Clinics and research in hepatology and gastroenterology最新文献

Background

Hepatocellular carcinoma (HCC) stands as the prevailing manifestation of primary liver cancer. Previous studies have implicated ARHGEF39 in various cancer progression processes, but its impact on HCC metastasis remains unclear.

Methods

Bioinformatics analysis and qRT-PCR were employed to test ARHGEF39 expression in HCC tissues and cells, identified enriched pathways associated with ARHGEF39, and investigated its regulatory relationship with E2F1. The impact of ARHGEF39 overexpression or knockdown on cellular phenotypes in HCC was assessed through the implementation of CCK-8 and Transwell assays. Accumulation of neutral lipids was determined by BODIPY 493/503 staining, while levels of triglycerides and phospholipids were measured using specific assay kits. Expression of E-cadherin, Vimentin, MMP-2, MMP-9, and FASN were analyzed by Western blot. The interaction between ARHGEF39 and E2F1 was validated through ChIP and dual-luciferase reporter assays.

Results

Our study demonstrated upregulated expression of both ARHGEF39 and E2F1 in HCC, with ARHGEF39 being associated with fatty acid metabolism (FAM) pathways. Additionally, ARHGEF39 was identified as a downstream target gene of E2F1. Cell-based experiments unmasked that high expression of ARHGEF39 mediated the promotion of HCC cell viability, migration, and invasion via enhanced FAM. Moreover, rescue assays demonstrated that the promotion of HCC cell metastasis by high ARHGEF39 expression was attenuated upon treatment with Orlistat. Conversely, the knockdown of E2F1 suppressed HCC cell metastasis and FAM, while the upregulation of ARHGEF39 counteracted the repressive effects of E2F1 downregulation on the metastatic potential of HCC cells.

Conclusion

Our findings confirmed the critical role of ARHGEF39 in HCC metastasis and unmasked potential molecular mechanisms through which ARHGEF39 fostered HCC metastasis via FAM, providing a theoretical basis for exploring novel molecular markers and preventive strategies for HCC metastasis.

Background

Inflammatory bowel disease (IBD) can have significant colonic involvement and carries a long-term risk of surgical resection. Chronic obstructive pulmonary disease (COPD) and IBD share multiple inflammatory pathways, suggesting a bidirectional relationship through proposed pulmonary-intestinal cross-talk. This study aimed to examine the association between COPD and 30-day outcomes following non-emergent colectomies for IBD.

Methods

Patients with IBD as the primary indication for colectomy were selected from National Surgical Quality Improvement Program (NSQIP) colectomy database 2012–2022. Emergency colectomy cases were excluded. A 1:3 propensity-score matching was used to balance the preoperative characteristics of COPD and non-COPD patients. Thirty-day postoperative outcomes were compared.

Results

Among 25,285 patients who underwent colectomy for IBD, 365 (1.44 %) had COPD. Patients with COPD were older and had more comorbidities. After propensity-score matching, all COPD patients were matched to 1,095 patients without COPD. COPD and non-COPD patients had comparable 30-day mortality (3.29 % vs 2.19 %, p = 0.25). However, COPD patients had higher pulmonary complications (14.79 % vs 7.21 %, p < 0.01) attributed to pneumonia (10.14 % vs 4.02 %, p < 0.01), sepsis (12.88 % vs 8.68 %, p = 0.02), prolonged postoperative nothing by mouth (NPO) or nasogastric tube (NGT) use (28.22 % vs 22.10 %, p = 0.02), discharge not to home (40.28 % vs 34.02 %, p = 0.04), and longer length of stay (p = 0.01).

Conclusion

Therefore, given their mortality rates, colectomy is an effective treatment for IBD patients with concurrent COPD, while their postoperative care should include close monitoring of pulmonary symptoms and timely interventions to prevent further complications. Future research should explore the long-term prognosis of COPD patients after colectomy for IBD.

Background and study aims

Peroral endoscopic myotomy (POEM) has become the first line treatment for achalasia, but controversies remain about the prevalence of gastro-esophageal reflux disease (GERD) after the procedure. The aim of this study was to evaluate post-POEM GERD by a retrospective analysis of a single center cohort.

Patients and methods

Achalasia patients aged 18 or above, who underwent POEM between 2012 and 2021, were included, provided they had an endoscopic control of reflux at least one year after POEM. GERD symptoms based on GerdQ questionnaire, and proton pomp inhibitors (PPI) consumption were also evaluated.

Results

Among a consecutive cohort of 422 patients treated by POEM, 254 patients were included. Endoscopic results were available after a mean follow-up of 1.9 ± 1.5 years. 71/254 patients (28 %) had erosive esophagitis (86 % Los Angeles Grade A or B). At the last follow-up (mean 4.5 ± 2.2 years), clinical success of POEM (Eckardt score ≤ 3) was achieved in 79.5 % of patients. 44.5 % of patients were on PPI. Mean GerdQ score was 2.2 ± 2.7, with only 13 patients (6.5 %) with a score ≥ 8.

