Therapeutic Advances in Gastroenterology最新文献

Background: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), can affect the hepatobiliary system and pancreas, substantially impacting the life quality of patients.

Objectives: To evaluate the quality of evidence and comprehensively assess the validity of associations of IBD with hepatobiliary and pancreatic diseases.

Design: We performed an umbrella review of existing meta-analyses in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) recommendations.

Data sources and methods: We systematically searched PubMed, Embase, and Web of Science from inception to April 2024, to identify and appraise meta-analyses examining IBD and risk of hepatobiliary and pancreatic manifestations. Methodologic quality was assessed with A Measurement Tool to Assess Systematic Reviews (AMSTAR 2) and the strength of evidence was graded according to prespecified criteria.

Results: A total of 14 meta-analyses of observational studies were included. The strongest-validity evidence suggested the significant associations between IBD and risk of gallstones (odds ratio (OR) = 1.72; 95% confidence interval (CI) = 1.40-2.12) and acute pancreatitis (OR = 3.11; 95% CI = 2.93-3.30). Highly suggestive evidence indicated a significantly increased risk of hepatobiliary cancer in UC (incidence rate ratio (IRR) = 2.05; 95% CI = 1.52-2.76) and CD (IRR = 2.31; 95% CI = 1.25-4.28). In addition, highly suggestive evidence indicated that IBD was associated with portal venous system thrombosis. Suggestive evidence showed a significantly higher prevalence of primary sclerosing cholangitis, non-alcoholic fatty liver disease, autoimmune hepatitis, and autoimmune pancreatitis in IBD patients than in the general population.

Conclusion: The associations between IBD and multiple hepatobiliary and pancreatic disorders showed varying levels of evidence and magnitude of risk. Further high-quality primary studies are needed to identify IBD patients who are more at risk and would benefit the most from screening and prevention programs.

Trial registration prospero: CRD42023451461.

Background: Acute variceal bleeding (AVB), a life-threatening complication of liver cirrhosis, can be effectively treated by endoscopy, but there is a risk of early rebleeding after endoscopic variceal treatment (EVT). Thrombocytopenia is the most common hemostatic abnormality in liver cirrhosis. However, it is still unclear about whether thrombocytopenia increases the failure of EVT in cirrhotic patients with AVB.

Objectives: We investigated the association between thrombocytopenia and the failure of EVT in cirrhotic patients with AVB.

Design: International multicenter, retrospective study.

Methods: Overall, 2467 cirrhotic patients with acute gastrointestinal bleeding who were enrolled into an international multicenter study between September 30, 2020 and June 30, 2023 were retrospectively screened. Thrombocytopenia was defined as platelet count below 150 × 10⁹/L and further classified as mild (100 × 10⁹/L-150 × 10⁹/L), moderate (50 × 10⁹/L-100 × 10⁹/L), and severe (<50 × 10⁹/L). A 1:1 propensity score matching (PSM) analysis was performed. Five-day failure to control bleeding was evaluated.

Results: Overall, 1079 patients were included, of whom 923 (85.5%) had thrombocytopenia, including mild (n = 241), moderate (n = 445), and severe (n = 237) thrombocytopenia. PSM analysis demonstrated that the rate of 5-day failure to control bleeding was not significantly different between patients with and without thrombocytopenia (mild: (12/153) 7.8% vs (7/153) 4.6%, p = 0.236; moderate: (9/155) 5.8% vs (7/155) 4.5%, p = 0.608; or severe: (5/132) 3.8% vs (7/132) 5.3%, p = 0.555).

Conclusion: Thrombocytopenia may not influence the efficacy of EVT in cirrhotic patients with AVB.

Background: Functional dyspepsia (FD) is one of the most common gastrointestinal disorders worldwide. Currently, anti-gastric drugs, gastric acid inhibitors, prokinetic drugs, and mucosal protective drugs are widely used in FD patients, however, only a small proportion of patients benefit from these drugs. Studies reported mirtazapine may improve symptoms of FD patients but the efficacy and safety of mirtazapine in the treatment of FD is unclear.

Objectives: To investigate the efficacy and safety of mirtazapine in FD patients.

