Equivalence Trial of the Non-Bismuth 10-Day Concomitant and 14-Day Hybrid Therapies for Helicobacter pylori Eradication in High Clarithromycin Resistance Areas.

Background and aim: We conducted an equivalence trial of quadruple non-bismuth "concomitant" and "hybrid" regimens for H. pylori eradication in a high clarithromycin resistance area. Methods: There were 321 treatment-naïve H. pylori-positive individuals in this multicenter clinical trial randomized to either the hybrid (esomeprazole 40 mg/bid, amoxicillin 1 g/bid for 7 days, then 7 days esomeprazole 40 mg/bid, amoxicillin 1 g/bid, clarithromycin 500 mg/bid, and metronidazole 500 mg/bid) or the concomitant regimen (all medications given concurrently bid for 10 days). Eradication was tested using histology and/or a 13C-urea breath test. Results: The concomitant regimen had 161 patients (90F/71M, mean 54.5 years, 26.7% smokers, 30.4% ulcer) and the hybrid regimen had 160 (80F/80M, mean 52.8 years, 35.6% smokers, 31.2% ulcer). The regimens were equivalent, by intention to treat 85% and 81.8%, (p = 0.5), and per protocol analysis 91.8% and 87.8%, (p = 0.3), respectively. The eradication rate by resistance, between concomitant and hybrid regimens, was in susceptible strains (97% and 97%, p = 0.6), clarithromycin single-resistant strains (86% and 90%, p = 0.9), metronidazole single-resistant strains (96% and 81%, p = 0.1), and dual-resistant strains (70% and 53%, p = 0.5). The side effects were comparable, except for diarrhea being more frequent in the concomitant regimen. Conclusions: A 14-day hybrid regimen is equivalent to a 10-day concomitant regimen currently used in high clarithromycin and metronidazole resistance areas. Both regimens are well tolerated and safe.

Prevalence of Small Intestinal Bacterial Overgrowth Syndrome in Patients with Non-Alcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis: A Cross-Sectional Study.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a multifactorial, wide-spectrum liver disorder. Small intestinal bacterial overgrowth (SIBO) is characterized by an increase in the number and/or type of colonic bacteria in the upper gastrointestinal tract. SIBO, through energy salvage and induction of inflammation, may be a pathophysiological factor for NAFLD development and progression. AIM/METHODS: Consecutive patients with histological, biochemical, or radiological diagnosis of any stage of NAFLD (non-alcoholic fatty liver [NAFL], non-alcoholic steatohepatitis [NASH], cirrhosis) underwent upper gastrointestinal endoscopy. Duodenal fluid (2cc) was aspirated from the 3rd-4th part of duodenum into sterile containers. SIBO was defined as ≥103 aerobic colony-forming units (CFU)/mL of duodenal aspirate and/or the presence of colonic-type bacteria. Patients without any liver disease undergoing gastroscopy due to gastroesophageal reflux disease (GERD) comprised the healthy control (HC) group. Concentrations (pg/mL) of tumor necrosis factor alpha (TNFα), interleukin (IL)-1ß, and IL-6 were also measured in the duodenal fluid. The primary endpoint was to evaluate the prevalence of SIBO in NAFLD patients, while the comparison of SIBO prevalence among NAFLD patients and healthy controls was a secondary endpoint. RESULTS: We enrolled 125 patients (51 NAFL, 27 NASH, 17 cirrhosis, and 30 HC) aged 54 ± 11.9 years and with a weight of 88.3 ± 19.6 kg (NAFLD vs. HC 90.7 ± 19.1 vs. 80.8 ± 19.6 kg, p = 0.02). Overall, SIBO was diagnosed in 23/125 (18.4%) patients, with Gram-negative bacteria being the predominant species (19/23; 82.6%). SIBO prevalence was higher in the NAFLD cohort compared to HC (22/95; 23.2% vs. 1/30; 3.3%, p = 0.014). Patients with NASH had higher SIBO prevalence (6/27; 22.2%) compared to NAFL individuals (8/51; 15.7%), but this difference did not reach statistical significance (p = 0.11). Patients with NASH-associated cirrhosis had a higher SIBO prevalence compared to patients with NAFL (8/17; 47.1% vs. 8/51; 15.7%, p = 0.02), while SIBO prevalence between patients with NASH-associated cirrhosis and NASH was not statistically different (8/17; 47.1% vs. 6/27; 22.2%, p = 0.11). Mean concentration of TNF-α, IL-1ß, and IL-6 did not differ among the different groups. CONCLUSION: The prevalence of SIBO is significantly higher in a cohort of patients with NAFLD compared to healthy controls. Moreover, SIBO is more prevalent in patients with NASH-associated cirrhosis compared to patients with NAFL.

