the above QR code.