Hepatobiliary & Pancreatic Diseases International最新文献

Background: Despite the insights into the role of aldehyde dehydrogenase 1 family member A1 (ALDH1A1) in various liver diseases, the expression and its prognostic significance in patients with hepatitis E virus-related acute liver failure (HEV-ALF) remain unclear. This study delved into the assessment of serum exosome-derived ALDH1A1 expression and its prognostic implications for HEV-ALF patients.

Methods: Between January 2018 and December 2023, a total of 226 individuals with acute hepatitis E (AHE) and 210 patients with HEV-ALF were recruited from member units of Chinese Consortium for the Study of Hepatitis E. According to the number of organ failure, we categorized 210 HEV-ALF patients into three groups: two organs failure (n = 131), three organs failure (n = 46), and more than three organs failure (n = 33). In addition, 200 health controls from Suzhou Municipal Hospital were included.

Results: The levels of serum exosome-derived ALDH1A1 in HEV-ALF patients were significantly higher than those in AHE patients and health controls (both P < 0.05). Furthermore, the levels of serum exosome-derived ALDH1A1 were the highest in more than three organs failure group, followed by three organs failure group and two organs failure group (all P < 0.001). Moreover, serum exosome-derived ALDH1A1 was positively correlated with total bilirubin in HEV-ALF patients (r = 0.315, P < 0.001). The comparisons of serum exosome-derived ALDH1A1 levels in treatment response showed that serum exosome-derived ALDH1A1 levels were decreased in the improvement group, while increased in the fluctuation and deterioration groups (all P < 0.001). Moreover, serum exosome-derived ALDH1A1 was an independent risk factor for predicting the 30-day mortality (P < 0.001). Furthermore, the area under the receiver operating characteristic curve was 0.943, with the sensitivity of 94.87 % and specificity of 87.72 %, indicating the robust decision-making ability. However, no significant differences were found in serum exosome-derived ALDH1A1 levels between patients aged < 60 and ≥ 60 years old (P = 0.131).

Conclusions: Serum exosome-derived ALDH1A1 can greatly predict the prognosis of HEV-ALF patients.

Background: Coronavirus disease 2019 (COVID-19) is a global pandemic with high mortality, and the treatment options for the severe patients remain limited. Previous studies reported the altered gut microbiota in severe COVID-19. But there are no comprehensive data on the role of microbial metabolites in COVID-19 patients.

Methods: We identified 153 serum microbial metabolites and assessed the changes in 72 COVID-19 patients upon admission and one-month after their discharge, comparing these changes to those in 133 healthy control individuals from the outpatient department during the same period.

Results: Our study revealed that microbial metabolites varied across different stages and severity of COVID-19 patients. These altered microbial metabolites included tryptophan, bile acids, fatty acids, amino acids, vitamins and those containing benzene. A total of 13 distinct microbial metabolites were identified in COVID-19 patients compared to healthy controls. Notably, correlations were found among these disrupted metabolites and organ injury and inflammatory responses related to COVID-19. Furthermore, these metabolites did not restore to the normal levels one month after discharge. Importantly, two microbial metabolites were the core microbial metabolites related to the severity of COVID-19 patients.

Conclusions: The microbial metabolites were altered in the acute and recovery stage, correlating with disease severity of COVID-19. These results indicated the important role of gut microbiota in the progression of COVID-19, and facilitated the potential therapeutic microbial target for severe COVID-19 patients.

Extracorporeal liver surgery (ELS), also known as liver autotransplantation, is a hybrid (cross-fertilized) surgery incorporating the technical knowledge from extreme liver and transplant liver surgeries, and recently became more embraced and popularized among leading centers. ELS could be summarized into three major categories, namely, ex-situ liver resection and autotransplantation (ELRA), ante-situm liver resection and autotransplantation (ALRA) and auxiliary partial liver autotransplantation (APLA). The successful development of ELS during the past 37 years is definitely inseparable from continuous efforts done by Chinese surgeons and researchers. Especially, the precision liver surgery paradigm has allowed to transform ELS into a modularized, more simplified, and standardized surgery, to upgrade surgical skills, to improve peri-operative outcome and long-term survival, to increase the capability of surgeons to select more complex diseases and to expand the level of medical service to the population. This review highlights the Chinese contributions to the field of ELS, focusing thereby on features of different surgical types, technical innovations, disease selection and surgical indication, patient prognosis and future perspectives.

Background: RNA N6-methyladenosine (m6A) regulators are essential for numerous biological processes and are implicated in various diseases. However, the comprehensive role of m6A regulators in the context of liver transplantation (LT) remains poorly understood. This study aimed to illustrate the relationship between m6A regulators and ischemia-reperfusion injury (IRI) following LT.

Methods: Datasets were acquired from the Gene Expression Omnibus database. Differential analysis of the merged data identified the differentially expressed m6A regulators. Random forest (RF) models and nomograms were used to forecast the incidence and assess the IRI risk following LT. m6A regulators were classified into distinct subgroups using cluster analysis. The differential gene expression was validated using immunohistochemistry, immunofluorescence, and Western blotting.

Results: We found significant disparities in the gene expression levels of the three m6A regulators between patients with and without LT. Wilms' tumor 1-associating protein (WTAP) expression was upregulated following LT. The RF models exhibited a high degree of accuracy in predicting IRI risk. Immune infiltration analysis showed that WTAP was an immune-associated m6A regulator that was closely associated with T and B cells. WTAP expression in the rat LT model was upregulated after 24 h of reperfusion, which was consistent with the results of the bioinformatics analysis.

