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(Fibro Scan?, 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.
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 numerouspsychosocial 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.
Background
Acute pancreatitis is a common and potentially lethal disease with increasing incidence. Severe cases are characterised by high mortality, and despite improvements in intensive care ...management, no specific treatment relevantly improves clinical outcomes of the disease. Meta‐analyses suggest that enteral nutrition is more effective than conventional treatment consisting of discontinuation of oral intake with use of total parenteral nutrition. However, no systematic review has compared different enteral nutrition formulations for the treatment of patients with acute pancreatitis.
Objectives
To assess the beneficial and harmful effects of different enteral nutrition formulations in patients with acute pancreatitis.
Search methods
We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Specialised Register of Clinical Trials, the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 7), MEDLINE (from inception to 20 August 2013), EMBASE (from inception to 2013, week 33) and Science Citation Index–Expanded (from 1990 to August 2013); we conducted full‐text searches and applied no restrictions by language or publication status.
Selection criteria
We considered randomised clinical trials assessing enteral nutrition in patients with acute pancreatitis. We allowed concomitant interventions if they were received equally by all treatment groups within a trial.
Data collection and analysis
Two review authors independently assessed trials for inclusion and extracted data. We performed the analysis using Review Manager 5 (Review Manager 2013) and both fixed‐effect and random‐effects models. We expressed results as risk ratios (RRs) for dichotomous data, and as mean differences (MDs) for continuous data, both with 95% confidence intervals (CIs). Analysis was based on an intention‐to‐treat principle.
Main results
We included 15 trials (1376 participants) in this review. We downgraded the quality of evidence for many of our outcomes on the basis of high risk of bias. Low‐quality evidence suggests that immunonutrition decreases all‐cause mortality (RR 0.49, 95% CI 0.29 to 0.80). The effect of immunonutrition on other outcomes from a subset of the included trials was uncertain. Subgrouping trials by type of enteral nutrition did not explain any variation in effect. We found mainly very low‐quality evidence for the effects of probiotics on the main outcomes. One eligible trial in this comparison reported a higher rate of serious adverse events leading to increased organ failure and mortality due to low numbers of events and low risk of bias. When we excluded this study as a post hoc sensitivity analysis, risks of mortality (RR 0.30, 95% CI 0.10 to 0.84), organ failure (RR 0.74, 95% CI 0.59 to 0.92) and local septic complications (RR 0.40, 95% CI 0.22 to 0.72) were lower with probiotics. In one trial assessing immunonutrition with probiotics and fibres, no deaths occurred, but hospital stay was shorter with immunonutrition (MD ‐5.20 days, 95% CI ‐8.73 to ‐1.67). No deaths were reported following semi‐elemental enteral nutrition (EN), and the effect on length of hospital stay was small (MD 0.30 days, 95% CI ‐0.82 to 1.42). Fibre‐enriched formulations reduced the number of other local complications (RR 0.52, 95% CI 0.32 to 0.87) and length of hospital stay (MD ‐9.28 days, 95% CI ‐13.21 to ‐5.35) but did not significantly affect all‐cause mortality (RR 0.23, 95% CI 0.03 to 1.84) and other outcomes. Very low‐quality evidence from the subgroup of trials comparing EN versus no intervention showed a decrease in all‐cause mortality with EN (RR 0.50, 95% CI 0.29 to 0.86).
Authors' conclusions
We found evidence of low or very low quality for the effects of immunonutrition on efficacy and safety outcomes. The role of supplementation of enteral nutrition with potential immunomodulatory agents remains in question, and further research is required in this area. Studies assessing probiotics yielded inconsistent and almost contrary results, especially regarding safety and adverse events, and their findings do not support the routine use of EN enriched with probiotics in routine clinical practice. However, further research should be carried out to try to determine the potential efficacy or harms of probiotics. Lack of trials reporting on other types of EN assessed and lack of firm evidence regarding their effects suggest that additional randomised clinical trials are needed. The quality of evidence for the effects of any kind of EN on mortality was low, and further studies are likely to have an impact on the finding of improved survival with EN versus no nutritional support. Evidence remains insufficient to support the use of a specific EN formulation.
