Prognostic Value of Circulating Cell-Free DNA Concentration and Neutrophil-to-Lymphocyte Ratio in Patients with Pancreatic Ductal Adenocarcinoma: A Prospective Cohort Study.

Circulating cell-free DNA (ccfDNA) quantity correlates with the clinical characteristics and prognosis of various cancer types. We investigated whether ccfDNA levels and the neutrophil-to-lymphocyte ratio (NLR) have prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC). Peripheral blood was collected from 82 patients with PDAC prior to any diagnostic procedure or the administration of chemotherapy. Plasma DNA was isolated, and ccfDNA concentration and NLR were determined. We found that ccfDNA levels were correlated with age and tumor burden. Moreover, higher values of NLR (≥3.31) were linked with worse overall survival (OS) (4 vs. 10 months; log rank p = 0.011), and an elevated ccfDNA concentration (≥25.79 ng/mL) was strongly associated with shorter OS (4 vs. 8 months; log rank p = 0.009). According to the results of the multivariable Cox regression analysis, the baseline concentration of ccfDNA was an independent prognostic factor for OS (HR 0.45, 95% CI 0.21-0.97, p = 0.041). Furthermore, the combination of ccfDNA levels with NLR greatly enhanced the prognostic accuracy of PDAC patients. Our study demonstrates that ccfDNA concentration and NLR are independent predictors of survival in PDAC. Subsequent studies should validate this combination as a prognostic indicator in PDAC patients and assess its utility for guiding therapeutic decisions.

Liquid biopsy for early detection of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly prevalent and lethal cancer globally. Over 90% of HCC cases arise in the context of liver cirrhosis, and the severity of the underlying liver disease or advanced tumor stage at diagnosis significantly limits treatment options. Early diagnosis is crucial, and all guidelines stress the importance of screening protocols for HCC early detection as a public health objective. As serum biomarkers are not optimal for early diagnosis, liquid biopsy has emerged as a promising tool for diagnosis, prognostication, and patients' stratification for personalized therapy in various solid tumors, including HCC. While circulating tumor cells (CTCs) are better suited for personalized therapy and prognosis, cell-free DNA (cfDNA) and extracellular vesicle-based technologies show potential for early diagnosis, HCC screening, and surveillance protocols. Evaluating the added value of liquid biopsy genetic and epigenetic biomarkers for HCC screening is a key goal in translational research. Somatic mutations commonly found in HCC can be investigated in cfDNA and plasma exosomes as genetic biomarkers. Unique methylation patterns in cfDNA or cfDNA fragmentome features have been suggested as innovative tools for early HCC detection. Likewise, extracellular vesicle cargo biomarkers such as miRNAs and long non-coding RNAs may serve as potential biomarkers for early HCC detection. This review will explore recent findings on the utility of liquid biopsy for early HCC diagnosis. Combining liquid biopsy methods with traditional serological biomarkers could improve the overall diagnostic accuracy for early HCC detection.

Real-Life Results of Palliative Chemotherapy in Metastatic Pancreatic Ductal Adenocarcinoma.

