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JAMA Internal Medicine May 2022Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been widely recommended for glucose control and cardiovascular risk reduction in patients with type 2... (Meta-Analysis)
Meta-Analysis
Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases: A Systematic Review and Meta-analysis of Randomized Clinical Trials.
IMPORTANCE
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been widely recommended for glucose control and cardiovascular risk reduction in patients with type 2 diabetes, and more recently, for weight loss. However, the associations of GLP-1 RAs with gallbladder or biliary diseases are controversial.
OBJECTIVE
To evaluate the association of GLP-1 RA treatment with gallbladder and biliary diseases and to explore risk factors for these associations.
DATA SOURCES
MEDLINE/PubMed, EMBASE, Web of Science, and Cochrane Library (inception to June 30, 2021), websites of clinical trial registries (July 10, 2021), and reference lists. There were no language restrictions.
STUDY SELECTION
Randomized clinical trials (RCTs) comparing the use of GLP-1 RA drugs with placebo or with non-GLP-1 RA drugs in adults.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data according to the PRISMA recommendations and assessed the quality of each study with the Cochrane Collaboration risk-of-bias tool. Pooled relative risks (RRs) were calculated using random or fixed-effects models, as appropriate. The quality of evidence for each outcome was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework.
MAIN OUTCOMES AND MEASURES
The primary outcome was the composite of gallbladder or biliary diseases. Secondary outcomes were biliary diseases, biliary cancer, cholecystectomy, cholecystitis, and cholelithiasis. Data analyses were performed from August 5, 2021, to September 3, 2021.
RESULTS
A total of 76 RCTs involving 103 371 patients (mean [SD] age, 57.8 (6.2) years; 41 868 [40.5%] women) were included. Among all included trials, randomization to GLP-1 RA treatment was associated with increased risks of gallbladder or biliary diseases (RR, 1.37; 95% CI, 1.23-1.52); specifically, cholelithiasis (RR, 1.27; 95% CI, 1.10-1.47), cholecystitis (RR, 1.36; 95% CI, 1.14-1.62), and biliary disease (RR, 1.55; 95% CI, 1.08-2.22). Use of GLP-1 RAs was also associated with increased risk of gallbladder or biliary diseases in trials for weight loss (n = 13; RR, 2.29; 95% CI, 1.64-3.18) and for type 2 diabetes or other diseases (n = 63; RR, 1.27; 95% CI, 1.14-1.43; P <.001 for interaction). Among all included trials, GLP-1 RA use was associated with higher risks of gallbladder or biliary diseases at higher doses (RR, 1.56; 95% CI, 1.36-1.78) compared with lower doses (RR, 0.99; 95% CI, 0.73-1.33; P = .006 for interaction) and with longer duration of use (RR, 1.40; 95% CI, 1.26-1.56) compared with shorter duration (RR, 0.79; 95% CI, 0.48-1.31; P = .03 for interaction).
CONCLUSIONS AND RELEVANCE
This systematic review and meta-analysis of RCTs found that use of GLP-1 RAs was associated with increased risk of gallbladder or biliary diseases, especially when used at higher doses, for longer durations, and for weight loss.
TRIAL REGISTRATION
PROSPERO Identifier: CRD42021271599.
Topics: Adult; Cholecystitis; Cholelithiasis; Diabetes Mellitus, Type 2; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Weight Loss
PubMed: 35344001
DOI: 10.1001/jamainternmed.2022.0338 -
BMJ Clinical Evidence Aug 2014Of people admitted to hospital for biliary tract disease, 20% have acute cholecystitis. Up to the age of 50 years, acute calculous cholecystitis is three times more... (Review)
Review
INTRODUCTION
Of people admitted to hospital for biliary tract disease, 20% have acute cholecystitis. Up to the age of 50 years, acute calculous cholecystitis is three times more common in women than in men, and about one and a half times more common in women than in men thereafter. About 95% of people with acute cholecystitis have gallstones. Optimal therapy for acute cholecystitis, based on timing and severity of presentation, remains controversial.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for acute cholecystitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 18 studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: early cholecystectomy, laparoscopic cholecystectomy, observation alone, open cholecystectomy, and percutaneous cholecystostomy.