Design: We performed a prospective, single-randomized, two-group parallel clinical trial involving 120 FD patients with poor traditional drug treatment outcomes to evaluate the efficacy and safety of mirtazapine.

Methods: Qualified patients identified through the screening assessments were randomly divided into two groups: mirtazapine group (n = 60) treated with mirtazapine 15 mg qn on top of traditional drugs, and control group (n = 60) who continued to be treated with traditional drugs. Subjects were evaluated for meal-related symptoms and severity, quality of life, gastrointestinal-specific anxiety, and body weight before and after the 8-week intervention. Adverse reactions were also recorded.

Results: At the end of 8-week treatment, dyspeptic symptoms in the mirtazapine group were significantly relieved compared with the baseline (7.95 ± 1.86 vs 11.17 ± 2.14, p < 0.001). Assessment of the impact of dyspepsia on patients' quality of life from the short form-Nepean Dyspepsia Index showed that patients generally feel better in mirtazapine group than control group (24.52 ± 2.87 vs 28.64 ± 4.32, p < 0.001). Mirtazapine group also showed significant weight gain and decreased visceral sensitivity index score.

Conclusion: Compared with control group, 8-week administration of mirtazapine significantly improved the overall severity of symptoms of dyspepsia (such as individual symptoms of postprandial fullness, early satiation, nausea, and vomiting), gastrointestinal-specific anxiety, quality of life, and increased weight in FD patients. This study provided clues to clinicians that mirtazapine may be a good choice for the treatment of FD patients.

Trial registration: This study was registered in the Chinese clinical trial registry (https://www.chictr.org.cn/index.html, protocol No. ChiCTR2100048304).

Background: The association between inflammatory bowel disease (IBD) activity and poor sleep quality is reported. However, most research subjectively investigated this issue and lacked long-term follow-up.

Objectives: Our study aimed to investigate the prevalence of sleep disturbance in IBD patients across disease activity and evaluate the long-term correlation between disease activity, sleep quality, and quality of life.

Design: This prospective observational study assessed sleep quality in patients with IBD.

Methods: Patients with IBD were categorized into groups based on clinical activity scores. The sleep questionnaire (Pittsburgh Sleep Quality Index (PSQI)) and IBD questionnaire (IBDQ) were evaluated monthly for 12 months. Seven-day sleep data from wrist actigraphy (Actiwatch^®) were collected at initiation and completion. Longitudinal correlation was analyzed.

Results: A total of 98 participants were enrolled, consisting of 68 remission, 21 mild, and 9 moderate-to-severe disease activities. At baseline, 60% of participants demonstrated poor sleep quality, defined by a PSQI of >5. The group with greater disease severity reported numerically poorer sleep quality; however, this difference was not statistically significant. On actigraphy, there was no statistically significant difference in sleep latency, wake after sleep onset, or sleep efficiency between the groups. During follow-up, 90 patients responded to questionnaires. The mean PSQI decreased from 7.1 to 5.4 among 22 patients whose active disease transitioned to remission (p < 0.001). However, the score did not change in 11 patients with remission and developed disease flare (5.9-5.8). The mean PSQI was 7.7 and 6.3 in 4 and 53 patients whose disease remained active and inactive during follow-up, respectively. Multivariable longitudinal analysis revealed that PSQI was independently associated with active disease (odds ratio = 1.22) and inversely associated with IBDQ (β = -2.23). Sleep latency was evaluated by PSQI, and actigraphy was significantly correlated.

Conclusions: Patients with IBD frequently experience poor sleep quality, which significantly correlates with active disease and worse quality of life longitudinally.

Background: Limited research exists on colorectal cancer (CRC) patients with bladder invasion, with survival outcomes post-cystectomy underexplored and a debate between partial and total cystectomy ongoing.

Objective: The study aimed to evaluate the effect of pathological bladder invasion on the long-term tumour prognosis of patients with clinically diagnosed bladder invasion in CRC after cystectomy.

Design: Retrospective, cohort study.

Methods: Our study involving 105 CRC patients with bladder invasion who had partial or total cystectomy from 2012 to 2020 collected surgical and pathological data. Groups were divided by pathological bladder invasion presence and compared for 3-year overall survival (OS) and recurrence-free survival (RFS) rates. Multiphoton imaging assessed collagen features in some samples.

