Deliang Liu

Chronic liver disease (CLD) constitutes a major global health burden, with high morbidity and mortality, limited treatment options for several etiologies, and an urgent need for novel therapeutic targets. Fibroblast growth factor 1 (FGF1) is a unique member of the FGF family capable of binding all four FGFR subtypes, thereby regulating multiple signaling pathways including PI3K/AKT, Ras/MAPK, and PLCγ, which are involved in metabolism, cell survival, proliferation, and tissue repair. Emerging evidence highlights the multifaceted and context-dependent roles of FGF1 in CLD. In drug-induced liver injury (DILI) caused by anti-tuberculosis drugs, acetaminophen, or doxorubicin, FGF1 confers protection by restoring bile acid homeostasis, reducing oxidative stress, inflammation, and apoptosis. In Metabolic dysfunction-associated steatotic liver disease (MASLD), FGF1 ameliorates hepatic steatosis, oxidative injury, and insulin resistance through downregulation of SREBP1, upregulation of PPARα, and activation of Nrf2-mediated antioxidant responses. Conversely, in primary sclerosing cholangitis (PSC), FGF1 aggravates ductular reaction, biliary senescence, and liver fibrosis via upregulation of SASP and TGF-β1, suggesting that inhibition of the FGF1/FGFR axis may be therapeutic. For alcohol-related liver disease (ALD), although direct experimental evidence is lacking, FGF1 is hypothesized to confer protection given its known activities against oxidative stress, lipid dysregulation, and cell death. Despite its promise, the mitogenic potential of FGF1 raises safety concerns; however, N-terminally modified FGF1 analogs (e.g., FGF1Δ) retain metabolic benefits with reduced proliferative activity. Collectively, FGF1 represents a versatile and disease-dependent regulator in CLD, warranting further mechanistic studies, safety evaluations, and development of targeted analogs as a novel therapeutic strategy for difficult-to-treat liver diseases.

Background/Objectives: Ulcerative colitis (UC) has a higher risk of developing colorectal polyps and colorectal cancer (CRC) than non-UC individuals. The aim of the study was to explore the risk factors for coexisted colorectal polyps in patients with UC, especially for coexisted colorectal adenoma. Methods: Patients diagnosed with UC who were admitted to our hospital between January 1, 2015, and December 31, 2022 were enrolled in the study. Patients’ data including demographic data, smoking history, alcohol consumption history, disease related parameters, were retrospectively collected through the Electronic Medical Record System. Results: A total of 549 patients with UC were enrolled, among whom, 261 patients were with colorectal polyps. Within the polyp group, 54 patients had adenomatous polyps. Seven patients were diagnosed with CRC. Multivariate logistic regression revealed age ≤ 40 years, disease duration >10 years, severe disease activity, and non-biologic treatment were risk factors for colorectal polyps in patients with UC; while age > 40 years, disease duration > 10 years, a chronic relapsing disease course, and larger polyps size were risk factors for adenomatous polyps in UC patients; and age > 40 years, disease duration > 10 years, and the presence of polyps were risk factors for CRC in patients with UC. Conclusions: UC patients with a junior age, long disease duration, severe disease activity, and non-biologic treatment are likely to have colorectal polyps. While patients with a senior age, long disease duration, a chronic relapsing disease course, and larger polyp size should be screened for adenomatous polyps, and with senior age, long disease duration, and the presence of polyps should be screened for CRC.