Topics: Cholecystectomy; Cholecystitis, Acute; Gallstones; Humans
PubMed: 25144428
DOI: No ID Found -
World Journal of Surgery Jan 2023Enhanced Recovery After Surgery (ERAS) has been widely applied in liver surgery since the publication of the first ERAS guidelines in 2016. The aim of the present... (Review)
Review
BACKGROUND
Enhanced Recovery After Surgery (ERAS) has been widely applied in liver surgery since the publication of the first ERAS guidelines in 2016. The aim of the present article was to update the ERAS guidelines in liver surgery using a modified Delphi method based on a systematic review of the literature.
METHODS
A systematic literature review was performed using MEDLINE/PubMed, Embase, and the Cochrane Library. A modified Delphi method including 15 international experts was used. Consensus was judged to be reached when >80% of the experts agreed on the recommended items. Recommendations were based on the Grading of Recommendations, Assessment, Development and Evaluations system.
RESULTS
A total of 7541 manuscripts were screened, and 240 articles were finally included. Twenty-five recommendation items were elaborated. All of them obtained consensus (>80% agreement) after 3 Delphi rounds. Nine items (36%) had a high level of evidence and 16 (64%) a strong recommendation grade. Compared to the first ERAS guidelines published, 3 novel items were introduced: prehabilitation in high-risk patients, preoperative biliary drainage in cholestatic liver, and preoperative smoking and alcohol cessation at least 4 weeks before hepatectomy.
CONCLUSIONS
These guidelines based on the best available evidence allow standardization of the perioperative management of patients undergoing liver surgery. Specific studies on hepatectomy in cirrhotic patients following an ERAS program are still needed.
Topics: Humans; Enhanced Recovery After Surgery; Preoperative Exercise; Teaching Rounds; Liver
PubMed: 36310325
DOI: 10.1007/s00268-022-06732-5 -
International Journal of Surgery... Sep 2022Validity of the laparoscopic approach in pancreatic head lesion remains debatable. This study aims to compare the safety and effectiveness of laparoscopic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Validity of the laparoscopic approach in pancreatic head lesion remains debatable. This study aims to compare the safety and effectiveness of laparoscopic pancreatoduodenectomy (LPD) and open pancreatoduodenectomy (OPD) and investigate the source of heterogeneity from surgeons' and patients' perspectives.
METHOD
We searched PubMed, Cochrane, Embase, and Web of Science for studies published before February 1, 2021. Of 6578 articles, 81 were full-text reviewed. The primary outcome was mortality. Three independent reviewers screened and extracted the data and resolved disagreements by consensus. Studies were evaluated for quality using ROB2.0 and ROBINS-I. According to different study designs, sensitivity and meta-regression analyses were conducted to explore the heterogeneity source. This meta-analyses was also conducted to explore the learning curve's heterogeneity. This study was registered with PROSPERO, CRD42021234579.
RESULTS
We analyzed 34 studies involving 46,729 patients (4705 LPD and 42,024 OPD). LPD was associated with lower (P = 0.025) in unmatched studies (P = 0.017). No differences in mortality existed in randomized controlled trials (P = 0.854) and matched studies (P = 0.726). Sensitivity analysis found no significant difference in mortality in elderly patients, patients with pancreatic cancer, and in high- and low-volume hospitals (all P > 0.05). In studies at the early period of LPD (<40 cases), higher mortality (P < 0.001) was found (all P < 0.05).LPD showed non-inferiority in length of stay, complications, and survival outcomes in all analyses.
CONCLUSION
In high-volume centers with adequate surgical experience, LPD in selected patients appears to be a valid alternative to LPD with comparable mortality, LOS, complications, and survival outcomes.
Topics: Aged; Hospitals, Low-Volume; Humans; Laparoscopy; Length of Stay; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Complications; Retrospective Studies
PubMed: 35988720
DOI: 10.1016/j.ijsu.2022.106799 -
Journal of Pediatric Gastroenterology... Aug 2018Alagille syndrome (ALGS) is an inherited multisystem disorder typically manifesting as cholestasis, and potentially leading to end-stage liver disease and death. The aim...