Results: Pathological bladder invasion was confirmed in 50 patients (48%). Of 94 who had partial cystectomy, 41 were in the bladder invasion (+) group. The 3-year OS and RFS rates were 62.97% and 57.35% for the bladder invasion (+) group, and 77.16% and 58.68% for the bladder invasion (-) group, with no significant differences in recurrence rates between groups (p > 0.05). There are also no significant differences in 3-year local recurrence and intravesical recurrence rates between the two groups (18.62% vs 25.83%, 7.73% vs 11.82%, p > 0.05). Distant metastasis was identified as an independent risk factor for OS and RFS by univariate and multivariate Cox regression analyses. Of the 24 samples that underwent multi-photon imaging, 142 collagen features extracted did not show statistical differences.

Conclusion: Pathological bladder invasion impacts CRC patients' post-cystectomy survival may be less than what clinical practice implies. Partial cystectomy in cases with pathological bladder invasion might offer similar survival rates to total cystectomy.

Trial registration: ChiCTR2300077861.

Background: Little is known about the involvement of gut microbiota in the disease course of diverticulitis and the potential benefits of manipulating the gut milieu. We propose to conduct a randomised placebo-controlled feasibility trial of faecal microbiota transplantation (FMT) given as capsules to patients with acute uncomplicated diverticulitis.

Objectives: The objective is primarily to investigate the feasibility of clinical safety, explore efficacy associated with FMT in this patient population, and examine changes in patient-reported quality of life and the composition and function of the gut microbiota.

Design: Study protocol for a randomised placebo-controlled trial.

Methods and analysis: Participants with acute, uncomplicated diverticulitis, as confirmed by computed tomography (CT) scan, will be recruited from Odense University Hospital (Denmark) and randomly assigned to either the intervention group or the control group. The intervention group will consist of 20 patients who receive encapsulated FMT. The control group will also consist of 20 patients, receiving placebo capsules. Primary safety endpoint: Patient safety is monitored by (a) the number of re-admissions and (b) the number of adverse events within 3 months of FMT/placebo; Primary efficacy endpoint: Reduction in the proportion of patients treated with antibiotics within 3 months following FMT/placebo; Secondary outcome: Change from baseline to 3 months in the GI-QLI questionnaire. Results will be analysed using an intention-to-treat approach. Adverse events or unintended consequences will be reported.

Ethics and discussion: This is the first study to investigate the safety and efficacy of FMT in patients with acute uncomplicated diverticulitis. The project has the potential to broaden the knowledge and literature on the role of the intestinal microbiota in diverticulitis, and we believe it will elevate our understanding of cause and effect.

Trial registration: Informed consent is obtained from all participants. The study is approved by the regional ethics committee (ref. S-20230023) and the Danish Data Protection Agency (ref. 24/2435). The trial was registered on clinicaltrials.gov (NCT06254625) on 10th February 2024.

Inflammatory bowel diseases (IBDs), primarily encompassing ulcerative colitis and Crohn's disease, represent a challenging spectrum of disorders with a multifaceted pathogenesis. Despite the array of available treatments, a demand for novel therapeutic options persists to achieve remission in a broader patient population. Research findings indicate that relying solely on a single biologic drug may limit future treatment choices, prompting consideration for a more suitable shift from step-up to top-down strategies in certain cases. In the backdrop of advancing drug development, reimagining the application of existing therapies presents a promising avenue. Among these innovative approaches is combination therapy. This review explores the outcomes of recent randomized clinical trials, systematic reviews, and case studies, focusing on dual biologic therapy. It underscores the effectiveness, safety, and tolerability of combining two biologic drugs in IBD, providing insights into a potentially impactful treatment strategy.

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality globally. Recent advancements in targeted therapies have improved outcomes for advanced HCC, yet therapeutic options remain limited. The CARES-310 trial demonstrated that camrelizumab plus rivoceranib significantly improves survival compared to sorafenib for advanced HCC.

Objectives: This study aimed to evaluate the cost-effectiveness of camrelizumab plus rivoceranib as a first-line treatment for unresectable HCC from the Chinese health system perspective.

Design: The cost-effectiveness analysis.

