Digestive and Liver Disease最新文献

Background: Availability of liver transplantation (LT) as a treatment for hepatocellular carcinoma (HCC) and other liver malignancies may determine heterogeneity of therapeutic strategies across different centers.

Aims: To investigate the practice between hepato-biliary centers without (HB centers) and with a LT program (LT centers), we launched a 38-item web-based national survey, with directors of centers as a target.

Methods: The survey, including 4 clinical vignettes, collected data on their approach to HCC and transplant oncology.

Results: After duplicates removal, 75 respondents were considered. Respondents from LT centers (n = 22, 29.3 %) were more in favor of LT in the case of HCC outside Milan criteria (90.9 % vs. 67.9 %, p = 0.037), recurrent HCC (95.5 % vs. 50.9 %, p = 0.002) and other malignancies such as cholangiocarcinoma or neuroendocrine tumors. No significant difference was observed concerning the proportion of centers favorable to LT for unresectable colorectal liver metastases (100 % vs. 88.7 %, p = 0.100).

Conclusion: This national survey showed how management of HCC and awareness of transplant oncology may differ between HB and LT centers. Effective networking between HB and LT centers is crucial to provide optimal treatment and access to LT.

Aim: This study aimed to investigate the outcomes and effectiveness of various treatment strategies in patients with hepatic artery stenosis (HAS) after pediatric liver transplantation (pLT).

Methods: This is a single center observational cohort study between January 1st, 2004 and August 1st, 2023, including pLT recipients aged <18 years. The primary outcome was graft and patient survival. The secondary outcomes included incidence of biliary complications, technical success of surgery or endovascular therapy (EVT), and changes in liver function. The cut-off for early and late HAS was 14 days after pLT.

Results: Among a total of 327 pLT patients, 4 % (n = 13) developed HAS (n = 3 early; n = 10 late). Treatments included surgical revascularization for one early HAS, conservative management with anticoagulation for one early and four late HAS, and EVT for one early and six late HAS. Over a median follow-up of 28.2 months after the diagnosis of HAS, graft survival was 100 % and 83 % in early and late HAS groups, and patient survival reached 100 % in both groups. One graft loss occurred in the conservative group. Conversely, graft survival in the EVT group was 100 %.

Conclusion: The long-term outcomes of HAS after pLT are excellent. Both EVT and conservative management exhibited high graft survival rates for late HAS, with EVT achieving high technical success.

Background: There is limited comparative data on patients with inflammatory bowel disease (IBD) switched from intravenous to subcutaneous infliximab and those continuing intravenously. This study aimed to compare the persistence and tolerance of subcutaneous and intravenous infliximab and the outcomes of patients resuming intravenous infliximab.

Methods: We conducted a retrospective single-centre cohort study involving IBD patients treated with maintenance intravenous infliximab. The switch to subcutaneous infliximab was offered to patients in clinical remission receiving an intravenous dose ≤ 10 mg kg^-1 every ≥ 6 weeks. The switch group was compared to controls remaining on intravenous infliximab due to refusal of the switch.

Results: With a median follow-up of 59 (46-67) weeks, subcutaneous infliximab was discontinued in 28/282 (10 %) patients and intravenous infliximab in 1/78 (1 %) patient (p = 0.01); after propensity score-matching of the two cohorts, persistence rates at 52 weeks were respectively 91 % (95 % CI 84-98) and 100 % (95 % CI 100-100, p = 0.01). Among the 28 who discontinued subcutaneous infliximab, 27 resumed intravenous infliximab, with 4 (1 % of the switch group) who permanently stopped infliximab.

Conclusion: Switching from intravenous to subcutaneous infliximab led to a lower treatment persistance. In cases of poor tolerance or relapse under subcutaneous infliximab, resuming intravenous infliximab is effective.

Background: The presence of acute kidney injury (AKI) significantly increases in-hospital mortality risk for cirrhotic patients. Early prognosis prediction for these patients is crucial. We aimed to develop and validate a machine learning model for in-hospital mortality prediction for cirrhotic patients with AKI.

Methods: Data from cirrhotic patients with AKI hospitalized at the First Affiliated Hospital of Zhejiang University between January 1, 2013, and December 31, 2020 were used to train and validate an extreme Gradient Boosting model to predict in-hospital mortality risk. The Boruta algorithm was used for variable selection. The optimal model was selected and named as PHM-CPA (Prediction of in-Hospital Mortality for Cirrhotic Patients with AKI). The PHM-CPA model was then externally validated in patients from eICU Collaborative Research Database (eICU-CRD) and Medical Information Mart for Intensive Care III dataset (MIMIC). The predictive performance of PHM-CPA model was compared with that of logistic regression (LR) model and 25 previously reported models.

