Effective surveillance of the hepatitis populations reduces liver cancer incidence and improves prognosis. This study aimed to develop an easy and non-invasive risk assessment model for this population. A total of 392 subjects were included in the present study, comprising 72 cases of chronic hepatitis, 31 cases of liver fibrosis, 152 cases of cirrhosis and 137 cases of liver cancer from diverse ethnic groups in China. Concurrent evaluation of the methylation levels of the GNB4 and Riplet genes in plasma, alongside the age-male-albumin-bilirubin-platelet (aMAP) score and serum AFP, was performed for each subject. Head-to-head comparisons demonstrated that methylation is a superior diagnostic biomarker for liver cancer relative to AFP and aMAP scores. The sensitivity and specificity of GNB4/Riplet methylation for detecting liver cancer were 87.59% (95% confidence interval [CI]: 80.61%-92.40%) and 93.33% (95% CI: 89.25%-95.95%), respectively. For TNM stage I and II liver cancer, methylation showed sensitivities of 69.70% (95% CI: 51.13%-83.79%) and 91.18% (95% CI: 75.19%-97.69%), respectively. The aMAP score yielded an area under the curve (AUC) of 0.745 (95% CI: 0.679–0.812) for differentiating hepatitis from fibrosis/cirrhosis/cancer samples, and an AUC of 0.764 (95% CI: 0.710–0.818) for differentiating hepatitis/fibrosis from cirrhosis/cancer samples. When combining the aMAP score with methylation, the corresponding AUCs increased to 0.825 (95% CI: 0.774–0.875) and 0.867 (95% CI: 0.829–0.905), respectively. The combination of aMAP score and plasma GNB4/Riplet gene methylation shows promise as a tool for risk stratification, which needs external validation in the future.

Accurate, non-invasive liver fibrosis detection is essential for chronic liver disease management, particularly with rising metabolic dysfunction-associated liver disease (MASLD) and chronic hepatitis B (CHB). While the Fibrosis-4 (FIB-4) index is widely used, its performance for advanced fibrosis is limited. We develop Met-FIB using metabolomics and machine learning, integrating FIB-4 parameters (age, aspartate aminotransferase, alanine aminotransferase, and platelet count) with tyrosine and taurocholic acid identified in a CHB discovery cohort (n = 3,251). Validation includes one CHB cohort (n = 729) and two MASLD cohorts (n = 149, n = 155). Met-FIB outperforms FIB-4, FibroScan, and other serum markers across all fibrosis stages. In CHB, Met-FIB achieves 96.3% rule-out sensitivity and 85.4% rule-in specificity for significant fibrosis, with rule-in specificity reaching 98.6% and 98.8% for advanced fibrosis and cirrhosis. In MASLD, corresponding values are 93.9% and 90.2% for significant fibrosis, with >97.9% specificity for late-stage disease. Met-FIB demonstrates clinical utility for non-invasive fibrosis staging across diverse etiologies.

Background and aims: Noninvasive preoperative radiologic prediction of histologic grade—a key prognostic factor—is invaluable. We aim to compare the diagnostic values of 3D magnetic resonance elastography (MRE), intravoxel incoherent motion (IVIM), and conventional contrast-enhanced magnetic resonance imaging (cMRI) in predicting the histologic grade of hepatocellular carcinoma (HCC). Methods: This institutional review board-approved retrospective study included patients who underwent MRI between December 2014 and October 2021. Sixty-eight patients with pathologically confirmed HCCs who underwent MRE, IVIM, and cMRI imaging were included in the analysis. Two radiologists measured HCC stiffness volumetrically and over a single slice, and also measured apparent diffusion coefficient (ADC), IVIM-derived parameters, and enhancement ratio (ER) on arterial phase images via cMRI. Student’s t-test or the Mann–Whitney U test was used for group comparisons. Receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic performance. Results: Histologically, fifty-three (78%) patients had well-differentiated or moderately differentiated HCCs, and fifteen (22%) patients had poorly differentiated HCCs. Both the volumetric stiffness and single-ROI tumor stiffness were significantly elevated in the poorly differentiated HCC group (P < 0.001, P = 0.001), and the volumetric stiffness was a better measurement of stiffness because it had a higher ROC curve value (0.816). However, the ADC, the true diffusion coefficient (D), the pseudodiffusion coefficient (D∗), the pseudodiffusion fraction (f), and ER during the arterial phases on cMRI were not significantly different between the two groups (P = 0.309, 0.187, 0.440, 0.350, and 0.714, respectively). Conclusions: Stiffness measured with 3D MRE may be useful for noninvasively predicting HCC histologic grade, and the volumetric measuring method achieved the highest ROC curve value, outperforming single-ROI HCC stiffness, IVIM parameters, and arterial-phase ER on cMRI.

