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Background: Hepatitis B Virus (HBV) remains a major global health challenge, with significant morbidity and mortality associated with chronic infections. Methods: This study examines the epidemiology, screening, and risk factors associated with HBV in Romania, focusing on a comprehensive national screening program, LIVE(RO)2, involving 320,000 individuals (majority of them considered vulnerable population). A questionnaire was used to collect information on the potential risk factors for HBV transmission. Results: The overall prevalence rate of HBV chronic infection among all the participants tested was 1.67% (confidence interval: 1.63-1.72%), with significant differences ( p = 0.0001) between participants from the main geographical regions of residence (North-East 1.89%, South 1.38%, South-East 2.06%, and South-West 1.54%). Male persons aged 30-49 or 60-69 years old, from the rural and Eastern parts of Romania and non-Romanian ethnia, with a low level of education, unvaccinated, not married, unemployed, with family members with hepatitis, with personal histories of blood or blood product transfusion, surgical interventions, tattooing, hospitalizations, imprisonment, haemodialysis, unsafe sexual contacts, or with sexual transmitted infectious diseases were risk factors associated with HBsAg seropositivity. Conclusions: Our findings highlight significant demographic and epidemiological patterns of reduced HBV prevalence even in vulnerable persons, as well as modified risk factors and the impact of socio-economic factors.

Background and Aims: Hepatocellular carcinoma (HCC) is a significant public health issue, with an increasing incidence and prevalence and a high incidence-to-mortality ratio. The prognosis of HCC depends on two competing factors, tumor burden and underlying liver disease severity, encompassed in the Barcelona Clinic Liver Cancer (BCLC) classification. To assess HCC staging and the way staging affects eligibility for treatment at the time of the first diagnosis in Romania in the setting of opportunistic diagnosis, in the absence of a national HCC screening policy., Methods: Data regarding HCC staging, underlying liver disease, and eligibility for treatment at the time of diagnosis was analyzed using a prospectively maintained multicentric database, which included patients from the five largest tertiary care hepatology units in the country between June 2016 and February 2020., Results: A consecutive series of 477 patients was included. The distribution within BCLC classes was as follows: very early (0) 7.1%, early (A) 34.3%, intermediate (B) 19.4%, advanced (C) 14.2%, terminal (D) 24.7%. At the time of the diagnosis, 198 (41.5%) were eligible for a curative intent treatment, while 359 (75.2%) were eligible for a disease-modifying therapy. 228 patients (47.8%) had decompensated liver disease at the time of diagnosis, the most common decompensating event being ascites (78.1%)., Conclusions: A large proportion of HCC cases are diagnosed at the time of a decompensating event, severely restricting the therapeutic potential. Proactive diagnostic strategies should be implemented to improve the rate of actionable diagnosis.

Background: The global burden of hepatitis D virus (HDV) infection represents a major medical challenge and a public health crisis worldwide. However, there is a lack of accurate data on the epidemiology and risk factors for HDV. Hepatitis B virus (HBV) and HDV coinfection causes the most severe form of viral hepatitis, leading to a higher cumulative incidence of liver-related events compared with HBV monoinfection, including the need for liver transplantation and death., Aim: To investigate the epidemiology, natural history, risk factors and clinical management of HBV and HDV coinfection in Romanian patients., Methods: This prospective study was conducted between January and July 2022 in six tertiary gastroenterology and hepatology referral centres in Romania. All consecutive adults admitted for any gastroenterology diagnosis who were HBV-positive were enrolled. Patients with acute hepatitis or incomplete data were excluded. Of the 25390 individuals who presented with any type of gastroenterology diagnosis during the study period, 963 met the inclusion criteria. Testing for anti-HDV antibodies and HDV RNA was performed for all participants. Demographic and risk factor data were collected by investigators using medical charts and patient questionnaires. All data were stored in an anonymized online database during the study., Results: The prevalence of HBV was 3.8%; among these patients, the prevalence of HBV/HDV coinfection was 33.1%. The median age of the study population was 54.0 years, and it consisted of 55.1% men. A higher prevalence of HBV/HDV coinfection was observed in patients 50-69 years old. Patients with HBV/HDV coinfection were significantly older than those with HBV monoinfection ( P = 0.03). Multivariate multiple regression analysis identified female gender ( P = 0.0006), imprisonment ( P < 0.0001), older age at diagnosis ( P = 0.01) and sexual contact with persons with known viral hepatitis ( P = 0.0003) as significant risk factors for HDV., Conclusion: This study shows that HDV infection among those with HBV remains endemic in Romania and updates our understanding of HDV epidemiology and associated risk factors. It emphasizes the need for systematic screening for HDV infection and collaborative initiatives for controlling and preventing HBV and HDV infection., Competing Interests: Conflict-of-interest statement: Medical writing support was provided by Joe Jones, PhD, of PharmaGenesis London, London, United Kingdom, with funding provided by Gilead Sciences Europe Ltd., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background and Objectives: Inflammatory bowel diseases (IBD) are chronic conditions with an unpredictable course and a remitting-relapsing evolution. Fatigue is a frequent complaint in patients with IBD, affecting approximately half of the newly diagnosed patients with IBD. The aim of this study was to analyze fatigue in patients with IBD in remission. Materials and Methods: One hundred nineteen consecutive outpatients diagnosed with IBD for over 3 months that were in corticosteroid-free clinical and biochemical remission at the time of assessment were included in this cross-sectional study. Out of them, 72 (60.5%) were male; the median age was 39 years (IQR 30-47). Seventy-seven patients (64.7%) were diagnosed with Crohn's disease and forty-two (35.3%) with ulcerative colitis, with a median disease duration of 6 years (IQR 2-10). Fatigue, health-related quality of life (HR-QoL), anxiety and depression were evaluated using the following self-administered questionnaires: FACIT Fatigue, IBDQ 32 and HADS. Results: The mean FACIT-Fatigue score was 41.6 (SD ± 8.62), and 38.7% of patients were revealed as experiencing fatigue when a cut-off value of 40 points was used. The mean IBDQ 32 score was 189.4 (SD ± 24.1). Symptoms of anxiety and depression were detected in 37% and 21% of the patients, respectively. In the multivariate analysis, fatigue was significantly associated with lower HR-QoL (OR 2.21, 95% CI: 1.42-3.44, p < 0.001), symptoms of anxiety (OR 5.04, 95% CI: 1.20-21.22, p = 0.008), female sex (OR 3.32, 95% CI: 1.02-10.76, p = 0.04) and longer disease duration (OR 1.13, 95% CI: 1.01-1.27, p = 0.04). Conclusions: Fatigue is highly prevalent even in patients with inactive IBD and is correlated with lower HR-QoL and anxiety, as well as with clinical factors such as longer disease duration and female sex.

