Antiviral therapy substantially reduces HCC risk in patients with chronic hepatitis B infection in the indeterminate phase.

BACKGROUND AND AIMS: HCC risk in chronic hepatitis B (CHB) is higher in the indeterminate phase compared with the inactive phase. However, it is unclear if antiviral therapy reduces HCC risk in this population. We aimed to evaluate the association between antiviral therapy and HCC risk in the indeterminate phase. APPROACH AND RESULTS: We analyzed 855 adult (59% male), treatment-naïve patients with CHB infection without advanced fibrosis in the indeterminate phase at 14 centers (USA, Europe, and Asia). Inverse probability of treatment weighting (IPTW) was used to balance the treated (n = 405) and untreated (n = 450) groups. The primary outcome was HCC development. The mean age was 46±13 years, the median alanine transaminase was 38 (interquartile range, 24-52) U/L, the mean HBV DNA was 4.5±2.1 log 10 IU/mL, and 20% were HBeAg positive. The 2 groups were similar after IPTW. After IPTW (n = 819), the 5-, 10-, and 15-year cumulative HCC incidence was 3%, 4%, and 9% among treated patients (n = 394) versus 3%, 15%, and 19%, among untreated patients (n = 425), respectively ( p = 0.02), with consistent findings in subgroup analyses for age >35 years, males, HBeAg positive, HBV DNA>1000 IU/mL, and alanine transaminase

Circulating Angiogenic Markers in Gastroenteropancreatic Neuroendocrine Neoplasms: A Systematic Review.

BACKGROUND: Neuroendocrine neoplasms are a heterogeneous group of tumors that raise challenges in terms of diagnosis, treatment and monitoring. Despite continuous efforts, no biomarker has showed satisfying accuracy in predicting outcome or response to treatment. METHODS: We conducted a systematic review to determine relevant circulating biomarkers for angiogenesis in neuroendocrine tumors. We searched three databases (Pubmed, Embase, Web of Science) using the keywords "neuroendocrine" and "biomarkers", plus specific biomarkers were searched by full and abbreviated name. From a total of 2448 publications, 11 articles met the eligibility criteria. RESULTS: VEGF is the most potent and the most studied angiogenic molecule, but results were highly controversial. Placental growth factor, Angiopoietin 2 and IL-8 were the most consistent markers in predicting poor outcome and aggressive disease behavior. CONCLUSIONS: There is no robust evidence so far to sustain the use of angiogenic biomarkers in routine practice, although the results show promising leads.

HLA Genotyping in Romanian Adult Patients with Celiac Disease, their First-degree Relatives and Healthy Persons.

BACKGROUND AND AIMS: Celiac disease is characterized by an inappropriate T-cell-mediated response to gluten in small bowel in genetically predisposed individuals, carriers of the DQ2 and/or DQ8 haplotypes of the human leukocyte antigen. The aim of our study was to asses HLA typing in adult patients with celiac disease, in their first degree relatives and in a healthy control group. METHODS: We conducted a prospective observational study on three cohorts: 117 patients diagnosed with celiac disease, 41 first-degree relatives of celiac patients and 57 asymptomatic healthy volunteers. Low resolution HLA typing for DQ alleles was performed in all study subjects with DNA extracted from peripheral blood, using SSP HLA-DQB1 kit (Innotrain Diagnostik GmbH, Germany).  Next Generation Sequencing (NGS) was used only in 18 patients for typing confirmation of DQB1 and DQA1 loci and whole gene sequencing. RESULTS: Prevalence of HLA-DQ2 was significantly higher in the CD group compared to the healthy subjects group (95.6% vs 29.8%, p <0.001), with no statistically significant differences in HLA-DQ8 and combined HLA-DQ2/DQ8 prevalences.Several HLA DQA1 and DQB1 alleles (HLA-DQA1* 05:01, HLA-DQB1*02:01, HLA-DQB1*02:02) and haplotypes (DQA1*02:01-DQB1*02:02,DQA1*05:01-DQB1*02:01) were strongly associated with celiac disease in our group: OR 4.28, 4.28, 4.67 and 5.43 and 4.28 respectively. Predominantly, patients presented with typical symptoms and iron deficiency anemia. 95.5% of them had histological Marsh type modifications ≥3a. A relatively poor response to gluten-free diet was observed and 9.4% developed complications (refractory celiac disease, enteropathy-associated T cell lymphoma, intestinal adenocarcinoma), with a death rate of 6.8%. 23% associated other autoimmune diseases.Screening adherence for 1st degree relatives was very low: only 16%. Familial screening diagnosed 4 cases of asymptomatic celiac disease. 32 relatives (78%) had HLA-DQ2 haplotype, 5 carried HLA-DQ8, 4 didn't carry any risk haplotype. CONCLUSIONS: This study demonstrated a higher prevalence of the HLA-DQ2 genotype in patients with celiac disease compared to the healthy population but not of HLA-DQ8 or combined HLA-DQ2/DQ8. Alleles HLA-DQA1* 05:01, HLA-DQB1*02:01, HLA-DQB1*02:02 and haplotypes (DQA1*02:01-DQB1*02:02,DQA1*05:01-DQB1*02:01) were strongly associated with celiac disease in our cohort.

