Journal of Gastroenterology最新文献

Background: Advanced liver fibrosis in cases of metabolic dysfunction-associated steatotic liver disease (MASLD) leads to cirrhosis and hepatocellular carcinoma. The current gold standard for liver fibrosis is invasive liver biopsy. Therefore, a less invasive biomarker that accurately reflects the stage of liver fibrosis is highly desirable.

Methods: This study enrolled 269 patients with liver biopsy-proven MASLD. Patients were divided into three groups (F0/1 (n = 41/85), F2 (n = 47), and F3/4 (n = 72/24)) according to fibrosis stage. We performed serum N-glycomics and identified glycan biomarker for fibrosis stage. Moreover, we explored the carrier proteins and developed a sandwich ELISA to measure N-glycosylation changes of carrier protein.

Results: Comprehensive N-glycomic analysis revealed significant changes in the expression of A2F bisect and its precursors as fibrosis progressed. The sum of neutral N-glycans carrying bisecting GlcNAc and core Fuc (neutral sum) had a better diagnostic performance to evaluate advanced liver fibrosis (AUC = 0.804) than conventional parameters (FIB4 index, aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), and serum level of Mac-2-binding protein glycol isomer (M2BPGi). The combination of the neutral sum and FIB4 index enhanced diagnostic performance (AUC = 0.840). IgM, IgA, and complement C3 were identified as carrier proteins with A2F bisect N-glycan. A sandwich ELISA based on N-glycans carrying bisecting GlcNAc and IgA showed similar diagnostic performance than the neutral sum.

Conclusions: A2F bisect N-glycan and its precursors are promising candidate biomarkers for advanced fibrosis in MASLD patients. Analysis of these glycan alterations on IgA may have the potential to serve as a novel ELISA diagnostic tool for MASLD in routine clinical practice.

Clinical trial number: UMIN000030720.

Background: Hepatitis B virus (HBV) RNA is an important serum biomarker of hepatic covalently closed circular DNA (cccDNA) transcriptional activity; however, its clinical characteristics remain unclear. This study evaluated the clinical utility of HBV RNA levels in patients with chronic hepatitis B (CHB).

Methods: We studied 87 CHB patients with serum HBV DNA levels ≥ 5.0 log IU/mL who initiated entecavir (ETV) treatment between 2000 and 2018. Serum HBV RNA levels were measured at three-time points: before ETV treatment, at 12 weeks, and at 48 weeks after starting ETV treatment. Clinical markers associated with the antiviral effects of ETV treatment were analyzed.

Results: Serum HBV RNA levels decreased in both HBeAg-positive and -negative patients during the observation period. In HBeAg-positive patients, multivariable analysis showed that lower HBV RNA levels at 48 weeks of ETV treatment were independently associated with HBeAg seroconversion. Additionally, lower baseline HBV RNA levels significantly predicted virologic response in those patients. In contrast, among HBeAg-negative patients, lower HBV core-related antigen (HBcrAg) levels and the FIB-4 index were independently associated with virologic response. In HBeAg-positive patients, those with higher baseline HBV RNA levels showed a more significant reduction in hepatitis B surface antigen levels.

Conclusion: Serum HBV RNA levels predicted HBeAg seroconversion and early HBV DNA reduction in HBeAg-positive patients, while HBcrAg was significantly associated with virologic response in HBeAg-negative patients. These findings highlight the different predictive roles of HBV RNA and HBcrAg based on HBeAg status, which may provide individualized treatment strategies.

Background: The automated classification of Helicobacter pylori infection status is gaining attention, distinguishing among uninfected (no history of H. pylori infection), current infection, and post-eradication. However, this classification has relatively low performance, primarily due to the intricate nature of the task. This study aims to develop a new multistage deep learning method for automatically classifying H. pylori infection status.

Methods: The proposed multistage deep learning method was developed using a training set of 538 subjects, then tested on a validation set of 146 subjects. The classification performance of this new method was compared with the findings of four physicians.

Results: The accuracy of our method was 87.7%, 83.6%, and 95.9% for uninfected, post-eradication, and currently infected cases, respectively, whereas that of the physicians was 81.7%, 76.5%, and 90.3%, respectively. When including the patient's H. pylori eradication history information, the classification accuracy of the method was 92.5%, 91.1%, and 98.6% for uninfected, post-eradication, and currently infected cases, respectively, whereas that of the physicians was 85.6%, 85.1%, and 97.4%, respectively.

Conclusion: The new multistage deep learning method shows potential for an innovative approach to gastric cancer screening. It can evaluate individual subjects' cancer risk based on endoscopic images and reduce the burden of physicians.

