Canadian Journal of Gastroenterology and Hepatology最新文献

Background: Triglyceride glucose (TyG) and its related index (TyG-body mass index, TyG-BMI) are recognized as markers for nonalcoholic fatty liver disease (NAFLD), but their associations with metabolic dysfunction-associated steatotic liver disease (MASLD) and significant liver fibrosis (SLF) risk are less studied. Therefore, this study explores the effectiveness of these indices in assessing MASLD and SLF risk in the U.S. population. Methods: Utilizing data from the National Health and Nutrition Examination Survey (NHANES), a cross-sectional study involving 5520 participants from the general population was performed. This research measured demographic, anthropometric, biochemical, comorbid, and lifestyle characteristics, all of which are considered risk factors for MASLD/SLF. Results: Upon controlling for confounding variables, only the TyG-BMI was found to have a consistent positive association with the risk of MASLD and SLF. Specifically, for each standard deviation increase, the odds ratio (OR) and 95% confidence interval (CI) were 4.44 (3.64-9.26, p for trend < 0.001) for MASLD and 2.48 (2.15-2.87, p for trend < 0.001) for SLF. Significant interactions were identified among age, sex, and the risk of MASLD associated with the TyG-BMI. The TyG-BMI also had a significant threshold effect on the risk of MASLD at a cutoff point of 180.71. Furthermore, the area under the receiver operating characteristic curve (AUC) revealed that the TyG-BMI better predicted the risk of MASLD and SLF (AUC 0.820, 95% CI 0.810-0.831; AUC 0.729, 95% CI 0.703-0.756, respectively). In addition, the integrated discrimination improvement (IDI), decision curve analysis (DCA), and net reclassification index (NRI) also demonstrated the satisfactory predictive ability of the TyG-BMI. Conclusions: Within this large dataset, the TyG-BMI was independently associated with both the MASLD score and the SLF in the MASLD cohort. Its predictive efficacy consistently surpassed that of TyG and other noninvasive models, indicating that TyG-BMI has potential for the early identification of MASLD and SLF risk.

Introduction: Metabolic dysfunction-associated fatty liver disease (MAFLD) is highly prevalent among people living with severe obesity (body mass index [BMI] ≥ 35 kg/m²). However, it remains unknown how sex and adipose tissue distribution are related to MAFLD onset and progression into metabolic dysfunction-associated steatohepatitis (MASH) or advanced stages of fibrosis. Methodology: We retrospectively studied patients with severe obesity who were eligible for bariatric surgery. Demographic characteristics, biomarkers, and cardiometabolic comorbidities were reported. Anthropometric indices such as BMI, waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), neck circumference (NC), lipid accumulation product (LAP), visceral adiposity index (VAI), body adiposity index (BAI), abdominal volume index (AVI), and body roundness index (BRI) were measured or calculated. MAFLD, MASH, and stages of fibrosis (F1-F4) were established from perioperative liver biopsies. Standardized univariate and multivariate logistic regression analyses were used to examine the association between demographic variables, anthropometric indices, cardiometabolic conditions, and the risk of MASH or severe fibrosis (F2-F4). Results: A total of 2091 participants with severe obesity were included in the analyses; BMI 47.9 ± 7.3 kg/m², age 46.2 ± 11.2 years, and 68.4% females. Overall, MAFLD prevalence was 79.5%, with 44.5% having MASH and 24.4% having severe fibrosis (Stage 2 or higher). No anthropometric indices of adiposity were associated with MASH or fibrosis severity. In this population, female sex was a risk factor for severe fibrosis (OR: 1.27, 95% CI 1.01-1.59, p < 0.05). Conclusions: MAFLD and MASH are highly prevalent in individuals living with severe obesity, but no anthropometric indices or laboratory tests are good predictors of MAFLD or MASH in this population. When MAFLD is diagnosed, our results suggest that females with severe obesity might be at higher risk of advanced stages of fibrosis.

Background: Although it is generally believed that infliximab dose optimization in patients with inflammatory bowel disease with low serum infliximab concentration at trough results in increased treatment persistence, empirical data to support this notion are lacking. This study evaluated the association of infliximab therapeutic drug monitoring (TDM) and TDM-associated dose optimization with persistence in real-world practice. Methods: Data from adults with Crohn's disease (CD) or ulcerative colitis (UC) who participated in a national patient support program (PSP) in Canada were analyzed. Participants who had a first TDM evaluation (with a recorded infliximab trough concentration) in the maintenance phase of treatment were assessed (excluding those who underwent prior dose optimization). Persistence was evaluated using time-dependent Cox proportional hazards models. Results: In the overall population of patients with CD or UC, TDM was not associated with longer persistence (n = 13,203). In patients with no prior dose optimization (n = 2729) who had a serum infliximab concentration of < 3 μg/mL, dose optimization within 9 weeks of TDM was associated with significantly longer persistence (HR: 0.36; 95% CI: 0.26, 0.50 for CD [n = 711] and HR: 0.30, 95% CI: 0.21, 0.43 for UC [n = 501]). Sensitivity analyses yielded similar results when using a threshold concentration of < 5 μg/mL. In an analysis excluding patients who received no further treatment after TDM, the association between dose optimization and longer persistence was not confirmed in patients with CD, and mostly confirmed in patients with UC at a threshold concentration of < 3 μg/mL. Conclusion: TDM-associated dose optimization in patients with UC with low serum infliximab concentrations was associated with longer persistence. This association was not confirmed in patients with CD. This study demonstrated that real-world data from a PSP-generated cohort can be evaluated to inform clinical practice and that this approach may be complementary to other types of cohort studies.