Abstract Background Previous studies have found that the production of platelets could enhance the therapeutic effects of stem cells. Nevertheless, there are still no articles reporting on the relationship between platelets and the clinical efficacy of umbilical cord mesenchymal stem cells (UCMSCs) for HBV-related acute-on-chronic liver failure (ACLF) and liver cirrhosis (LC). Methods In this retrospective observational study, patients who met the criteria were included. Patients were divided into subgroups according to the aims of this study. In the first part, the platelet count changes of ACLF and patients with LC after UCMSC therapy were compared and analyzed. Subgroup analysis based on UCMSC infusion times and patient age was also performed. In the second part, patients in the ACLF group and LC group were further divided into subgroups according to their platelet levels. Their clinical characteristics, demographics, and biochemical factors were compared. Results This study enrolled 64 patients with ACLF and 59 patients with LC. In both groups, platelet levels declined similarly. Compared with the short-course UCMSC treatment group (≤4 times), patients with ACLF and patients with LC with long-course UCMSC treatment (>4 times) showed an overall increasing trend. Younger patients with LC (<45 years) had significantly higher platelet levels than older patients with LC (≥45 years). However, this age difference was not present in the ACLF group. The median TBIL decrease and cumulative TBIL decrease were not significantly different between patients with high PLT and patients with low PLT after UCMSC transfusions. For patients with ACLF, the cumulative TBIL decrease and the median TBIL decrease were significantly greater than those of patients with LC at the same platelet level after UCMSC treatment. However, this difference was not observed at all time points. Conclusion Trend of the platelet levels for HBV-related patients with ACLF and LC after UCMSC treatment did not parallel and varied according to treatment times and patients’ age. Platelet levels did not affect the efficacy of MSCs for patients with ACLF or LC.

Currently, interferon add-on therapy brings hope for clinical cure of chronic hepatitis B patients with low HBsAg. However, in clinical practice patients with poor responses to their first interferon therapy were often switched to nucleos(t)ide analog therapy and then labeled as unsuitable patients for interferon therapy. Even if their HBsAg levels dropped to a low level, they were reluctant or not recommended to take interferon again, which caused them to miss out on interferon add-on therapy and clinical cure. Therefore, it is urgent to elucidate the effectiveness of interferon add-on therapy to get clinical cure for these interferon-experienced patients with low HBsAg. The purpose of this study was to investigate whether interferon-experienced patients could achieve the same HBsAg clearance and HBsAg seroconversion rates as interferon-naive patients. Also, the associated factor of HBsAg clearance and seroconversion were aimed to be clarified. 292 patients, including 85 interferon-experienced patients, were enrolled with HBsAg< 1500 IU/ml, HBeAg negative and HBV-DNA negative. And then, peg-interferon α-2b add-on therapy was performed. The results showed that the week 48 HBsAg clearance and seroconversion rates of all patients were 29.8% and 22.0%. There was no statistically significant difference between interferon-experienced and interferon-naive patients in week 48 HBsAg clearance and seroconversion rates, suggesting satisfactory clinical cure of the interferon add-on therapy for interferon-experienced patients. The age, baseline HBsAg, and week 12 HBsAg were negative correlated factors for week 48 HBsAg clearance and seroconversion. Furthermore, the age, baseline HBsAg and week 12 HBsAg for predicting the week 48 HBsAg clearance were cut off at 40.5 years, at 152.0 IU/ml and at 34.99 IU/ml, and for predicting seroconversion were cut off at 40.5 years, at 181.9 IU/ml and at 34.99 IU/ml, correspondingly. Significantly, interferon-experienced patients with low HBsAg were suggested with interferon add-on therapy to achieve clinical cure as soon as possible. This research provided evidences and cut-offs for the interferon add-on therapy against chronic hepatitis B.