PURPOSE: To assess the efficacy of FOLFIRINOX(FFX), gemcitabine-based regimens (GB), and gemcitabine monotherapy (Gem) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). METHODS: This is a retrospective study that included 83 patients with mPDAC treated with first-line chemotherapy (L1) with either FFX, GB or Gem between 2015 and 2017. Progression-free survival (PFS) for L1 and second-line chemotherapy (L2) (PFS-L1 and PFS-L2) and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS: Median PFS-L1 for FFX, GB and Gem groups was 9 months (95% (Confidence Interval) CI 2.76-15.24), 5 months (95%CI 3.44-6.56), and 5 months (95%CI 3.76-6.24), respectively (p = 0.04). OS was 14 months (95%CI 11.16-16.85), 12 months (95%CI: 9.44-11.56), and 7 months (95%CI: 5.7-8.3) for patients treated with FFX, GB, and Gem, respectively (p = 0.0001). ECOG-PS (0/1) (Hazard Ratio (HR) 6.74, p = 0.002), age > 70 years (HR 0.25, p = 0.04), body tumors (HR 2.8, p = 0.048), CA19-9 > 39 U/mL (HR 0.26, p = 0.02), and neutrophil-to-lymphocyte ratio (NLR) > 4.15 (HR 6.76, p = 0.001) were independent prognostic factors for PFS-L1. Male gender (HR 3.02, p = 0.026), ECOG-PS (0/1) (HR 4.21, p = 0.003), L1 with FFX (HR 0.255, p = 0.007), and NLR > 4.15 (HR 2.65, p = 0.04) were independent prognostic factors of OS. PFS-L2 (HR 6.91, p = 0.013) and OS-L2 (HR 6.95, p = 0.037) were significantly higher in patients first treated with FFX. CONCLUSIONS: The OS of patients who receive FFX or GB is comparable. The best PFS-L1 belongs to the FFX group. Male gender, ECOG-PS 0/1, the FFX regimen, and NLR > 4.15 were independent predictors of OS. PFS-L2 and OS-L2 were favorably impacted by L1 with FFX.

Endoscopic ultrasound-guided fine-needle aspiration pancreatic adenocarcinoma samples yield adequate DNA for next-generation sequencing: A cohort analysis.

BACKGROUND: Genetic tests are increasingly performed for the management of unresectable pancreatic cancer. For genotyping aimed samples current guidelines recommend using core specimens, although based on moderate quality evidence. However, in clinical practice among the endoscopic ultrasound (EUS) guided tissue acquisition methods, fine needle aspiration (FNA) is the most widely performed. AIM: To assess the adequacy for next generation sequencing (NGS) of the DNA yielded from EUS-FNA pancreatic adenocarcinoma (PDAC) samples. METHODS: Between November 2018 and December 2021, 105 patients with PDAC confirmed by EUS-FNA were included in the study at our tertiary gastroenterology center. Either 22 gauge (G) or 19G FNA needles were used. One pass was dedicated to DNA extraction. DNA concentration and purity (A260/280, A260/230) were assessed by spectrophotometry. We assessed the differences in DNA parameters according to needle size and tumor characteristics (size, location) and the adequacy of the extracted DNA for NGS (defined as A260/280 ≥ 1.7, and DNA yield: ≥ 10 ng for amplicon based NGS, ≥ 50 ng for whole exome sequencing [WES], ≥ 100 ng for whole genome sequencing [WGS]) by analysis of variance and t-test respectively. Moreover, we compared DNA purity parameters across the different DNA yield categories. RESULTS: Our cohort included 49% male patients, aged 67.02 ± 8.38 years. The 22G needle was used in 71% of the cases. The DNA parameters across our samples varied as follows: DNA yield: 1289 ng (inter quartile range: 534.75-3101), A260/280 = 1.85 (1.79-1.86), A260/230 = 2.2 (1.72-2.36). DNA yield was > 10 ng in all samples and > 100 ng in 93% of them (one sample < 50 ng). There were no significant differences in the concentration and A260/280 between samples by needle size. Needle size was the only independent predictor of A260/230 which was higher in the 22G samples (P = 0.038). NGS adequacy rate was 90% for 19G samples regardless of NGS type, and for 22G samples it reached 89% for WGS adequacy and 91% for WES and amplicon based NGS. Samples with DNA yield > 100 ng had significantly higher A260/280 (1.89 ± 0.32 vs 1.34 ± 0.42, P = 0.013). Tumor characteristics were not corelated with the DNA parameters. CONCLUSION: EUS-FNA PDAC samples yield DNA adequate for subsequent NGS. DNA amount was similar between 22G and 19G FNA needles. DNA purity parameters may vary indirectly with needle size.

Host and immunosuppression-related factors influencing fibrosis occurrence post liver transplantation.

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.

Liquid Biopsy in Squamous Cell Carcinoma of the Esophagus and of the Head and Neck.

