Goran Hauser

Peginterferon alpha‐2a is associated with higher sustained virological response than peginterferon alfa‐2b in chronic hepatitis C: Systematic review of randomized trials

A combination of weekly pegylated interferon (peginterferon) alpha and daily ribavirin represents the standard of care for the treatment of chronic hepatitis C according to current guidelines. It is not established which of the two licensed products (peginterferon alpha‐2a or peginterferon alfa‐2b) is most effective. We performed a systematic review of head‐to‐head randomized trials to assess the benefits and harms of the two treatments. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and LILACS through July 2009. Using standardized forms, two reviewers independently extracted data from each eligible trial report. We statistically combined data using a random effects meta‐analysis according to the intention‐to‐treat principle. We identified 12 randomized clinical trials, including 5,008 patients, that compared peginterferon alpha‐2a plus ribavirin versus peginterferon alfa‐2b plus ribavirin. Overall, peginterferon alpha‐2a significantly increased the number of patients who achieved a sustained virological response (SVR) versus peginterferon alfa‐2b (47% versus 41%; risk ratio 1.11, 95% confidence interval 1.04–1.19; P = 0.004 [eight trials]). Subgroup analyses of risk of bias, viral genotype, and treatment history yielded similar results. The meta‐analysis of adverse events leading to treatment discontinuation included 11 trials and revealed no significant differences between the two peginterferons. Conclusion: Current evidence suggests that peginterferon alpha‐2a is associated with higher SVR than peginterferon alfa‐2b. However, the paucity of evidence on adverse events curbs the decision to definitively recommend one peginterferon over the other, because any potential benefit must outweigh the risk of harm. (HEPATOLOGY 2010.)

Differences in the health-related quality of life, affective status and personality between Irritable Bowel Syndrome and Inflammatory Bowel Disease patients

Objectives To investigate differences in the health-related quality of life (HRQoL), number of stressful life events, affective status, and some personality characteristics between patients with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) as well as their possible role in disease activity. Methods Fifty-six IBS outpatients, age range 25–75 years (mean = 48.64; SD = 13.04) and 43 outpatients with IBD, age range 19–74 years (mean = 42.90; SD = 15.44), participated in this study. Patients filled out the following questionnaires: Short-Form 36 Health Survey, Beck Depression Inventory, Spielbergers Trait-Anxiety Inventory, Big Five Inventory, and Stressful Life Events Questionnaire. Results There were significant differences in the physical component (F = 10.80, P<0.001) of the general HRQoL as well as in anxiety (F = 7.23, P<0.01) and neuroticism (F = 8.90, P<0.01) between patients with IBS and IBD. IBS patients showed a significantly higher level of anxiety and neuroticism and better physical aspects of general HRQoL compared with IBD patients. The results of standard regression analyses indicated that a significant predictor (&bgr; = −0.44, P<0.01) for the perceived disease activity in IBS was neuroticism as a personality trait. Conclusion The results of this study show that the patients with IBS are more prone to the effect of psychosocial variables on gastrointestinal symptoms compared with patients with organic gastrointestinal diseases such as IBD. IBS patients experienced a higher level of anxiety and expressed a higher level of neuroticism as a personality trait compared with IBD patients.

FibroTest/Fibrosure for Significant Liver Fibrosis and Cirrhosis in Chronic Hepatitis B: A Meta-Analysis

OBJECTIVES:Extent of liver fibrosis is one of the most important factors in determining prognosis and the need for active treatment in chronic hepatitis B (CHB). Noninvasive alternatives such as FibroTest/Fibrosure (FT) have been developed in order to overcome the shortcomings of liver biopsy (LB). We aimed to systematically review studies describing the diagnostic accuracy of FT for predicting CHB-related fibrosis.METHODS:MEDLINE and EMBASE searches and hand searching methods were performed to identify studies that assessed the diagnostic accuracy of FibroTest in HB patients using LB as a reference standard. We used a hierarchical summary receiver operating curves model and the bivariate model to produce summary receiver operating characteristic curves and pooled estimates of sensitivity and specificity.RESULTS:We included 16 studies (N=2494) and 13 studies (N=1754) in the heterogenous meta-analysis for liver fibrosis and cirrhosis, respectively. The area under the hierarchical summary receiver operating curve for significant liver fibrosis and for all included studies was 0.84 (95% confidence interval (CI): 0.78–0.88). At the FT threshold of 0.48, the sensitivity, specificity, and diagnostic odds ratio (DOR) of FT for significant fibrosis were 61 (48–72%), 80 (72–86%), and 6.2% (3.3–11.9), respectively. The area under the hierarchical summary receiver operating curve for liver cirrhosis and for all included studies was 0.87 (95% CI: 0.85–0.90). At the FT threshold of 0.74, the sensitivity, specificity, and DOR of FT for cirrhosis were 62 (47–75%), 91 (88–93%), and 15.7% (8.6–28.8), respectively.CONCLUSIONS:FibroTest is of value in exclusion of patients with CHB-related cirrhosis, but has suboptimal accuracy in the detection of significant fibrosis and cirrhosis. It is necessary to further improve the test or combine it with other noninvasive modalities in order to improve accuracy.