Background and aims: Effective hepatic blood flow (EHBF) decreases with liver disease progression, and identifying liver pathology is critical for patients with liver disease. This study was designed to elucidate the correlation between EHBF and liver pathology and explore the potential of EHBF for predicting the degree of liver pathology. Methods: In this study, 207 patients with hepatitis B virus (HBV) who underwent liver biopsy and indocyanine green (ICG) clearance tests were enrolled. EHBF was measured using the ICG clearance test, and liver tissue was histologically analyzed to determine the pathological stage according to the Scheuer scoring system. Demographic data, biochemical indexes, and FibroScan data were collected for statistical analysis. Results: EHBF levels decreased as the liver histological stages of inflammation and fibrosis increased (P < 0.01). EHBF was significantly negatively associated with the levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, aspartate aminotransferase-to-platelet ratio index, fibrosis index based on the four factors, and liver stiffness measurement (P < 0.05). The EHBF levels of patients without liver inflammation (G0) were significantly higher than those of patients with liver inflammation (G1-4) (P < 0.001). The area under the receiver operating characteristic curve (AUROC) value for discriminating patients without liver inflammation was 0.827, and the optimal cutoff value was 0.936 L/min. The EHBF levels of patients with severe liver inflammation (G4) were significantly lower than those of patients with G0-3 liver inflammation (P < 0.001). The AUROC value for discriminating patients with severe liver inflammation was 0.792, and the optimal cutoff value was 0.552 L/min. The EHBF levels of patients without liver fibrosis (S0) were significantly higher than those of patients with liver fibrosis (S1-4) (P < 0.001). The AUROC value for discriminating patients without liver fibrosis was 0.633, and the optimal cutoff value was 1.173 L/min. The EHBF levels of patients with liver cirrhosis (S4) were significantly lower than those of patients with S0-3 liver fibrosis (P < 0.001). The AUROC value for discriminating patients with liver cirrhosis (S4) was 0.630, and the optimal cutoff value was 0.562 L/min. Conclusions: EHBF levels and liver pathology are significantly correlated. EHBF could effectively reflect liver inflammation and fibrosis in patients infected with HBV, especially for patients without liver inflammation or liver fibrosis. (c) 2021 The Third Affiliated Hospital of Sun Yat-sen University. Publishing services by Elsevier B. V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Abstract Background The results of a previous study verified that umbilical cord mesenchymal stem cells (UCMSCs) have good therapeutic effects for the treatment of HBV-related acute-on-chronic liver failure (ACLF) and liver cirrhosis (LC). Nevertheless, it is still unknown whether the effects of UCMSCs are affected by recipient age. Methods Patients treated with UCMSCs who met the criteria of HBV-related ACLF and liver cirrhosis were identified in this retrospective observational study. Patients were divided into subgroups according to the World Health Organization (WHO) age criteria (< 45 vs. ≥ 45 years). Group A included young ACLF patients (< 45 y), and group B included older ACLF patients (≥ 45 y). Young LC patients (< 45 y) were assigned to group C, and group D included older LC patients (≥ 45 y). Patients’ clinical characteristics, demographics, biochemical factors, and model for end-stage liver disease (MELD) scores were compared for 24 weeks. Results Sixty-four ACLF patients and 59 LC patients were enrolled in this study. Compared with patients in groups B and C, patients in group A did not show significant superiority in terms of the levels of ALT, AST, TBIL, AFP, and PTA and MELD scores. However, the median decrease and cumulative decrease in the TBIL and ALT levels of patients in group C were larger than those of patients in group D after four weeks of UCMSC transfusions. For older patients (≥ 45 y), the cumulative decrease and the median decrease in the TBIL of ACLF patients were significantly greater than those of LC patients after UCMSC treatment. However, the median decrease in ALT levels of ACLF patients was significantly greater than that of LC patients during UCMSC treatment, and the cumulative decrease in ALT levels of ACLF patients was significantly greater than that of LC patients at all time points. Conclusion The therapeutic effects of UCMSCs for HBV-related acute-on-chronic liver failure and liver cirrhosis varied partly by patient age. Assessing patient age is necessary prior to UCMSC clinical use.