Squamous cell carcinomas of the esophagus (ESCC) and of the head and neck (HNSCC) are two neoplasms that share common risk factors and have the same embryological origin, but a very different prognosis, the 5-year survival of HNSCC being almost double (40-50%) compared to the 5-year survival of ESCC (20%). Current guidelines emphasize the importance of screening for ESCC in patients diagnosed with head and neck cancers. A liquid biopsy is a novel tool for diagnosis, prognostic stratification, and personalized therapy. Liquid biopsy biomarkers for these two malignancies could help both their early detection, facilitate residual disease identification, and provide prognosis information. The present systematic review of the literature was aimed at describing the liquid biopsy biomarkers present in these two malignancies, with an emphasis on potential clinical applications.

Assessment of Sarcopenia Related Quality of Life Using SarQoL® Questionnaire in Patients With Liver Cirrhosis.

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.

Bowel Ultrasound: a Non-invasive, Easy to Use Method to Predict the Need to Intensify Therapy in Inflammatory Bowel Disease Patients.

BACKGROUND AND AIMS: Bowel ultrasound (BU) is a non-invasive, inexpensive, widely available tool, valuable for inflammatory bowel disease (IBD) assessment. The aim of the present study was to investigate the clinical utility of BU to predict the need to intensify therapy in IBD patients. METHODS: One hundred seventeen IBD patients (89 Crohn's disease, and 28 ulcerative colitis) diagnosis established at least 6 months before enrolment, undergoing maintenance therapy were prospectively included in the study. Bowel ultrasound investigated the following parameters: the bowel wall thickness (BWT), loss of wall stratification, the presence of the bowel wall Doppler signal, the visible lymph nodes, the mucosal hyperechoic spots, and the irregular external bowel wall. The patients were followed-up for 6 months, registering the need to escalate the treatment regimen. Subgroup analyses were conducted for patients requiring immediate treatment intensification (37 subjects), due to active disease at baseline and patients with subsequent treatment intensification, in the 6 months follow-up period (21 cases) in comparison to patients that required no therapeutic optimization (59). RESULTS: During the follow-up, 49.6% of patients needed treatment escalation. All the investigated BU variables were significantly associated with the main outcome. In the multivariate analysis, the mean BWT (p<0.0001), and the presence of the bowel wall Doppler signal (p=0.007) were independent predictors of the main outcome. For the subgroup analyses: mean BWT (p=0.0001) and the presence of the bowel wall Doppler signal (p=0.01) were independent predictors for immediate treatment intensification (active disease at baseline) and mean BWT (p=0.0003) and the lack of bowel wall stratification (p=0.05) were independent predictors for the need of subsequent therapeutic optimization. Logistic regression prediction models and prediction scores (BU score) had the best AUROC values (>0.91) when compared to traditional biomarkers of active inflammation, such as C reactive protein or fecal calprotectin. CONCLUSION: Bowel ultrasound could be used as a non-invasive, easy to use diagnostic tool to predict the need to intensify therapy in patients with IBD.

Prediction of late allograft dysfunction following liver transplantation by immunological blood biomarkers.

BACKGROUND: An accelerated course of hepatic fibrosis may occur in liver transplantation (LT) patients despite normal or slightly abnormal liver blood tests. AIM: To identify screening tools based on blood biomarkers to predict late allograft dysfunction in LT recipients. METHODS: 174 LT recipients were enrolled. Liver biopsy, liver functional tests, cytokine quantitation in serum, as well as soluble MHC class I polypeptide-related sequence A and B (sMICA/sMICB) and soluble UL16 binding protein 2 (sULBP2) were performed. RESULTS: Patients with late graft dysfunction had a significantly higher donor age, lower albumin level, higher alanine (ALT) and aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total bilirubin and alkaline phosphatase (ALP), higher sMICA, sULBP2, higher interleukin (IL) 6, interferon γ and lower IL10 in serum as compared to recipients without allograft dysfunction. In order to provide a better statistical accuracy for discriminating 5-year allograft dysfunction from other less progressive subtype of allograft injury, we established a predictive model, based on 7 parameters (serum ALP, ALT, AST, GGT, sMICA, IL6 and albumin) which provided an Area Under the Receiver Operating Characteristics (AUROC) curve of 0.905. CONCLUSIONS: Blood-based biomarkers can significantly improve prediction of late liver allograft outcome in LT patients. The new developed score comprising serum parameters, with an excellent AUROC, can be reliably used for diagnosing late allograft dysfunction in transplanted patients.