Conclusion

In this cohort of achalasia patients with an endoscopic follow-up at least 1 year after POEM, GERD did not appear a major threat concern: clinical symptoms were mild in most cases, as was the degree of erosive esophagitis. Furthermore, at the time of last follow up, less than half of patients required treatment with PPI.

Background

Autoimmune hepatitis (AIH) patients can present with advanced fibrosis at diagnosis or may progress to the same if biochemical remission on treatment is not achieved.

Methods

We conducted a single-center retrospective analysis of 34 pediatrics and 39 adult AIH patients. Three pathologists, blinded to clinical information, reviewed the diagnostic liver biopsy (DLB) slides of AIH patients. We evaluated the impact of clinical, laboratory, and histopathologic parameters on outcomes including biochemical remission (BR).

Results

Incidence of advanced (Ludwig stage 3 or 4) fibrosis on DLB was 45.2 %. AIH patients with advanced fibrosis had higher median Ishak score (p < 0.001) and higher IgG level (p = 0.01) at diagnosis. The incidence of BR at 6-month (31.2% vs. 88.6 %, p = 0.001) and 1-year (68.8% vs. 88.6 %, p = 0.04) post-diagnosis was significantly lower in AIH patients with advanced fibrosis. Although not statistically significant, a higher proportion of AIH patients with advanced fibrosis were on high dose of steroids (58% vs. 37.9 %, p = 0.1) at 1 year post diagnosis. Higher serum IgG level at diagnosis was associated with lower odds of achieving BR at 6-month (p = 0.004) and 1-year (p = 0.03) post-diagnosis in multivariate analysis. Pediatric age at diagnosis (p = 0.02) was associated with higher steroid dose at 1-year post-diagnosis in univariate analysis.

Conclusions

Findings of advanced fibrosis on DLB of AIH patients was accompanied by more pronounced necro-inflammatory activity and higher serum IgG level, which translated to lower rates of BR and higher exposure to steroids during the first year after diagnosis.

Background and aims

The prevalence and mortality of chronic liver disease has risen significantly. In end stage liver disease (ESLD) the survival of patients is approximately 2 years. Despite the poor prognosis and high symptom burden of these patients, integration of palliative care is reduced. We aim to analyze the agreement between palliative care and hepatology physicians of clinical scenarios that could require palliative care intervention.

Methods

A cross-sectional study was conducted. Palliative care and hepatology physicians were surveyed. Using a five-point Likert scale, their perceptions of palliative care in ESLD were rated. Their agreement in clinical scenarios that could require palliative care intervention were evaluated. Analyses were conducted to assess any differences by primary role (hepatology vs. palliative care) and length of practice (<10 years vs. 10 years).

Results

A total of 123 responses were obtained: 52% from palliative care and 48% from hepatology. The majority (66.7%) work in the field for up to ten years. There was a great consensus in 4 of the 8 clinical scenarios. In scenarios with less consensus, the area of activity and length of practice influence the reliance of physicians on palliative care. Involvement of palliative care in ESLD was considered “rare” by 30% and 61% consider difficult to predict the prognosis. More than 90% support medical training in both areas of activity.

Conclusion

The current involvement of palliative care is considered low, but there are clinical conditions that reveal a clear consensus and there's a unanimous view of the relevance of training.

Background

The relationship between non-alcoholic fatty liver disease (NAFLD) and cholelithiasis is intricate, with alterations in the microenvironment potentially mediating this interplay. Thus, this study aimed to explore the biliary microbiota and metabolites of patients with cholelithiasis and detect changes induced by comorbid NAFLD.

Methods

In this study, 16S rRNA gene sequencing and metabolome analysis were performed on biliary samples collected from 35 subjects. Then, patients were stratified into two groups: the comorbidity group (n = 18), consisting of cholelithiasis patients with NAFLD, and the non-comorbidity group (n = 17), comprising cholelithiasis patients without NAFLD.

Results

Comorbid NAFLD did not significantly increase α-diversity but affected β-diversity. A statistically significant difference was observed in the abundance of biliary metabolites between the two groups. Specifically, differences in the abundance of 4 phyla, 19 genera, and 28 metabolites were significant between the two groups. Correlation analysis demonstrated positive associations among 12α-hydroxylated bile acid levels, Pyramidobacter and Fusobacterium abundance, AST levels, and the fibrosis-4 index (p < 0.05, r > 0.3), all of which were increased in patients with cholelithiasis and comorbid NAFLD.

Conclusions

The relationship between cholelithiasis and NAFLD influences the biliary microbial and metabolic profile, creating a detrimental microenvironment that promotes the disease progression.

Liver cancer is one of the most common and devastating causes of cancer-related deaths worldwide. Hepatocellular carcinoma (HCC) accounts for approximately 90% of primary liver cancers and represents a significant global health issue. There is currently no effective systemic treatment for patients with advanced liver cancer. One study suggests that sorafenib may be effective against hepatocellular carcinoma. Sorafenib can significantly extend the median survival time of patients, but only by 3–5 months. Furthermore, it is linked to severe adverse side effects and frequently leads to drug resistance. In this review, we offer a critical analysis of the factors contributing to sorafenib resistance in HCC.