Background and Aims: The sofosbuvir (SOF) / velpatasvir (VEL) / voxilaprevir (VOX) combination has been evaluated in more than 800 patients enrolled in phase II and phase III studies, where it demonstrated excellent safety and efficacy, achieving overall sustained viral response (SVR) rates of more than 95%. We aimed to assess the efficacy and safety of SOF/VEL/VOX in a real-world study, including patients previously treated for genotype 1b hepatitis C virus (HCV) infection that did not obtain a sustained viral response with previous direct-acting antivirals (DAAs) therapy., Methods: In Romania, through a nationwide government-funded program in 2019-2020, 213 patients with chronic hepatitis C non-responders to previous DAAs therapy, received treatment with SOF/VEL/ VOX 400/100/100 mg/day for 12 weeks. We performed a retrospective longitudinal study that included 143 individuals who were treated in Bucharest, Iași, Craiova and Constanța clinics, all with genotype 1b HCV infection. Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post-treatment (SVR12). Serious adverse events (SAE) were registered., Results: Our cohort comprised 53% males with a median age of 60 years (27÷77); 47% were pre-treated with ombitasvir/paritaprevir/ritonavir+dasabuvir ± ribavirin, 40% with ledipasvir/SOF, 13% with elbasvir/ grazoprevir. 42% of patients associated co-morbidities, 45% had compensated liver cirrhosis, 2% had treated hepatocellular carcinoma (HCC) and 1% had hepatitis B virus co-infection. SVR by intention to treat was reported in 139/143 (97.2%) and per protocol in 141/143 (98.6%). No predictive factors for SVR were identified. Rate of liver decompensation in patients with cirrhosis was 6% and was statistically associated in multivariate analysis with Child-Pugh score (p<0.01) and with severe steatosis (p=0.004). Occurrence of new HCC was reported in 3.6% of all patients with cirrhosis and was associated with poor liver function [higher Child-Pugh score (p=0.001) and low albumin levels (p=0.02)]. Serious adverse events related to therapy were reported in 1/143(0.7%)., Conclusions: SOF/VEL/VOX was highly efficient in our population of patients with a 97.2% SVR. Liver decompensation occurred in 6% of cirrhotic patients at SVR, related to hepatic dysfunction.

Background and Aims: Differences between countries in NAFLD patient care pathways and management need to be understood prior to defining supranational guidelines., Approach and Results: We conducted an anonymous survey in France, Germany, Hong Kong, Italy, Romania, Spain, the United Kingdom, and the United States among physicians providing specialist care for patients with NAFLD. Modalities of patient referral, patterns of practice (diagnosis, staging, monitoring, and indications for liver biopsy), therapeutic management, and expectations for future NASH pharmacotherapies were assessed, with 664 physicians completing the survey. Referral to surveyed physicians (SPs) mostly came from primary care. Prior to referral, NAFLD was rarely diagnosed, and noninvasive tests were not performed. Screening for comorbidities by SPs was incomplete and cardiovascular risk not calculated. Elastometry in combination with a serum biomarker was the most common first-line method for fibrosis staging. Liver biopsy, when performed, was often delayed by at least 1 year after diagnosis. It was, however, recommended even if noninvasive methods indicated advanced fibrosis. Frequent, biannual monitoring was conducted, including HCC surveillance in Stage 3 fibrosis. SPs rarely implemented and followed dietary and lifestyle changes themselves, and local availability of such programs was highly heterogenous. SPs favored pharmacotherapy based on mechanism of action adapted to the stage of the disease, including for early stages such as steatohepatitis with mild fibrosis., Conclusions: This international survey revealed major deficiencies and delays in referral pathways, suboptimal screening for comorbidities or managing of lifestyle modifications by SPs, and limited local availability for nonpharmacological interventions. Monitoring practices are not aligned with current guidelines., (© 2022 American Association for the Study of Liver Diseases.)

Post liver transplantation (LT) fibrosis has a negative impact on graft function. Cytokine production in the host immune response after LT may contribute to the variable CYP3A-dependent immunosuppressive drug disposition, with subsequent impact on liver fibrogenesis, together with host-related factors. We aimed to investigate whether the cytochrome P4503A5*3 (CYP3A5*3) or TBX21 genotypes impact post-LT liver fibrogenesis. Furthermore, the impact of immunosuppressants on cellular apoptosis has been evaluated using human hepatocytes harvested from cirrhotic explanted livers. We have enrolled 98 LT recipients that were followed for occurrence of liver fibrosis for at least 12 months. There was a statistically significant higher trough level of TAC in patients with homozygous CC-TBX21 genotype (7.83 ± 2.84 ng/ml) vs. 5.66 ± 2.16 ng/ml in patients without this genotype ( p = 0.009). The following variables were identified as risk factors for fibrosis ≥2: donor age ( p = 0.02), neutrophil to lymphocyte ratio ( p = 0.04) and TBX21 genotype CC ( p = 0.009). In the cell culture model cytometry analysis has indicated the lowest apoptotic cells percentage in human cirrhotic hepatocytes cultures treated with mycophenolate mofetil (MMF) (5%) and TAC + MMF (2%) whereas the highest apoptosis percentage was registered for the TAC alone (11%). The gene expression results are concordant to cytometry study results, indicating the lowest apoptotic effect for MMF and MMF + TAC immunosuppressive regimens. The allele 1993C of the SNP rs4794067 may predispose to the development of late significant fibrosis of the liver graft. MMF-based regimens have a favourable anti-apoptotic profile in vitro , supporting its use in case of LT recipients at high risk for liver graft fibrosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Iacob, Iacob, Manea, Uta, Chiosa, Dumbrava, Becheanu, Stoica, Popa, Brasoveanu, Hrehoret, Gheorghe, Gheorghe, Dima and Popescu.)

Background and Objectives: Inflammatory bowel diseases (IBD) are chronic conditions with an unpredictable evolution that can have a negative impact on patients’ quality of life (QoL). Even though patients in remission have a better QoL compared to patients with active disease, they still have a lower QoL compared to healthy people. The aim of this study is to identify the factors that are associated with a lower QoL in patients with IBD in clinical remission, in a tertiary IBD center in Romania. Materials and Methods: Ninety-seven adult patients with a current diagnosis of IBD for over 3 months who were in clinical remission were enrolled in this study. Pregnant women, patients with ostomy, perianal disease, extraintestinal manifestations or other significant comorbidities were excluded. Out of the 97 patients, 63.9% were men. The median age was 39 years (IQR 29−47), and the median disease duration was 5 years (IQR 2−10). Disease activity was assessed using the SCCAI score for ulcerative colitis and HBI score for Crohn’s disease. Remission was defined for SCCAI score ≤ 1 and HBI score ≤ 4. The health-related quality of life (HR-QoL) was assessed using the IBDQ32 score. FACIT-Fatigue was used to evaluate the level of fatigue. Patients with symptoms of anxiety or depression were identified with the HADS score. Symptoms of anxiety were considered when HADS-A >7 points and symptoms of depression when HADS-D >7 points. Results: Sixty-five patients (67%) were diagnosed with CD and the remaining 32 (33%) with UC. Ninety-three patients (95.9%) were on biological therapy. The mean IBDQ score (total score) was 190.54 points (SD +/− 8.2). The mean FACIT Fatigue score was 42.5 (SD +/− 8.2), with 6.2% of patients suffering from severe fatigue (FACIT Fatigue < 30 points). A total of 33% of patients had symptoms of anxiety and 16.5% of depression. Exposure to more than one biologic therapy (p = 0.02), fatigue (p < 0.001) and symptoms of anxiety (p < 0.001) were associated with a lower HR-QoL in the multivariate analysis. Female patients, patients with Crohn’s disease, patients with anemia and patients with symptoms of depression also had a lower HR-QoL, but this did not reach statistical significance in our study. Conclusions: Exposure to a higher number of biological agents (patients that switched multiple biologics), the presence of fatigue and symptoms of anxiety impair the HR-QoL of patients with IBD in clinical remission. Further studies should assess in a prospective manner whether early identification of these factors with prompt clinical interventions could lead to a better HR-QoL in these patients.