Results: A total of 519 cirrhotic patients with AKI were enrolled in model training cohort, of whom 118 (23%) died during hospitalization. Fifteen variables from common laboratory tests were selected to develop the PHM-CPA model. The PHM-CPA model achieved an AUROC of 0.816 (95% CI, 0.763-0.861) in the internal validation cohort and 0.787 (95% CI, 0.745-0.830) in the external validation cohort. The PHM-CPA model consistently outperformed the LR model and 25 previously reported models.

Conclusion: We developed and validated the PHM-CPA model, comprising readily available clinical variables, which demonstrated superior performance and calibration in predicting in-hospital mortality for cirrhotic patients with AKI.

Background: Early life factors for inflammatory bowel disease are likely to impact the gut microbiota.

Aim: We investigated the associations between early exposures and inflammatory bowel disease.

Methods: This case-control study was nested within the CO·MMUNITY cohort. Cases of Crohn's disease (CD) and ulcerative colitis (UC) were identified using validated algorithms. All cases and randomly selected controls were invited to complete a questionnaire including early life exposures. Analyses were conducted by logistic regression and causal mediation (direct/indirect effects for passive/active smoking).

Results: Early introduction of solid foods at 3-6 months tended to increase CD risk compared to later introduction (>6 months): OR = 1.23; 95 % CI: 0.96-1.56, but not of UC. Exclusive breastfeeding tended to decrease the risk of CD (OR = 0.77; 95 % CI: 0.55-1.08), less so for UC. Antibiotics tended to decrease CD (OR = 0.89; 95 % CI: 0.74-1.07) and UC (OR = 0.88; 95 % CI: 0.71-1.09). No association was found between pets and CD or UC. Passive smoking increased CD risk (OR = 1.23; 95 % CI: 1.00-1.51), 20 % of which was mediated by active smoking, but not UC.

Conclusion: Differences were noticed in early risk factors for CD and UC. The impact of passive smoking was largely independent of active smoking, highlighting its importance for prevention.

Background: Living donor liver transplantation (LDLT) is an established and endorsed alternative for deceased donor liver transplantation with better recipient outcomes. Nevertheless, while extensive evaluation of potential donors is crucial, evaluation algorithms differ between transplant centres and guidelines.

Methods: We included 317 individuals evaluated for LDLT between 07/2007-07/2022 in a retrospective analysis. The evaluation process was analysed to identify the key reasons for declining 77 potential donors. Additionally, 146 donors that underwent LDLT were analysed regarding risk factors for complications.

Results: The main reasons for donor refusal were liver volumetry (40.3 %) and metabolic factors including obesity or steatotic liver disease (20.8 %). Contrast-enhanced computed tomography (CECT) identified 63.6 % of all declined donors; CECT combined with assessment of medical history, physical examination, blood testing and ultrasonography, identified 87.0 % of declined potential donors. Associated with this selection, complication rates in donors were low (≥II in 17.1 %; none with ≥IVb). Notably, higher age was a risk factor for developing a complication ≥II after hemi-hepatectomy (p = 0.0373).

Conclusions: We propose a progressive 4-step evaluation algorithm that begins with a very basic assessment combined with up-front CECT. This early phase of testing is expected to identify nearly 90 % of ineligible donors, thereby conserving critical resources, time and money, as well as minimising burden for potential donors.

Funding: J.M.W. received funding by grant We-4675/6-1 from the Deutsche Forschungsgemeinschaft (DFG) in Bonn, Germany.

Background: Fecal calprotectin (FC) is a non-invasive biomarker of gut inflammation, but its role in celiac disease (CD) and non-celiac enteropathies (NCEs) is undefined.

Aims: To retrospectively evaluate FC in patients with CD and NCEs as a tool for assessing disease activity and predicting long-term outcomes.

Methods: Patients with uncomplicated and complicated CD, and NCEs with data on FC, evaluated at our center between June-2008 and December-2023, were enrolled. The relationship between elevated FC (>50 mg/kg) and disease activity was statistically analysed and Cox regression adjusted for age and sex was used to compare development of complications and mortality in patients with elevated and normal FC.

Results: 177 patients (109F, mean age at diagnosis 39±20 years, 132 CD, 17 complicated CD, 28 NCEs) were enrolled. 55 patients had elevated FC, which was associated with lack of clinical and histological response to therapy (both p < 0.001). During a median follow-up of 103 months (IQR 54-176), 22 patients developed complications (15.4 %) and 21 died (11.9 %). Elevated FC was significantly more common in complicated CD (70.6 %) and NCEs (67.9 %) than in uncomplicated CD (18.2 %), p < 0.001. Elevated FC was independently predictive of developing complications (HR 4.8,95 %CI 1.4-17.7, p = 0.01) and mortality (HR 4.8,95 %CI 1.6-14.3, p < 0.01).

