Intraprocedural gastric juice analysis as compared to rapid urease test for real-time detection of Helicobacter pylori

BACKGROUND Endofaster is an innovative technology that can be combined with upper gastrointestinal endoscopy(UGE)to perform gastric juice analysis and real-time detection of Helicobacter pylori(H.pylori).AIM To assess the diagnostic performance of this technology and its impact on the management of H.pylori in the real-life clinical setting.METHODS Patients undergoing routine UGE were prospectively recruited.Biopsies were taken to assess gastric histology according to the updated Sydney system and for rapid urease test(RUT).Gastric juice sampling and analysis was performed using the Endofaster,and the diagnosis of H.pylori was based on real-time ammonium measurements.Histological detection of H.pylori served as the diagnostic gold standard for comparing Endofaster-based H.pylori diagnosis with RUT-based H.pylori detection.RESULTS A total of 198 patients were prospectively enrolled in an H.pylori diagnostic study by Endofasterbased gastric juice analysis(EGJA)during the UGE.Biopsies for RUT and histological assessment were performed on 161 patients(82 men and 79 women,mean age 54.8±19.2 years).H.pylori infection was detected by histology in 47(29.2%)patients.Overall,the sensitivity,specificity,accuracy,positive predictive value,and negative predictive value(NPV)for H.pylori diagnosis by EGJA were 91.5%,93.0%,92.6%,84.3%,and 96.4%,respectively.In patients on treatment with proton pump inhibitors,diagnostic sensitivity was reduced by 27.3%,while specificity and NPV were unaffected.EGJA and RUT were comparable in diagnostic performance and highly concordant in H.pylori detection(κ-value=0.85).CONCLUSION Endofaster allows for rapid and highly accurate detection of H.pylori during gastroscopy.This may guide taking additional biopsies for antibiotic susceptibility testing during the same procedure and then selecting an individually tailored eradication regimen.

Adverse events with bismuth salts for Helicobacter pylori eradication:Systematic review and meta-analysis

AIM: To assess the safety of bismuth used in Helico- bacter pylori (H pylori) eradication therapy regimens. METHODS: We conducted a systematic review and meta-analysis. MEDLINE and EMBASE were searched (up to October 2007) to identify randomised controlled tri- als comparing bismuth with placebo or no treatment, or bismuth salts in combination with antibiotics as part of eradication therapy with the same dose and duration of antibiotics alone or, in combination, with acid suppres- sion. Total numbers of adverse events were recorded. Data were pooled and expressed as relative risks with 95% confidence intervals (CI). RESULTS: We identified 35 randomised controlled tri- als containing 4763 patients. There were no serious adverse events occurring with bismuth therapy. There was no statistically significant difference detected in total adverse events with bismuth [relative risk (RR) = 1.01; 95% CI: 0.87-1.16], specific individual adverse events, with the exception of dark stools (RR = 5.06; 95% CI: 1.59-16.12), or adverse events leading to withdrawal of therapy (RR = 0.86; 95% CI: 0.54-1.37). CONCLUSION: Bismuth for the treatment of H pylori is safe and well-tolerated. The only adverse event oc- curring significantly more commonly was dark stools.

Helicobacter pylori vac A genotype is a predominant determinant of immune response to Helicobacter pylori CagA