Introduction: Sarcopenia, malnutrition, physical deconditioning, and frailty contribute to a significantly altered quality of life (QoL) in patients with cirrhosis and sarcopenia., Aim: To investigate the sarcopenia-linked alterations of QoL by SarQoL® questionnaire in patients with end-stage liver disease., Methods: Consecutive patients with liver cirrhosis, admitted to our department between May and August 2021, completed the SarQoL® questionnaire by themselves. They were evaluated for sarcopenia according to the 2019 European Working Group on Sarcopenia in Older People (EWGSOP) definition [hand grip cut-offs and skeletal muscle index (SMI) calculation at CT scan]., Results: A total of 71 patients with liver cirrhosis were included in the study, with a median age of 54 years. Sarcopenia was present in 31.2% of patients with Child-Pugh class A, in 58.3% with class B, and in 93.5% with class C. The SarQoL® score was statistically significant and lower in Child-Pugh class C vs. class B and class A (70.2 vs. 66.5 vs. 52.5 points, p = 0.0002). The SarQoL® score was evaluated according to different complications of cirrhosis, with statistically significant lower scores in patients with sarcopenia ( p < 0.0001), in patients with ascites requiring paracentesis ( p = 0.0006), and in patients with hepatic encephalopathy ( p < 0.0001). A cut-off level of 75.9 points for SarQoL® score can accurately detect sarcopenia in patients with end-stage liver disease [area under the receiver operating characteristic (AUROC) curve of.823, SE of 92.1%, SP of 45.5%, positive predictive value (PPV) and negative predictive value (NPV) of 66 and 83.3%, respectively, correctly classified 73.2% of cirrhotic patients with sarcopenia]., Conclusions: The use of SarQoL® questionnaire in cirrhotic patients can, at the same time, evaluate the quality of life and identify subjects with sarcopenia and altered QoL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Iacob, Mina, Mandea, Iacob, Vadan, Boar, Ionescu, Buzescu, Gheorghe and Gheorghe.)

Recurrent or de novo non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) following liver transplantation (LT) is a frequent event being increasingly recognized over the last decade, but the influence of recurrent NASH on graft and patient outcomes is not yet established. Taking into consideration the long term survival of liver transplanted patients and long term complications with associated morbidity and mortality, it is important to define and minimize risk factors for recurrent NAFLD/NASH. Metabolic syndrome, obesity, dyslipidemia, diabetes mellitus are life style risk factors that can be potentially modified by various interventions and thus, decrease the risk of recurrent NAFLD/NASH. On the other hand, genetic factors like recipient and/or donor PNPLA3, TM6SF2, GCKR, MBOAT7 or ADIPOQ gene polymorphisms proved to be risk factors for recurrent NASH. Personalized interventions to influence the different metabolic disorders occurring after LT in order to minimize the risks, as well as genetic screening of donors and recipients should be performed pre-LT in order to achieve diagnosis and treatment as early as possible., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Iacob, Beckebaum, Iacob, Gheorghe, Cicinnati, Popescu and Gheorghe.)

Several biologic treatments are available in addition to intravenous also in subcutaneous form for treatment of chronic diseases. Benefits of the subcutaneous application of drugs include self-administration by the patient, shorter time of application process with less infusion related adverse events and consequently lower healthcare costs. With appropriate education and support patients are able to administer their treatments at home. This leads to improvement of quality of life, reduction of time needed to travel to the healthcare institution and consequently also reduces costs also for the patient.Over one million residents in the USA and 2.5 million in Europe are estimated to have inflammatory bowel disease (IBD), with substantial costs for health care. These estimates do not factor in the 'real' price of IBD, which can impede career aspirations, instil social stigma and impair quality of life in patients.The Virtual Community Meeting, which offered an exchange of experience and opinions from healthcare professionals who are active in treating IBD, and patients with this chronic disease, revealed in-depth arguments and answers to some essential questions: which patients prefer subcutaneous over intravenous dosing; which patients continue to favour intravenous infusions; what are the limitations regarding both applications; what is the patient's role in therapeutical decision-making and how does IBD affect the patient's work, finances and quality of life? The aim of this article is to discuss the differences between subcutaneous and intravenous dosing from the health-economic, scientific, and personal perspectives.The meeting offered strong confirmation that most of the patients and healthcare professionals prefer subcutaneous over intravenous drug administration but emphasise the management of risks associated with treatment compliance. Patient education provided by the IBD team in this regard is mandatory. Quality of life of patients is poorer during active disease, but the findings that it can improve over time, including as a result of home- or self-administration of biologics, may be encouraging for individuals with this chronic disease., (© 2021. The Author(s).)

Background and Aims: The evidence regarding the use of anticoagulant (AC) agents in portal vein thrombosis (PVT) is increasing and, most patients undergo chronic treatment with low molecular weight heparin (LMWH) or vitamin K antagonists (VKA). Nevertheless, there are no clear data about who should receive antithrombotic therapy, when to initiate it, how long and what dose should be used for this set of patients. The aim of the study was to assess the outcome of patients with cirrhosis and portal vein thrombosis who received AC therapy, in terms of thrombus regression, bleeding events and survival rates., Methods: This observational and retrospective study included 107 cirrhotic patients diagnosed with PVT in a single tertiary center between 2010-2019. 54 received low molecular weight heparin or vitamin K antagonist (AC treatment group) and 53 were untreated. All patients were periodically follow-up to assess the evolution of PVT (regression, progression, stable thrombus) and potential occurrence of bleeding events., Results: The regression of portal vein thrombosis was significantly higher in the AC treatment group (OR=2.430; 95% CI=1.11-6.167; p=0.026), more than 50% of on-treatment patients experiencing regression of the thrombus. However, bleeding events were significantly more frequent in the AC treatment group (18.5% vs. 7.5%) and the risk of bleeding was associated with thrombocytes less than 50x103/mm3 (OR=8.266; 95%CI: 2.310-39.211; p=0.002). Survival was better in the AC treatment group (68.4% vs 48.7% at 5 years and 92.7% vs 77.8% at 1 year, p=0.038) and was lower in patients that experienced bleeding events (37.22% survival at 5 years, mean time survival 44 months, p=0.008)., Conclusions: In our cohort of cirrhotic patients with PVT more than 50% of patients receiving AC therapy presented regression of the thrombus; most of them obtained partial recanalization. The bleeding complication rate was higher than expected, reaching 18%. The overall mortality was lower in the treated group.