Diet as an environmental trigger in inflammatory bowel disease: a retrospective comparative study in two European cohorts

BACKGROUND AND AIMS: inflammatory bowel disease development has been associated with several environmental factors, among which, diet can play a key role, probably due to a westernized lifestyle. However, its involvement in the pathogenesis of inflammatory bowel disease (IBD) is difficult to demonstrate. The aim of this study was to analyze dietary composition in a Romanian and Belgian population with IBD. METHODS: an observational retrospective comparative study was performed using two European cohorts (Romanian and Belgian). The IBD group included 76 Romanian and 53 Belgian patients with an IBD diagnosis, while the control group included a total of 56 healthy people (35 Romanians and 21 Belgians). All subjects were interviewed and asked to fill in a questionnaire regarding diet. RESULTS: in the entire IBD cohort (Romanian + Belgian), a significantly increased consumption of sweets (OR 3.36 [95 % CI 1.6,7]), processed and high fat meat (OR 2.5 [95 % CI 1.4, 4.7], fried food (OR 9.5 [3.8, 23.6]), salt (OR 2.8 [1.5, 5.3]), ice cream (OR 3.25 [1.1, 9.8]), mayonnaise (OR 3.49 [1.1, 10.3]), margarine (OR 5.63 [1.64, 19.33]) and chips/nachos/other snacks (OR 2.3 [0.97, 5.73]) were found compared to the healthy control group. The intake of seeds, nuts (OR 0.26 [0.14, 0.52]) and yoghurt consumption (OR 0.44 [0.23, 0.83]) was lower in the IBD group compared to the control group. CONCLUSION: a westernized diet with increased consumption of sweets, processed food, high fat meat, fried food, salt, margarine, snacks, ice cream and mayonnaise seems to be a risk factor for IBD in Romanian and Belgian IBD patients. Intake of seeds, nuts and yoghurt may be a protective factor

No disponible

Diet as an environmental trigger in inflammatory bowel disease: a retrospective comparative study in two European cohorts.

BACKGROUND AND AIMS: inflammatory bowel disease development has been associated with several environmental factors, among which, diet can play a key role, probably due to a westernized lifestyle. However, its involvement in the pathogenesis of inflammatory bowel disease (IBD) is difficult to demonstrate. The aim of this study was to analyze dietary composition in a Romanian and Belgian population with IBD. METHODS: an observational retrospective comparative study was performed using two European cohorts (Romanian and Belgian). The IBD group included 76 Romanian and 53 Belgian patients with an IBD diagnosis, while the control group included a total of 56 healthy people (35 Romanians and 21 Belgians). All subjects were interviewed and asked to fill in a questionnaire regarding diet. RESULTS: in the entire IBD cohort (Romanian + Belgian), a significantly increased consumption of sweets (OR 3.36 [95 % CI 1.6,7]), processed and high fat meat (OR 2.5 [95 % CI 1.4, 4.7], fried food (OR 9.5 [3.8, 23.6]), salt (OR 2.8 [1.5, 5.3]), ice cream (OR 3.25 [1.1, 9.8]), mayonnaise (OR 3.49 [1.1, 10.3]), margarine (OR 5.63 [1.64, 19.33]) and chips/nachos/other snacks (OR 2.3 [0.97, 5.73]) were found compared to the healthy control group. The intake of seeds, nuts (OR 0.26 [0.14, 0.52]) and yoghurt consumption (OR 0.44 [0.23, 0.83]) was lower in the IBD group compared to the control group. CONCLUSION: a westernized diet with increased consumption of sweets, processed food, high fat meat, fried food, salt, margarine, snacks, ice cream and mayonnaise seems to be a risk factor for IBD in Romanian and Belgian IBD patients. Intake of seeds, nuts and yoghurt may be a protective factor.

Signification of Serum Alpha-Fetoprotein Levels in Cases of Compensated Cirrhosis and Hepatitis C Virus without Hepatocellular Carcinoma.

