Antibiotic prophylaxis to prevent spontaneous bacterial peritonitis in people with liver cirrhosis:a network meta-analysis

BACKGROUND:Approximately 2.5% of all hospitalisations in people with liver cirrhosis are for spontaneous bacterial peritonitis. Spontaneous bacterial peritonitis is associated with significant short-term mortality; therefore, it is important to prevent spontaneous bacterial peritonitis in people at high risk of developing it. Antibiotic prophylaxis forms the mainstay preventive method, but this has to be balanced against the development of drug-resistant spontaneous bacterial peritonitis, which is difficult to treat, and other adverse events. Several different prophylactic antibiotic treatments are available; however, there is uncertainty surrounding their relative efficacy and optimal combination. OBJECTIVES:To compare the benefits and harms of different prophylactic antibiotic treatments for prevention of spontaneous bacterial peritonitis in people with liver cirrhosis using a network meta-analysis and to generate rankings of the different prophylactic antibiotic treatments according to their safety and efficacy. SEARCH METHODS:We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers to November 2018 to identify randomised clinical trials in people with cirrhosis at risk of developing spontaneous bacterial peritonitis. SELECTION CRITERIA:We included only randomised clinical trials (irrespective of language, blinding, or status) in adults with cirrhosis undergoing prophylactic treatment to prevent spontaneous bacterial peritonitis. We excluded randomised clinical trials in which participants had previously undergone liver transplantation, or were receiving antibiotics for treatment of spontaneous bacterial peritonitis or other purposes. DATA COLLECTION AND ANALYSIS:We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio, rate ratio, and hazard ratio (HR) with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. MAIN RESULTS:We included 29 randomised clinical trials (3896 participants; nine antibiotic regimens (ciprofloxacin, neomycin, norfloxacin, norfloxacin plus neomycin, norfloxacin plus rifaximin, rifaximin, rufloxacin, sparfloxacin, sulfamethoxazole plus trimethoprim), and 'no active intervention' in the review. Twenty-three trials (2587 participants) were included in one or more outcomes in the review. The trials that provided the information included people with cirrhosis due to varied aetiologies, with or without other features of decompensation, having ascites with low protein or previous history of spontaneous bacterial peritonitis. The follow-up in the trials ranged from 1 to 12 months. Many of the trials were at high risk of bias, and the overall certainty of evidence was low or very low. Overall, approximately 10% of trial participants developed spontaneous bacterial peritonitis and 15% of trial participants died. There was no evidence of differences between any of the antibiotics and no intervention in terms of mortality (very low certainty) or number of serious adverse events (very low certainty). However, because of the wide CrIs, clinically important differences in these outcomes cannot be ruled out. None of the trials reported health-related quality of life or the proportion of people with serious adverse events. There was no evidence of differences between any of the antibiotics and no intervention in terms of proportion of people with 'any adverse events' (very low certainty), liver transplantation (very low certainty), or the proportion of people who developed spontaneous bacterial peritonitis (very low certainty). The number of 'any' adverse events per participant was fewer with norfloxacin (rate ratio 0.74, 95% CrI 0.59 to 0.94; 4 trials, 546 participants; low certainty) and sulfamethoxazole plus trimethoprim (rate ratio 0.19, 95% CrI 0.02 to 0.81; 1 trial, 60 participants; low certainty) versus no active intervention. There was no evidence of differences between the other antibiotics and no intervention in the number of 'any' adverse events per participant (very low certainty). There were fewer other decompensation events with rifaximin versus no active intervention (rate ratio 0.61, 65% CrI 0.46 to 0.80; 3 trials, 575 participants; low certainty) and norfloxacin plus neomycin (rate ratio 0.06, 95% CrI 0.00 to 0.33; 1 trial, 22 participants; low certainty). There was no evidence of differences between the other antibiotics and no intervention in the number of decompensations events per participant (very low certainty). None of the trials reported health-related quality of life or development of symptomatic spontaneous bacterial peritonitis. One would expect some correlation between the above outcomes, with interventions demonstrating effectiveness across several outcomes. This was not the case. The possible reasons for this include sparse data and selective reporting bias, which makes the results unreliable. Therefore, one cannot draw any conclusions from these inconsistent differences based on sparse data. There was no evidence of any differences in the subgroup analyses (performed when possible) based on whether the prophylaxis was primary or secondary. FUNDING:the source of funding for five trials were organisations who would benefit from the results of the study; six trials received no additional funding or were funded by neutral organisations; and the source of funding for the remaining 18 trials was unclear. AUTHORS' CONCLUSIONS:Based on very low-certainty evidence, there is considerable uncertainty about whether antibiotic prophylaxis is beneficial, and if beneficial, which antibiotic prophylaxis is most beneficial in people with cirrhosis and ascites with low protein or history of spontaneous bacterial peritonitis. Future randomised clinical trials should be adequately powered, employ blinding, avoid postrandomisation dropouts (or perform intention-to-treat analysis), and use clinically important outcomes such as mortality, health-related quality of life, and decompensation events

Serum amylase and lipase and urinary trypsinogen and amylase for diagnosis of acute pancreatitis