Direct‐acting antivirals for chronic hepatitis C Jakobsen, Janus C; Nielsen, Emil Eik; Feinberg, Joshua ...
Cochrane database of systematic reviews,
09/2017, Volume:
2017, Issue:
9
Journal Article
Peer reviewed
Open access
Background
Millions of people worldwide suffer from hepatitis C, which can lead to severe liver disease, liver cancer, and death. Direct‐acting antivirals (DAAs), e.g. sofosbuvir, are relatively new ...and expensive interventions for chronic hepatitis C, and preliminary results suggest that DAAs may eradicate hepatitis C virus (HCV) from the blood (sustained virological response). Sustained virological response (SVR) is used by investigators and regulatory agencies as a surrogate outcome for morbidity and mortality, based solely on observational evidence. However, there have been no randomised trials that have validated that usage.
Objectives
To assess the benefits and harms of DAAs in people with chronic HCV.
Search methods
We searched for all published and unpublished trials in The Cochrane Hepato‐Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, LILACS, and BIOSIS; the Chinese Biomedical Literature Database (CBM), China Network Knowledge Information (CNKI), the Chinese Science Journal Database (VIP), Google Scholar, The Turning Research into Practice (TRIP) Database, ClinicalTrials.gov, European Medicines Agency (EMA) (www.ema.europa.eu/ema/), WHO International Clinical Trials Registry Platform (www.who.int/ictrp), the Food and Drug Administration (FDA) (www.fda.gov), and pharmaceutical company sources for ongoing or unpublished trials. Searches were last run in October 2016.
Selection criteria
Randomised clinical trials comparing DAAs versus no intervention or placebo, alone or with co‐interventions, in adults with chronic HCV. We included trials irrespective of publication type, publication status, and language.
Data collection and analysis
We used standard methodological procedures expected by Cochrane. Our primary outcomes were hepatitis C‐related morbidity, serious adverse events, and health‐related quality of life. Our secondary outcomes were all‐cause mortality, ascites, variceal bleeding, hepato‐renal syndrome, hepatic encephalopathy, hepatocellular carcinoma, non‐serious adverse events (each reported separately), and SVR. We systematically assessed risks of bias, performed Trial Sequential Analysis, and followed an eight‐step procedure to assess thresholds for statistical and clinical significance. We evaluated the overall quality of the evidence, using GRADE.
Main results
We included a total of 138 trials randomising a total of 25,232 participants. The trials were generally short‐term trials and designed primarily to assess the effect of treatment on SVR. The trials evaluated 51 different DAAs. Of these, 128 trials employed matching placebo in the control group. All included trials were at high risk of bias. Eighty‐four trials involved DAAs on the market or under development (13,466 participants). Fifty‐seven trials administered DAAs that were discontinued or withdrawn from the market. Study populations were treatment‐naive in 95 trials, had been exposed to treatment in 17 trials, and comprised both treatment‐naive and treatment‐experienced individuals in 24 trials. The HCV genotypes were genotype 1 (119 trials), genotype 2 (eight trials), genotype 3 (six trials), genotype 4 (nine trials), and genotype 6 (one trial). We identified two ongoing trials.
We could not reliably determine the effect of DAAs on the market or under development on our primary outcome of hepatitis C‐related morbidity or all‐cause mortality. There were no data on hepatitis C‐related morbidity and only limited data on mortality from 11 trials (DAA 15/2377 (0.63%) versus control 1/617 (0.16%); OR 3.72, 95% CI 0.53 to 26.18, very low‐quality evidence). We did not perform Trial Sequential Analysis on this outcome.