AIM To evaluate the frequency of Helicobacter pylori(H. pylori) Cag A antibodies in H. pylori infected subjects and to identify potential histopathological and bacterial factors related to H. pylori Cag A-immune response.METHODS Systematic data to H. pylori isolates, blood samples, gastric biopsies for histological and molecular analyses were available from 99 prospectively recruited subjects. Serological profile(anti-H. pylori, anti-Cag A) was correlated with H. pylori isolates(cag A, EPIYA, vac A s/m genotype), histology(Sydney classification) and mucosal interleukin-8(IL-8) m RNA and protein expression. Selected H. pylori strains were assessed for H. pylori Cag A protein expression and IL-8 induction in co-cultivation model with AGS cells.RESULTS Thirty point three percent of microbiologically confirmed H. pylori infected patients were seropositive for Cag A. Majority of H. pylori isolates were cag A gene positive(93.9%) with following vac A polymorphisms: 42.4% vac A s1m1, 23.2% s1m2 and 34.3% s2m2. Anti-Cag AIg G seropositivity was strongly associated with atrophic gastritis, increased mucosal inflammation according to the Sydney score, IL-8 and cag A m RNA expression. V a c A s a n d m p o l y m o r p h i s m s w e r e t h e m a j o r determinants for positive(vac A s1m1) or negative(vac A s2m2) anti-Cag A serological immune response, which also correlated with the in vitro inflammatory potential in AGS cells. In vitro co-cultivation of representative H. pylori strains with AGS cells confirmed functional Cag A translocation, which showed only partial correlation with Cag A seropositivity in patients, supporting vac A as major co-determinant of the immune response.CONCLUSION Serological immune response to H. pylori cag A + strain in H. pylori infected patients is strongly associated with vac A polymorphism, suggesting the crucial role of bacterial factors in immune and clinical phenotype of the infection.

Breath and string test: A diagnostic package for the identification of treatment failure and antibiotic resistance of Helicobacter pylori without the necessity of upper gastrointestinal endoscopy

AIM: Helicobacter pylori ( H pylofi) resistance after failed eradication has a major impact on the outcome of a further treatment regimen. The aim of this study was to assess the validity of a non-invasive strategy using the 13C-urea breath test (UBT) and the gastric string test in identifying post-treatment resistance of Hpylori.METHODS: The UBT was routinely performed 4 to 6 wk after H pylorieradication therapy. Forty-two patients (24 females, 18 males, mean age 48 years) with a positive UBT were included in the study. A gastric string test using a capsule containing a 90 cm-long nylon fiber was performed.Before the capsule was swallowed, the free end of the string was taped to the cheek. After one hour in the stomach, the string was withdrawn. The distal 20 cm of the string was inoculated onto an agar plate and processed under microaerophilic conditions. Following the string test, upper gastrointestinal endoscopy was performed to obtain gastric biopsies for conventional culture.RESULTS: H pyloriwas successfully cultured from the gastric string in 34 patients (81%), but not in 5 patients due to contamination with oropharyngeal flora. Hpyloriwas cultured from the gastric biopsies obtained at endoscopy in 39 patients (93%).CONCLUSION: The UBT followed by the gastric string test in the case of treatment failure is a valid diagnostic strategy with the aim of determining the post-therapeutic antibiotic resistance of Hpyloriwith little inconvenience to the patient.Upper GI-endoscopy can be avoided in several cases by applying consequently this diagnostic package.

Current biomarkers for hepatocellular carcinoma: Surveillance, diagnosis and prediction of prognosis

Biomarkers for surveillance, diagnosis and prediction of prognosis in patients with hepatocellular carcinoma(HCC) are currently not ready for introduction into clinical practice because of limited sensitivity and specificity. Especially for the early detection of small HCC novel biomarkers are needed to improve the current effectiveness of screening performed byultrasound. The use of high-throughput technologies in hepatocellular research allows to identify molecules involved in the complex pathways in hepatocarcinogenesis. Several invasive and non-invasive biomarkers have been identified already and have been evaluated in different clinical settings. Gene signatures with prognostic potential have been identified by gene expression profiling from tumor tissue. However, a single "all-in-one" biomarker that fits all-surveillance, diagnosis, prediction of prognosis-has not been found so far. The future of biomarkers most probably lies in a combination of non-invasive biomarkers, imaging and clinical parameters in a surveillance setting. Molecular profiling of tumorous and non-tumorous liver tissue may allow a prediction of prognosis for the individual patient and hopefully clear the way for individual treatment approaches. This article gives an overview on current developments in biomarker research in HCC with a focus on currently available and novel biomarkers, in particular on micro RNA.