Phenotypic assessment of liver-derived cell cultures during in vitro expansion.

Background: Liver cells represent an attractive source of cells for autologous regenerative medicine. The present study assesses the liver cells' stability during in vitro expansion, as a prerequisite for therapeutic use. Results: The human liver cell cultures in this study were propagated efficiently in vitro for at least 12 passages. No significant changes in morphology, intracellular ultrastructures and characteristic markers expression were found during in vitro expansion of cells from all analyzed donors. However, expanded cells derived from male donors of >60 years old, lost the Y chromosome. Conclusion: Liver-derived cell cultures adopt a proliferative, stable mesenchymal phenotype, through an epithelial to mesenchymal transition process. The molecular and phenotypic changes of the cells during propagation are uniform, despite the heterogeneity of the different donors. Loss of Y chromosome occurs after cells' propagation in elder male donors.

Genetic and Life Style Risk Factors for Recurrent Non-alcoholic Fatty Liver Disease Following Liver Transplantation.

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.

Inflammatory Bowel Disease Management in a Romanian Tertiary Gastroenterology Center: Challenges of the COVID-19 Pandemic.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) patients management has been challenging during the ongoing coronavirus disease 2019 (COVID-19) pandemic, due to lockdowns, limitation of access to medical facilities and new recommendations regarding patient management. The implications of the COVID-19 pandemic on IBD patients' management were assessed in our Tertiary Gastroenterology Center in Bucharest, Romania. METHODS: Medical records of IBD patients admitted between 15th of March and 15th of August 2020 were retrospectively reviewed and compared to a control cohort of consecutive IBD patients admitted to our unit during the corresponding period of 2019. RESULTS: There was a highly significant shift towards one-day hospitalization during the referral period in 2020 for IBD cases (91% in 2020 vs 82.2% in 2019, p=0.0001). There was no statistically significant difference between the distribution of patient's gender, IBD phenotype or newly diagnosed IBD cases. A significantly lower proportion of admitted patients received 5-aminosalicylic acid (29% vs 41.2%, p=0.0001), whereas a substantially higher number of patients were prescribed biological therapy in 2020 in comparison to the corresponding 2019-time frame (79.5% vs 57.9%, p<0.0001). The distribution of the biological agent used was significantly different in 2019 in comparison to the 2020 period mainly due to the increase in vedolizumab prescription in 2020 (p<0.0001). During the study period in 2020, seven IBD patients (1.7%) were diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) infection, all of them with mild symptoms without impact on the IBD course. CONCLUSIONS: The COVID-19 pandemic led to reorganizing medical care, limiting the hospital admissions in favor of severe IBD cases, favoring telemedicine for mild disease and optimization of treatment for moderate to severe IBD with an increased use of biologicals aimed to maximize the risk/benefit ratio. Incidence of SARS-Cov2 infection during the first wave of COVID-19 infection in our study group was 1.7% and did not adversely impact the IBD disease course.

The Prevalence of HCV Infection and Risk Factors in a Hospital- Based Population Screening, a First Step to the Micro-Elimination of HCV Infection in Medical Institutions from Romania - Results of the HepC ALERT Study.

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.

Pre and post-liver transplant outcome of cirrhotic patients with acute on chronic liver failure.

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.

Plasma Small Extracellular Vesicles Derived miR-21-5p and miR-92a-3p as Potential Biomarkers for Hepatocellular Carcinoma Screening.