Background and Aims: Identifying the risk factors for extraintestinal manifestations (EIMs) in inflammatory bowel diseases (IBD) may optimize the therapeutic decision. We aimed to assess the prevalence of EIMs in IBD patients in Romania and to determine the risk factors., Methods: We analyzed 2,626 patients registered in the Romanian IBD Prospect National Registry. We performed a descriptive cross-sectional study to assess the point prevalence of EIMs, calculating global prevalence and analyzing the different types of EIMs and their respective frequencies were carried out. Demographic and clinical risk factors were researched as possible predictors for EIMs development, based on the results of the univariate and multivariate logistic regression analysis., Results: The overall point prevalence of EIMs was 16.3%. A significantly higher frequency of EIMs in Crohn's disease (CD) was noted in comparison to ulcerative colitis (UC) and IBD unclassified (IBDU) (23.2% vs 11.3% and 16.3%, respectively, p<0.001). The most frequent type of EIM was peripheral arthropathy (8.3%), significantly associated with CD (p<0.001). Univariate analysis highlighted the significant independent common predictive risk factors for EIMs, in both CD and UC patients: female gender, patient's urban area of origin, anemia, hypoalbuminemia, and high level of C-reactive protein (CRP), while significant independent IBD phenotype-related risk factors were ileocolonic location and concomitant involvement of upper gastrointestinal tract for CD, non-smoker status and both moderate and severe disease activity for UC (p<0.05). Multivariate analysis determined that female CD patients with moderate or severe disease activity, with other than isolated ileal disease, and female UC patients with moderate or severe extensive colitis are the most likely to develop EIMs., Conclusions: IBD patients are experiencing EIMs in a large proportion, with higher rates for CD. As EIMs negatively affect patient outcomes, foreseeing the risk by identifying independent and associated predictive factors could be a first step to optimal work-up and treatment.

Patient and liver graft survival rates have improved significantly in the last decades, leading to complications mainly related to long-term immunosuppression. Prevention of, screening for metabolic syndrome, cardiovascular disease, de novo diabetes mellitus, renal dysfunction, and malignancies and their management are mandatory due to important causes of morbidity and mortality in this patient population. Quality of life (QoL) and functional benefits are clearly better compared to preoperative status; however, post-liver transplantation (LT) complications may impair and alter QoL scores. Individualized immunosuppression managed by transplant physicians and collaboration with other non-transplant specialists for recognition and treatment of medical complications and comorbidities after LT is the key to enhanced QoL and life expectancy of this patient population.

Background and Aims: We assessed the clinical and economic impact of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) in England, Italy, Romania and Spain., Methods: An HCV progression Markov model was developed considering DAA eligibility and population data during the years 2015-2019. The period of time to recover the investment in DAAs was calculated as the cost saved by avoiding estimated clinical events for 1000 standardized treated patients. A delayed treatment scenario because of coronavirus disease (COVID-19) was also developed., Results: The estimated number of avoided hepatocellular carcinoma, decompensated cirrhosis and liver transplantations over a 20-year time horizon was: 1,057 in England; 1,221 in Italy; 1,211 in Romania; and 1,103 in Spain for patients treated during 2015-2016 and 640 in England; 626 in Italy; 739 in Romania; and 643 in Spain for patients treated during 2017-2019. The cost-savings ranged from € 45 to € 275 million. The investment needed to expand access to DAAs in 2015-2019 is estimated to be recovered in 6.5 years in England; 5.4 years in Italy; 6.7 years in Romania; and 4.5 years in Spain. A delay in treatment because of COVID-19 will increase liver mortality in all countries., Conclusion: Direct-acting antivirals have significant clinical benefits and can bring substantial cost-savings over the next 20 years, reaching a Break-even point in a short period of time. When pursuing an exit strategy from strict lockdown measures for COVID-19, providing DAAs should remain high on the list of priorities in order to maintain HCV elimination efforts., (© The Authors. Liver International published by John Wiley & Sons Ltd.)

Background and Aims: Elimination of hepatitis C worldwide is more feasible if micro-elimination screening strategies are adopted. We aimed to screen hepatitis C virus (HCV) in specific high-risk populations in certain sub-regions of Romania and link them to antiviral treatment., Methods: A multicenter prospective study was conducted among the hospitalized or ambulatory adult patients from March 2019 to March 2020 in more than 20 medical institutions from 4 Romanian cities (Bucharest, Iasi, Timisoara, Cluj-Napoca). A rapid diagnostic test for HCV diagnosis was performed to all admitted patients and the positive ones were sent to gastroenterology departments for confirming the active infection, staging and treatment prescription., Results: In total, 25,141 subjects signed the informed consent and were consequently enrolled into the study. The prevalence of anti-HCV antibodies was 1.39% (95%CI: 1.25-1.54) and increased with the number of risk factors presented by one subject. There was a positive association between the presence of anti-HCV antibodies and female gender (p<0.001), rural area of residence (p<0.001), advanced age (p<0.001), as well as a negative association with the education level (p<0.001)., Conclusions: In a hospital-based screening micro-elimination program in Romania, HCV prevalence was lower than previously reported. This is a first step towards a cost-effective screening in a well-defined group of persons at risk and provides sufficient capacity to deliver access to HCV treatment and linkage to care in Romania.

Acute on chronic liver failure (ACLF) is a dynamic syndrome, but frequently associated with a high 1 month mortality rate. This is the first study applying the new European Association for the Study of the Liver- chronic liver failure consortium criteria to explore mortality on the waiting list (WL) and early after liver transplantation (LT) in a cohort of Romanian cirrhotic patients that improved or recovered after an episode of ACLF.To assess frequency and waitlist mortality for different grades of ACLF.An observational study was conducted; 257 patients with liver cirrhosis included on the WL between 2015 and 2017 were analyzed. The cumulative incidence of waitlist mortality or removal was calculated for combination of competing events using multivariable competing risks regression.ACLF-1 occurred in 12.07%, ACLF-2 in 7.39% and ACLF-3 in 8.56% of patients. Median Model for End Stage Liver Diseases (MELD) score at the moment of ACLF was 29. The main event while on the WL was death, followed by ACLF; patients with ACLF-3 had a significantly greater subhazard ratio for mortality of 2.25 (1.55-3.26) compared to patients with ACLF-1 or 2. LT proved to be associated with a significantly lower risk of death on the WL at 6 months after inclusion. One and 12 months post-transplant survival of patients with or without ACLF was similar (P = .77).Occurrence of an ACLF episode while on the WL is associated with a significantly high mortality rate, as well as MELD score at inclusion on the WL, renal and liver failure, presence of hepatic encephalopathy. Overall patient short and long term survival after LT is similar to non-ACLF patients in good selected cases.

Background and objective: The incidence of inflammatory bowel disease (IBD) over the past years in Romania has been on the rise, but epidemiologic data are lacking. The aim of this study was to define the characteristics of IBD, the trends and phenotype among IBD patients in Romania. Material and methods: We conducted a prospective study over a period of 12 years, from 2006 to 2017. All patients diagnosed with IBD on clinical, radiological, endoscopic and histological features were included. We divided the country into eight regions: west (W), north-east (NE), north-west (NW), south-east (SE), south-west (SW), south (S), central (C) and Bucharest-Ilfov (B), and data were analyzed accordingly. Results: A total of 2724 patients were included in this database, but only 2248 were included in the final analysis, with all data available. Of the 2248 patients, 935 were Crohn's disease (CD), 1263 were ulcerative colitis (UC) and 50 were IBD-undetermined. In UC phenotypes we observed more frequent left-sided colitis (50.5%, p < 0.0001), and in CD phenotype we observed more frequent colonic and ileo-colonic localization (37.8% and 37.6%, p < 0.0001). The region with the most IBD cases was NE (25.1%) and with the least IBD cases was SW (4.9%). UC was found more frequently in NE (32%), while CD was found more frequently in Bucharest (28.6%). Conclusions: In Romania, ulcerative colitis is more frequent than CD. UC is predominant in the northern part of Romania, while CD has become predominant in the southern part of the country. IBD occurs more in the male population, and in urban and industrialized areas. There are differences between the regions in Romania regarding IBD phenotypes, gender distributions, age distribution, treatment, smoking status and complications.