Budesonide induces complete remission in autoimmune hepatitis

瞄准：泼尼松和 azathioprine 为自体免疫的肝炎(AIH ) 代表标准疗法。然而，仅仅， 65% 病人进入完全的组织学的宽恕。最近， budesonide (芽) 被报导是一种有希望的选择。在这研究，我们在 AIH 估计了芽的功效和安全。方法：十八个病人(12 个女人， 6 个男人；吝啬的年龄 45.4+/-21 年) 与芽(Budenofalk ) 与 AIH 被对待在上面三次每日、跟随的 3 mg 为至少 24 wk.Seven，病人们也有主要胆汁性肝硬变(n=5 ) 或主要致硬化的胆管炎(n=2 ) 的特征。先进的肝纤维变性或肝硬化在 6 个病人是在场的。结果：十五(83%) 病人们有完全的临床、生物化学的宽恕。十个病人，与尖锐肝炎包括五，作为首要的治疗被给芽，哪个七进入宽恕。三个病人，二与肝肝硬化，没改善。有第二线的治疗的所有病人经历了长期的宽恕。组织学的宽恕也在三个病人被看见。临床上相关的导致芽的副作用与肝肝硬化(n=4 ) 仅仅在病人被记录。结论：芽在在我们有 AIH.Side 效果的病人的多数的宽恕正式就职是有效的，治疗失败主要与肝肝硬化在病人被观察。

Different antibiotic susceptibility between antrum and corpus of the stomach,a possible reason for treatment failure of Helicobacter pylori infection

AIM:To assess whether antibiotic resistance varies between the antrum and corpus of the stomach of patients that are either Helicobacter pylori(H.pylori)therapy-naive or pre-treated.METHODS:H.pylori strains were isolated from antrum and corpus biopsies from 66 patients that received a diagnostic gastroduodenoscopy for variant clinical indications.Antimicrobial susceptibility to amoxicillin,clarithromycin,tetracycline,metronidazole,levofloxacin and rifabutin was tested with the E-test method on IsoSensitest agar with 10 vol%defibrinated horse blood.In patients with a different antibiotic susceptibility pattern between the isolates from the antrum and corpus,DNA fingerprinting via random amplified polymorphic DNA analysis was performed to detect differences among DNA patterns of H.pylori isolates.RESULTS:Primary,secondary and tertiary resistance to clarithromycin was 6.9%,53.8%and 83.3%,retrospectively.Metronidazole and levofloxacin resistance also increased according to the number of previous treatments(17.2%,69.2%,83.3%;13.8%,23.1%,33.3%).Tertiary resistance to rifabutin was detected in12.5%of patients.In none of the 66 patients a resistance against amoxicillin or tetracycline was detectable.Discordant antibiotic susceptibility between antrum and corpus isolates for different antibiotics was seen in 15.2%(10/66)of the patients.Two out of those ten patients were naive to any H.pylori antibiotic treatment.The remaining eight patients previously received at least one eradication therapy.DNA fingerprinting analysis revealed no substantial differences among DNA patterns between antrum and corpus isolates in the majority of patients suggesting an infection with a single H.pylori strain.CONCLUSION:Different antibiotic susceptibility between antrum and corpus biopsies is a common phenomenon and a possible explanation for treatment failure.Resistant H.pylori strains may be missed if just one biopsy from one anatomic site of the stomach is taken for H.pylori susceptibility testing.