Evaluating treatments with rifabutin and amoxicillin for eradication of Helicobacter pylori infection in adults: a systematic review.

INTRODUCTION: Helicobacter pylori causes dyspepsia, peptic ulcer, and gastric malignancies. Treatments for Helicobacter pylori are mostly empirical depending on regional antibiotic resistances and the patient's history and less frequently susceptibility guided. Helicobacter pylori has a low resistance to rifabutin and has been proposed as an alternative for third-line treatment and beyond but recently has also gained attention for use as first- and second-line treatment. AREAS COVERED: In this review, the authors systematically searched medical databases in order to present the current eradication rates for any treatment based on the two antibiotics, rifabutin and amoxicillin with a potent acid inhibitor. They also assessed the safety and tolerance of all the relative regimens. EXPERT OPINION: Treatment with a rifabutin- and amoxicillin-containing regimen is a valuable option when treating difficult to eradicate Helicobacter pylori infections. Its efficacy is overall 71.4%, and it is not influenced by previous antibiotics, gender, smoking habits, and age. Its results were better when used as a first- or second-line treatment. In third-line therapy and beyond, eradication rates are lower. Adverse effects of all rifabutin regimens occurred in 23% of patients and were mostly mild with bone marrow suppression being very low and reversible.

Predictors of Re-bleeding and Mortality Among Patients with Refractory Variceal Bleeding Undergoing Salvage Transjugular Intrahepatic Portosystemic Shunt (TIPS).

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) has proven clinical efficacy as rescue therapy for cirrhotic patients with acute portal hypertensive bleeding who fail endoscopic treatment. AIMS: To investigate predictive factors of 6-week and 1-year mortality in patients undergoing salvage TIPS for refractory portal hypertensive bleeding. METHODS: A total of 144 consecutive patients were retrospectively evaluated. Three logistic regression multivariate models were estimated to individualize prognostic factors for 6-week and 12-month mortality. Log-rank test was used to evaluate survival according to Child-Pugh classes and Bureau's criteria. RESULTS: Mean age 51 ± 10 years, 66% male, mean MELD 18.5 ± 8.3, Child-Pugh A/B/C 8%/38%/54%. TIPS failure occurred in 23(16%) patients and was associated with pre-TIPS portal pressure gradient and pre-TIPS intensive care unit stay. Six-week and 12-month mortality was 36% and 42%, respectively. Pre-TIPS intensive care unit stay, MELD, and Child-Pugh score were independently associated with mortality at 6 weeks. Independent predictors of mortality at 12 months were pre-TIPS intensive care unit stay and Child-Pugh score. CONCLUSIONS: In this large cohort of patients undergoing salvage TIPS, MELD and Child-Pugh scores were predictive of short- and long-term mortality, respectively. Pre-TIPS intensive care unit stay was independently associated with TIPS failure and mortality at 6 weeks and 12 months. Salvage TIPS is futile in patients with Child-Pugh score of 14-15.

Hybrid therapy as first-line regimen for Helicobacter pylori eradication in a high clarithromycin resistance area: a prospective open-label trial.