Background and Aims: Prevalence of malnutrition in inflammatory bowel diseases (IBD) varies between 16% and 75%. Data on the nutritional status at initial diagnosis of ulcerative colitis (UC) or Crohn's Disease (CD) are scarce. It is believed that more than 50% of IBD patients suffer significant weight loss prior to diagnosis. The aims of our study were to assess malnutrition in patients recently diagnosed with IBD and to determine its predictive factors., Methods: We retrospectively included 625 IBD patients registered in the Romanian "IBD Prospect" database between January 2006 and July 2017. All patients were diagnosed within 6 months prior to registration. We defined malnutrition as weight loss of more than 5% of the initial weight during the 3 months prior to registration., Results: There were 361 new cases of UC, 241 CD and 23 cases of unclassified IBD. There was a slight male predominance (M/F=1.2). Prevalence of overall malnutrition was 36.3%. It was significantly more frequent in CD than in UC patients (41.1% vs. 32.4%, p=0.031). In multivariate analysis, malnutrition in UC patients was associated with male gender (p=0.001), more severe disease (p<0.0001) and more extensive disease (p=0.027), while in CD it was associated with younger age (p=0.013) and more severe disease (p<0.0001)., Conclusions: About 1 in 3 newly diagnosed IBD patients presents with malnutrition at the time of diagnosis.

Nonalcoholic liver disease (NAFLD) is a hot topic for gastroenterologists and hepatologists and clinical practitioners must be kept abreast with the rapid progress of knowledge in this field. The Romanian Society of Gastroenterology and Hepatology (RSGH) has elaborated this review dedicated to evidence-based data on pathogenesis, diagnosis and therapy of this condition. The term NAFLD includes two distinct conditions, with different histologic features and prognosis: non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), the second with the highest risk of evolution to cirrhosis and its complications, including hepatocellular carcinoma (HCC). Non-alcoholic fatty liver disease is considered the hepatic manifestation of the metabolic syndrome. Therefore, NAFLD is associated not only with an increase of liver-related mortality, but also of the overall mortality, especially cardiovascular and malignancies. Noninvasive techniques, such as biological tests and elastography can be used for the evaluation of NAFLD patients. Liver biopsy should be recommended in selected cases, for diagnostic, therapeutic and prognostic purposes. Patients with NAFLD would benefit from their lifestyle changes by progressive weight loss through exercise and low fat and sugar diet. Pharmacotherapy should be reserved for patients with NASH, particularly for those with significant fibrosis. Until now, there are no FDA approved therapies for NASH.

Background and Aims: To evaluate the predictive factors for recurrence of the disease and overall survival (OS) after achieving complete response (CR) in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE)., Methods: From January 2013 to December 2017, 168 treatment-naïve patients diagnosed with HCC underwent TACE as a first-line therapy and the gathered data was retrospectively reviewed. We determined the predictive factors for complete response (CR), for recurrence after CR and for survival using the Cox proportional hazard model., Results: Median follow-up was 27.4 months (range 4-65 months). The mean patient age was 62.2+/-7.9 years. Eighty-three patients had an α-fetoprotein (AFP) level > 20ng/mL. The median maximal diameter of the tumors was 3.5 cm. Sixty-three patients (37.5%) achieved CR after TACE, and recurrence after CR was detected in 37 patients (58.7%). In multivariate analysis, tumor size ( 25 ng/mL and multiple tumors were demonstrated to have a significant relationship with recurrence after CR, with HRs of 1.650 (p=0.05) and 3.932 (p=0.038), respectively. Increased initial serum AFP > 22 ng/mL, tumor size > 4.5 cm, outside Milan criteria, not receiving a liver transplant and presence of portal vein thrombosis (PVT) were correlated with poor survival., Conclusions: In patients treated with TACE as an initial therapy, tumor size (≤4.5 cm) and single tumor were predictive factors for CR. Multiple nodules and an elevated serum AFP > 25 ng/mL were predictive factors for recurrence after CR. Outside Milan criteria tumors, elevated AFP levels and the presence of PVT were significantly correlated with decreased survival.

Background and Aims: Diverticular disease of the colon is a common clinical condition in developed countries, and is associated with significant (direct and indirect) economic burden. The aim of this Position Paper is to provide clinical guidance for appropriate definition, prevalence, risk factors, diagnosis, and treatment of colonic diverticular disease., Methods: A working group of recognized experts established by the Board of the Romanian Society of Gastroenterology and Hepatology (RSGH) screened the literature and the available guidelines on colonic diverticular disease. Statements were formulated based on literature evidence. These statements were discussed within the working group and decision for each of them was taken by consensus., Results: Thirty two statements were elaborated. The grade of recommendation, according to the level of evidence was established for each statement. Short comments with literature support accompany each statement., Conclusion: This Position Paper represents a practical guide for clinicians dealing with patients affected by colonic diverticular disease.

Background: Liver transplant (LT) recipients are at increased risk for developing metabolic syndrome. Early detection of NAFLD and other components of the metabolic syndrome is an important step in reducing morbidity and mortality. Methods: We assessed 60 liver transplant recipients for clinical and biological features, performed abdominal ultrasound and transient elastography (TE) Fibroscan© with controlled attenuation parameter (CAP), calculated non-invasive scoring systems APRI, FIB-4, NAFLD score, cardiovascular risk (Framingham risk score) and for the presence of metabolic syndrome and performed two biomarkers: beta 7 integrin and carbonic anhydrase IX. Results: Sixty liver transplant recipients underwent clinical and biochemical evaluation, abdominal ultrasound and TE with CAP. The median age was 56.5 years and the median time from transplantation 35 months. The Spearman correlation coefficient of beta 7 integrin and the liver stiffness measurement values obtained via Fibroscan© we obtained a moderate correlation r=0.31, but a significant association (p=0.01). The univariate analysis showed significant association between both biomarkers and liver fibrosis assessed with a cut-off value of advanced fibrosis of 8.7 kPa. The carbonic anhydrase IX showed a better correlation when compared to the liver stiffness with a correlation coefficient of 0.43 and p-value=0.0007 and a moderate correlation when compared to both FIB-4 (r=0.27) and APRI (r=0.27) score for liver fibrosis but with a significant p value=0.04, respectively 0.03., Conclusion: We consider very important for our patients the development of new non-invasive biomarkers for early diagnosis of NAFLD and NASH, as the "gold-standard" of liver biopsy is not easily accepted in clinical practice. Also NAFLD and NASH are dynamic processes that need prospective and repeated assessments, a need that cannot be met by the classical liver biopsy., (Celsius.)