Methods: A partitioned survival model was constructed to estimate clinical and economic outcomes for patients with unresectable or metastatic HCC. The model included three health states: progression-free, progression disease, and death. The hypothetical cohort consisted of patients aged ⩾18 with HCC who had not received systemic therapy, reflecting the CARES-310 trial. Clinical data were derived from the CARES-310 trial and extrapolated using standard parameter distributions. Direct medical costs and utilities were sourced from the CARES-310 trial and published literature.

Results: The 10-year cost of camrelizumab plus rivoceranib was higher than sorafenib (USD 28,148.01 vs USD 20,997.86). Camrelizumab plus rivoceranib yielded an additional 0.26 quality-adjusted life-years (QALYs) with an incremental cost of USD 7150.15, resulting in an incremental cost-effectiveness ratio of USD 27,633.75/QALY. Sensitivity analyses confirmed the robustness of the base-case results.

Conclusion: Camrelizumab plus rivoceranib is likely a cost-effective first-line treatment for unresectable HCC from a Chinese health system perspective. This study highlights the need for additional real-world data to validate these findings and guide clinical decision-making for HCC.

Background: Treatment options for patients with refractory inflammatory bowel disease (IBD) or concomitant IBD and extraintestinal manifestations (EIM) are often limited.

Objective: This study aimed to examine the efficacy and safety of combining biologics or small molecules in patients with refractory IBD, active EIM, or active immune-mediated inflammatory disease (IMID).

Design: This was a retrospective and multicenter study.

Methods: We retrospectively collected demographics and disease characteristics from 47 patients with IBD who received dual-targeted therapy in 3 hospitals from January 2022 to June 2024. The primary endpoint was clinical remission based on the Harvey-Bradshaw index or patient-reported outcome 2 after at least 4 months of combination therapy. The secondary endpoints included clinical response, endoscopic response, and endoscopic remission, as well as all adverse events that occurred within the period of combination therapy.

Results: In total, 47 IBD patients including 37 with refractory IBD, 5 with active EIM, and 5 with active IMID received dual-targeted therapy, of which 37 achieved clinical response (78.7%) and 27 achieved clinical remission (57.4%) at a median follow-up time of 13.0 months. Among these 47 patients, 29 patients underwent endoscopic follow-up, of which 15 (51.7%) achieved endoscopic response and 8 (27.6%) achieved endoscopic remission at a median follow-up time of 9.0 months. Mild and moderate adverse events were reported in 17 (36.2%) patients within the period of combination therapy, and serious adverse events requiring hospitalization occurred in 1 patient (2.1%).

Conclusion: The combination therapy of biologics and small molecules for refractory IBD or those with concomitant EIM/IMID is effective and safe.

Background: Despite its significant health burden, there is a lack of national-level temporal patterns in gastrointestinal bleeding (GIB) mortality.

Objectives: To comprehensively decipher the annual and monthly trend of GIB-related mortality in the United States.

Design: Cross-sectional study.

Methods: We analyzed the National Vital Statistic System database, which documents more than 99% of the annual deaths in the United States for GIB-related deaths from January 2010 to May 2023. Annual and monthly age-standardized mortality rates were estimated and categorized by age, sex, and bleeding site. Joinpoint regression was performed for trend analysis. Prediction modeling was conducted to determine the GIB-associated excess mortality.

Results: A total of 529,094 and 210,641 GIB-associated deaths occurred before and after 2020, respectively. Following a stably decreasing trend between 2010 and 2019, there was an excess mortality rate during the pandemic which peaked in 2021. The monthly mortality trend showed spikes corresponding to the outbreak of variants. Importantly, excess GIB-related mortality resolved in 2023, with the convergence of predicted and observed mortality rates. Subgroup analysis showed that young males (aged 19-44 years) were affected the most during the pandemic, with excess mortality rates of 35.80%, 52.77%, and 31.46% in 2020, 2021, and 2022, respectively. While the increasing trend of upper GIB was accentuated during the pandemic, lower GIB showed a reversal of the pre-pandemic decreasing trend.

Conclusion: Our findings demonstrate the trend of GIB-related mortality, underscoring an increased excess death during the pandemic followed by a resolution in 2023. We identify subpopulations vulnerable to the pandemic.