Canadian Journal of Gastroenterology and Hepatology最新文献

To claim the features of nontumor tissue in gastric cancer patients, especially in those who have undergone gastrectomy, and to identify the molecular subtypes, we collected the immunogenic and hallmark gene sets from gene set enrichment analysis. The activity changes of these gene sets between tumor (375) and nontumor (32) tissues acquired from the Cancer Genome Atlas (TCGA-STAD) were calculated, and the novel molecular subtypes were delineated. Subsequently, prognostic gene sets were determined using least absolute shrinkage and selection operator (lasso) regression prognostic method. In addition, functional analysis was conducted. Totally, three subtypes were constructed in the present study, and there were differences in survival among three groups. Functional analysis showed genes from normal gene set were related to cell adhesion, and genes from tumor gene set were associated with focal adhesion, PI3K-Akt signaling pathway, regulation of actin cytoskeleton, and VEGF signaling pathway. Our study created lasting value beyond molecular subtypes and underscored the significance of normal tissues in gastric cancer development, which drawn a novel prognostic model for gastric treatment.

Backgrounds: Noninvasive detection of histological abnormalities remains challenging in patients with HBeAg-negative chronic HBV infection with normal or mildly elevated levels of alanine aminotransferase (ALT). This study aimed to assess the utility of serum quantitative hepatitis B surface antigen (qHBsAg) in identifying significant histological lesions in this population.

Methods: This is a single-center study with retrospective analysis of 392 treatment-naive patients of HBeAg-negative chronic HBV infection with normal or mildly elevated levels of ALT.

Results: In this cohort, significant necroinflammation and fibrosis were found in 69.4% and 61.5% of patients, respectively. Patients with qHBsAg >1000 IU/mL (N = 236) had more hepatic inflammation of ≥G2 (75.4% vs. 60.9%, P < 0.01) or fibrosis ≥ S2 (66.1% vs. 54.5%, P < 0.05) compared to those without (N = 156). Serum HBsAg (cutoff point = 1000 IU/mL), aspartate aminotransferase (AST) level (cutoff point = 25 IU/L), age (cutoff point = 40 years), and HBV family history were identified as independent predictors of significant histological abnormalities in multivariate logistic analysis.

Conclusions: A significantly higher proportion of patients with histological abnormalities were found in patients with qHBsAg >1000 IU/mL than those without. The qHBsAg level together with age, AST, and family history of HBV infection could be used as an algorithm to help noninvasive patient selection for antiviral therapy.

Objectives: We assessed the potential of glial cell line-derived neurotrophic factor (GDNF) as a useful biomarker to predict cirrhosis in chronic hepatitis B (CHB) patients.

Methods: A total of 735 patients from two medical centers (385 CHB patients and 350 healthy controls) were included to determine the association of serum and tissue GDNF levels with biopsy-proven cirrhosis. The diagnostic accuracy of serum GDNF (sGDNF) was estimated and compared with other indices of cirrhosis.

Results: We showed significantly higher levels of sGDNF in CHB patients with fibrosis (28.4 pg/ml vs. 11.6 pg/ml in patients without) and patients with cirrhosis (33.8 pg/ml vs. 23.5 pg/ml in patients without). The areas under receiver operating curve (AUROCs) of sGDNF were 0.83 (95% confidence interval (CI): 0.80-0.87) for predicting liver fibrosis and 0.84 (95% CI: 0.79-0.89) for cirrhosis. Findings from the serum protein level and hepatic mRNA expression were consistent. Using the best cutoff to predict cirrhosis, we categorized the patients into sGDNF-high and sGDNF-low groups. The sGDNF-high group had significantly larger Masson's trichrome and reticulin staining-positive area, higher Scheuer score, and METAVIR fibrosis stage (all p < 0.001) but not steatosis. On multivariable regression, sGDNF was independently associated with cirrhosis with an odds ratio of 6.98 (95% CI: 1.10-17.94). Finally, we demonstrated that sGDNF outperformed AST to platelet ratio index, FIB-4, fibroscore, forn index, and fibrometer in differentiating F4 vs. F3.

Conclusion: Using serum, tissue mRNA, and biopsy data, our study revealed a significant potential of sGDNF as a novel noninvasive biomarker for cirrhosis in CHB patients.

Background: There is a need for a more tolerable preoperative biliary drainage (PBD) method for perihilar cholangiocarcinoma (PHCC). In recent years, inside stents (ISs) have attracted attention as a less suffering PBD method. Few studies have compared IS with a fully covered self-expandable metallic stent (FCSEMS) as PBD for resectable PHCC. The aim of this study is to compare them.

Methods: This study involved 86 consecutive patients (IS: 51; FCSEMS: 35). The recurrent biliary obstruction (RBO) rate until undergoing surgery or being diagnosed as unresectable, time to RBO, factors related to RBO, incidence of adverse events related to endoscopic retrograde cholangiography, and postoperative complications associated with each stent were evaluated retrospectively.