Background: Nowadays, interferon-free therapy using new direct-acting antivirals (DAA) has dramatically increased the cure rate across different HCV-infected patient populations, including groups traditionally viewed as difficult-to-treat (patients with co-infections, cirrhosis and liver transplant - LT recipients) with marked improvement in safety and tolerability., Aim: To present our experience with DAA therapy in LT recipients, as well as to compare pre- and post-treatment liver stiffness (LS) and noninvasive fibrosis scores., Methods: Our cohort consisted of 89 patients with genotype 1 (GT1) recurrent hepatitis C after LT. Seventy six patients received ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin and 13 sofosbuvir/ledipasvir+/-ribavirin. Fibroscan®, FIB4 and APRI scores were performed in all patients before and 12 weeks after DAA therapy., Results: We analyzed 45 (50.5%) males and 44 (49.5%) females with a mean age of 55+/-7.7 years. Median time since LT was 20.9 months. At baseline, 53 (59.6%) of patients had severe necroinflammation at Fibromax®; advanced fibrosis (F3, F4) was encountered in 35 (39.4%) and grade 3 steatosis in 33 (37.1%) of LT recipients. End of therapy (EOT) virological response (VR) was 100%. Sustained virological response 12 weeks after therapy (SVR12) was 97.7% in the intention-to-treat analysis and 100% in per protocol analysis. There was a significant improvement in LS between antiviral therapy initiation and SVR12: 11.9+/-1.05kPa vs 8.8+/-0.6kPa (p<0.0001), as well as in APRI (2.7+/-0.3 vs 0.4+/-0.05, p<0.0001) and FIB4 (4.6+/-0.5 vs 2.5+/-0.2, p<0.0001) scores., Conclusions: In HCV positive recipients, DAA regimens are highly effective and safe. A significant decrease of LS by transient elastography and fibrosis non-invasive scores can be observed after successful therapy.

Background: Direct antiviral agents (DAA) showed very good results in terms of efficacy and safety in clinical trials, but real-life data are still needed in order to confirm this profile., Material and Methods: In Romania, through a nationwide government-funded programme in 2015-2016, approx.5800 patients with virus C cirrhosis received fully reimbursed DAA therapy with OBV/PTV/r+DSV+RBV for 12 weeks. We analysed a national prospective cohort enrolling the first 2070 patients, all with genotype 1b. The only key inclusion criteria was advanced fibrosis (Metavir stage F4) confirmed by Fibromax testing (or liver biopsy/Fibroscan). Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post-treatment (SVR12)., Results: Forty patients stopped the treatment because of hepatic decompensation (1.9%), 21 stopped because of other adverse events and one was lost to follow-up. This cohort was 51% females, mean age 60 years (25÷82), 67% pretreated, 70% associated NASH, 67% with severe necro-inflammation (severity score 3-Fibromax), 37% with comorbidities, 10.4% with Child Pugh A6, 0.5% B7. The median MELD score was 8.09 (6 ÷ 22). SVR by intention-to-treat was reported in 1999/2070(96.6%), 55/2070 failed to respond. Liver decompensation was statistically associated in multivariate analysis with platelets< 10 5 /mm 3 (P = .03), increased total bilirubin (P < .001), prolonged INR (P = .02), and albumin<3.5 g/dL (P = .03)., Conclusions: OBV/PTV/r+DSV+RBV proved to be highly efficient in our population of cirrhotics with a 96.6% SVR. Serious adverse events related to therapy were reported in 61/2070(2.9%), most of them liver decompensation (1.9%), related to hepatic dysfunction, and lower platelet count., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

All-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis at stage F2 or higher, 29 (83%) had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber, and 34 (97%) had no additional restrictions for people co-infected with HIV and hepatitis C virus. These findings have implications for meeting WHO targets, with evidence of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background and Aims: Literature data suggest that HCV genotype-1b is present in 93-99% of the Romanian patients infected with hepatitis C virus (HCV). We present the genotyping tests recently performed on patients with HCV and advanced fibrosis eligible for the Direct-Acting Antiviral (DAA) therapy, as well as the prevalence of these cases across Romania., Methods: The genotyping method was performed on 7,421 HCV patients with advanced fibrosis. The detection method was automatic real time PCR platform M2000 (Abbott). Every subject was introduced into a database including age, sex, county and address., Results: Genotype 1b was almost exclusively present: 7,392/7,421 (99.6%). Genotype 1b patients were 19.6% from Bucharest, 49% were males, with a median age of 60 years. Genotype non-1b was encountered in 29/7,421 subjects (0.4%), 62% were males, 69% from Bucharest and the median age was 52 years. Most of the subjects (75%) were in the 6th and 7th age decade. The prevalence of these cases varied significantly across Romanian counties: the highest was in Bucharest (61.3/105), Bihor (47/105), Iasi (46/105) and Constanta (43/105), and the lowest in Ilfov (2.8/105), Harghita (3.7/105), Covasna (5.4/105) and Maramures (8.8/105) (p<0.001)., Conclusions: Genotype 1b is encountered in 99.6% of patients with chronic hepatitis C and advanced fibrosis from Romania. The presence of genotypes non-1b is more common in Bucharest, in males and at a younger age. There are significant differences regarding the distribution of these cases across Romania: the highest rates are in Bucharest, Bihor, Iasi and Constanta.

Advanced age has been a major limitation of interferon-based treatment for chronic hepatitis C virus (HCV) infection because of its poor response and tolerability. Direct-acting antiviral (DAA) drug regimens are safe and highly effective, allowing administration of treatment also in elderly. This study aims to assess the efficacy and safety of paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD) with ribavirin for the treatment of patients aged ≥70 years with HCV genotype 1b compensated cirrhosis.A total of 1008 patients with HCV genotype 1b compensated cirrhosis were prospectively treated with PrOD + ribavirin for 12 weeks, between December 2015 and July 2016. Sustained virologic response 12 weeks after the end of treatment (SVR12), adverse effects (AEs), comorbidities, discontinuation, and death rates were recorded. Efficacy and safety of therapy were assessed in patients aged ≥70 years and compared with data from patients <70 years.There were 117 patients aged ≥70 years, preponderantly females (58.9%), mean age 73.3 ± 2.8 years (range 70-82), and 37 (31.6%) were treatment-experienced. Comorbidities were reported in 60.6% of patients ≥70 years and in 39.8% of those <70 years (P < .001). SVR12 rates based on intention-to-treat and per-protocol analyses were 97.4% and 100%, respectively, in patients ≥70 years, compared to 97.8% and 99.6%, respectively, in patients <70 years (P = ns and P = ns). Severe AEs were reported in 4 (3.4%) patients ≥70 years, compared to 23 (2.6%) in those <70 years (P = ns). One death was recorded in a patient aged 79 years (0.9%) and 6 deaths (0.8%) in those <70 years (P = ns).Treatment with PrOD + ribavirin in patients 70 years of age or older with HCV genotype 1b compensated cirrhosis proved as effective, safe, and well tolerated, as it did in younger patients., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Ombitasvir/Paritaprevir/ritonavir/Dasabuvir (OBV/PTV/r+DSV) is one of the elective direct-acting antivirals (DAAs) recommended by international guidelines and the only one covered by the National Insurance System in Romania until November 2016. Our aim was to present the first prospective Romanian cohort evaluating the effectiveness and safety in clinical practice of this 3DAA combination in patients with HCV genotype-1b Child A liver cirrhosis., Methods: 681 patients received OBV/PTV/r+DSV+RBV for 12 weeks and were assessed clinically and biologically at baseline, week 4, 8, 12 (end of treatment, EOT), and 12 weeks after therapy (sustained viral response, SVR)., Results: Per protocol, EOT virological response was 99.8% and SVR12 rate was 99.4%. Adverse events were present in 36.4% of patients. Permanent discontinuation of 3DAA regimen due to side effects was reported in 11 patients (1.6%). In 47.6% (185/389) of patients, Transient Elastography values were >20kPa (defined as clinically significant portal hypertension, CSPH) at baseline. Independent variables associated with CSPH were: baseline cholesterol level (p=0.003), platelet count <120,000/mm³ (p=0.02), MELD score (p=0.01). Liver stiffness measurement has significantly improved between baseline (26.6+/-12.7kPa) and SVR12 (21.6+/-11.8kPa) (p<0.0001). The same was true for APRI score (2.66+/-0.15 at baseline vs 0.85+/-0.02 at SVR12, p<0.0001) and FIB4 score (5.53+/-0.28 vs 3.24+/-0.08, p<0.0001), but not for Lok score (0.57+/-0.01 vs 0.63+/-0.01, p<0.0001)., Conclusions: We report a high efficacy of the 3DAA regimen in a homogeneous compensated HCV genotype-1b liver cirrhosis population, in a real-life setting. Noninvasive fibrosis scores significantly improved at SVR12.