Transient elastography (FibroScan(®)) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease - Where do we stand?

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Currently, the routinely used modalities are unable to adequately determine the levels of steatosis and fibrosis (laboratory tests and ultrasonography) or cannot be applied as a screening procedure (liver biopsy). Among the non-invasive tests, transient elastography (FibroScan(®), TE) with controlled attenuation parameter (CAP) has demonstrated good accuracy in quantifying the levels of liver steatosis and fibrosis in patients with NAFLD, the factors associated with the diagnosis and NAFLD progression. The method is fast, reliable and reproducible, with good intra- and interobserver levels of agreement, thus allowing for population-wide screening and disease follow-up. The initial inability of the procedure to accurately determine fibrosis and steatosis in obese patients has been addressed with the development of the obese-specific XL probe. TE with CAP is a viable alternative to ultrasonography, both as an initial assessment and during follow-up of patients with NAFLD. Its ability to exclude patients with advanced fibrosis may be used to identify low-risk NAFLD patients in whom liver biopsy is not needed, therefore reducing the risk of complications and the financial costs.

Probiotics for Standard Triple Helicobacter pylori Eradication: A Randomized, Double-blind, Placebo-controlled Trial.

AbstractThe primary objective in the study is determination of efficacy of probiotic preparation as a supportive therapy in eradication of Helicobacter pylori.The study was multicenter, prospective, randomized, placebo controlled, and double-blind. The subjects first filled out a specially designed questionnaire to assess the severity of the 10 symptoms, which can be related to eradication therapy to be monitored during the trial. Each subject then received 28 capsules of probiotic preparation or matching placebo capsules, which they were supposed to take over the following 14 days, twice a day, at least 2 hours prior to or after the antibiotic therapy administration.A total of 804 patients were enrolled in the trial, of which 650 (80.85%) were included in the analysis. The results show a significantly larger share of cured subjects in the probiotic arm versus the placebo arm (87.38% vs 72.55%; P < 0.001). Additionally, presence and intensity of epigastric pain, bloating, flatulence, taste disturbance, loss of appetite, nausea, vomiting, heartburn, rash, and diarrhea were monitored over the study period. At 15 days postinclusion, probiotic treatment was found superior to placebo in 7 of 10 mentioned symptoms. Average intensity for symptoms potentially related to antibiotic therapy was significantly higher in the placebo group, 0.76 vs 0.55 (P < 0.001).Adding probiotics to the standard triple therapy for H pylori eradication significantly contributes to treatment efficacy and distinctly decreases the adverse effects of therapy and the symptoms of the underlying disease.

Minimally invasive treatment of pancreatic pseudocysts

A pancreatic pseudocyst (PPC) is typically a complication of acute and chronic pancreatitis, trauma or pancreatic duct obstruction. The diagnosis of PPC can be made if an acute fluid collection persists for 4 to 6 wk and is enveloped by a distinct wall. Most PPCs regress spontaneously and require no treatment, whereas some may persist and progress until complications occur. The decision whether to treat a patient who has a PPC, as well as when and with what treatment modalities, is a difficult one. PPCs can be treated with a variety of methods: percutaneous catheter drainage (PCD), endoscopic transpapillary or transmural drainage, laparoscopic surgery, or open pseudocystoenterostomy. The recent trend in the management of symptomatic PPC has moved toward less invasive approaches such as endoscopic- and image-guided PCD. The endoscopic approach is suitable because most PPCs lie adjacent to the stomach. The major advantage of the endoscopic approach is that it creates a permanent pseudocysto-gastric track with no spillage of pancreatic enzymes. However, given the drainage problems, the monitoring, catheter manipulation and the analysis of cystic content are very difficult or impossible to perform endoscopically, unlike in the PCD approach. Several conditions must be met to achieve the complete obliteration of the cyst cavity. Pancreatic duct anatomy is an important factor in the prognosis of the treatment outcome, and the recovery of disrupted pancreatic ducts is the main prognostic factor for successful treatment of PPC, regardless of the treatment method used. In this article, we review and evaluate the minimally invasive approaches in the management of PPCs.