Echo-enhanced ultrasound with pulse inversion imaging: A new imaging modality for the differentiation of cystic pancreatic tumours

瞄准：在膀胱的胰腺的损害的鉴别诊断描述并且讨论提高回响的 sonography。方法：脉搏倒置技术(与 2.4 mL SonoVue 的静脉注射) 或在第二泛音成像的条件下面的 power-Doppler 模式(与 4 g Levovist 的静脉注射) 被用于提高回响的 sonography。结果：Cystadenomas 经常沿着纤维变性海滨显示出许多容器。在另一方面，包囊腺癌是糟糕并且混乱 vascularized。“年轻假包囊”经常被发现有一面高度脉管的 ised 墙。然而，“旧假包囊”的墙是糟糕 vascularized。从未来的研究的数据证明基于这些成像标准，在膀胱的胰腺的群众的区别的提高回响的 sonography 的敏感和特性是 】90% 。结论：膀胱的胰腺的群众在提高回响的 sonography 有一个不同血管形成模式。这些特征为他们的鉴别诊断是有用的，但是组织学仍然是标准答案。

Drug treatment of functional dyspepsia

有在药治疗以后的机能性消化不良的病人的征兆的改进经常在不超过 60% 病人不完全、获得。因为机能性消化不良是异构的疾病，这是可能的。尽管大进展与罗马的一致定义被完成了我和 II 标准，仍然关于机能性消化不良的定义有一些方面要求澄清。罗马标准明确地认识到腹上部的疼痛或不快 must 是在作为受不了机能性消化不良标记的病人的占优势的抱怨。然而，这个严格的定义能在每天主要的照顾创造问题临床的实践，有机能性消化不良的病人在此与多重症状介绍。在开始药治疗前，向病人提供疾病过程和安慰的解释被建议。彻底的体格检查和实验室数据和内视镜检查法的明智的使用也被显示。一般来说，基于他们的主要症状与机能性消化不良对待病人的途径实际、有效。通常，病人们应该与如果占优势的症状是腹上部的，使用质子泵禁止者的镇压治疗伤害的酸或胃的食道的倒流症状被对待。尽管在机能性消化不良的 Helicobacter pylori (H pylori ) 的角色继续是争论的一件事，最近的数据显示有在有机能性消化不良的病人的 H pylori 的根除的谦虚却清楚的利益。另外， H pylori 是胃的致癌物，如果发现，它应该被消除。尽管为有 FD 的病人没有特定的食谱，在健康锻练和吃的习惯指导病人可能是有用的。

Modified Helicobacter test using a new test meal and a 13C-urea breath test in Helicobacter pylori positive and negative dyspepsia patients on proton pump inhibitors

AIM To determine the sensitivity and specificity of the ^(13)C-urea breath test(UBT) in patients taking proton pump inhibitors(PPIs), using a new test meal Refex. METHODS One hundred and fourteen consecutive patients with dyspepsia, 53 Helicobacter pylori(H. pylori) positive, 49 H. pylori negative, were included in the study. The patients were then given esomeprazole 40 mg for 29 consecutive days, and the ^(13)C-UBT with the new test meal was performed the next morning. RESULTS The sensitivity of the ^(13)C-UBT with a cut off 2.5‰ was92.45%(95%CI: 81.79%-97.91%) by per-protocol(PP) analysis and 78.13 %(95%CI: 66.03%-87.49%) by intention-to-treat(ITT) analysis. The specificity of the ^(13)C-UBT test was 96.00 % in the ITT population(95%CI: 86.29%-99.51%) and 97.96% in the PP population(95%CI: 89.15%-99.95%).CONCLUSION The new test meal based ^(13)C-UBT is highly accurate in patients on PPIs and can be used in those unable to stop their PPI treatment.

Meta-analysis of single strain probiotics for the eradication of Helicobacter pylori and prevention of adverse events