BACKGROUND: Hybrid therapy is a promising first-line regimen for Helicobacter pylori (H. pylori) eradication. We evaluated a hybrid therapy, assessing the impact of antibiotic resistance on eradication outcome. METHODS: This was a prospective study that included 155 treatment-naïve patients diagnosed with H. pylori infection by positive CLO-test, confirmed with histology and/or culture. The hybrid therapy consisted of 40 mg esomeprazole and 1 g amoxicillin for 14 days, with the addition of 500 mg clarithromycin and 500 mg metronidazole for the final 7 days (all b.i.d.). Eradication was defined by negative 13C-urea breath test or histology. RESULTS: The eradication rates were 85.8% (133/155; 95% confidence interval [CI] 79.4-90.5%) by intention-to-treat and 90.2% (129/143; 95%CI 84.1-94.2%) by per-protocol analysis in a setting of high antibiotic resistance (clarithromycin 25.9%, metronidazole 31.1%, dual resistance 8.9%). Adverse events occurred in 29.7% and 1.3% discontinued treatment because of adverse events. Adherence >90% was achieved in 96.6%. The eradication rate in patients with dual clarithromycin/metronidazole resistance (50%) was markedly lower compared to those with single clarithromycin resistance (91.4%), single metronidazole resistance (90.5%) or dual susceptibility (97.8%). Dual resistance was the only factor to correlate with the failure of hybrid therapy (odds ratio 14.4, 95%CI 3.8-54.9, P=0.0003). CONCLUSIONS: Hybrid therapy is an effective and safe first-line regimen in populations with relatively high rates of antibiotic resistance. However, dual clarithromycin/metronidazole resistance may significantly compromise its efficacy.

Randomized clinical trial comparing ten day concomitant and sequential therapies for Helicobacter pylori eradication in a high clarithromycin resistance area.

BACKGROUND: Currently only a few studies compare sequential and concomitant non-bismuth Helicobacter pylori therapies referring to high antibiotic resistance populations. MATERIALS AND METHODS: This multicenter prospective randomized clinical trial included 353 H. pylori positive, treatment naïve, patients. All patients had positive CLO-test and/or histology and culture. They received sequential (esomeprazole 40mg, amoxicillin 1g/bid for 5days, followed by 5days of esomeprazole 40mg, clarithromycin 500mg and metronidazole 500mg bid), or concomitant treatment (all drugs taken concomitantly bid for 10days). Eradication was confirmed by (13)C-urea breath test or histology 4-6weeks after treatment. Adverse events and adherence were evaluated. RESULTS: Allocated to concomitant were 175 (72F/103M, mean 52.3years, 38.3% smokers, 25.7% ulcer disease) and 178 (87F/91M, mean 52years, 31% smokers, 19.1% ulcer disease) patients to sequential treatment. There were 303/353 (85.8%) positive cultures, with the following resistances: 34% metronidazole, 27.7% clarithromycin, and 7.9% dual. Eradication rates were, respectively, 89.1% (156/175) vs. 78.7% (140/178) by intention to treat (p=0.01, 95% CI=2.7-18) and 93.4%(156/167) vs. 82.8% (140/169) per protocol (p=0.004, 95% CI=3.6-17.6). Overall, adherence was (98.9%, 95% CI=97-100). Eradication rates according to resistance were the following: dual susceptible strains 67/69 (97.1%), 62/67 (92%) (p=0.4), metronidazole single resistant 38/39 (97.4%), 31/39 (79.5%) (p=0.03, 95% CI=3.5-33), clarithromycin single resistant 25/28 (89.3%), 26/31 (83.9%) (p=0.8), and dual resistant 9/12 (75%), 4/11 (36.4%) (p=0.1) for concomitant and sequential regimens, respectively. Side effects were comparable among regimens, except from diarrhea being more frequent among patients treated with concomitant treatment. CONCLUSIONS: Concomitant treatment eradication rate overcomes 90% per protocol and has a significant advantage over sequential therapy. This is probably due to its better efficacy on metronidazole resistant strains. Both regimens were well tolerated and safe.

The early plasma concentration of 51Cr-EDTA in patients with cirrhosis and ascites: a comparison of three models.