AFP (alpha-fetoprotein) levels are increased during the development of HCC (hepatocellular carcinoma); nonetheless, it can also be produced by non-tumoral hepatocytes in conditions of high cell turnover. Our study aims to provide additional data regarding the causes of elevated AFP in patients with liver cirrhosis due to hepatitis C virus (HCV) infection. We conducted an observational prospective cohort study that included 2068 patients with compensated cirrhosis and chronic hepatitis C genotype 1b infection. The two main inclusion criteria were the presence of advanced liver fibrosis - Metavir stage F4 - diagnosed by FibroMax testing, Fibroscan or liver biopsy, and the presence of detectable HCV RNA in the serum. Plasmatic AFP levels were determined through the electrochemiluminescence method, with a standard value ranging from 0 to 7 ng/ml. All data were obtained from the Romanian National Health Agency. The average AFP serum levels in patients with compensated cirrhosis without HCC were 9.4 ng/ml (range 0.5 ÷ 406 ng/ml); 30.1% of patients had significantly increased levels of AFP (>15 ng/ml). High values of serum AFP in patients with compensated liver cirrhosis without HCC was correlated with more advanced age (p<0.001), severe necroinflammatory activity detected by FibroMax (p<0.001), severe NASH (p<0.001), severe steatosis (p<0.001), low platelets (p<0.001), increased values of AST and ALT (p<0.001).

Environmental Factors in Romanian and Belgian Patients with Inflammatory Bowel Disease - a Retrospective Comparative Study.

Background:Several environmental factors have been associated with onset of inflammatory bowel diseases (IBD): smoking, hygiene, microorganisms, oral contraceptive pills (OCPs), non-steroid anti-inflammatory drugs, antibiotics, appendectomy, diet, breastfeeding, vitamin D, stress and ambient air pollution. The aim of this study was to investigate the prevalence of these factors in a Romanian and Belgian population with IBD. Material and methods:A total of 129 patients with an IBD diagnosis (76 from Romania and 53 from Belgium) participated in an interview and were asked to fill in a questionnaire regarding environmental factors before and after the onset of IBD; 35 Romanian and 21 Belgian healthy individuals constituted the control group. Results:A total of 40 patients with ulcerative colitis (UC) and 89 with Crohn's disease (CD) were included. Gender distribution was 43% males and 57% females. They had a median age of 42 years (range between 19-74 years), a median disease duration of eight years and 79% were in clinical remission. Both Romanian and Belgian IBD patients reported an increased antibiotic consumption before IBD onset compared to controls: 58% vs 10% (p<0.001) and 51% vs 5% (p<0.001), respectively. Belgian IBD patients declared significantly more frequent OCP use (53% vs 9%, p <0.001), they were breastfed in a lower proportion (49% vs 76%, p <0.001) and had experienced a higher level of psychosocial stress (p<0.001). Conclusion:Antibiotic consumption before IBD onset may play a pivotal role in IBD development in both Romanian and Belgian populations. In Belgian patients, OCP consumption, a higher level of psychosocial stress and lack of breastfeeding may also be involved.

Recurrence rate of hepatocellular carcinoma in patients with treated hepatocellular carcinoma and hepatitis C virus-associated cirrhosis after ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin therapy.

Introduction: Recent studies have suggested a higher recurrence rate of hepatocellular carcinoma (HCC) in patients with a history of HCC and hepatitis C virus (HCV)-associated cirrhosis treated with direct-acting antiviral (DAA) agents. Material and methods: We conducted a prospective analysis of 24 patients with HCV-associated cirrhosis and treated HCC who received ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin for 12 weeks. Prior therapies for HCC included resection (9/24 patients), radiofrequency ablation (RFA) (7/24) and trans-arterial chemoembolization (TACE) (8/24). All patients were eligible for treatment if they had no HCC recurrence 6 months after their last procedure. A control group was defined. All patients were followed every 6 months, with dynamic computed tomography and/or magnetic resonance imaging. Results: The sustained virological response rate per protocol was 21/24 (87.5%). The study group included 14 (59%) males, median age 64 years (51-77), 50% with associated non-alcoholic steatohepatitis and 24% with Child-Pugh A6 points. HCC recurrence rate/100 patient-years was lower in the DAA-HCC group versus control: 5.5 versus 24.6% patient-years for the resection+RFA group (p = 0.044), respectively, and 18.6 versus 72.7% patient-years for TACE group (p = 0.002). Survival without recurrence was higher in the resection+RFA group (45 compared to 18 months (p < 0.001)) and also in the TACE group (44 compared to 11.5 months (p = 0.002)). Conclusions: DAA therapy significantly reduced the recurrence rate of HCC and improved survival without recurrence in patients with treated HCV-associated HCC.