AIM:To assess the efficacy and safety of single strain probiotics for the:(1) eradication of Helicobacter pylori(H.pylori);(2) prevention of adverse events;and(3) prevention of antibiotic-associated diarrhea associated with eradication therapy.METHODS:We searched Pub Med(1960-2014),EMBASE(1974-2014),Cochrane Database of Systematic Reviews(1990-2014),and ISI Web of Science(2000-2014).Additionally,we conducted a grey literature search including contact with National Institutes of Health Clinical Trials Registry,abstracts from annual infectious disease and gastroenterology meetings,experts in the field and correspondence with authors.Randomized controlled trials of H.pylori positive adults or children treated with eradication therapy and assessing the adjunctive therapy with a single strain of probiotics were included.The primary outcomes were the rates of eradication of H.pylori and frequency of patients with adverse events or antibiotic-associated diarrhea.Outcomes were pooled using fixed or random-effects models to calculate the relative risk and corresponding 95%CI and weighted on study size.To explore possible explanations for heterogeneity,a priori subgroup analyses were conducted on daily probiotic dose,study population,and quality of the study.The overall quality of the evidence for each probiotic strain was assessed using the GRADE criteria.RESULTS:A total of 25 randomized controlled trials(28 treatment arms,with a total of 3769 participants) assessed one of six single probiotic strains as adjunctive treatments to standard eradication therapy.Only one probiotic strain significantly improved H.pylori eradication rates:Saccharomyces boulardii(S.boulardii) CNCM I-745 [pooled relative risks(p RR) = 1.11,95%CI:1.07-1.16].Only one probiotic strain(S.boulardii CNCM I-745) significantly prevented any adverse events(p RR = 0.42,95%CI:0.28-0.62).Both S.boulardii CNCM I-745 and Lactobacillus rhamnosus GG significantlyreduced antibiotic-associated diarrhea(p RR = 0.47,95%CI:0.37-0.60 and p RR = 0.29,95%CI:0.17-0.48,respectively) associated with H.pylori eradication therapy.Meta-regression of sub-groups did not detect significant differences by dose,adult vs pediatric,symptom status,or study quality,but did find significant differences by the strain of probiotic.Potential mild publication bias was found for antibiotic-associated diarrhea,but not for eradication or adverse event outcomes.Analysis of the study quality illuminated areas for improvement in future studies(use of placebos,study size calculations,attrition reasons and discussion of limitations and generalizability).CONCLUSION:The pooled evidence suggests that the adjunctive use of a few probiotic strains may improve H.pylori eradication rates and prevent the development of adverse events and antibiotic-associated diarrhea in those treated with standard eradication therapies.The type of probiotic strain was the most important factor in predicting efficacy.

Prevalence of H pylori associated 'high risk gastritis' for development of gastric cancer in patients with normal endoscopic findings

AIM: To investigate the prevalence of H pylori associated corpus-predominant gastritis (CPG) or pangastritis, severe atrophy, and intestinal metaplasia (IM) in patients without any signifi cant abnormal fi ndings during upper- GI endoscopy. METHODS: Gastric biopsies from 3548 patients were obtained during upper GI-endoscopy in a 4-year period. Two biopsies from antrum and corpus were histologically assessed according to the updated Sydney-System. Eight hundred and forty-fi ve patients (mean age 54.8 ± 2.8 years) with H pylori infection and no peptic ulcer or abnormal gross fi ndings in the stomach were identifi ed and analyzed according to gastritis phenotypes using different scoring systems. RESULTS: The prevalence of severe H pylori associated changes like pangastritis, CPG, IM, and severe atrophy increased with age, reaching a level of 20% in patients of the age group over 45 years. No differences in frequencies between genders were observed. The prevalence of IM had the highest increase, being 4-fold higher at the age of 65 years versus in individuals less than 45 years. CONCLUSION: The prevalence of gastritis featuring at risk for cancer development increases with age. These findings reinforce the necessity for the histological assessment, even in subjects with normal endoscopic appearance. The age-dependent increase in prevalence of severe histopathological changes in gastric mucosa, however, does not allow estimating the individual risk forgastric cancer development-only a proper follow-up can provide this information.