INTRODUCTION: Liquid biopsy using circulating microvesicles and exosomes is emerging as a new diagnostic tool that could improve hepatocellular carcinoma (HCC) early diagnosis and screening protocols. Our study aimed to investigate the utility of plasma exosomal miR-21-5p and miR-92-3p for HCC diagnosis during screening protocols. METHODS: The study group included 106 subjects: 48 patients diagnosed with HCC during screening, who underwent a potentially curative treatment (surgical resection or liver transplantation), 38 patients with liver cirrhosis (LC) on the waiting list for liver transplantation, and 20 healthy volunteers. The exosomes were isolated by precipitation with a reagent based on polyethylene glycol and were characterized based on morphological aspects (i.e., diameter); molecular weight; CD63, CD9, and CD81 protein markers; and exosomal miR-21-5p and miR-92a-3p expression levels. RESULTS: We first demonstrate that the exosome population isolated with the commercially available Total Exosome Isolation kit respects the same size ranging, morphological, and protein expression aspects compared to the traditional ultracentrifugation technique. The analysis of the expression profile indicates that miR-21-5p was upregulated (p = 0.017), and miR-92a-3p was downregulated (p = 0.0005) in plasma-derived exosomes from HCC subjects, independently from the patient's characteristics. AUROC for HCC diagnosis based on AFP (alpha-fetoprotein) was 0.72. By integrating AFP and the relative expression of exosomal miR-21-5p and miR-92a-3p in a logistic regression equation for HCC diagnosis, the combined AUROC of the new exosomal miR HCC score was 0.85-significantly better than serum AFP alone (p = 0.0007). CONCLUSION: Together with serum AFP, plasma exosomal miR-21-5p and miR-92a-3p could be used as potential biomarkers for HCC diagnosis in patients with LC subjected to screening and surveillance.

Geographic Distribution, Phenotype and Epidemiological Tendency in Inflammatory Bowel Disease Patients in Romania.

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.

Malnutrition Prevalence in Newly Diagnosed Patients with Inflammatory Bowel Disease - Data from the National Romanian Database.

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.

Very Early Onset Pancreatic Adenocarcinoma - Clinical Presentation, Risk Factors and Therapeutic Options.

Background: Pancreatic cancer (PC) is usually diagnosed in the 7th decade, but cases diagnosed in younger patients are associated with a greater disease burden, through the potential years of life lost. The aim of our study was to compare the differences in risk factors, clinical presentation and treatment options between patients diagnosed with pancreatic adenocarcinoma below 45 years of age (very early onset pancreatic adenocarcinoma - VEOPC), and those diagnosed over 45 years. Methods: A retrospective study has been conducted by registering in standardized Excel Worksheets all PC cases diagnosed in our tertiary referral center between 01.01.2015 and 31.12.2017. Only patients with a documented diagnosis of pancreatic adenocarcinoma (PDAC) were included in the statistical analysis that has been conducted using the NCSS v9 Statistical Software package. Categorical data have been compared using Chi2 test or Fisher Exact as appropriate, with a statistical significance p value 0.05. Results: There were 296 patients diagnosed with pancreatic solid tumors during the study period, 183 cases with documented histology: 80.87% PDAC, 17.5% neuroendocrine tumors, 2 cases of LMNH and 1 MANEC tumor. In our study group there were 24 patients (16.22%) with VEOPC. Family history of pancreatic neoplasia (33.3% vs 1.03%, p=0.0004) and alcohol consumption (42.86% vs 5.41%, p=0.01) were significantly more prevalent in young patients. Pain, as primary symptom, was reported at higher rates in patients with VEOPC (60% vs 22.94%, p=0.006). Tumors were more frequently located in the head of the pancreas in younger patients (56.52%) and in the body of the pancreas in older patients (52.07%, p=0.02). There was no significant difference in therapy or death rate during follow-up period between the two study groups, although patients diagnosed under 45 years were more frequently subjected to a radical resection (33.3% vs 22.69%). Conclusions: Our study has identified alcohol consumption and family history of pancreatic neoplasia as risk factors for VEOPC. Pain is the primary symptom at diagnosis in young patients with PDAC. In our cohort, therapeutic options do not differ significantly in PDAC patients with age of onset.

100% sustained virological response and fibrosis improvement in real-life use of direct acting antivirals in genotype-1b recurrent hepatitis C following liver transplantation.

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.