BACKGROUND AND AIM
Alagille syndrome (ALGS) is an inherited multisystem disorder typically manifesting as cholestasis, and potentially leading to end-stage liver disease and death. The aim of the study was to perform the first systematic review of the epidemiology, natural history, and burden of ALGS with a focus on the liver component.
METHODS
Electronic databases and proceedings from key congresses were searched in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 guidelines. This analysis included publications reporting epidemiology, natural history, economic burden or health-related quality of life (HRQoL) outcomes in patients with ALGS.
RESULTS
Of 525 screened publications, 20 met the inclusion criteria. Liver-related features included cholestasis (87%-100% of patients), jaundice (66%-85%), and cirrhosis (44%-95%). Between 15% and 47% of patients underwent liver transplantation and 4% to 14% received partial biliary diversion. Pruritus affected the majority of patients (59%-88%, of whom up to 45% had severe pruritus) and manifested during the first 10 years of life. Children with ALGS had significantly impaired HRQoL compared with healthy controls and those with other diseases. Itching was the symptom that most affected children with ALGS. No study assessed the economic burden of ALGS.
CONCLUSIONS
Our findings consolidate information on the clinical course of ALGS, and highlight gaps in knowledge, most notably the absence of any research on the economic consequences of the disease. Further research is needed to establish the incidence of genetically confirmed ALGS. Disease-specific tools are also needed to improve the measurement of symptoms, such as itching, and better understand the impact of ALGS on HRQoL.
Topics: Alagille Syndrome; Child; Humans
PubMed: 29543694
DOI: 10.1097/MPG.0000000000001958 -
BMJ (Clinical Research Ed.) Jun 2022To examine the association between dipeptidyl peptidase-4 inhibitors and gallbladder or biliary diseases. (Meta-Analysis)
Meta-Analysis
Dipeptidyl peptidase-4 inhibitors and gallbladder or biliary disease in type 2 diabetes: systematic review and pairwise and network meta-analysis of randomised controlled trials.
OBJECTIVE
To examine the association between dipeptidyl peptidase-4 inhibitors and gallbladder or biliary diseases.
DESIGN
Systematic review and pairwise and network meta-analysis.
DATA SOURCES
PubMed, EMBASE, Web of Science, and CENTRAL from inception until 31 July 2021.
ELIGIBILITY CRITERIA
Randomised controlled trials of adult patients with type 2 diabetes who received dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors compared with placebo or other antidiabetes drugs.
MAIN OUTCOME MEASURES
Composite of gallbladder or biliary diseases, cholecystitis, cholelithiasis, and biliary diseases.
DATA EXTRACTION AND DATA SYNTHESIS
Two reviewers independently extracted the data and assessed the quality of the studies. The quality of the evidence for each outcome was assessed using the Grading of Recommendations, Assessment, Development and Evaluations framework (GRADE) approach. The meta-analysis used pooled odds ratios and 95% confidence intervals.
RESULTS
A total of 82 randomised controlled trials with 104 833 participants were included in the pairwise meta-analysis. Compared with placebo or non-incretin drugs, dipeptidyl peptidase-4 inhibitors were significantly associated with an increased risk of the composite of gallbladder or biliary diseases (odds ratio 1.22 (95%confidence interval 1.04 to 1.43); risk difference 11 (2 to 21) more events per 10 000 person years) and cholecystitis (odds ratio 1.43 (1.14 to 1.79); risk difference 15 (5 to 27) more events per 10 000 person years) but not with the risk of cholelithiasis and biliary diseases. The associations tended to be observed in patients with a longer duration of dipeptidyl peptidase-4 inhibitor treatment. In the network meta-analysis of 184 trials, dipeptidyl peptidase-4 inhibitors increased the risk of the composite of gallbladder or biliary diseases and cholecystitis compared with sodium-glucose cotransporter-2 inhibitors but not compared with glucagon-like peptide-1 receptor agonists.
CONCLUSIONS
Dipeptidyl peptidase-4 inhibitors increased the risk of cholecystitis in randomised controlled trials, especially with a longer treatment duration, which requires more attention from physicians in clinical practice.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021271647.