[This corrects the article DOI: 10.1155/2021/8825123.].

Background: Aims: Carboxylesterase (Ces)1f is implicated in protection against hepatic inflammation, but it is unclear whether the enzyme has an influence in polarization of Kupffer cells (KCs), the innate immune cells mediating hepatic inflammatory injury including acute liver failure (ALF). In the present study, we aim to explore KC polarization induced by Ces1f in mice with lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced ALF. Methods: We adopted a novel delivery system, β-1,3-D-glucan-encapsulated Endoporter-siRNA particles, to specifically target KC Ces1f knockdown via tail vein injection in mice. Results: Ces1f knockdown increased LPS/D-GalN-induced lethality as well as serum levels of alanine and aspartate transaminases, deteriorated hepatic inflammatory injury, and imbalanced hepatic oxidative stress molecules including myeloperoxidase, malondialdehyde, and superoxide dismutase in ALF. Ces1f knockdown also increased the levels of proinflammatory cytokines (tumor necrosis factor-α and interleukin-6) and decreased the levels of anti-inflammatory cytokine (interleukin-10) in LPS/D-Gal-induced ALF. Ces1f knockdown promoted KC M1 phenotype and marker expression (including CD86 and interleukin-1β), but inhibited M2 phenotype and marker expression (including CD163, CD206, and Arginase 1). Conclusions: Our results suggest that Ces1f plays a hepatoprotective role through regulating KC polarization, which might contribute to anti-inflammatory and antioxidative effects in LPS/D-Gal-induced ALF mice.

Background: Esophageal variceal (EV) diameter is a critical, independent risk factor for hemorrhage, and plays a key role in guiding choices of endoscopic treatment techniques. We developed a novel tool, the virtual ruler (VR), which offers increased precision and expediency in EV diameter (EVD) measurements. This study investigates the clinical value of VR for assessing EVD during the endoscopic treatment of cirrhotic EVs. Methods: We performed a retrospective multicenter review of 345 cirrhotic patients with EVs who received endoscopic treatment. EVD was measured using VR, and several outcomes, including rebleeding rates, vascular eradication rates, mortality, and complication incidences, were compared in patients stratified by EVD as measured by both VR and endoscopists. Results: There was moderate agreement between VR and endoscopist measurements of EVD (Kappa = 0.591, p < 0.001). In patients with EVD > 1 cm, the VR group had a lower rebleeding rate after endoscopic treatment compared to the endoscopist group (3.8% vs. 11.3%; p=0.048). No significant between-group differences in outcomes were noted in patients with EVD ≤ 1 cm. Additionally, comparisons of endoscopic variceal ligation and endoscopic injection sclerotherapy within the VR-based diameter groups showed no substantial differences in treatment efficacy or adverse events (p > 0.05). Conclusion: Using VR to accurately measure EVD may help decrease endoscopist misjudgment of larger EVD values and may reduce postoperative rebleeding rates after endoscopic treatment. VR holds potential clinical significance in guiding endoscopic EV treatment. Trial Registration: Clinical Trial Registry identifier: ChiCTR2200064028.

Objective: The aim of this study was to explore the association between interleukin-6 (IL-6) concentration before radiotherapy (RT) and the prognosis after RT for patients with hepatocellular carcinoma (HCC). Methods: The clinical data for 101 patients with HCC who received RT from October 2016 to June 2021 were retrospectively analyzed. In these patients, the tumors were confined to the liver, and IL-6 concentration was measured before RT. The survival rate was calculated using the Kaplan-Meier method, and the Cox proportional hazards regression model was used to explore the independent factors affecting the patients' prognosis. X-tile software was used to obtain the optimal cut-off value of pre-RT IL-6 concentration (7.8 pg/mL) for overall survival (OS). Results: The 1-, 2-, and 3-year OS rates were 84.4%, 55.8%, and 34.7%, respectively, for patients with a pre-RT IL-6 concentration > 7.8 pg/mL versus 96.0%, 80.1%, and 80.1%, respectively, for those with a pre-RT IL-6 concentration ≤ 7.8 pg/mL. The OS rates of the two groups were significantly different (p < 0.001). The median progression-free survival (PFS) time was 7.5 months versus 15.1 months for patients with pre-RT IL-6 concentrations > 7.8 pg/mL and ≤ 7.8 pg/mL, respectively (p=0.001). Pre-RT IL-6 concentration was an independent prognostic factor of OS (hazard ratio [HR] = 3.421, 95% confidence interval [CI]: 1.477-7.927, p=0.004). Pre-RT IL-6 concentration (HR = 2.235, 95% CI: 1.176-4.246, p=0.014) and age (HR = 0.615, 95% CI: 0.383-0.987, p=0.044) were independent prognostic factors for PFS. Conclusions: The prognosis of HCC patients receiving RT was worse for those with a pre-RT serum IL-6 concentration > 7.8 pg/mL than those with a pre-RT serum IL-6 concentration ≤ 7.8 pg/mL. Pre-RT IL-6 concentrations may affect the prognosis of HCC patients.