Chronic liver disease (CLD) constitutes a major global health burden, with high morbidity and mortality, limited treatment options for several etiologies, and an urgent need for novel therapeutic targets. Fibroblast growth factor 1 (FGF1) is a unique member of the FGF family capable of binding all four FGFR subtypes, thereby regulating multiple signaling pathways including PI3K/AKT, Ras/MAPK, and PLCγ, which are involved in metabolism, cell survival, proliferation, and tissue repair. Emerging evidence highlights the multifaceted and context-dependent roles of FGF1 in CLD. In drug-induced liver injury (DILI) caused by anti-tuberculosis drugs, acetaminophen, or doxorubicin, FGF1 exerts protective effects by restoring bile acid homeostasis, reducing oxidative stress, inflammation, and apoptosis. In metabolic-associated fatty liver disease (MAFLD), FGF1 ameliorates hepatic steatosis, oxidative injury, and insulin resistance through downregulation of SREBP1, upregulation of PPARα, and activation of Nrf2-mediated antioxidant responses. Conversely, in primary sclerosing cholangitis (PSC), FGF1 aggravates ductular reaction, biliary senescence, and liver fibrosis via upregulation of SASP and TGF-β1, suggesting that inhibition of the FGF1/FGFR axis may be therapeutic. For alcohol-related liver disease (ALD), although direct experimental evidence is lacking, FGF1 is hypothesized to confer protection given its known activities against oxidative stress, lipid dysregulation, and cell death. Despite its promise, the mitogenic potential of FGF1 raises safety concerns; however, N-terminally modified FGF1 analogs (e.g., FGF1Δ) retain metabolic benefits with reduced proliferative activity. Collectively, FGF1 represents a versatile and disease-dependent regulator in CLD, warranting further mechanistic studies, safety evaluations, and development of targeted analogs as a novel therapeutic strategy for difficult-to-treat liver diseases.

Background Glue extrusion bleeding is a major complication of endoscopic cyanoacrylate glue injection for the treatment of gastric varices. However, its risk factors remain unclear. Aims This retrospective study aimed to evaluate the risk factors for bleeding associated with glue extrusion. Methods This study analyzed the medical data of cirrhotic patients who underwent endoscopic obliteration for gastric varices using cyanoacrylate glue between January 2016 and December 2022. The data within 1 year after therapy were carried out with logistic regression. A nomogram model was constructed based on the factors. Results 269 patients were enrolled. Risk factors associated with glue extrusion bleeding included the volume of the glue (≥ 4 mL)(OR 1.289, 95% CI 1.051–1.580; P = 0.015), massive ascites (OR 5.645, 95% CI 2.260–14.097; P = 0.000), active hemorrhage during endoscopy (OR 2.830, 95% CI 1.284–6.234; P = 0.010), and the use of β-blockers was a protective factor (OR 0.185, 95% CI 0.07–0.485; P = 0.001). The nomogram model had good prediction accuracy, with an area under the curve of 0.74 (95% CI 0.658–0.822; P < 0.001). Conclusion Massive ascites, active hemorrhage during endoscopy, glue volume ≥ 4 mL, and the use of β-blockers are associated with glue extrusion bleeding. At-risk patients may benefit from controlling the volume of the glue, undergoing endoscopic ultrasound and using β-blockers.

Background Peroral endoscopic myotomy (POEM) is an emerging effective treatment for achalasia. However, a significant proportion of patients do not respond well to the treatment. After over a decade of clinical practice, potential risk factors associated with POEM failure have been identified. This meta-analysis aimed to summarize the evidence of risk factors for POEM failure. Methods A systematic literature search was conducted on PubMed, Embase, Web of Science, and Cochrane Library from inception to June 10th, 2022. We included English studies that reported POEM outcomes in achalasia patients and identified risk factors for POEM failure. Relevant information was extracted and analyzed using fixed- or randomized-effect models to pool the effect size. Results A total of 27 studies comprising 9371 patients with achalasia were included in this review. The pooled failure rate was 8% (90% CI 7%–10%). We identified sigmoid esophagus (OR 1.90, 95% CI 1.45–2.47), type I achalasia (OR 1.30, 95% CI 1.04–1.63), and type III achalasia (OR 1.26, 95% CI 0.89–1.78) were associated with a worse clinical response. Conversely, type II achalasia was associated with a better response (OR 0.59, 95% CI 0.47–0.75). Prior treatment with Heller myotomy (OR 5.75, 95% CI 3.97–8.34) and prior balloon dilation (OR 1.18, 95% CI 1.07–1.29) were also associated with a higher risk of clinical failure. Conclusion Our meta-analysis results demonstrated that sigmoid esophagus, manometric achalasia subtype, and prior treatment were associated with POEM failure. This information could be used to guide treatment decisions and improve the success rate of POEM in achalasia patients.