Iron deficiency in a tertiary gastroenterology center in Romania: prevalence and significancy.

Introduction:Iron deficiency has been known to cause significant functional impairment, lower quality of life and higher morbidity and mortality. The aim of this study was to estimate the prevalence and significance of iron deficiency in our patients and medical staff. Material and methods:We performed a prospective cross-sectional study: In July 2016, 383 persons were screened for the presence of iron deficiency (ID): 325 patients and 58 people from the medical staff. Transferrin saturation (TSAT), serum ferritin (SF) and complete blood count were performed. Absolute ID was diagnosed if SF <100 ng/ml and TSAT <20%. Relative ID was defined by SF >100 ng/ml and TSAT <20%. Results:The group of medical staff was younger and had a greater proportion of women. The prevalence of absolute ID was 22.5% in patients and 43.1% in medical staff; relative ID was present in 15% of patients and 1.7% of medical staff. Among patients, the absolute ID was significantly correlated with the female sex (p=0.002) and pre-menopausal status (p=0.01) but did not correlate with diagnosis, age, BMI, nonsteroidal anti-inflammatory drug (NSAID), aspirin or acenocoumarol consumption. The relative ID is associated with advanced age (p=0.03) and diagnosis of cancer and liver cirrhosis (p=0.01). Conclusions:Absolute ID had a high prevalence among patients (22.5%), but there was even a bigger issue among the medical staff (43.1%). Absolute ID was correlated with female sex and pre-menopausal status. Relative ID was related to advanced age, cancer and liver cirrhosis. Abbreviations: serum ferritine- SF, transferrin saturation coefficient- TSAT, iron deficiency- ID, inflammatory bowel diseases- IBD, quality of life- QoL, GI- gastrointestinal.

A Comparative Study of Efficacy and Safety of Two Eradication Regimens for Helicobacter pylori Infection.

INTRODUCTION: Helicobacter pylori infection is one of the most frequent diseases around the world, affecting about half of the world population. The infection is known to be associated with upper gastrointestinal diseases. The aim of this paper is to identify which of the following two first-line therapy options (ECA vs ECM - see abbreviations below) is more efficient and to assess the improvement in the quality of life among these patients. MATERIAL AND METHODS: 96 patients with proven Helicobacter pylori infection were divided in two treatment groups, as follows: 47 patients received a 10-day triple therapy with esomeprazole 80 mg/day, amoxicillin 2000 mg/day and clarithromycin 1000 mg/day (ECA) and the rest of 49 received a 10-day sequential therapy: esomeprazole 40 mg and amoxicillin 1000 mg twice daily for five days, followed by esomeprazole 40 mg, clarithromycin 500 mg and metronidazole 500 mg (ECM) twice daily for another five days. Assessment of Helicobacter pylori infection was performed using the stool antigen test one month after the patient finished therapy. At the beginning of the study and at the follow-up visit, every subject was asked to complete the Gastrointestinal Quality of Life Index (GIQLI). RESULTS: Twenty three patients did not come for the follow-up visit (24% drop-out rate). The ECA therapy group had an efficacy rate of 94%, while the rate of the ECM treated group was 95% (per protocol analysis). There was no significant difference regarding the baseline characteristics between the two groups. The entire group treatment tolerability was approximately 85%, with no statistical difference between groups (p-value = 0.824). Quality of life improvement was 11.18 points in the ECA treated group and 13.4 points in the ECM treated group (p=NS). Regarding the quality of life improvement, the results were positive, irrespective of type of peptic disease, but the most important results were obtained in peptic ulcer disease, functional dyspepsia and chronic gastritis. CONCLUSIONS: Both ECA and ECM regimens are almost equally effective in Helicobacter pylori eradication and significantly improve the quality of life irrespective of type of peptic disease. The limitation of this study was the significant drop-out rate (24%) that may have overestimated the results.