Hepatocellular carcinoma (HCC) is a common malignancy with poor prognosis and high mortality. To identify key genes associated with HCC and the underlying mechanisms, we performed weighted correlation network analysis (WGCNA) of potential key genes of HCC. We identified 17 key genes closely related to HCC by yellow module combined with PPI analysis. Verification of the role of these genes revealed that SPC25 knockdown results in a significant decrease in proliferation and metastasis of HCC cells and increased protein levels of components of the p53 pathway in vitro. In summary, we identified that SPC25 is a potential tumor‐promoting factor in HCC and may act via the p53 pathway.

BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases that may progress to liver fibrosis or cancer. The present study aimed to investigate the role of microRNA-125b-5p (miR-125b-5p) in NAFLD and to further explore underlying molecular mechanisms.METHODS:A mouse model of NAFLD was constructed by high cholesterol diet feeding and a cell-model was developed by treating the mouse liver cell line NCTC1469 with palmitic acid. Gain- and loss-of-function experiments were performed to determine the effects of miR-125b-5p, integrin α8 (ITGA8), and the RhoA signaling pathway on liver fibrosis in NAFLD. After the expression levels of miR-125b-5p, ITGA8, and RhoA were determined, liver fibrosis was evaluated in vivo and in vitro. The binding relationship of miR-125b-5p and ITGA8 was then validated. Finally, miR-125b-5p promoter methylation in NAFLD liver tissues and cells was determined.RESULTS:In NAFLD clinical samples, mouse model, and cell-model, miR-125b-5p expression was reduced, while ITGA8 expression was increased. Moreover, miR-125b-5p targeted and downregulated ITGA8, leading to inhibition of the RhoA signaling pathway. In NAFLD liver tissues and cells, the CpG island in the miR-125b-5p promoter was methylated, causing epigenetic silencing of miR-125b-5p. Both miR-125b-5p silencing and ITGA8 overexpression promoted in vitro and in vivo liver fibrosis in NAFLD via activation of the RhoA signaling pathway.CONCLUSIONS:Collectively, epigenetic silencing of miR-125b-5p upregulates ITGA8 expression to activate the RhoA signaling pathway, leading to liver fibrosis in NAFLD.

Background and Aims Little is known about the mechanisms of IL-17 secreting T cells accumulation in HBV-transfected livers. Here, we investigated the role of the chemokines CCL17, CCL20 and CCL22 in this process. Methods Peripheral blood and liver tissues were obtained from 30 chronic hepatitis B (CHB) patients and 15 healthy volunteers and were evaluated by flow cytometric analysis and immunohistochemistry. Chemokine production by monocyte-derived dendritic cells (MoDCs) cocultured with HBV-transfected or untransfected Huh7 cells was measured by quantitative real-time PCR and enzyme-linked immunosorbent assay. The chemotactic activity of the culture supernatants was also tested. Results The proportions of IL-17 secreting CD4 (Th17) and CD8 (Tc17) T cells were both increased in liver and peripheral blood mononuclear cells of CHB patients compared to those in HVs. CHB patients showed higher intrahepatic levels of CCL17 mRNA, CCL22 mRNA, CCR6 mRNA and CCR4 mRNA than HVs. The expression of CCR6 and CCR4 on the surface of Th17 and Tc17 cells in CHB patients was also significantly higher than that in HVs. Significant correlations existed between the CCR4/CCR6 levels and both the alanine transaminase levels and HBV DNA loads. Contact between MoDCs and pBlue-HBV-transfected Huh7 cells induced the expression of CCL17 and CCL22 dependent on the dose of HBV DNA. However, CCL20 expression was lower in CHB patients than in HVs. Transwell experiments showed that upregulation of CCL17 and CCL22 enhanced the migration of IL-17 secreting T cells. Conclusions Contact of HBV-transfected cells with MoDCs induces CCL17 and CCL22 chemokine production, which may favour the recruitment of Th17 and Tc17 cells to liver tissue in CHB. Our results reveal the mechanism of IL-17 secreting T cells recruitment to liver tissue and thus provide new immunotherapy targets for CHB patients.