Background and Aims: Hepatitis C virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments have become available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country., Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention was created and these were discussed and rated. Decisions were taken by consensus., Recommendations: We present here the second part of the Society's recommendations for chronic HCV infection treatment. An agreement between experts was reached regarding the therapy of the special categories of patients infected with HCV, complications and monitoring of the therapy, follow-up of the patients who reached sustained virologic response and re-treatment of the patients with therapy failure., Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to real-life conditions in Romania.

Background and Aims: Liver stiffness (LS) measurement by Transient Elastography (TE) has been widely accepted as a tool for fibrosis assessment. The aim of this study was to assess LS dynamics in a group of patients with HCV liver cirrhosis after interferon free treatment (IFT)., Methods: This two-center clinical trial included 225 patients with compensated HCV cirrhosis (all genotype 1b), who received IFT for 12 weeks. All patients were evaluated by means of TE at the beginning and at the end of treatment (EOT), and a subgroup (170 patients) also 12 weeks after EOT; all of them had sustained viral response (SVR). Reliable LS measurements (LSM) were defined as a median value of 10 valid LSM, with IQR <30% and SR >/=60%. Both M and XL probes were used. For diagnosing cirrhosis we used a cut-off value of 12kPa as proposed by the Tsochatzis meta-analysis. We considered a decrease or increase of more than 10% in LSM as being significant., Results: Out of 225 subjects, reliable measurements were obtained in 93.7%, so that the final analysis included 211 patients. The mean LS values decreased significantly after IFT: 26.4+/-11.7 vs. 23.5+/-13.3 kPa (p=0.01). Most patients, 59.2% (125/211) presented more than 10% decrease in LS values, 24.1% (51/211) had stable LS values, while in 16.4% (35/211) cases, the LS values increased. In the subgroup of 170 patients with LSM also performed 12 weeks after EOT (SVR), the mean LS values were significantly lower as compared to baseline: 21.3+/-11 kPa vs. 27.4+/-11.9 kPa (p<0.0001) and also as compared to EOT: 21.3+/-11 kPa vs. 23.7+/-13.3 kPa (p<0.0001)., Conclusion: In our patients with HCV liver cirrhosis, the mean LS values evaluated by TE significantly decreased after antiviral treatment at EOT and also 12 weeks after EOT as compared to baseline. Overall, about 60% of patients had LS values at EOT lower than at baseline, while 12 weeks after EOT about 75% of patients had LS values lower than at baseline.

Background and Aims: Hepatitis C Virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania the mean prevalence is about 3%. New treatments became available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country., Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention has been created. These items were discussed and rated. Decisions were taken by consensus., Recommendations: We present here the first of the two parts of our Society's recommendations for chronic HCV infection treatment. An agreement was reached regarding the diagnostic tools, the assessment of severity and the up-dated therapy schedules., Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to the real-life conditions in this country.

Background: The objective of this study is to assess the outcome of the patients treated for hepatocellular carcinoma (HCC) in a General Surgery and Liver Transplantation Center. Methods: This retrospective study includes 844 patients diagnosed with HCC and surgically treated with curative intent methods. Curative intent treatment is mainly based on surgery, consisting of liver resection (LR), liver transplantation (LT). Tumor ablation could become the choice of treatment in HCC cases not manageable for surgery (LT or LR). 518 patients underwent LR, 162 patients benefited from LT and in 164 patients radiofrequency ablation (RFA) was performed. 615 patients (73%) presented liver cirrhosis. Results: Mordidity rates of patient treated for HCC was 30% and mortality was 4,3% for the entire study population. Five year overall survival rate was 39 % with statistically significant differences between transplanted, resected, or ablated patients (p 0.05) with better results in case of LT followed by LR and RFA. Conclusions: In HCC patients without liver cirrhosis, liver resection is the treatment of choice. For early HCC occurred on cirrhosis, LT offers the best outcome in terms of overall and disease free survival. RFA colud be a curative method for HCC patients not amenable for LT of LR., (Celsius.)

Background: Liver transplantation (LT) has become an established treatment for end-stage liver disease, with more than 20.000 procedures yearly worldwide. The aim of this study was to analyze the results of Romanian National Program of LT. Methods: Between April 2000 and April 2017, 817 pts received 852 LTs in Romania. Male/female ratio was 487/330, while adult/pediatric ratio was 753/64, with a mean age of 46 years (median 50 yrs; range 7 months - 68 yrs). Main LT indications were HBV cirrhosis (230 pts; 28.2%), HCC (173 pts; 21.2%), and HCV cirrhosis (137 pts; 16.8%). Waiting time and indications for LT, patient and donor demographics, graft features, surgical procedures, and short and long-term outcomes were analyzed. Results: DDLT was performed in 682 pts (83.9%): whole LT in 662 pts (81%), split LT in 16 pts (2.3%), reduced LT in 2 pts (0.2%), and domino LT in 1 pts (0.1%). LDLT was performed in 135 pts (16.5%): right hemiliver in 93 pts (11.4%), left lateral section in 28 pts (3.4%), left hemiliver in 8 pts (1%), left hemiliver with segment 1 in 4 pts (0.5%), and dual graft LDLT in 2 pts (0.2%). Overall major morbidity rate was 31.4% (268 pts), while perioperative mortality was 7.9% (65 pts). Retransplantation rate was 4.3% (35 pts): 27 whole LTs, 3 reduced LTs, 3 split LTs, and 2 LDLT. Long-term overall 1-, 3-, and 5-year estimated survival rates for patients were 87.9%, 81.5%, and 79.1%, respectively. One-, 3-, and 5-year overall mortality on waiting list also decreased significantly over time from 31.4%, 54.1% and 63.5%, to 4.4%, 13.9% and 23.6%, respectively. Conclusions: The Romanian National program for liver transplantation addresses all causes of acute and chronic liver failure or liver tumors in adults and children, using all surgical techniques, with good long-term outcome. The program constantly evolved over time, leading to decreased mortality rate on the waiting list., (Celsius.)