OBJECTIVES: The aim of the study was to determine which of three two-parameter fitting functions (exponential, linear-log, and negative-power function of time) most accurately models early chromium-51-EDTA (51Cr-EDTA) plasma concentration data prior to 120 min in patients with cirrhosis and ascites and understand how these fitting functions affect the calculation of the area under the plasma concentration curve (AUC). METHODS: A bolus, antecubital intravenous injection of 2.6 MBq of 51Cr-EDTA was given to 13 patients with cirrhosis and ascites. Up to 16 blood samples were drawn at time points ranging from 5 to 1440 min following injection. The concentration data prior to 120 min were used as reference data. Early time concentration values, estimated by fitting exponential, linear-log, and negative-power functions of time to the time samples at 120, 180, and 240 min, were then compared with reference data. The AUC was calculated for each patient using the exponential, Bröchner-Mortensen-corrected exponential, and linear-log functions, and these values were compared. RESULTS: The withheld, observed plasma concentrations were (a) most accurately estimated by linear-log functions (Wilcoxon P=0.4548), (b) significantly underestimated by exponential functions (Wilcoxon P=0.0002), and (c) significantly overestimated by negative-power functions (Wilcoxon P=0.0034). The relative errors when ranked from best to worst were those for the linear-log (12.0%, 9.0%), exponential (22.9%, 14.2%), and negative-power (31.9%, 48.4%) functions of time, respectively (median, interquartile range). For each patient, the values for AUC calculated by the exponential function differed significantly (range=3.4-15.3%, median=8.3%) from those calculated by the corrected Bröchner-Mortensen exponential, as to a lesser extent did those values calculated using linear-log functions (range=0.4-8.0%, median=3.0%). CONCLUSION: In patients with cirrhosis, linear-log functions were significantly more accurate than exponential or power functions in estimating early time plasma concentrations (<120 min). However, the improved linear-log early time plasma concentration model does not provide as much correction to the total AUC as does the corrected Bröchner-Mortensen exponential method. This is likely because of the large contribution of late time data to the AUC, and future work is suggested to explore the late time fit problem.

Antiviral interventions for liver transplant patients with recurrent graft infection due to hepatitis C virus.

BACKGROUND: Antiviral therapy for recurrent hepatitis C infection after liver transplantation is controversial due to unresolved balance between benefits and harms. OBJECTIVES: To compare the therapeutic benefits and harms of different antiviral regimens in patients with hepatitis C re-infected grafts after liver transplantation. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 1, 2013), MEDLINE, EMBASE, and Science Citation Index Expanded to February 2013. SELECTION CRITERIA: We considered only randomised clinical trials (irrespective of language, blinding, or publication status) comparing various antiviral therapies (alone or in combination) in the treatment of hepatitis C virus recurrence in liver transplantation for the review. DATA COLLECTION AND ANALYSIS: Two authors collected the data independently. We calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) using the fixed-effect and the random-effects models based on available case-analysis. In the presence of only trials for a dichotomous outcome, we performed the Fisher's exact test. MAIN RESULTS: Overall, 17 trials with 736 patients met the inclusion criteria for this review. All trials had high risk of bias. Five hundred and one patients randomised in 11 trials provided information for various comparisons in this systematic review after excluding post-randomisation drop-outs and patients from trials that did not report any of the outcomes of interest for this review. The comparisons for which outcomes were available included pegylated (peg) interferon versus control; peg interferon plus ribavirin versus control; ribavirin plus peg interferon versus peg interferon; peg interferon (1.5 µg/kg/week) plus ribavirin versus peg interferon (0.5 µg/kg/week) plus ribavirin; amantadine plus peg interferon plus ribavirin versus peg interferon plus ribavirin; interferon versus control; interferon plus ribavirin versus control; ribavirin versus interferon; and ribavirin versus placebo. Long-term follow-up was not available in these trials. There were no significant differences in mortality, retransplantation, graft rejections requiring retransplantation or medical treatment, or fibrosis worsening between the groups in any of the comparisons in which these outcomes were reported. Quality of life and liver decompensation were not reported in any of the trials. There was a significantly higher proportion of participants who developed serious adverse events in the ribavirin plus peg interferon combination therapy group than in the peg interferon monotherapy group (1 trial; 56 participants; 17/28 (60.7%) in the intervention group versus 5/28 (17.9%) in the control group; RR 3.40; 95% CI 1.46 to 7.94). There was no significant difference in proportion of participants who developed serious adverse events or in the number of serious adverse events between the intervention and control groups in the other comparisons that reported serious adverse events. AUTHORS' CONCLUSIONS: Considering the lack of clinical benefit, there is currently no evidence to recommend or refute antiviral treatment for recurrent liver graft infection with hepatitis C virus. Further randomised clinical trials with low risk of bias and low risk of random errors with adequate duration of follow-up are necessary.