Conclusion: WTAP has a high diagnostic value for IRI in LT and influences the immune status of patients. Hence, WTAP, as a significant regulator of m6A, is a potential biomarker for the detection and implementation of immunotherapy for IRI following LT.

Background: The endoscopic appearance of the major duodenal papilla influences biliary cannulation and complications. This study aimed to investigate the role of major duodenal papillae in the endoscopic treatment of common bile duct (CBD) stones.

Methods: This retrospective study was conducted at Bishan Hospital of Chongqing Medical University between January 2018 and August 2022. Patients with native papillae who underwent endoscopic treatment for CBD stones were recruited and divided into four groups according to Haraldsson's classification of papillae (types I-IV). Univariate and multivariate logistic regression analyses were used to identify risk factors for difficult cannulation and post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP).

Results: A total of 596 patients with CBD stones were enrolled. The proportion of patients with type I papilla was the highest (n = 231, 38.8 %), followed by type III papilla (n = 175, 29.4 %), type IV papilla (n = 101, 16.9 %) and type II papilla (n = 89, 14.9 %). Difficult cannulation occurred in 188 of 596 patients (31.5 %), with most cases occurring in those with type III papilla (71/175, 40.6 %, P = 0.020). Multivariate analysis revealed that age [odds ratio (OR) = 1.034, 95 % confidence interval (CI): 1.021-1.047, P < 0.001], type III papilla (OR = 2.255, 95 % CI: 1.439-3.535, P < 0.001), gallbladder in situ (OR = 2.486, 95 % CI: 1.346-4.590, P = 0.004), and CBD diameter < 10 mm (OR = 1.600, 95 % CI: 1.049-2.441, P = 0.029) were risk factors for difficult cannulation. The total incidence of PEP was 10.9 %. Compared with the other types of papillae, the rate of PEP was the highest in those with type I papilla (15.2 %, P = 0.030). Multivariate analysis demonstrated that PEP was associated with difficult cannulation (OR = 1.811, 95 % CI: 1.044-3.143, P = 0.035) and white blood cells (WBCs) < 10 × 10⁹/L (OR = 2.199, 95 % CI: 1.051-4.600, P = 0.036).

Conclusions: The endoscopic appearance of the major papilla is an important factor that influences both biliary cannulation and outcomes. Type III papilla is more frequently difficult to cannulate in the endoscopic treatment of CBD stones.

Background: The efficacy of adjuvant treatment (AT) in ampullary cancer (AmC) remains controversial. This systematic review and meta-analysis aimed to evaluate the role of AT for AmC.

Data sources: A comprehensive systematic search was performed in PubMed, EMBASE, Cochrane Library, and Web of Science databases. Studies comparing overall survival (OS) and recurrence-free survival (RFS) of patients who underwent AT or not following AmC resection were included.

Results: A total of 3971 patients in 21 studies were analyzed. Overall pooled data showed no significant difference in effect on the OS by AT [hazard ratio (HR) = 0.998, 95% confidence interval (CI): 0.768-1.297]. No significant difference in recurrence between the AT and non-AT (nAT) groups was noted (HR = 1.158, 95% CI: 0.764-1.755). In subgroup analysis, patients who received AT showed favorable outcomes in the OS compared with those who received nAT in nodal-positive AmC (HR = 0.627, 95% CI: 0.451-0.870). Neither AT consisted of adjuvant chemotherapy with radiotherapy (HR = 0.804, 95% CI: 0.563-1.149) nor AT with adjuvant chemotherapy (HR = 0.883, 95% CI: 0.642-1.214) showed any significant effect on the OS.

Conclusions: The effect of AT in AmC on survival and recurrence did not show a significant benefit. Furthermore, effectiveness according to AT strategies did not show enhancement in survival. AT had an advantage in survival compared with nAT strategy in nodal-positive AmC. In cases of AmC with positive lymph nodal involvement, AT may be warranted regardless of detailed strategies.

Background: The combination of senescence triggers with senolytic drugs is considered a promising new approach to cancer therapy. Here, we studied the efficacy of the genotoxic agent etoposide (Eto) and irradiation in inducing senescence of Panc02 pancreatic cancer cells, and the capability of the Bcl-2 inhibitor navitoclax (ABT-263; Nav) to trigger senolysis.

Methods: Panc02 cells were treated with Eto or irradiated with 5-20 Gy before exposure to Nav. Cell survival, proliferation, and senescence were assessed by trypan blue staining, quantification of DNA synthesis, and staining of senescence-associated β-galactosidase (SA-β-Gal)-positive cells, respectively. Levels of mRNA were determined by real-time polymerase chain reaction, and protein expression was analyzed by immunoblotting. Panc02 cells were also grown as pancreatic tumors in mice, which were subsequently treated with Eto and Nav.

Results: Eto and irradiation had an antiproliferative effect on Panc02 cells that was significantly or tendentially enhanced by Nav. In vivo, Eto and Nav together, but not Eto alone, significantly reduced the proportion of proliferating cells. The expression of the senescence marker γH2AX and tumor infiltration with T-cells were not affected by the treatment. In vitro, almost all Eto-exposed cells and a significant proportion of cells irradiated with 20 Gy were SA-β-Gal-positive. Application of Nav reduced the percentage of SA-β-Gal-positive cells after irradiation but not after pretreatment with Eto. In response to triggers of senescence, cultured Panc02 cells showed increased protein levels of γH2AX and the autophagy marker LC3B-II, and higher mRNA levels of Cdkn1a, Mdm2, and PAI-1, while the effects of Nav were variable.

Conclusions: In vitro and in vivo, the combination of senescence triggers with Nav inhibited tumor cell growth more effectively than the triggers alone. Our data also provide some evidence for senolytic effects of Nav in vitro.