Background: Liver resection (LR) is the treatment of choice for most benign and malignant focal liver lesions, as well as in selected patients with liver trauma. Few other therapies can compete with LR in selected cases, such as liver transplantation in hepatocellular carcinoma (HCC) and ablative therapies in small HCCs or liver metastases. The present paper analyses a single center experience in LR, reviewing the indications of LR, the operative techniques and their short-term results., Material and Method: Between January 2000 and December 2016, in "œDan Setlacec" Center of General Surgery and Liver Transplantation were performed 3165 LRs in 3016 patients, for pathologic conditions of the liver. In the present series, liver resections for living-donor liver transplantation were excluded. The median age of the patients was 56 years (mean 58 years; range 1-88), with male/female ratio 1524/1492 and adult/pediatric patient ratio 2973/43. Results: Malignant lesions were the main indication for LR (2372 LRs; 74.9%). Among these, colorectal liver metastases were the most frequent indication (952 LRs; 30.1%), followed by hepatocellular carcinoma (575 patients, 18.2%). The highest number of resected tumors per patient was 21, and the median diameter of the largest tumor was 40 mm (mean 51 mm; range 3-250). Major resections rate was 18.6% (588 LRs) and anatomical LRs were performed in 789 patients (24.9%). The median operative time was 180 minutes (mean 204 minutes; range 45-920). The median blood loss was 500 ml (mean 850 ml; range 500-9500), with a transfusion rate of 41.6% (1316 LRs). The morbidity rate was 40.1% (1270 LRs) and the rate of major complications (Dindo-Clavien IIIa or more) was 13.2% (418 LRs). Mortality rate was 4.2% (127 pts)., Conclusion: LRs should be performed in specialized high-volume centers to achieve the best results (low morbidity and mortality rates)., (Celsius.)

Introduction: Nonalcoholic fatty liver disease (NAFLD) has an increasing incidence worldwide, reflecting the epidemics of obesity and metabolic syndrome. Data on knowledge, attitude and management by the Romanian gastroenterologists with regard to NAFLD are lacking., Methods: We assessed current diagnostic and treatment patterns of the management of NAFLD among 102 Romanian board certified gastroenterologists using a survey developed to collect information regarding participants' clinical practice, diagnostic tools and usage of medication in patients with NAFLD., Results: 71.6% of the surveyed gastroenterologists (SG) had more than 5 years of gastroenterology practice, were university affiliated and 37.3% had predominant activity in hepatology (>60%). In Romania, 60.8% of the SG would diagnose NAFLD only if all other causes of liver disease were absent. All practitioners use a noninvasive tool for staging NAFLD, 45.1% use both serum markers and transient elastography. Liver biopsy is performed by 61.8% of the SG in the presence of a discordant result in two noninvasive methods of fibrosis evaluation. The most frequently prescribed drugs are: silymarin (88.2%), vitamin E (78.4%) and ursodeoxycholic acid (77.4%)., Conclusion: The results of this survey suggest that clinical practice patterns among Romanian gastroenterologists for the diagnosis (mainly liver biopsy) and management of NAFLD frequently diverge from published practice guidelines. Nonalcoholic steatohepatitis is probably underdiagnosed, especially in patients with normal transaminase levels and is also overtreated with drugs that are not recommended in the guidelines.

Background: The epidemiology of inflammatory bowel disease [IBD] in Eastern Europe is poorly understood, particularly with regard to diagnostic delay. Here we investigated the factors leading to delayed diagnosis and the effect of the delay on several disease progression and outcome measures., Methods: A total of 1196 IBD cases [682 ulcerative colitis [UC], 478 Crohn's disease [CD], 36 indeterminate colitis] from the Romanian national registry IBDPROSPECT were reviewed. Standard clinical and demographic factors were evaluated as predictors of a long diagnostic delay in both CD and UC. Diagnostic delay was subsequently evaluated as a potential risk factor for bowel stenoses, bowel fistulas, perianal fistulas, perianal surgery, and intestinal surgery in CD patients., Results: The median diagnostic delay was significantly longer in CD [5 months] than in UC [1 month] patients [p < 0.001]. Compared with 5 months for UC patients, 75% of CD patients were diagnosed within 18 months of symptom onset. In CD patients, extra-ileal location was a protective factor (odds ratio [OR], 0.5; p = 0.03), whereas being an active smoker [OR, 2.09; p = 0.01] and symptom onset during summer [OR, 3.35; p < 0.001] were independent risk factors for a long diagnostic delay [> 18 months]. In UC patients, an age > 40 years was a protective factor [OR, 0.68; p = 0.04] for a long delay. Regarding outcomes, a long diagnostic delay in CD patients positively correlated with bowel stenoses [OR, 3.38; p < 0.01] and any IBD-related surgery [OR, 1.95; p = 0.03] and had a positive trend for intestinal fistulas [OR, 2.64; p = 0.08] and perianal fistulas [OR, 2.9; p = 0.07]. Disease duration since diagnosis positively correlated with bowel stenoses [OR, 1.04; p = 0.04], any IBD-related surgery [OR, 1.04; p = 0.02], and intestinal surgery [OR, 1.07; p < 0.01]., Conclusions: A long diagnostic delay in IBD correlates with an increased frequency of bowel stenoses and need for IBD-related surgery., (Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Hepatitis delta virus (HDV) infection is associated with accelerated progression of fibrosis, early occurrence of hepatic decompensation and an increased risk for hepatocellular carcinoma. Epidemiological data on hepatitis delta virus (HDV) in Romania are still lacking., Aim: To assess the prevalence, virological, clinical and epidemiological features of HDV infection in Romanian patients., Methods: We conducted a multicenter study in 10 centers. Data on sociodemographic characteristics and potential risk factors were collected through a questionnaire. Virological markers of HBV and HDV infection, biochemical and clinical features of liver disease were evaluated., Results: The study population comprised 2,761 HBsAg(+) patients with a mean age of 43.8+/-13.8 years, out of whom 5.2% were HBeAg(+) and 55.7% were males. Liver cirrhosis was detected in 17.9% of patients, while 80.4% had chronic hepatitis. The prevalence of IgG anti-HDV(+) patients was 23.1%, out of whom 16.4% were HDV RNA positive. The highest prevalence of HDV infection was encountered in patients aged 50-59 years (28.9%) and patients aged >/= 60 (24.8%) (p=0.0001). Seroprevalence of HDV was significantly higher in AgHBs(+) cirrhotics vs. noncirrhotics (43.4% vs 19.0%, p=0.0001). Risk factors for HDV infection were: occupational hazard, no HCV chronic infection, lack of anti-HBV vaccination, presence of blood transfusions, any previous surgery, frequent hospitalization or endoscopies, tattoos, body piercing, use of glass syringes, number of female sexual partners., Conclusions: HBsAg(+) population in Romania is characterized by a high prevalence of HBeAg(-) HBV infection as well as HDV co-infection. A cohort phenomenon for HDV prevalence is also observed similar to that of HCV/HBV monoinfections.