Development of a modified sampling and calculation method for isotope plasma clearance assessment of the glomerular filtration rate in patients with cirrhosis and ascites.

AIM: The aim of this study was to identify a practical sampling regimen and calculation method that could be used to measure the glomerular filtration rate in patients with ascites using plasma sampling. PATIENTS AND METHODS: Thirteen potential liver transplant patients with cirrhosis and ascites were injected with Cr-51 ethylenediaminetetraacetic acid, and plasma samples were obtained at up to 16 time points for each patient. Reference clearance values were calculated using the area under the plasma clearance curve, which was calculated using all the available data points. Clearance calculations were then performed using three and four data points from each patient and three different calculation methods to identify a sampling regimen and calculation method that yielded good agreement with the reference values. RESULTS: The reference clearances ranged from 6 to 80 ml/min. Sampling at 2, 4, 8 and 24 h and calculation of the area under the plasma clearance curve using a log-linear trapezoidal rule with extrapolation to zero and infinity yielded a relative root mean square difference from the reference of less than 7%. CONCLUSION: This method for measuring glomerular filtration rate in patients with cirrhosis and ascites was found to be more accurate than the slope-intercept technique and is a practical alternative to urine collection.

Clinical evaluation of a ten-day regimen with esomeprazole, metronidazole, amoxicillin, and clarithromycin for the eradication of Helicobacter pylori in a high clarithromycin resistance area.

BACKGROUND: Increasing clarithromycin resistance reduces Helicobacter pylori eradication rates with conventional triple regimens. We evaluated effectiveness and safety of a 10-day-quadruple nonbismuth containing regimen, as first-line treatment or second-line treatment (after conventional triple) for H. pylori, and assessed impact of antibiotic resistance on treatment success. MATERIALS AND METHODS: Eligible patients had upper GI endoscopy and positive CLO-test, also confirmed by histology and/or culture. The eradication scheme comprised: Esomeprazole 40 mg, Metronidazole 500 mg, Amoxicillin 1000 mg, and Clarithromycin 500 mg, twice daily, for 10 days. Treatment adherence and adverse effects were recorded. Eradication was tested by (13) C-urea breath test or histology. RESULTS: One hundred and ninety out of 198 patients (115M/83F, aged 18-81, mean 52 years, 37% smokers, 27% ulcer disease) who completed the study protocol were evaluated for eradication. Adherence to treatment was 97.7% (95% CI 95.9-99.6). Six (3.2%) patients experienced severe side effects and discontinued treatment. Intention to treat and per protocol analysis in first line was 91.5% (95% CI 86.2-94.8) and 95% (95% CI 90.4-97.4) and in second line was 60.6% (95% CI 43.6-75.3) and 64.5% (95% CI 46.9-78.8), respectively. Antibiotic susceptibility tests were performed in 106 of 124 (85%) patients who gave consent. Among them 42 (40%) harbored clarithromycin resistant strains. Eradication rates were significantly higher in sensitive and single clarithromycin or metronidazole resistant (37/37, 100% and 43/47, 91%) than in dual resistant strains (12/22, 55%) (p < .0001). Specifically, concomitant regimen eradicated 7/10, 70% of dual resistant strains as first-line treatment and 5/12, 42% as second-line treatment. Multivariate analysis showed that dual resistance was the only independent significant predictor of treatment failure. CONCLUSIONS: The 10-days "concomitant" regimen is effective and safe first-line H. pylori treatment, in a high clarithromycin resistance area, although dual antibiotic resistance may compromise its effectiveness.

Nonbismuth quadruple "concomitant" therapy versus standard triple therapy, both of the duration of 10 days, for first-line H. pylori eradication: a randomized trial.