Treatment of uncomplicated reflux disease

Uncomplicated reflux disease comprises the non-erosive reflux disease (NERD) and erosive reflux disease (ERD).The objectives of treatment are the adequate control of symptoms with restoration of quality of life, healing of lesions and prevention of relapse. Treatment of NERD consists in the administration of proton pump inhibitors (PPI) for 2-4 wk, although patients with NERD show an overall poorer response to PPI treatment than patients with ERD owing to the fact that patients with NERD do not form a pathophysiologically homogenous group. For long-term management on-demand treatment with a PPI is probably the best option. In patients with ERD, therapy with a standard dose PPI for 4-8 wk is always recommended.Long-term treatment of ERD is applied either intermittently or as continuous maintenance treatment with an attempt to reduce the daily dosage of the PPI (step-down principle).In selected patients requiring long-term PPI treatment,antireflux surgery is an alternative option. In patients with troublesome reflux symptoms and without alarming features empirical PPI therapy is another option for initial management. Therapy should be withdrawn after initial success. In the case of relapse, the long-term care depends on a careful risk assessment and the response to PPI therapy.

Prognostic value of serum microRNA-122 in hepatocellular carcinoma is dependent on coexisting clinical and laboratory factors

BACKGROUND There is ongoing search for new noninvasive biomarkers to improve management of patients with hepatocellular carcinoma(HCC).Studies,mostly from the Asian-Pacific region,demonstrated differential expression of liverspecific microRNA-122(miR-122)in tissue as well as in sera of patients with hepatitis B virus-and hepatitis C virus-induced HCC.AIM To evaluate prognostic value of miR-122 in patients with HCC in a European population and determine potential factors related to alteration of miR-122 in sera.METHODS Patients with confirmed HCC(n=91)were included in the study over a two-year period.Patients were characterized according to Child-Pugh score,Barcelona clinic liver cancer(BCLC)staging system,etiology of liver disease,laboratory parameters and overall survival.MiR-122 was measured in sera using TaqMan assay normalized to spiked-in cel-miR-39.RESULTS Serum miR-122 quantity was independent of the Child-Pugh score,the BCLC stage or the underlying etiology.Significant positive correlation was found between miR-122 and alanine aminotransferase(P<0.0001),aspartate aminotransferase(P=0.0001),alpha-fetoprotein(AFP)(P=0.0034)and hemoglobin concentration(P=0.076).Negative correlation was observed between miR-122 level and creatinine concentration(P=0.0028).AFP,Child-Pugh score and BCLC staging system were associated with survival differences.In overall cohort low miR-122 in sera was only associated with a trend for a better overall survival without reaching statistical significance.Subgroup analysis revealed that low miR-122 was significantly associated with better prognosis in patients with advanced cirrhosis(Child-Pugh class B/C),advanced tumor stage(BCLC B/C/D)and normal AFP(<7 ng/mL).CONCLUSION Our results strongly support the value of miR-122 as potential biomarker of liver injury and probably prognosis.Nevertheless,the value of miR-122 in prediction of prognosis of HCC patients was limited to certain patients’subgroups.Since circulating miR-122 may be influenced by impaired renal function,AFP and hemoglobin concentration,those factors need to be considered while interpreting miR-122 level.

Pancreatic cancer–Endosonography

EUS is the most sensitive imaging procedure for the detection of small solid pancreatic masses and is accurate in determining vascular invasion of the portal venous system. Even compared to the new CT-techniques EUS provides excellent results in preoperative staging of solid pancreatic tumors. Compared to helical CT-techniques EUS is less accurate in detecting tumor involvement of superior mesenteric artery. EUS staging and EUS-guided FNA can be performed in a single-step procedure, to establish the diagnosis of cancer. There is no known negative impact of tumor cell seeding due to EUS-FNA. Without FNA EUS and additional methods are not able to reliably distinguish between inflammatory and malignant masses.