There is very low quality evidence that DAAs on the market or under development do not influence serious adverse events (DAA 5.2% versus control 5.6%; OR 0.93, 95% CI 0.75 to 1.15 , 15,817 participants, 43 trials). The Trial Sequential Analysis showed that there was sufficient information to rule out that DAAs reduce the relative risk of a serious adverse event by 20% when compared with placebo. The only DAA that showed a lower risk of serious adverse events when meta‐analysed separately was simeprevir (OR 0.62, 95% CI 0.45 to 0.86). However, Trial Sequential Analysis showed that there was not enough information to confirm or reject a relative risk reduction of 20%, and when one trial with an extreme result was excluded, the meta‐analysis result showed no evidence of a difference.
DAAs on the market or under development may reduce the risk of no SVR from 54.1% in untreated people to 23.8% in people treated with DAA (RR 0.44, 95% CI 0.37 to 0.52, 6886 participants, 32 trials, low quality evidence). Trial Sequential Analysis confirmed this meta‐analysis result.
Only 1/84 trials on the market or under development assessed the effects of DAAs on health‐related quality of life (SF‐36 mental score and SF‐36 physical score).
There was insufficient evidence from trials on withdrawn or discontinued DAAs to determine their effect on hepatitis C‐related morbidity and all‐cause mortality (OR 0.64, 95% CI 0.23 to 1.79; 5 trials, very low‐quality evidence). However, these DAAs seemed to increase the risk of serious adverse events (OR 1.45, 95% CI 1.22 to 1.73; 29 trials, very low‐quality evidence). Trial Sequential Analysis confirmed this meta‐analysis result.
None of the 138 trials provided useful data to assess the effects of DAAs on the remaining secondary outcomes (ascites, variceal bleeding, hepato‐renal syndrome, hepatic encephalopathy, and hepatocellular carcinoma).
Authors' conclusions
The evidence for our main outcomes of interest come from short‐term trials, and we are unable to determine the effect of long‐term treatment with DAAs. The rates of hepatitis C morbidity and mortality observed in the trials are relatively low and we are uncertain as to how DAAs affect this outcome. Overall, there is very low quality evidence that DAAs on the market or under development do not influence serious adverse events. There is insufficient evidence to judge if DAAs have beneficial or harmful effects on other clinical outcomes for chronic HCV. Simeprevir may have beneficial effects on risk of serious adverse event. In all remaining analyses, we could neither confirm nor reject that DAAs had any clinical effects. DAAs may reduce the number of people with detectable virus in their blood, but we do not have sufficient evidence from randomised trials that enables us to understand how SVR affects long‐term clinical outcomes. SVR is still an outcome that needs proper validation in randomised clinical trials.
Aim. Our aim was to investigate the association among elastographic parameters of liver steatosis and fibrosis, controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), with ...gastroesophageal reflux disease (GERD). Methods. In this prospective, cross-sectional study, we have evaluated 937 patients with one or more components of the metabolic syndrome who had an esophagogastroduodenoscopy (EGD) due to GERD symptoms. In all patients, a laboratory analysis, an abdominal ultrasound, and FibroScan measurements were done. GERD was defined by EGD. Results. The mean body mass index (BMI) of the study population was 30.95 ± 5.45 kg/m2. The prevalence of increased CAP was 82.6% (774/937). Patients with increased CAP were younger, were more obese, had higher prevalence of hypertension, diabetes, and dyslipidemia, and had higher values of aminotransferases. Similar results of higher prevalence in patients with elevated CAP were observed with GERD, hiatal hernia, and insufficient cardia (defined as deficient or absent closure of the gastric inlet in relation to the esophagus). Additionally, patients with elevated CAP had a higher prevalence of GERD grades B and C in comparison to those without elevated CAP. Consequently, patients who did not have elevated CAP had a higher prevalence of GERD grade A. Even though we have found an upward trend in the prevalence of GERD, hiatal hernia, and insufficient cardia, there was no significant difference between subjects with fibrosis (F) 1-2 and F3-4 stage of fibrosis or F1 and F2-4. In a binary logistic regression, a significant positive association with GERD was obtained for CAP. Furthermore, a significant positive association with hiatal hernia was obtained for BMI and CAP. Finally, a significant positive association with hiatal hernia was obtained with CAP in multivariate analysis. Conclusion. To the best of our knowledge, our study is the first to reveal a positive association between CAP as a surrogate marker of liver steatosis and GERD after adjustments for other clinical variables.