GOALS: To compare the efficacy, compliance, and tolerability of a quadruple, nonbismuth-containing concomitant therapy with standard triple therapy, both of the duration of 10 days, for Helicobacter pylori eradication. BACKGROUND: Eradication rates obtained with standard therapies are declining as antibiotic resistance becomes more prevalent worldwide. New first-line treatment strategies are needed. STUDY: Two hundred fifty-seven patients with H. pylori infection were included in the study. Patients were randomized to receive 10-day concomitant therapy comprising esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg, all bid, or 10-day standard triple therapy comprising of esomeprazole 40 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, all bid. Cure rates were defined as a negative 13C urea breath test 8 weeks after the start of treatment. RESULTS: Two hundred forty-six patients completed the study. The intention-to-treat cure rates were 90.5% [95% confidence interval (CI): 84.1%-95%] and 73.8% (95%CI, 65.6%-80.7%), whereas the per protocol cure rates were 93.3% (95%CI, 87.2% -97.1%) and 78.5% (95%CI, 70.3%-84.9%), respectively. The eradication rate was significantly higher in the concomitant group compared with the triple therapy group in both the intention-to-treat (P=0.0006) and per protocol (P=0.0014) populations. Adverse events were generally of mild/moderate intensity and did not interfere significantly with compliance, which was excellent for both treatment groups (96.6% and 98.5%, respectively, P=0.44). CONCLUSIONS: Performance of a 10-day conventional triple regimen is suboptimal. A 10-day concomitant regimen achieved a significantly higher eradication rate and seems to be an effective, safe, and well-tolerated treatment option for H. pylori eradication.

Screening for gastric premalignant lesions with narrow band imaging, white light and updated Sydney protocol or both?

BACKGROUND: Narrow band imaging (NBI) can accurately discriminate gastritis but premalignant lesions (PMLs) are difficult to detect. AIMS: The purpose of this study was to compare white light endoscopy (WLE) and histopathologic findings using the updated Sydney protocol (USP) with NBI and targeted biopsies (TB). METHODS: One hundred nineteen symptomatic patients referred for upper GI endoscopy were included in this prospective open study. All patients were assessed for gastritis and PMLs using WLE and NBI by two endoscopists selected in a random manner. Biopsies were taken according to USP and targeted from any area suspicious for PML. Imaging and histological findings between protocols were compared. RESULTS: In total 45 patients (38 %) had atrophy of whom 39 (32.7 %) were detected with WLE-USP and 28 (23.5 %) with NBI-TB (p = 0.03), 25 (21 %) had intestinal metaplasia (IM) of whom 19 (16 %) were detected with WLE-USP and 18 (15.1 %) with NBI-TB (p = 0.7) and 14 (12 %) had dysplasia of whom 12 (10 %) were detected with WLE-USP and 7 (7 %) with NBI-TB (p = 0.5), and 1 (0.8 %) case of gastric cancer only detected with WLE-USP. Accuracies for atrophy and IM were 93 and 90 % for the WLE-USP and 80 and 82 % for NBI-TB. The NBI-TB detected six cases of atrophy (13 %), 5 (20 %) of IM, and 2 (14 %) of dysplasia missed by WLE-USP as agreement was moderate. Accuracies of the NBI patterns for body and antral gastritis were 80 and 84 %. CONCLUSIONS: In a non high-risk population NBI-TB has less accuracy in detecting premalignant lesions compared to WLE-USP. However, it may be used as an important and easy-to-use complementary method which increases overall detectability for gastric premalignant lesions.

Inflammatory infiltration of metaplastic epithelium and correlation to previous diagnosis of esophagitis and Barrett's length.

OBJECTIVE: The contact of the gastric refluxate with the lower esophagus results in an inflammatory-mediated tissue damage. The role of inflammation both in the development and in the advance of Barrett's esophagus (BE) has not been elucidated. The aim of this study was to assess the inflammatory infiltration in metaplastic Barrett's epithelium and to explore the association of microscopic inflammation to healed esophagitis and Barrett's length. MATERIAL AND METHODS: Inflammatory infiltration was qualitatively evaluated in well-characterized Barrett's specimens. Esophagitis was healed prior to histological sampling. Univariate comparative analysis was performed based on BE length. RESULTS: Ninety-eight patients (78 male, mean age 58.3 ± 13.3 yrs) were retrospectively studied. Thirty-three cases with long segment BE (LSBE) (33.7%) were spotted. Inflammatory infiltration was mild, moderate, and severe in 35 (35.7%), 54 (55.1%), and 9 (9.1%) specimens, respectively. The samples with moderate/severe inflammatory infiltration were obtained from patients who had more frequently been diagnosed with esophagitis (p = 0.025). Hiatal hernia (p = 0.001), esophagitis (p = 0.019), and previous use of anti-secretory drugs (p = 0.005) were more common in LSBE. CONCLUSIONS: Inflammatory infiltration of Barrett's epithelium was largely moderate despite preceding healing of erosions with PPIs. Previous diagnosis of esophagitis correlated to the degree of inflammation. No association of inflammation to Barrett's length was established.