Cognitive behavioral approach to understanding irritable bowel syndrome

Irritable bowel syndrome (IBS) is considered a biopsychosocial disorder, whose onset and precipitation are a consequence of interaction among multiple factors which include motility disturbances, abnormalities of gastrointestinal sensation, gut inflammation and infection, altered processing of afferent sensory information, psychological distress, and affective disturbances. Several models have been proposed in order to describe and explain IBS, each of them focusing on specific aspects or mechanisms of the disorder. This review attempts to present and discuss different determinants of IBS and its symptoms, from a cognitive behavioral therapy framework, distinguishing between the developmental predispositions and precipitants of the disorder, and its perpetuating cognitive, behavioral, affective and physiological factors. The main focus in understanding IBS will be placed on the numerous psychosocial factors, such as personality traits, early experiences, affective disturbances, altered attention and cognitions, avoidance behavior, stress, coping and social support. In conclusion, a symptom perpetuation model is proposed.

Diagnosis of Irritable Bowel Syndrome: Role of Potential Biomarkers

Irritable bowel syndrome is a disorder diagnosed on symptom-based criteria without inclusion of any objective parameter measurable by known diagnostic methods. Heterogeneity of the disorder and overlapping with more serious organic diseases increase uncertainty for the physicians work and increase the cost of confirming the diagnosis. This paper is an attempt to summarize the efforts to find adequate biomarkers for irritable bowel syndrome, which should shorten the time to diagnosis and reduce the cost. Most of the reviewed papers were observational studies from secondary care institutions. Since publication of the Rome III criteria in 2006, most recent studies use these for the recruitment of IBS patients. This is a positive step forward as future studies should use the same criteria, facilitating comparison of their results. Among the studied biomarkers, most evidence is provided for fecal calprotectin. Cutoff values for fecal calprotectin have still to be investigated prior to inclusion in the irritable bowel syndrome diagnostic algorithm.

Erythrocyte sedimentation rate - Possible role in determining the existence of the low grade inflammation in Irritable Bowel Syndrome patients

Irritable Bowel Syndrome (IBS), the most prevalent functional gastrointestinal disorder, is best described by the presence of recurrent symptoms of abdominal pain, diarrhea and/or constipation. It has been thought that IBS is stress-related disorder with no known structural abnormalities, e.g. infectious, biochemical or metabolic causes. But, recent evidence suggests that inflammation within the gastrointestinal tract may be of great importance in the pathogenesis of IBS. Our question is could the conventional and widely available general biological markers of inflammation such as erythrocyte sedimentation rate (ESR) be indicator of microscopic inflammatory process in some IBS patients? We hypothesize that mild inflammation in IBS patients could be detected by meaning of a sensitive but cheap and ubiquitous test - ESR. Furthermore we assume that ESR would be related with the disease severity index and decreased general and disease-specific health-related quality of life (HRQoL). A pilot study has been conducted with 86 outpatients (65% female) with IBS, average age 47.76 (SD=13.68). The preliminary results were partly in favor of our hypothesis. They showed that IBS patients with higher ESR expressed lower disease-specific HRQoL (e.g. they expressed more bowel symptoms, social and emotional disturbances related to disease). No significant correlations were found between ESR and the disease severity as well as general HRQoL.

Preventing post-endoscopic retrograde cholangiopancreatography pancreatitis: What can be done?

Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most common complication of endoscopic retrograde cholangiopancreatography. The incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis varies substantially and is reported around 1%-10%, although there are some reports with an incidence of around 30%. Usually, PEP is a mild or moderate pancreatitis, but in some instances it can be severe and fatal. Generally, it is defined as the onset of new pancreatic-type abdominal pain severe enough to require hospital admission or prolonged hospital stay with levels of serum amylase two to three times greater than normal, occurring 24 h after ERCP. Several methods have been adopted for preventing pancreatitis, such as pharmacological or endoscopic approaches. Regarding medical prevention, only non-steroidal anti-inflammatory drugs, namely diclofenac sodium and indomethacin, are recommended, but there are some other drugs which have some potential benefits in reducing the incidence of post-ERCP pancreatitis. Endoscopic preventive measures include cannulation (wire guided) and pancreatic stenting, while the adoption of the early pre-cut technique is still arguable. This review will attempt to present and discuss different ways of preventing post-ERCP pancreatitis.