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 Helicobacter pylori （H pylorl） 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 suppresion. 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 trials 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 rrelative 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 py/ori is safe and well-tolerated. The only adverse event occurring significantly more commonly was dark stools.

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

To evaluate the frequency of Helicobacter pylori (H. pylori) CagA antibodies in H. pylori infected subjects and to identify potential histopathological and bacterial factors related to H. pylori CagA-immune response. METHODSSystematic 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-CagA) was correlated with H. pylori isolates (cagA, EPIYA, vacA s/m genotype), histology (Sydney classification) and mucosal interleukin-8 (IL-8) mRNA and protein expression. Selected H. pylori strains were assessed for H. pylori CagA protein expression and IL-8 induction in co-cultivation model with AGS cells. RESULTSThirty point three percent of microbiologically confirmed H. pylori infected patients were seropositive for CagA. Majority of H. pylori isolates were cagA gene positive (93.9%) with following vacA polymorphisms: 42.4% vacA s1m1, 23.2% s1m2 and 34.3% s2m2. Anti-CagA-IgG seropositivity was strongly associated with atrophic gastritis, increased mucosal inflammation according to the Sydney score, IL-8 and cagA mRNA expression. VacA s and m polymorphisms were the major determinants for positive (vacA s1m1) or negative (vacA s2m2) anti-CagA 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 CagA translocation, which showed only partial correlation with CagA seropositivity in patients, supporting vacA as major co-determinant of the immune response. CONCLUSIONSerological immune response to H. pylori cagA+ strain in H. pylori infected patients is strongly associated with vacA polymorphism, suggesting the crucial role of bacterial factors in immune and clinical phenotype of the infection.

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

AIM： Prednisone and azathioprine represent the standard treatment for autoimmune hepatitis （AIH）. However, only 65% of the patients enter complete histological remission. Recently, budesonide （BUD） was reported to be a promising alternative. In this study we assessed the efficacy and safety of BUD in AIH. METHODS： Eighteen patients （12 women, 6 men; mean age 45.4±21 years） with AIH were treated with BUD （Budenofalk） 3 mg thrice daily and followed up for at least 24 wk. Seven patients also had features of primary biliary cirrhosis （n = 5） or primary sclerosing cholangitis （n = 2）. Advanced liver fibrosis or cirrhosis was present in RESULTS： Fifteen （83%） patients had a complete clinical and biochemical remission. Ten patients, including five with acute hepatitis, were given BUD as first-line therapy, of which seven enter remission. Three patients, two with liver cirrhosis, did not improve. All patients with second-line therapy experienced long-term remission. A histological remission was also seen in three patients. Clinically relevant BUD-induced side effects were recorded only in patients with liver cirrhosis （n = 4）. CONCLUSION： BUD is effective in remission induction in the majority of our patients with AIH. Side effects and treatment failure was mainly observed in patients with liver cirrhosis.

Drug treatment of functional dyspepsia

Symptomatic improvement of patients with functional dyspepsia after drug therapy is often incomplete and obtained in not more than 60% of patients. This is likely because functional dyspepsia is a heterogeneous disease. Although great advance has been achieved with the consensus definitions of the Rome I and II criteria, there are still some aspects about the definition of functional dyspepsia that require clarification. The Rome criteria explicitly recognise that epigastric pain or discomfort must be the predominant complaint in patients labelled as suffering from functional dyspepsia. However, this strict definition can create problems in the daily primary care clinical practice, where the patient with functional dyspepsia presents with multiple symptoms. Before starting drug therapy it is recommended to provide the patient with an explanation of the disease process and reassurance. A thorough physical examination and judicious use of laboratory data and endoscopy are also indicated. In general, the approach to treat patients with functional dyspepsia based on their main symptom is practical and effective. Generally, patients should be treated with acid suppressive therapy using proton-pump inhibitors if the predominant symptoms are epigastric pain or gastroesophageal reflux symptoms. Although the role of Helicobacter pylori （H pylon） in functional dyspepsia continues to be a matter of debate, recent data indicate that there is modest but clear benefit of eradication of H pylori in patients with functional dyspepsia. In addition, H pylori is a gastric carcinogen and if found it should be eliminated. Although there are no specific diets for patients with FD, it may be helpful to guide the patients on healthy exercise and eating habits.

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.

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

AIM： To describe and discuss echo-enhanced sonography in the differential diagnosis of cystic pancreatic lesions. METHODS： The pulse inversion technique （with intravenous injection of 2.4 mL SonoVue） or the power-Doppler mode under the conditions of the 2^nd harmonic imaging （with intravenous injection of 4 g Levovist） was used for echo-enhanced sonography. RESULTS： Cystadenomas frequently showed many vessels along fibrotic strands. On the other hand, cystadenocarcinomas were poorly and chaotically vascularized. ＂Young pseudocysts＂ were frequently found to have a highly vascularised wall. However, the wall of the ＂old pseudocysts＂ was poorly vascularized. Data from prospective studies demonstrated that based on these imaging criteria the sensitivities and specificities of echoenhanced sonography in the differentiation of cystic pancreatic masses were 〉 90%. CONCLUSION： Cystic pancreatic masses have a different vascularization pattern at echo-enhanced sonography. These characteristics are useful for their differential diagnosis, but histology is still the gold standard.