Adalimumab versus infliximab in treating post-operative recurrence of Crohn’s disease: a national cohort study

Aim: Perform a comparison between adalimumab (ADA) and infliximab (IFX) in treating post-operative recurrence of Crohn’s disease (a comparative analysis of efficacy and safety). Methods: From the 267 patients treated with adalimumab or infliximab between January 2005 and June 2014 in Romania, 44 received anti-TNF (tumor necrosis factor) therapy for prevention of post-operative recurrence. A comparison between patients treated with IFX and ADA was made with the Chi-square and t-student test, with the aid of the statistical program Mini Tab 17. Results: Twenty-one patients received IFX and 23 ADA. This included 49% males (22/44), with a mean age of 41 years, mean disease duration of 6 years, and 84.1% had previously received azathioprine. The IFX group is comparable with the ADA group regarding most of the parameters, except for therapy duration. Mean duration of therapy was 33 months. The rate of complete response was comparable between the two groups: 67% in the IFX group vs. 78.3% in the ADA group, the same as the rate of reresection, 19.1% vs. 4.4% and the rate of endoscopic recurrence, 29 vs. 33% at 12 months. Risk factors for postoperative recurrence (POR) (male sex, younger age, ileocolonic location, stricturing or penetrating behaviour) were studied, only ileocolonic location was found to be associated with Crohn’s disease recurrence in patients treated with ADA. Conclusions: Overall infliximab and aalimumab are equally efficient in patients with resected Crohn’s disease (CD) with a complete response of 72.7%, a rate of re-resection of 11.4% and a rate of endoscopic recurrence of 35%. Ileocolonic location might be a predictive factor for loss of response to adalimumab in resected Crohn’s disease patients (AU)

No disponible

Adalimumab versus infliximab in treating post-operative recurrence of Crohn's disease: a national cohort study.

AIM: Perform a comparison between adalimumab (ADA) and infliximab (IFX) in treating post-operative recurrence of Crohn's disease (a comparative analysis of efficacy and safety). METHODS: From the 267 patients treated with Adalimumab or Infliximab between January 2005 and June 2014 in Romania, 44 received anti- TNF (tumor necrosis factor) therapy for prevention of post-operative recurrence. A comparison between patients treated with IFX and ADA was made with the Chi- square and t- student test, with the aid of the statistical program Mini Tab 17. RESULTS: Twenty-one patients received IFX and 23 ADA. This included 49% males (22/44), with a mean age of 41 years, mean disease duration of 6 years, and 84.1% had previously received azathioprine. The IFX group is comparable with the ADA group regarding most of the parameters, except for therapy duration. Mean duration of therapy was 33 months. The rate of complete response was comparable between the two groups: 67% in the IFX group vs. 78.3% in the ADA group, the same as the rate of re-resection, 19.1% vs. 4.4% and the rate of endoscopic recurrence, 29 vs. 33% at 12 months. Risk factors for postoperative recurrence (POR) (male sex, younger age, ileocolonic location, stricturing or penetrating behaviour) were studied, only ileocolonic location was found to be associated with Crohn's disease recurrence in patients treated with ADA. CONCLUSIONS: Overall infliximab and aalimumab are equally efficient in patients with resected Crohn's disease (CD) with a complete response of 72.7%, a rate of re-resection of 11.4 % and a rate of endoscopic recurrence of 35%. Ileocolonic location might be a predictive factor for loss of response to adalimumab in resected Crohn's disease patients.

Fecal Microbiota Transplantation in Recurrent NAP1/B1/027 Clostridium Difficile Infection (CDI) Resistant to Vancomycin and Metronidazole in a Patient with Ulcerative Colitis (UC): A Case Report.

Most of the studies showed that IBD patients inflammatory bowel diseases (IBD) with CDI have more of the whole range of short- and long-term worst outcomes than those without CDI. Initial infection with the BI/NAP1/027 epidemic clone was found to be a significant risk factor for relapse. However, current literature is suggesting increasingly that for patients with infections that fail to resolve with traditional antibiotic regimens, FMAT's average cure rate of >90%. We report a case of a 40-year-old man, diagnosed with ulcerative colitis (UC) in 2012 who presented in our clinic for 20 watery stools per day with mucus and blood, hypogastric pain, pyrexia and chills. Rectosigmoidoscopy and histopathological examination diagnosed a ctive lesions of ulcerative colitis with Clostridium difficile toxins A/B enzyme immunoassays (EIA) testing initially negative. The patient was non-responder at day 10 of intravenous (iv) corticotherapy and received induction therapy with Infliximab 5 mg/kg. EIA testing for Clostridium difficile was repeated at day 12 of hospitalization with positive results for toxins A/B, and associated oral therapy with Vancomycin and Metronidazole was initiated without clinical response in day 7, reasons for what intravenously therapy with Tigecycline was started with good response. Patient was discharged after 10 days of Tigecycline, but came back twice for two relapses of Clostridium difficile colitis treated successfully with Tigecycline, reasons for what fecal transplantation was performed in Matei Bals Institute, which induced remission of both CDI and UC.