Background: Acute variceal hemorrhage (AVH) is a frequent cause of upper gastrointestinal bleeding (UGIB) in liver cirrhosis. Most cases require urgent endoscopic intervention due to potentially life-threatening courses. Different endoscopic hemostasis techniques can be used, in particular endoscopic variceal ligation (EVL) and endoscopic sclerotherapy (EST), depending on the bleeding side (esophageal, fundal, and gastric) as well as radiological interventions (e.g., embolization and transjugular intrahepatic portosystemic shunt [TIPS]). This study aimed to investigate trends in incidence, treatment modalities, and outcome parameters, such as in-hospital mortality and adverse events in Germany. Methods: We evaluated the current epidemiological trends, therapeutic strategies, and in-hospital mortality of AVH in Germany based on the standardized hospital discharge data provided by the German Federal Statistical Office from 2010 to 2019. Results: A total of 65,357 AVH cases, predominately males (68.3%), were included in the analysis. The annual incidence rate (hospitalization cases per 100,000 persons) was 8.9. The in-hospital mortality was 18.6%. The most common underlying disease was alcohol-related liver cirrhosis (60.6%). The most common clinical complication was bleeding anemia (60.1%), whereas hypovolemic shock (12.8%) was the less frequent. In esophageal variceal hemorrhage (EVH), EVL was the most frequently performed endoscopic therapy, while in gastric variceal hemorrhage (GVH), EST and fibrin glue injection were the most commonly performed therapies. EVL showed the lowest in-hospital mortality (12.3%) in EVH, while EST showed favorable results (14% in-hospital mortality) in GVH. Combination therapies overall showed a higher in-hospital mortality and were more frequent in GVH. The presence of hypovolemic shock, AKI, sepsis, artificial ventilation, ARDS, bleeding anemia, hepatic encephalopathy, and male sex was associated with a significantly worse outcome. Conclusion: Our study provides detailed insight into the incidence, patient-related risk factors, endoscopic treatment, and in-hospital mortality in a sizeable AVH collective in Germany. These data might help improve risk stratification and treatment strategies for AVH patients in the future.

Background: This study aimed to examine whether repeated measurements on noninvasive fibrosis scores during follow-up improve long-term nonalcoholic fatty liver disease (NAFLD) outcome prediction.

Methods: A cohort study of 2,280 NAFLD patients diagnosed at the Seoul National University Hospital from 2001 to 2015 was conducted. Multivariable Cox regression models with baseline and designated time-point measurements of the fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) were used to assess the association between these scores and overall mortality, liver-related outcomes, and cardiovascular events.

Results: Higher baseline NFS (high versus low probability for advanced fibrosis groups) was associated with higher risk of mortality (adjusted hazard ratio (aHR), (95% confidence interval (CI)), 2.80, [1.39-5.63]) and liver-related outcomes (3.70, [1.27-10.78]). Similar findings were observed for the association of baseline FIB-4 with mortality (2.49, [1.46-4.24]) and liver-related outcomes (11.50, [6.17-21.44]). In models considering designated time-point measurements of the scores, stronger associations were noted. For NFS, a higher time-point measurement was associated with a significantly higher risk of mortality (3.01, [1.65-5.49]) and liver-related outcomes (6.69, [2.62-17.06]). For FIB-4, higher time-point measurements were associated with significantly higher mortality (3.01, [1.88-4.82]) and liver-related outcomes (13.26, [6.89-25.53]). An annual increase in FIB-4 (2.70, [1.79-4.05]) or NFS (4.68, [1.52-14.44]) was associated with an increased risk of liver-related outcomes. No association between NFS/FIB-4 and risk of cardiovascular events was observed in both models.

Conclusions: Higher aHRs describing the associations of FIB-4/NFS with overall mortality and liver-related outcomes were observed in the models that included designated time-point measurements of the scores. In addition to the baseline measurement, a routine monitoring on these scores may be important in predicting prognosis of NAFLD patients.