Abstract Background. We aimed to analyze the influencing factors of virus duration and virus clearance in coronavirus disease 2019 (COVID-19) in Shenzhen, China, and to provide our experience in the treatment and management of COVID-19. Methods. The clinical data and laboratory test results of COVID-19 inpatients admitted to the Third People's Hospital of Shenzhen, Guangdong Province from January 2020 to March 2020 were retrospectively collected. In COVID-19 rehabilitation patients, two consecutive negative RT-PCR results on nasopharyngeal swabs were defined as virus clearance. The time from onset of the disease to virus clearance was defined as the virus duration. We analyzed the virus clearance rate at different time points and the impact of clinical features and treatments on virus clearance. Results. A total of 201 patients with COVID-19, including 89 women (44.3%) and 112 men (55.7%), were included in our study. According to the severity of the disease, the patients were divided into no severe patients and severe patients. The overall median virus duration for all patients was 17 days. The overall virus clearance rates within 1, 2, 3, 4, 5, and 6 weeks after onset were 1.5%, 36.6%, 73.4%, 90.2%, 97.3%, and 100%, respectively. A multiple linear regression model was performed to analyze the factors influencing virus clearanc.The factors influencing virus clearance within 2 weeks were treatment timing and glucocorticoid usage. The influencing factors for virus clearance within 4 weeks were treatment timing, glucocorticoid usage and age. Conclusion. Treatment timing was related to virus clearance. The earlier the treatment was initiated, the faster the virus clearance. For COVID-19 patients, early detection and early treatment strategies should be adopted. Glucocorticoid usage may be detrimental to virus clearance and should be more restricted. Age > 60 years may also be a detrimental factor for virus clearance.

Background: This study aimed to investigate the therapeutic effect of umbilical cord mesenchymal stem cells (UCMSCs) on HBV-related liver failure and liver cirrhosis and to compare the different efficacies of UCMSCs after different treatment courses. Methods: This was an observational study that retrospectively considered a three-year period during which 513 patients who received stem cell infusion met the criteria of hepatic failure and liver cirrhosis were identified from databases of the Third Affiliated Hospital of Sun Yat-sen University. Eligible patients were categorized into the liver failure group and liver cirrhosis group. The two groups were divided into different subgroups according to the times of stem cell therapy. In the liver failure group, group A received more than 4 weeks and group B received less than 4 weeks. In the liver cirrhosis group, patients who received more than 4 weeks of stem cell therapy belonged to group C, and group D received less than 4 weeks. The patients were followed up for 24 weeks. The demographics, clinical characteristics, biochemical factors, and MELD scores were recorded and compared among different groups. Results: A total of 64 patients met the criteria of liver failure, and 59 patients met the criteria of liver cirrhosis. After UCMSC treatments, the levels of ALT, AST, and TBIL at all postbaseline time points were significantly lower than those at baseline in the liver failure group and liver cirrhosis group; the PTA and MELD scores only gradually improved in the liver failure group. Four weeks after UCMSC treatment, patients with prolonged treatment with UCMSCs had higher TBIL decline levels than patients who terminated treatment with UCMSCs. After more than 4 weeks of UCMSC treatment, there was no statistically significant difference in the levels of change for ALT, AST, TBIL, PTA value and the MELD score between patients with liver failure with prolonged treatment with UCMSCs and patients with liver cirrhosis with prolonged treatment with UCMSCs at all observation weeks. However, the median decline and cumulative decline in the TBIL level of patients with liver failure with a standard 4-week treatment course were higher than those of patients with liver cirrhosis with a standard 4-week treatment course. Conclusion: Peripheral infusion of UCMSCs showed good therapeutic effects for HBV-related liver failure and liver cirrhosis. Prolonging the treatment course can increase the curative effect of UCMSCs for end-stage liver disease, especially for patients with cirrhosis.