The treatment of people with acute abdominal pain differs if they have acute pancreatitis. It is important to know the diagnostic accuracy of serum amylase, serum lipase, urinary trypsinogen-2, and urinary amylase for the diagnosis of acute pancreatitis, so that an informed decision can be made as to whether the person with abdominal pain has acute pancreatitis. There is currently no Cochrane review of the diagnostic test accuracy of serum amylase, serum lipase, urinary trypsinogen-2, and urinary amylase for the diagnosis of acute pancreatitis

Nutritional supplementation for nonalcohol-related fatty liver disease: a network meta-analysis (Review)

BackgroundThe prevalence of non-alcohol-related fatty liver disease (NAFLD) varies between 19% and 33% in different populations. NAFLD decreases life expectancy and increases risks of liver cirrhosis, hepatocellular carcinoma, and the requirement for liver transplantation. Uncertainty surrounds relative benefits and harms of various nutritional supplements in NAFLD. Currently no nutritional supplement is recommended for people with NAFLD. Objectives • To assess the benefits and harms of different nutritional supplements for treatment of NAFLD through a network meta-analysis • To generate rankings of different nutritional supplements according to their safety and efficacy Search methods We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Science Citation Index Expanded, Conference Proceedings Citation Index-Science, the World Health Organization International Clinical Trials Registry Platform, and trials registers until February 2021 to identify randomised clinical trials in people with NAFLD. Selection criteria We included only randomised clinical trials (irrespective of language, blinding, or status) for people with NAFLD, irrespective of method of diagnosis, age and diabetic status of participants, or presence of non-alcoholic steatohepatitis (NASH). We excluded randomised clinical trials in which participants had previously undergone liver transplantation.Data collection and analysisWe performed a network meta‐analysis with OpenBUGS using Bayesian methods whenever possible and calculated differences in treatments using hazard ratios (HRs), odds ratios (ORs), and rate ratios with 95% credible intervals (CrIs) based on an available‐case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance.Main resultsWe included in the review a total of 202 randomised clinical trials (14,200 participants). Nineteen trials were at low risk of bias. A total of 32 different interventions were compared in these trials. A total of 115 trials (7732 participants) were included in one or more comparisons. The remaining trials did not report any of the outcomes of interest for this review.Follow‐up ranged from 1 month to 28 months. The follow‐up period in trials that reported clinical outcomes was 2 months to 28 months. During this follow‐up period, clinical events related to NAFLD such as mortality, liver cirrhosis, liver decompensation, liver transplantation, hepatocellular carcinoma, and liver‐related mortality were sparse.We did not calculate effect estimates for mortality because of sparse data (zero events for at least one of the groups in the trial). None of the trials reported that they measured overall health‐related quality of life using a validated scale. The evidence is very uncertain about effects of interventions on serious adverse events (number of people or number of events).We are very uncertain about effects on adverse events of most of the supplements that we investigated, as the evidence is of very low certainty. However, people taking PUFA (polyunsaturated fatty acid) may be more likely to experience an adverse event than those not receiving an active intervention (network meta‐analysis results: OR 4.44, 95% CrI 2.40 to 8.48; low‐certainty evidence; 4 trials, 203 participants; direct evidence: OR 4.43, 95% CrI 2.43 to 8.42). People who take other supplements (a category that includes nutritional supplements other than vitamins, fatty acids, phospholipids, and antioxidants) had higher numbers of adverse events than those not receiving an active intervention (network meta‐analysis: rate ratio 1.73, 95% CrI 1.26 to 2.41; 6 trials, 291 participants; direct evidence: rate ratio 1.72, 95% CrI 1.25 to 2.40; low‐certainty evidence).Data were sparse (zero events in all groups in the trial) for liver transplantation, liver decompensation, and hepatocellular carcinoma. So, we did not perform formal analysis for these outcomes. The evidence is very uncertain about effects of other antioxidants (antioxidants other than vitamins) compared to no active intervention on liver cirrhosis (HR 1.68, 95% CrI 0.23 to 15.10; 1 trial, 99 participants; very low‐certainty evidence).The evidence is very uncertain about effects of interventions in any of the remaining comparisons, or data were sparse (with zero events in at least one of the groups), precluding formal calculations of effect estimates.Data were probably because of the very short follow‐up period (2 months to 28 months). It takes follow‐up of 8 to 28 years to detect differences in mortality between people with NAFLD and the general population. Therefore, it is unlikely that differences in clinical outcomes are noted in trials providing less than 5 to 10 years of follow‐up.Authors' conclusionsThe evidence indicates considerable uncertainty about effects of nutritional supplementation compared to no additional intervention on all clinical outcomes for people with non‐alcohol‐related fatty liver disease.Accordingly, high‐quality randomised comparative clinical trials with adequate follow‐up are needed. We propose registry‐based randomised clinical trials or cohort multiple randomised clinical trials (study design in which multiple interventions are trialed within large longitudinal cohorts of patients to gain efficiencies and align trials more closely to standard clinical practice) comparing interventions such as vitamin E, prebiotics/probiotics/synbiotics, PUFAs, and no nutritional supplementation. The reason for the choice of interventions is the impact of these interventions on indirect outcomes, which may translate to clinical benefit. Outcomes in such trials should be mortality, health‐related quality of life, decompensated liver cirrhosis, liver transplantation, and resource utilisation measures including costs of intervention and decreased healthcare utilisation after minimum follow‐up of 8 years (to find meaningful differences in clinically important outcomes).</div