Background
We aimed to determine if there was a higher incidence of small intestinal bacterial overgrowth (SIBO) in non‐alcoholic fatty liver disease (NAFLD) than in patients without NAFLD. Moreover, ...we assessed whether patients with significant fibrosis (SF) had a higher incidence of SIBO compared with patients with non‐significant or no liver fibrosis.
Methods
NAFLD was diagnosed in 117 patients by using Fibroscan with a controlled attenuation parameter (CAP) as well as liver biopsy (LB). SIBO was defined by esophagogastroduodenoscopy with an aspiration of the descending duodenum.
Results
Patients with non‐alcoholic steatohepatitis (NASH) and those with SF on LB had a significantly higher incidence of SIBO than patients without NASH and those without SF, respectively (P < .05). According to histological characteristics, there was a higher proportion of patients in the SIBO group with higher steatosis and fibrosis grade, lobular and portal inflammation, and ballooning grade (P < .001). In multivariate analysis, significant predictors associated with SF and NASH were type 2 diabetes mellitus (T2DM) and SIBO. Moreover, in multivariate analysis, significant predictors that were independently associated with SIBO were T2DM, fibrosis stage and ballooning grade (OR 8.80 (2.07‐37.37), 2.50 (1.16‐5.37) and 27.6 (6.41‐119), respectively). The most commonly isolated were gram‐negative bacteria, predominantly Escherichia coli and Klebsiella pneumoniae.
Conclusion
In this relatively large population of patients, we used a gold standard for both SIBO (quantitative culture of duodenum's descending part aspirate) and NAFLD (LB), and we demonstrated that NASH patients and those with SF had a higher incidence of SIBO. Moreover, significant predictors independently associated with SIBO were T2DM, fibrosis stage and ballooning grade. Although TE is a well‐investigated method for steatosis and fibrosis detection, in our study, independent predictors of SIBO were histological characteristics of NAFLD, while elastographic parameters did not reach statistical significance.
Background
Functional dyspepsia (FD) is one of the most common conditions in clinical practice. In spite of its prevalence, FD is associated with major uncertainties in terms of its definition, ...underlying pathophysiology, diagnosis, treatment, and prognosis.
Methods
A Delphi consensus was initiated with 41 experts from 22 European countries who conducted a literature summary and voting process on 87 statements. Quality of evidence was evaluated using the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 36 statements.
Results
The panel agreed with the definition in terms of its cardinal symptoms (early satiation, postprandial fullness, epigastric pain, and epigastric burning), its subdivision into epigastric pain syndrome and postprandial distress syndrome, and the presence of accessory symptoms (upper abdominal bloating, nausea, belching), and overlapping conditions. Also, well accepted are the female predominance of FD, its impact on quality of life and health costs, and acute gastrointestinal infections, and anxiety as risk factors. In terms of pathophysiological mechanisms, the consensus supports a role for impaired gastric accommodation, delayed gastric emptying, hypersensitivity to gastric distention, Helicobacter pylori infection, and altered central processing of signals from the gastroduodenal region. There is consensus that endoscopy is mandatory for establishing a firm diagnosis of FD, but that in primary care, patients without alarm symptoms or risk factors can be managed without endoscopy. There is consensus that H. pylori status should be determined in every patient with dyspeptic symptoms and H. pylori positive patients should receive eradication therapy. Also, proton pump inhibitor therapy is considered an effective therapy for FD, but no other treatment approach reached a consensus. The long‐term prognosis and life expectancy are favorable.
Conclusions and Inferences
A multinational group of European experts summarized the current state of consensus on the definition, diagnosis and management of FD.
Key summary
Current knowledge
Functional dyspepsia is one of the most common conditions encountered in clinical practice.
There is a lack of guidance for clinicians in guiding diagnosis and treatment of this prevalent condition.