Background In recent years, the incidence of gastrointestinal neuroendocrine tumors (GI-NETs) has remarkably increased due to the widespread use of screening gastrointestinal endoscopy. Currently, the most common treatments are surgery and endoscopic resection. Compared to surgery, endoscopic resection possesses a higher risk of resection margin residues for the treatment of GI-NETs. Methods A total of 315 patients who underwent surgery or endoscopic resection for GI-NETs were included. We analyzed their resection modality (surgery, ESD, EMR), margin status, Preoperative marking and Prognosis. Results Among 315 patients included, 175 cases underwent endoscopic resection and 140 cases underwent surgical treatment. A total of 43 (43/175, 24.57%) and 10 (10/140, 7.14%) patients exhibited positive resection margins after endoscopic resection and surgery, respectively. Multivariate regression analysis suggested that no preoperative marking and endoscopic treatment methods were risk factors for resection margin residues. Among the patients with positive margin residues after endoscopic resection, 5 patients underwent the radical surgical resection and 1 patient underwent additional ESD resection. The remaining 37 patients had no recurrence during a median follow-up of 36 months. Conclusions Compared with surgery, endoscopic therapy has a higher margin residual rate. During endoscopic resection, preoperative marking may reduce the rate of lateral margin residues, and endoscopic submucosal dissection may be preferred than endoscopic mucosal resection. Periodical follow-up may be an alternative method for patients with positive margin residues after endoscopic resection.

肝硬化患者患上消化道肿瘤风险增加, 尤其是酒精性肝硬化患者. 随着内镜检查的推广及普及, 越来越多的上消化道早癌得以早期发现及治疗. 内镜治疗已成为上消化道早癌的首选治疗方式, 肝硬化患者由于可能存在血小板减少、凝血功能障碍、合并食管胃静脉曲张等情况, 内镜治疗过程中出血、感染等风险较大. 近年来国内外已有部分研究探讨内镜治疗肝硬化伴上消化道早癌的安全性及有效性. 本文总结了近年来发表的内镜治疗肝硬化伴上消化道早癌的研究结果, 简要综述其风险及防治策略, 为临床提供指导.

Current evidence shows an inter-country inconsistency in the effect of lesion size on the technical difficulty of gastric endoscopic submucosal dissection (ESD). We aimed to evaluate the specific correlation and quantify the ensuing risks. This retrospective study consisted of 405 ESD cases with gastric single lesion from April 2015 to April 2023. The correlation and risk prediction of lesion size with technical difficulty was explored to provide further clinical evidence. An additive generalized model and recursive algorithm were used to describe the non-linear association, and a linear two-piece regression was constructed to analyze the inflection point. Subgroup analysis and interaction were used to explore intergroup characteristics. Overall, difficult cases had larger lesion sizes, and the more significant the increase, the higher the risk of technical difficulty. In the full model, after adjusting for all covariates, each 1 mm, 3 mm, 5 mm, 7 mm, and one standard increase in lesion size increased the risk of technical difficulty by 8%, 26%, 42%, 72%, and 125%, respectively. There is a nonlinear positive correlation between lesion size and risk of technical difficulty, and the premeditated inflection point was 40 (mm) via two-piecewise linear regression and recursive algorithm. Subgroup analysis showed a stronger correlation between lesion size and difficult ESD in the upper site and submucosal fibrosis groups. Available evidence suggests that lesion size as a risk signal nonlinearly increases the technical difficulty of gastric ESD procedure, especially in cases of upper site and submucosal fibrosis, which deserves further investigation.