Expression of cytokeratins in Helicobacter pylori-associated chronic gastritis of adult patients infected with cagA+strains:An immunohistochemical study

瞄准：为了与长期的胃炎在成年病人的胃的上皮调查不同 cytokeratins (CK ) 的表示，与 Helicobacter pylori (H pylori ) 感染了 cagA+ 紧张。方法：CK 7 的表示， 8， 18， 19 和 20 在 84 个病人的窦的胃的活体检视组织化学地是学习免疫。所有 CK 是在 cagA+H pylori 胃炎(57 个案例) 染色的免疫， non-H pylori 胃炎(17 个案例) 和正常胃粘膜(10 个案例) 。结果：在 cagA+ H pylori 胃炎， CK8 从表面上皮可比较地被表示到正常的窦粘膜到深腺。CK18 和 CK 19 的分发是未改变的，即表示的 transmucosal，而是紧张在与正常相比的小凹的区域是不同的胃粘膜。Cytokeratin 18 免疫反应在与 H pylori 否定的胃炎和控制相比的 H pylori 积极的胃炎的小凹的上皮是显著地更高的。相反，在 CK19 免疫反应的减少发生在 H pylori 积极的胃炎的小凹的上皮。在没有 H pylori 感染的正常、煽动的窦粘膜， CK20 在表面上皮和上面的小凹的区域强烈 / 中等并且同类地被表示，但是在 H， pylori 导致了胃炎在小凹的区域的表示的重要减少被注意。通常，在正常窦的粘膜和 H pylori 否定的胃炎，， CK7 的表示没被观察在关于半 cagA+ ， H 感染 pylori 的病人，节制颈的焦点的 CK7 免疫反应，卷的腺区域被登记，特别在区域与更严重煽动性渗入。结论：在 CK 7 的表示的改变， 18， 19 和 20 在感染 cagA+ 紧张的成年病人和 CK8 的正常表示发生在 H 联系 pylori 的长期的胃炎的窦粘膜。在不同 cytokeratins 表示力量的改变贡献在 H 感染 pylori 的胃粘膜观察的上皮的紧密的连接变弱。

Acute exacerbation of autoimmune hepatitis induced by Twinrix

We report on a 26-year-old man who presented with severe jaundice and elevated serum liver enzyme activities after having received a dose of Twinrix(○R). In his past medical history, jaundice or abnormal liver function tests were never recorded. Following admission, an elevated immunoglobulin G level and antinuclear antibodies at a titer of 320 with a homogenous pattern were found. Histology of a liver biopsy showed marked bridging liver fibrosis and a chronic inflammation, compatible with autoimmune hepatitis. Treatment was started with budesonide and ursodeoxycholic acid,and led to complete normalization of the pathological liver function tests. We believe that Twinrix(○R) led to an acute exacerbation of an unrecognized autoimmune hepatitis in our patient. The pathogenesis remains to be clarified. It is tempting to speculate that inactivated hepatitis A virus and/or recombinant surface antigen of the hepatitis B virus -as seen in patients with chronic hepatitis C and unrecognized autoimmune hepatitis who were treated with interferon alpha-might have been responsible for disease exacerbation.

Polymorphisms of micro RNA target genes IL12B, INSR, CCND1 and IL10 in gastric cancer

AIM To evaluate associations between mi RNA target genes IL12B,INSR,CCND1 and IL10 polymorphisms and gastric cancer(GC)in European population.METHODS Gene polymorphisms were analyzed in 508 controls and474 GC patients from 3 tertiary centers in Germany,Lithuania and Latvia.Controls were patients from the out-patient departments,who were referred for upper endoscopy because of dyspeptic symptoms and had no history of previous malignancy.Gastric cancer(GC)patients had histopathological verification of gastric adenocarcinoma.Genomic DNA was extracted using salting out method from peripheral blood mononuclear cells.IL12B T>G(rs1368439),INSR T>C(rs1051690),CCND1 A>C(rs7177)and IL10 T>C(rs3024498)SNPs were genotyped by the real-time polymerase chain reaction.Associations between gene polymorphism and GC were evaluated using multiple logistic regression analysis with adjustment for sex,age and country of birth.RESULTS We observed similar distribution of genotypes and allelic frequencies of all polymorphisms between GC patients and controls except of INSR rs1051690.The frequency of the T allele of INSR gene was significantly higher in GC patients than in controls(23.26%and 19.19%respectively,P=0.028).CT genotype was also more prevalent in patients compared to control group(38.48%and 30.12%respectively,P<0.021).Logistic regression analysis revealed that only one polymorphism(rs1051690 in INSR gene)was associated with increased risk of GC.Carriers of CT genotype had higher odds of GC when compared to CC genotype(OR=1.45,95%PI:1.08-1.95,P=0.01).Similar association was observed in a dominant model for INSR gene,where comparison of TT+CT vs CC genotypes showed an increased risk of GC(OR=1.44,95%PI:1.08-1.90,P=0.01).Other analyzed SNPs were not associated with the presence of GC.CONCLUSION INSR rs1051690 SNP is associated with increased risk of GC,while polymorphisms in IL12B,CCND1 and IL10genes are not linked with the presence of GC.