Background: We aim to comprehensively analyze and validate the prognostic efficacy of tetraspanin 4 (TSPAN4) and several other migrasome-related markers in hepatocellular carcinoma (HCC).

Methods: The expression, diagnostic, and prognostic efficacy of five migrasome-related genes in HCC were analyzed using several databases. Five pairs of adjacent non-tumor tissues and HCC tissues were used to validate the expression. The prognostic efficacy of TSPAN4 was validated in a HCC cohort. TSPAN4 was knocked down in Huh-7 cells, EdU, and CCK-8, and wound healing assays were conducted to analyze its effects on cell proliferation and migration. In addition, transcriptomic sequencing was used to identify differentially expressed genes.

Results: Compared with those in normal tissues, four genes (TSPAN4, PIGK, NDST1, and CPQ) were elevated in liver hepatocellular carcinoma (LIHC), but not TSPAN7. Of these, only elevated TSPAN4 predicted unfavorable prognosis of HCC patients. The expression and prognostic efficacy of TSPAN4 were further confirmed in a HCC cohort (97 patients); and patients in the TSPAN4^high group showed unfavorable overall survival (log-rank P = 0.0055). Functional analysis showed that TSPAN4 knockdown significantly suppressed cell migration, but not cell proliferation. Moreover, TSPAN4 knockdown induced disturbances of the metabolic pathways, mainly pentose and glucuronate interconversions.

Conclusions: TPSAN4 is a promising prognostic and therapeutic target for HCC treatment and may be involved in the metabolic pathways that affect disease progression.

Background: To explore the complex interactions between the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) and the loss of β-cell mass, further elucidating the mechanisms of type 3c diabetes mellitus (T3cDM) onset.

Methods: Single-cell RNA sequencing was employed to analyze the PDAC TME, identifying cell interactions and gene expression changes of endocrine cells. Pathological changes and paraneoplastic islets were assessed in the proximal paratumor (PP) and distal paratumor (DP). Fractional β-cell area and islet density were compared among normal pancreas from donors and paraneoplastic tissues from non-diabetes mellitus (NDM) and T3cDM patients. TUNEL staining, RT-qPCR and CCK8 assay were applied to demonstrate the β-cell apoptosis.

Results: Tumor cells, immune cells and fibroblasts could interact with endocrine cells, and apoptotic pathways were activated in endocrine cells of the PP. The PDAC TME was characterized by marked inflammation, sever fibrosis and atrophy. The islets in the PP had lower fractional β-cell area (0.68 ± 0.65% vs. 0.86 ± 1.02%, P = 0.037) and islet density (0.54 ± 0.42 counts/mm² vs. 0.83 ± 0.90 counts/mm², P = 0.001) compared to those in the DP. The PDAC TME in T3cDM exerted a more significant impact on the paraneoplastic islets compared to NDM. Moreover, β-cell apoptosis was markedly increased in the PP compared to the DP in PDAC patients without diabetes, particularly in smaller islets. Apoptosis-related genes were highly expressed in INS-1E cells exposed to PANC-1 medium.

Conclusion: Our research revealed that the PDAC TME is usually accompanied by some pathological changes, including inflammation, fibrosis, and atrophy. These pathological changes are related to a reduction in β-cell mass and trigger the development of T3cDM.

Background: Covert hepatic encephalopathy (CHE) significantly impacts the quality of life and prognosis in patients with liver cirrhosis. This study aims to analyze the prevalence and risk factors of CHE to identify high-risk patients who would benefit from therapeutic interventions.

Methods: This single-center, retrospective observational study included 126 patients without a history of overt hepatic encephalopathy (OHE). CHE was defined as a score above the age-based cutoff value in the Stroop test. Factors associated with the occurrence of CHE and the subsequent development of OHE were evaluated.

Results: CHE was detected in 47 patients (37.3%). A multiple logistic regression analysis identified serum zinc levels (per + 1 µg/dL, odds ratio 0.95, P = 0.0007) as the only risk factor associated with CHE, with a cutoff value of 60 µg/dL (AUC 0.71, P = 0.0001). Neither blood ammonia levels nor liver function were predictive of CHE. During a median observation period of 211 days, OHE developed in 18 patients (14.3%). The administration of more than 20 mg of furosemide was identified as a risk factor for developing OHE (hazard ratio 23.52, P = 0.0207).

Conclusion: Cirrhotic patients with serum zinc levels below 60 µg/dL exhibit a high risk of developing CHE, regardless of blood ammonia levels. These patients face a significant risk of developing OHE. Therefore, early zinc supplementation is recommended for the prevention of OHE, particularly for those prescribed 20 mg or more of furosemide.