Topics: Adult; Cholecystitis; Cholelithiasis; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Glucagon-Like Peptide-1 Receptor; Glucose; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sodium; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 35764326
DOI: 10.1136/bmj-2021-068882 -
Systematic Reviews Dec 2022Symptomatic cholelithiasis is a common surgical disease and accounts for half of the over one million cholecystectomies performed in the USA annually. Despite its...
BACKGROUND
Symptomatic cholelithiasis is a common surgical disease and accounts for half of the over one million cholecystectomies performed in the USA annually. Despite its prevalence, only one prior systematic review has examined the evidence around treatment strategies and it contained a narrow scope. The goal of this systematic review was to analyze the clinical effectiveness of treatment options for symptomatic cholelithiasis, including surgery, non-surgical therapies, and ED pain management strategies.
METHODS
Literature search was performed from January 2000 through June 2020, and a narrative analysis was performed as studies were heterogeneous.
RESULTS
We identified 12 publications reporting on 10 trials (9 randomized controlled trials and 1 observational study) comparing treatment methods. The studies assessed surgery, observation, lithotripsy, ursodeoxycholic acid, electro-acupuncture, and pain-management strategies in the emergency department. Only one compared surgery to observation.
CONCLUSION
This work presents the existing data and underscores the current gap in knowledge regarding treatment for patients with symptomatic cholelithiasis. We use these results to suggest how future trials may guide comparisons between the timing of surgery and watchful waiting to create a set of standardized guidelines. Providing appropriate and timely treatment for symptomatic cholelithiasis is important to streamline care for a costly and prevalent disease.
TRIAL REGISTRATION
PROSPERO Protocol Number: CRD42020153153.
Topics: Humans; Cholelithiasis; Treatment Outcome; Emergency Service, Hospital; Prevalence; Observational Studies as Topic
PubMed: 36510302
DOI: 10.1186/s13643-022-02135-8 -
Digestive Surgery 2020Bile duct injury (BDI) is a devastating complication following cholecystectomy. After initial management of BDI, patients stay at risk for late complications including...
BACKGROUND
Bile duct injury (BDI) is a devastating complication following cholecystectomy. After initial management of BDI, patients stay at risk for late complications including anastomotic strictures, recurrent cholangitis, and secondary biliary cirrhosis.
METHODS
We provide a comprehensive overview of current literature on the long-term outcome of BDI. Considering the availability of only limited data regarding treatment of anastomotic strictures in literature, we also retrospectively analyzed patients with anastomotic strictures following a hepaticojejunostomy (HJ) from a prospectively maintained database of 836 BDI patients.
RESULTS
Although clinical outcomes of endoscopic, radiologic, and surgical treatment of BDI are good with success rates of around 90%, quality of life (QoL) may be impaired even after "clinically successful" treatment. Following surgical treatment, the incidence of anastomotic strictures varies from 5 to 69%, with most studies reporting incidences around 10-20%. The median time to stricture formation varies between 11 and 30 months. Long-term BDI-related mortality varies between 1.8 and 4.6%. Of 91 patients treated in our center for anastomotic strictures after HJ, 81 (89%) were treated by percutaneous balloon dilatation, with a long-term success rate of 77%. Twenty-four patients primarily or secondarily underwent surgical revision, with recurrent strictures occurring in 21%.
CONCLUSIONS
The long-term impact of BDI is considerable, both in terms of clinical outcomes and QoL. Treatment should be performed in tertiary expert centers to optimize outcomes. Patients require a long-term follow-up to detect anastomotic strictures. Strictures should initially be managed by percutaneous dilatation, with surgical revision as a next step in treatment.
Topics: Anastomosis, Roux-en-Y; Bile Ducts; Cholangitis; Cholecystectomy; Constriction, Pathologic; Dilatation; Humans; Iatrogenic Disease; Jejunum; Liver Cirrhosis, Biliary; Prognosis; Quality of Life; Recurrence; Reoperation; Retrospective Studies
PubMed: 30654363
DOI: 10.1159/000496432 -
Journal of Hepatology Sep 2021Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many... (Meta-Analysis)
Meta-Analysis
BACKGROUNDS & AIMS
Primary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening.
METHODS
We combined new and existing genotype data for 10,516 cases and 20,772 controls from 5 European and 2 East Asian cohorts.