Evaluation of a four-drug, three-antibiotic, nonbismuth-containing "concomitant" therapy as first-line Helicobacter pylori eradication regimen in Greece.

BACKGROUND: The eradication rates of Helicobacter pylori (H. pylori) with standard treatments are decreasing worldwide as in Greece. Studies with new antibiotic combinations are needed to find better methods of eradication. Therefore, the aim of this study was to evaluate efficacy and tolerability of a 10-day, four-drug, three-antibiotic, nonbismuth-containing concomitant regimen. MATERIALS AND METHODS: This is a prospective, open-label, multicenter study that included 131 patients infected with H. pylori. All patients were diagnosed with peptic ulcer disease or nonulcer dyspepsia by endoscopy. H. pylori infection was established by at least two positive tests among rapid urease test, gastric histology, and (13) C-urea breath test. For 10 days, all patients received esomeprazole 40mg, amoxycillin 1000mg, clarithromycin 500mg, and metronidazole 500mg, all b.d. eradication was assessed with (13) C urea breath test 8weeks after the start of treatment. Intention-to-treat and per-protocol eradication rates were determined. RESULTS: One hundred and twenty-seven of the 131 patients completed the study. At intention-to-treat analysis, the eradication rate was 91.6% (95% confidence interval (CI), 85.5-95.7%). For the per-protocol analysis, the eradication rate was 94.5% (95% CI, 89-97.8%). Adverse events were noted in 42 of 131 (32.1%); drug compliance was excellent with 96.9% of the patients taking more than 90% of the prescribed medication. CONCLUSION: A 10-day concomitant regimen appears to be an effective, safe, and well-tolerated treatment option for first-line H. pylori eradication in Greece.

Increased expression of VEGF, COX-2, and Ki-67 in Barrett's esophagus: does the length matter?

BACKGROUND: Barrett's esophagus (BE) is a major complication of gastroesophageal reflux disease due to its neoplastic potential. The length of the metaplastic epithelium has been associated with cancer risk. Angiogenesis, inflammation, and increased cell proliferation are early events in the malignant sequence. Vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) and Ki-67 are indirect markers of these complex mechanisms. AIMS: To examine the expression of VEGF, COX-2 and Ki-67 in BE and investigate whether there is an association to Barrett's length. METHODS: Immunohistochemistry for VEGF, COX-2, and Ki-67 was performed in well-characterized Barrett's samples, evaluated using a qualitative scale and compared between long (LSBE) and short (SSBE) segments. RESULTS: The study population consisted of 98 patients (78 men). LSBE and SSBE was diagnosed in 33 (33.7%) and 65 (66.3%) cases, respectively. VEGF was expressed in vascular endothelium of all Barrett's specimens. COX-2 and Ki-67 expression in metaplastic epithelia was strong in 81.6 and 61.2% of the samples, respectively. Ki-67 expression was significantly stronger in LSBE (p = 0.035), whereas VEGF expression was significantly increased in SSBE (p = 0.031). COX-2 expression was not associated with Barrett's length. CONCLUSIONS: VEGF, COX-2, and Ki-67 were overexpressed in the majority of Barrett's samples. The length was inversely associated with VEGF expression and directly associated with Ki-67 expression.

Validation of Tikhonov adaptively regularized gamma variate fitting with 24-h plasma clearance in cirrhotic patients with ascites.