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 pylori) 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 H pylori. METHODS: The UBT was routinely performed 4 to 6 wk after H pylori eradication 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 micro-aerophilic conditions. Following the string test, upper gastrointestinal endoscopy was performed to obtain gastric biopsies for conventional culture. RESULTS: H pylori was successfully cultured from the gastric string in 34 patients (81%), but not in 5 patients due to contamination with oropharyngeal flora. H py/oriwas 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 H pylori with little inconvenience to the patient. Upper Gl-endoscopy can be avoided in several cases by applying consequently this diagnostic package.

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 significant abnormal findings 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-five patients （mean age 54.8 ± 2.8 years） with H pylori infection and no peptic ulcer or abnormal gross findings in the stomach were identified and analyzed according to gastritis phenotypes using different scodng systems. RESULTS： The prevalence of severe H pylori associated changes like pangastritis, CPG, IN, 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 for gastric 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.

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

AIM： To investigate the expression of different cytokeratins （CKs） in gastric epithelium of adult patients with chronic gastritis infected with Helicobacter pylori （H pylon） cagA ＋ strains. METHODS： The expression of CK 7, 8, 18, 19 and 20 was studied immunohistochemically in antral gastric biopsies of 84 patients. All the CKs were immunostained in cagA＋Hpylori gastritis （57 cases）, non-Hpylori gastritis （17 cases） and normal gastric mucosa （10 cases）. RESULTS： In cagA＋ H pylori gastritis, CK8 was expressed comparably to the normal antral mucosa from surface epithelium to deep glands. Distribution of CK18 and CK 19 was unchanged, i.e. transmucosal, but intensity of the expression was different in foveolar region in comparison to normal gastric mucosa. Cytokeratin 18 immunoreactivity was significantly higher in the foveolar epithelium of H pylori-positive gastritis compared to both Hpylori-negative gastritis and controls. On the contrary, decrease in CK19 immunoreactivity occurred in foveolar epithelium of H pylori-positive gastritis. In both normal and inflamed antral mucosa without Hpyloriinfection, CK20 was expressed stronglyl moderately and homogenously in surface epithelium and upper foveolar region, but in H pylod -induced gastritis significant decrease of expression in foveolar region was noted. Generally, in both normal antral mucosa and H pylori-negative gastritis, expression of CK7 was not observed, while in about half cagA＋ H pylori-infected patients, moderate focal CK7 immunoreactivity of the neck and coiled gland areas was registered, especially in areas with more severe inflammatory infiltrate. CONCLUSION： Alterations in expression of CK 7, 18, 19 and 20 together with normal expression of CK8 occur in antral mucosa of H pylori-associated chronic gastritis in adult patients infected with cagA＋ strains. Alterations in different cytokeratins expression might contribute to weakening of epithelial tight junctions observed in H pylori-infected gastric mucosa.

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.

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.

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? 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 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.

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.

Upregulation of cathepsin W-expressing T cells is specific for autoimmune atrophic gastritis compared to other types of chronic gastritis

AIM： To investigate a pathophysiological role of cathepsin W （CatW）, a putative thiol-dependent cysteine protease, which is specifically expressed in cytotoxic lymphocytes, in different types of chronic inflammation of the gastric mucosa. METHODS： Gastric and duodenal biopsies of patients with Heliobacter pylori （ Hpylort）-assodated active gastritis （Hp, n = 19）, chemically induced reactive gastritis （CG, n = 17）, autoimmune atrophic gastritis （AIG, n = 20）, lymphocytic corpus gastritis （LG, n = 29）, celiac disease （CD, n = 10）, and corresponding controls （n = 24） were analyzed by immunohistochemistry for the expression of CatW and CD45. Furthermore, immunohistochemical double staining with anti-CD3 and anti-cathepsin was performed for the samples of AIG. RESULTS： Median values of CatW-expressing cells among CD45-positive immune cells were between 2% and 6% for normal gastric mucosa, CG, and LG, whereas the corresponding value was significantly increased for AIG （24.7%, P〈0.001） and significantly decreased for HP （0.7%, P〈0.05）. Double staining with anti-CD3 and antiCatW antibodies revealed that 〉90% of CatW-expressing cells in gastric mucosa of AIG were T cells. Duodenal mucosa had significantly more CatW/CD45-positive cells than normal gastric mucosa （median： 17.8% vs 2%, P〈0.01）. The corresponding proportion of CatW/CD45-positive cells was decreased in CD compared to duodenal mucosa （median： 2.1% vs 17.8%, P〈0.05）. CONCLUSION： The opposite findings regarding the presence of CatW-positive cells in AIG （increase） and CD （decrease） reflects the different cellular composition of immune cells involved in the pathogenesis of these diseases.