No treatments are currently approved for the treatment of functional dyspepsia in Europe.
What is new here
A Delphi panel consisting of 41 experts from 22 European countries established the level of consensus on 87 statements regarding functional dyspepsia.
The statements reaching consensus serve to guide clinicians in recognizing, diagnosing and treating FD in clinical practice.
Endoscopy is mandatory for establishing a firm diagnosis of functional dyspepsia D, but in primary care patients without alarm symptoms or risk factors can be managed without endoscopy.
Helicobacter pylori status should be determined in every patient with dyspeptic symptoms and H. Pylori positive patients should receive eradication therapy.
Proton pump inhibitor‐therapy is considered an effective therapy for FD, but no other treatment approach reached consensus support.
Parkinson's disease (PD) is neurodegenerative disease with a multifactorial etiopathogenesis with accumulating evidence identifying microbiota as a potential factor in the earliest, prodromal phases ...of the disease. Previous research has already shown a significant difference between gut microbiota composition in PD patients as opposed to healthy controls, with a growing number of studies correlating gut microbiota changes with the clinical presentation of the disease in later stages, through various motor and non-motor symptoms. Our aim in this systematic review is to compose and assess current knowledge in the field and determine if the findings could influence future clinical practice as well as therapy in PD.
We have conducted a systematic review according to PRISMA guidelines through MEDLINE and Embase databases, with studies being selected for inclusion via a set inclusion and exclusion criteria.
20 studies were included in this systematic review according to the selected inclusion and exclusion criteria. The search yielded 18 case control studies, 1 case study, and 1 prospective case study with no controls. The total number of PD patients encompassed in the studies cited in this review is 1,511.
The link between gut microbiota and neurodegeneration is a complex one and it depends on various factors. The relative abundance of various microbiota taxa in the gut has been consistently shown to have a correlation with motor and non-motor symptom severity. The answer could lie in the products of gut microbiota metabolism which have also been linked to PD. Further research is thus warranted in the field, with a focus on the metabolic function of gut microbiota in relation to motor and non-motor symptoms.
Aim. The primary objective of this study was to evaluate the prevalence of increased controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) as surrogate markers of liver ...steatosis and fibrosis in liver transplant recipient (LTR). Secondary objectives were to determine the predictors of increased CAP and LSM in population of LTR. Methods. In this prospective, cross-sectional study, we have evaluated 175 LTRs’ mean age as 61 (53–65) with a functioning graft for more than one year who came for regular outpatient examinations to the Department of Gastroenterology, University Hospital (UH) Merkur, Zagreb, Croatia. Results. Of 175 analyzed LTRs, 34.28% had obesity, 64.00% had hypertension, 38.28% had diabetes, and 58.85% had hyperlipidemia. The prevalence of liver steatosis was 68.57%, while the prevalence of severe liver steatosis was 46.85%. On multivariate analysis, independent factors associated with liver steatosis were male gender, total cholesterol as positive predictor, and HDL as negative predictor, and independent factors positively associated with severe liver steatosis were higher body mass index (BMI) and higher triglyceride levels. The prevalence of moderate liver fibrosis was 54.85%, while the prevalence of advanced liver fibrosis was 24%. On multivariate analysis, independent factors positively associated with moderate fibrosis were gamma-glutamyl transferase (GGT) and CAP, while the independent factor positively associated with advanced fibrosis was GGT. Conclusion. Our study showed high prevalence of increased CAP and LSM measurements as surrogate markers of liver steatosis and fibrosis. Metabolic syndrome components were highly present and were associated with CAP and LSM values as well as in the pretransplant setting. Due to high prevalence of metabolic comorbidities and nonalcoholic fatty liver disease in LTRs and the lack of the abnormal liver test in a significant number of these patients, TE with CAP may be a reasonable initial assessment for LTRs with one or more components of the metabolic syndrome.
Post-endoscopic retrograde cholangiopancreatographypancreatitis(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 pancreatictype 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.
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