PURPOSE: The aim was to compare late-time extrapolation of plasma clearance (CL) from Tikhonov adaptively regularized gamma variate fitting (Tk-GV) and from mono-exponential (E1) fitting. METHODS: Ten (51)Cr-ethylenediaminetetraacetic acid bolus IV studies in adults--8 with ascites--assessed for liver transplantation, with 12-16 plasma samples drawn from 5-min to 24-h, were fit with Tk-GV and E1 models and CL results were compared using Passing-Bablok fitting. RESULTS: The 24-h CL(Tk-GV) values ranged from 11.4 to 79.7 ml/min. Linear regression of 4- versus 24-h CL(Tk-GV) yielded no significant departure from a slope of 1, whereas the 4- versus 24-h CL(E1) slope, 1.56, was significantly increased. For CL(Tk-GV-24-h) versus CL(E1-24-h), there was a biased slope and intercept (0.85, 5.97 ml/min). Moreover, the quality of fitting of 24-h data was significantly better for Tk-GV than for E1, as follows. For 10 logarithm of concentration curves, higher r values were obtained for each Tk-GV fit (median 0.998) than for its corresponding E1 fit (median 0.965), with p < 0.0001 (paired t-test of z-statistics from Fisher r-z transformations). The E1 fit quality degraded with increasing V/W [volume of distribution (l) per kg body weight, p = 0.003]. However, Tk-GV fit quality versus V/W was uncorrelated (p = 0.8). CONCLUSION: CL(E1) values were dependent on sample time and the quality of fit was poor and degraded with increasing ascites, consistent with current opinion that CL(E1) is contraindicated in ascitic patients. CL(Tk-GV) was relatively more accurate and the good quality of fit was unaffected by ascites. CL(Tk-GV) was the preferred method for the accurate calculation of CL and was useful despite liver failure and ascites.

Pitfalls in assessing renal function in patients with cirrhosis--potential inequity for access to treatment of hepatorenal failure and liver transplantation.

Serum creatinine is universally used to assess renal function in clinical practice. Creatinine and changes in serum creatinine are used to define acute kidney injury and hepatorenal syndrome (HRS) in patients with progressive liver disease. In addition, creatinine is a key variable in the calculation used to determine priority for liver transplantation in many countries. As there is no universal standardized creatinine assay, there is variation in creatinine determinations between laboratory assays, compounded by assay interference due to chromogens, including bilirubin. This leads to patients with the same actual renal function potentially being offered different treatment options, in terms of access to therapy for HRS and priority waiting time for liver transplantation. Alternative methods for assessing renal function either also tend to overestimate renal function or are too time consuming and expensive to provide practical alternatives for standard clinical practice. Standardization of creatinine assays with readily available reference standards would help minimize interlaboratory variation; of the current creatinine assays, enzymatic creatinine appears more accurate, but even this is inaccurate at high bilirubin concentrations. Further work is required to determine whether interpatient variation can be reduced by correcting creatinine and cystatin measurements for muscle mass.

Serum ferritin is a discriminant marker for both fibrosis and inflammation in histologically proven non-alcoholic fatty liver disease patients.

INTRODUCTION: Differentiation between steatosis and non-alcoholic steatohepatitis (NASH) in non-alcoholic fatty liver disease (NAFLD) is important as NASH progress to cirrhosis. No specific laboratory/imaging technique exists either to diagnose NASH or to select patients for liver biopsy. PATIENTS AND METHODS: We evaluated serum ferritin and the features of metabolic syndrome with respect to histological inflammation and/or fibrosis in NAFLD patients. The Kleiner scoring system was used to classify NAFLD in consecutive liver biopsies. One hundred and eleven patients: median age 52.6, 64 males, obesity 62, diabetes mellitus (DM) 58, arterial hypertension 26 and hyperlipidaemia 40%. RESULTS: Histologically, 40.7 had fatty liver, 30.6% had borderline NASH, 28.7% had NASH and 11% had cirrhosis. Multivariate regression showed that diabetes, serum ferritin concentrations, body mass index (BMI) and AST were independently associated with NASH: together, the areas under the receiver operating characteristic (AUROC) was 0.91 (95% confidence interval 0.86-0.96); fibrosis was associated with ferritin concentrations and BMI: AUROC 0.87, portal inflammation with ferritin and DM: AUROC 0.82, while lobular inflammation was associated with BMI, DM and ferritin: AUROC 0.85. CONCLUSION: Serum ferritin concentrations and BMI are strongly associated with fibrosis, portal and lobular inflammation in NAFLD patients. Both ferritin and BMI are potential discriminant markers to select patients for liver biopsy and are associated with inflammation and fibrosis.