Conclusion: FC is a promising non-invasive biomarker for assessing disease severity and long-term outcomes in CD and NCEs.

Background and aims: Small bowel capsule endoscopy (SBCE) has an established role in patients with non-responsive celiac disease (CeD). A non-invasive method to quantify small bowel atrophy is still lacking.

Methods: We analysed SBCE frames from CeD patients from 2018 to 2020. Histology was the reference standard, with atrophy defined as Marsh-Oberhuber score ≥ 3a. Three regions of interest (ROI) were blindly selected from each frame by an expert gastroenterologist and analysed using a National Institute of Health J image-processing software into a numerical scale. A 3D surface plot macro identified intestinal villi density through isolines plots.

Results: We acquired 306 ROIs from 57 frames with macroscopic atrophy and 45 with normal mucosa. Frames were classified as atrophic (n = 63) or non-atrophic (n = 39) per Marsh-Oberhuber classification. Median density score significantly differed between atrophic and non-atrophic frames (p < 0.001). The morphometric analysis showed a sensitivity of 77 % and a specificity of 79 % in discriminating between atrophic or non-atrophic mucosa with a 14.10 cut-off (Youden Index) and an overall AUC of 0.805 (CI 95 % 0.712-0.897).

Conclusions: Our newly developed SBCE software can effectively quantify villous atrophy. Further studies are needed to validate its applicability in an external cohort.

Background: We aimed to evaluate the role of Contrast-enhanced intraoperative ultrasound (CE-IOUS) with perfluorobutane microbubbles (Sonazoid) in improving the prognosis of patients with unresectable colorectal cancer liver metastases (CRLM).

Methods: A total of 130 Patients with unresectable CRLM who underwent curative hepatic resection at our institute were retrospectively analyzed. Of these 130 enrolled patients, 67 underwent intraoperative ultrasound alone (IOUS group); 63 underwent additional CE-IOUS and IOUS (CE-IOUS group). Normalized inverse probability treatment weighting (IPTW) was employed to balance baseline characteristics between groups. Hepatic recurrence-free survival (HRFS) and overall survival (OS) were compared.

Results: The treatment strategy was altered in 25 patients (25/63, 39.9%) due to the additional use of CE-IOUS. After applying IPTW, the CE-IOUS group exhibited a significantly lower rate of hepatic recurrence (hazard ratio [HR], 0.55; 95% confidence interval [CI] 0.32-0.95; P = 0.032). Subgroup analysis showed that CE-IOUS provided a significant benefit over IOUS in patients with bilobar liver metastases (P = 0.007), or with a number of live tumors < 3 (P = 0.021), or without DLM (P = 0.018), or with extrahepatic metastasis (P = 0.034), or with a minimum of 6 cycles of systemic therapy (P = 0.03).

Conclusions: CE-IOUS is necessary for unresectable CRLM after preoperative chemotherapy, as it enhances detection accuracy and improves the prognosis of unresectable CRLM patients.

Background: Cirrhosis is associated with a proinflammatory environment.

Aims: To analyse aetiology-specific inflammation patterns in compensated cirrhosis in animal models and patients.

Methods: Portal pressure (PP), fibrosis (collagen proportionate area [CPA]) and hepatic inflammation were measured in cirrhotic rat models (thioacetamide [TAA;n = 12]; choline-deficient high-fat diet [CDHFD;n = 12]; bile duct ligation [BDL;n = 16]). Compensated cirrhotic patients (alcohol-related liver disease [ALD;n = 67]; metabolic dysfunction-associated steatohepatitis [MASH;n = 50]; cholestatic liver disease [primary biliary cholangitis [PBC]/primary sclerosing cholangitis [PSC];n = 22]) undergoing hepatic venous pressure gradient (HVPG) measurement were included.

Results: In rats, hepatic proinflammatory gene expression was highest in CDHFD and lowest in TAA, despite comparable PP levels. Across all animal models, Tnfa/Il6 correlated positively with CPA, and Mcp1 with elevated PP. Mcp1 was also associated with increased CPA in TAA/CDHFD. Mcp1/Cxcl1 showed a model-independent positive correlation to transaminases. Il1b correlated positively with CPA/PP in BDL and with transaminases in CDHFD. In patients, CRP/IL-6 were lower in MASH compared to ALD or PBC/PSC, regardless of hepatic function. IgA/IgG were highest and complement factors lowest in ALD. More pronounced systemic inflammation was linked to higher HVPG primarily in ALD/MASH.

Conclusion: Proinflammatory pathways are upregulated across all liver disease aetiologies, yet their association with fibrosis and portal hypertension can vary.