Circulating miR-21-5p level has limited prognostic value in patients with hepatocellular carcinoma and is influenced by renal function

BACKGROUND MicroRNAs(miRNAs)have been suggested as biomarkers for malignant diseases including hepatocellular carcinoma(HCC).Specifically,hsa-miR-21-5p(miR-21)is among the most frequently deregulated miRNA in cancer.The diagnostic and prognostic value of miR-21 has been demonstrated in HCC tissue,mostly in the Asian population.Although the impact of various factors has been recently reported for circulating hsa-miR-122-5p(miR-122),at present only limited knowledge is available for miR-21.AIM To evaluate the value of miR-21 for the assessment of prognosis in HCC patients and to delineate the influence of clinical and preanalytical factors on miR-21 level in sera.METHODS Patients with confirmed HCC from our European cohort with predominantly alcohol-associated liver damage were included in the study.All subjects were characterized according to their clinical and laboratory work-up and overall survival data were obtained.Quantitative real-time polymerase chain reaction was performed for miR-21 and spiked-in cel-miR-39-3p.The results were compared to previously reported miR-122 data.RESULTS Survival of HCC patients was comparable between patients with low and high serum miR-21 concentration.No association was observed between miR-21 level in sera and Child-Pugh score,Barcelona Clinic Liver Cancer staging system,or etiology of HCC/liver disease.Age,gender,or pretreatment had no association with miR-21 level.A positive correlation was observed between miR-21 and aspartate aminotransferase(r=0.2854,P=0.0061),serum miR-122(r=0.2624,P=0.0120),and the International Normalized Ratio(r=0.2065,P=0.0496).Negative correlation of miR-21 with serum creatinine(r=-0.2215,P=0.0348)suggests renal function as a potential influencing factor in miR-21 biogenesis in blood.CONCLUSION The results from this work do not support clinically relevant prognostic value of circulating miR-21 in HCC patients in real-life settings.Following systematic evaluation,we identified renal function and aspartate aminotransferase as potential factors that may affect miR-21 concentration in blood.This knowledge should be considered in future miRNA-based biomarker studies not only for HCC but also for other diseases.

Impact of endoscopy-based research on quality of life in healthy volunteers

AIM:To study the impact of an endoscopy-based long-term study on the quality of life in healthy volunteers(HV).METHODS:Ten HV were included into a long-term prospective endoscopy-based placebo-controlled trial with 15 endoscopic examinations per person in 5 different drug phases.Participants completed short form-36(SF-36) and visual analog scale-based questionnaires(VAS) for different abdominal symptoms at days 0,7 and 14 of each drug phase.Analyses wereperformed according to short-and long-term changes and compared to the control group.RESULTS:All HV completed the study with duration of more than 6 mo.Initial quality of life score was comparable to a general population.Analyses of the SF-36 questionnaires showed no significant changes in physical,mental and total scores,either in a short-term perspective due to different medications,or to potentially endoscopic procedure-associated long-term cumulative changes.Analogous to SF-36,VAS revealed no significant changes in total scores for pathological abdominal symptoms and remained unchanged over the time course and when compared to the control population.CONCLUSION:This study demonstrates that quality of life in HV is not significantly affected by a longterm endoscopy-based study with multiple endoscopic procedures.