Results: There was no significant difference between the two groups in the incidence of adverse events after stent insertion. After propensity score matching, the mean (SD) time to RBO was 37.9 (30.2) days in the IS group and 45.1 (35.1) days in the FCSEMS group, with no significant difference (P=0.912, log-rank test). A total of 7/51 patients in the IS group and 3/35 patients in the FCSEMS group developed RBO. The only risk factor for RBO was bile duct obstruction of the future excisional liver lobe(s) due to stenting (HR 29.8, P=0.008) in the FCSEMS group, but risk factors could not be indicated in the IS group. There was no significant difference in the incidence of bile leakage or liver failure. In contrast, pancreatic fistula was significantly more common in the FCSEMS group (13/23 patients) than in the IS group (3/28 patients) (P < 0.001), especially in patients who did not undergo pancreatectomy (P=0.001).

Conclusions: As PBD, both IS and FCSEMS achieved low RBO rates. Compared with FCSEMS, IS shows no difference in RBO rate, is associated with fewer postoperative complications, and is considered an appropriate means of PBD for resectable PHCC. This trail is registered with UMIN000025631.

Afamin is a member of the hepatokine that are strongly associated with various metabolic diseases. The relationship between afamin and nonalcoholic fatty liver disease (NAFLD) remains unclear. This study aimed to explore the correlation between serum afamin levels and NAFLD. We analyzed 88 NAFLD patients and 88 age- and sex-matched healthy controls who took their health examinations at the First Affiliated Hospital, Zhejiang University School of Medicine. The association was further confirmed in 22 biopsy-confirmed NAFLD patients and 36 healthy controls. Serum afamin levels were evaluated using an enzyme-linked immunosorbent assay (ELISA). NAFLD patients had significantly higher serum afamin levels than the healthy controls (14.79 ± 5.04 mg/L versus 10.83 ± 3.24 mg/L; P < 0.001). Serum afamin levels were positively correlated with metabolic parameters including the body mass index, waist circumference, systolic blood pressure, liver enzymes, and lipid profiles. A multiple regression analysis showed that serum afamin levels were independently related to the risk of NAFLD (OR: 1.289, 95% CI, 1.141-1.456; P < 0.001). The receiver operating characteristic (ROC) analysis showed that the area under curve (AUC) of serum afamin plus the BMI for detecting NAFLD was 0.878. In participants with liver biopsies, the serum afamin plus the BMI detected NAFLD with an AUC of 0.758. In conclusion, serum afamin levels were positively associated with prevalence and risk of NAFLD, and serum afamin plus the BMI had a high diagnostic performance for NAFLD. This study provides epidemiological evidence of afamin in NAFLD.

Background: Gastric low-grade intraepithelial neoplasia (LGIN) is a precancerous lesion of gastric cancer. Endoscopic therapies represented by radiofrequency ablation (RFA) and argon plasma coagulation (APC) have been applied to treat gastric LGIN in recent years. However, no comparative study examining the effectiveness and safety profiles of RFA and APC has been reported.

Methods: A single-center, large-scale, retrospective study, including 73 and 50 patients treated with RFA and APC, respectively, was conducted in the First Medical Center of Chinese PLA General Hospital from October 2015 to October 2020, with a two-year follow-up. Effectiveness, complications, operative factors, and other data were assessed.

Results: At 2 years of follow-up, cure, relapse, recurrence, and progression rates were 90.4%, 9.6%, 9.6%, and 2.7% in the RFA group, respectively, versus 90%, 10%, 12%, and 4% in the APC group, respectively, with no statistically significant differences between the two groups (all p > 0.05). However, the mean lesion size was significantly larger in the RFA group (2.6 ± 1.0 cm) than in the APC group (1.5 ± 0.6 cm) (p < 0.001); there was also a significant difference in the composition ratio of large lesions between the two groups (p < 0.001). No serious postoperative complications showed in either group, and the abdominal pain was the most common symptom in the short term after surgery.

Conclusions: RFA and APC are both safe and effective destructive therapies for gastric LGIN. RFA is more suitable for flat and large lesions, while APC is more suitable for small lesions, especially those with slight local uplift or depression. An intraoperative submucosal injection is expected to be an effective method for relieving postoperative abdominal pain.

Background: Patients with early gastric cancer undergoing noncurative endoscopic submucosal dissection (ESD) have a risk of tumor recurrence and metastasis, and some patients need additional surgery. The purpose of this study was to explore the risk factors of cancer residue and lymph node (LN) metastasis after noncurative ESD for early gastric cancer and to compare the short outcome of early and delayed additional surgery.