RESULTS
We identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57 genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, which each play key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, JAK-STAT signalling, and differentiation of T helper (T)1 and T17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some of which are well-established in the treatment of other autoimmune disorders.
CONCLUSIONS
This study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders.
LAY SUMMARY
Primary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10,516 people with PBC and 20,772 healthy individuals recruited in Canada, China, Italy, Japan, the UK, or the USA. We identified several genetic regions associated with PBC. Each of these regions contains several genes. For each region, we used diverse sources of evidence to help us choose the gene most likely to be involved in causing PBC. We used these 'candidate genes' to help us identify medications that are currently used for treatment of other conditions, which might also be useful for treatment of PBC.
Topics: Genome-Wide Association Study; Humans; Liver Cirrhosis, Biliary
PubMed: 34033851
DOI: 10.1016/j.jhep.2021.04.055 -
World Journal of Gastroenterology Aug 2019Post endoscopic retrograde cholangiopancreatography (ERCP) is comparatively complex application. Researchers has been investigated prevention of post-ERCP pancreatitis...
BACKGROUND
Post endoscopic retrograde cholangiopancreatography (ERCP) is comparatively complex application. Researchers has been investigated prevention of post-ERCP pancreatitis (PEP), since it has been considered to be the most common complication of ERCP. Although ERCP can lead various complications, it can also be avoided.AIMSTo study the published evidence and systematically review the literature on the prevention and treatment for PEP.
METHODS
A systematic literature review on the prevention of PEP was conducted using the electronic databases of ISI Web of Science, PubMed and Cochrane Library for relevant articles. The electronic search for the review was performed by using the search terms "Post endoscopic retrograde cholangiopancreatography pancreatitis" AND "prevention" through different criteria. The search was restricted to randomized controlled trials (RCTs) performed between January 2009 and February 2019. Duplicate studies were detected by using EndNote and deleted by the author. PRISMA checklist and flow diagram were adopted for evaluation and reporting. The reference lists of the selected papers were also scanned to find other relevant studies.
RESULTS
726 studies meeting the search criteria and 4 relevant articles found in the edited books about ERCP were identified. Duplicates and irrelevant studies were excluded by screening titles and abstracts and assessing full texts. 54 studies were evaluated for full text review. Prevention methods were categorized into three groups as (1) assessment of patient related factors; (2) pharmacoprevention; and (3) procedural techniques for prevention. Most of studies in the literature showed that young age, female gender, absence of chronic pancreatitis, suspected Sphincter of Oddi dysfunction, recurrent pancreatitis and history of previous PEP played a crucial role in posing high risks for PEP. 37 studies designed to assess the impact of 24 different pharmacologic agents to reduce the development of PEP delivered through various administration methods were reviewed. Nonsteroidal anti-inflammatory drugs are widely used to reduce risks for PEP. Rectal administration of indomethacin immediately prior to or after ERCP in all patients is recommended by European Society for Gastrointestinal Endoscopy guidelines to prevent the development of PEP. The majority of the studies reviewed revealed that rectally administered indomethacin had efficacy to prevent PEP. Results of the other studies on the other pharmacological interventions had both controversial and promising results. Thirteen studies conducted to evaluate the efficacy of 4 distinct procedural techniques to prevent the development of PEP were reviewed. Pancreatic Stent Placement has been frequently used in this sense and has potent and promising benefits in the prevention of PEP. Studies on the other procedural techniques have had inconsistent results.
CONCLUSION
Prevention of PEP involves multifactorial aspects, including assessment of patients with high risk factors for alternative therapeutic and diagnostic techniques, administration of pharmacological agents and procedural techniques with highly precise results in the literature.
Topics: Administration, Rectal; Anti-Inflammatory Agents; Biliary Tract Diseases; Catheterization; Cholangiopancreatography, Endoscopic Retrograde; Drainage; Humans; Pancreas; Pancreatitis; Phosphodiesterase 5 Inhibitors; Postoperative Complications; Preoperative Care; Risk Assessment; Risk Factors; Somatostatin; Sphincter of Oddi; Stents
PubMed: 31413535
DOI: 10.3748/wjg.v25.i29.4019