Methods: The clinicopathological characteristics of 30 early gastric cancer patients who received noncurative ESD and additional surgery were studied retrospectively. Multivariable regression was utilized to examine the independent risk factors for residual cancer and LN metastasis. Receiver operating characteristic curve was used to analyze the multivariable model's predictive performance. Furthermore, the perioperative safety and radical tumor performance of early surgery (≤30 days, n = 11), delayed surgery (>30 days, n = 11) after ESD, and upfront surgery (n = 59) were compared.

Results: Multivariable regression showed that diffuse type of Lauren classification, submucosal invasion, and positive human epidermal growth factor receptor-2 (HER-2) were risk factors for residual cancer. Undifferentiated carcinoma, vascular invasion, and positive vertical margin were risk factors for LN metastasis. The area under the curve (AUC) of the multifactor model predicting cancer residue and LN metastasis was 0.761 and 0.792, respectively. The early surgery group experienced higher intraoperative blood loss and a longer operation time than the delayed surgery and upfront surgery groups. There was no significant difference in the number of LN dissections, LN metastasis rate, and postoperative complications among the three groups.

Conclusion: Diffuse type of Lauren classification, submucosal invasion, and positive HER-2 are risk factors for residual cancer, while undifferentiated carcinoma, vascular invasion, and positive vertical margin are risk factors for LN metastasis. Delayed additional surgery after ESD (>30 days) has higher intraoperative safety, without affecting the radical resection in early gastric cancer patients.

Purpose: To develop and validate a radiomic nomogram based on texture features from out-of-phase T1W images and clinical biomarkers in prediction of liver fibrosis.

Materials and methods: Patients clinically diagnosed with chronic liver fibrosis who underwent liver biopsy and noncontrast MRI were enrolled. All patients were assigned to the nonsignificant fibrosis group with fibrosis stage <2 and the significant fibrosis group with stage ≥2. Texture parameters were extracted from out-of-phase T1-weighted (T1W) images and calculated using the Artificial Intelligent Kit (AK). Boruta and LASSO regressions were used for feature selection and a multivariable logistic regression was used for construction of a combinational model integrating radiomics and clinical biomarkers. The performance of the models was assessed by using the receiver operator curve (ROC) and decision curve.

Results: ROC analysis of the radiomics model that included the most discriminative features showed AUCs of the training and test groups were 0.80 and 0.78. A combinational model integrating RADscore and fibrosis 4 index was established. ROC analysis of the training and test groups showed good to excellent performance with AUC of 0.93 and 0.86. Decision curves showed the combinational model added more net benefit than radiomic and clinical models alone.

Conclusions: The study presents a combinational model that incorporates RADscore and clinical biomarkers, which is promising in classification of liver fibrosis.

Background: Few studies explored whether anti-hepatitis B virus (HBV) therapy should be initiated during postpartum hepatitis flare.

Aim: This study aimed to analyze the effect of anti-HBV therapy on postpartum hepatitis flare and evaluate the prognosis within 4 years postpartum.

Methods: This retrospective study enrolled hepatitis B surface antigen (HBsAg)-positive and hepatitis B e antigen (HBeAg)-positive pregnant women with HBV DNA ≥ 10⁶ IU/mL. A total of 152 pregnant women were included: 103 in the prophylactic anti-HBV therapy group (PT-G) and 49 in the non-prophylactic anti-HBV therapy group (NPT-G). The women with a postpartum flare were assigned to the anti-HBV therapy group (AT-G) and non-anti-HBV therapy group (NAT-G) to analyze the effect of postpartum anti-HBV therapy on hepatitis flare. Virological and biochemical parameters were assessed.

Results: Taking postpartum 12 weeks as the cutoff point, the ALT recovered time for postpartum flare women is shorter in AT-G (n = 16, 42.1%) or PT-G (n = 23, 34.8%) than in NAT-G (n = 14, 23.0%; x ² = 4.067, P=0.044) or NPT-G (n = 4, 11.1%; x ² = 5.579, P=0.018). Taking postpartum 26 weeks as the cutoff point, the ALT recovered time is shorter in AT-G (n = 35, 57.3%) or PT-G (n = 44, 66.7%) than in NAT-G (n = 32, 84.2%; x ² = 7.707, P=0.006) or NPT-G (n = 16, 44.4%; x ² = 4.749, P=0.029). Postpartum flare recovery time was positively correlated with HBV DNA level at delivery [r = 0.223, P=0.025, 95%CI (0.022～0.41)]. The hepatitis re-flare rates within postpartum 4 years in AT-G (n = 3, 9.68%) is lower than that in NAT-G (n = 24, 45.4%; x ² = 14.003, P ≤ 0.001). The HBeAg, HBsAg, HBV DNA, and ALT level at postpartum 4 years in AT-G were lower than that in NAT-G (P < 0.001).

Conclusion: Anti-HBV therapy for postpartum hepatitis flare of women with chronic HBV could shorten the ALT recovery time and reduce hepatitis re-flare rates within 4 years of postpartum.