背景 经粘膜下隧道内镜肿瘤切除术(submucosal tunneling endoscopic resection,STER)是近年出现治疗粘膜下肿瘤的新方法,该方法微创,并发症少,患者恢复快.本研究通过对我院实施该手术患者的病例资料统计分析,探讨该手术治疗粘膜下肿瘤的可行性、有效性及安全性.目的 探讨STER治疗食管贲门粘膜下肿瘤的有效性、安全性及临床应用价值.方法 收集我院消化科2018-03/2019-03间行STER的食管贲门粘膜下肿瘤病例60例.观察患者超声内镜诊断,手术成功率,术后并发症发生率,术后病理诊断,并进行统计学分析.结果 所有患者均完成STER,手术成功率100％.粘膜下肿瘤直径1.0-5.0 cm,平均直径1.83 cm±1.37 cm.手术耗时31-123 min,平均耗时81.73 min±23.23 min.粘膜下隧道长度为4-8 cm,平均隧道长度为5.88 cm±1.17cm.术前超声内镜:平滑肌瘤45例,间质瘤15例.术后病理:平滑肌瘤为42例,间质瘤18例.术后并发症发生率:2例出现皮下气肿,经内科保守治疗痊愈出院.患者住院时间为7-11 d,平均住院天数9.96 d±2.24 d.结论 STER治疗来源于固有肌层的食管贲门粘膜下肿瘤疗效确切有效,并发症少,安全性高,值得临床推广应用.

目的 对比研究长期接受核苷(酸)药物治疗的慢性乙肝患者联合或序贯聚乙二醇干扰素α-2a治疗的安全性方面的差异.方法 回顾性研究长期接受核苷(酸)药物治疗的慢性乙肝患者共181例.其中93例患者是联合聚乙二醇干扰素α-2a治疗(联合治疗组),88例患者是停用核苷(酸)药物并接受聚乙二醇干扰素α-2a治疗(序贯治疗组).统计干扰素治疗0、12、24和48周时血清HBV DNA、血常规、肝功能、甲状腺功能及发热等症状和指标,记录结果并利用SPSS 16.0软件进行分析.结果 在接受聚乙二醇干扰素α-2a治疗12、24和48周时,联合治疗组患者和序贯治疗组患者在骨髓抑制、流感样综合征发生率、甲状腺功能异常、血糖升高、抗核抗体升高和其他少见不良反应发生率方面均差异无统计学意义(P＞0.05);序贯治疗组患者比联合治疗组患者在治疗结束时具有更高的肝功能异常率和HBV DNA升高率,差异有统计学意义(P＜0.05).结论 对长期接受核苷(酸)药物的慢性乙型肝炎患者,聚乙二醇干扰素α-2a联合核苷(酸)药物治疗和序贯于核苷(酸)药物治疗其安全性无差异.

丙型肝炎病毒(HCV)是全球范围内导致慢性病毒性肝炎的重要病原体之一,长期隐匿性感染可能会引发肝纤维化、肝硬化和肝癌等晚期肝病.干扰素和利巴韦林联合用药广泛用于HCV感染的治疗,但这一疗法治疗效果有限,并且具有很强的不良反应.近几年来口服直接抗病毒药物(DAA)应用于丙型肝炎抗病毒治疗,给患者带来了极大的受益,然而又会面临一些用药问题;需要我们平时用药护理方面给与相对应指导和对策.

Objective To analyze the mRNA expression and significance of fibroblast activation protein (FAP) in HBV related hepatocellular carcinoma (HCC),cirrhosis and chronic hepatitis.Methods We collected specimens from 47 HCC patients with surgical resection,29 HBV related liver cirrhosis and 22 chronic hepatitis;and 17 normal liver tissues were also collected as control.Real-time PCR was performed to analyze the expression of FAP mRNA.Enzyme-linked immunosorbent assay was used to measure FAP protein concentrations.Results The mRNA expression of FAP in liver tissues from HCC,cirrhosis,hepatitis and normal controls was 4.73 ± 1.60,1.86 ± 1.04,0.98 ± 0.80 and 1.00 ± 0.00;among which there were significant differences (F =7.156,P ＜ 0.05).Enzyme-linked immunosorbent assay showed that the concentrations of FAP in 1 μg total protein in liver tissues from HCC,cirrhosis,chronic hepatitis and normal controls were (1 288.28 ± 695.82) pg/mL,(1 176.11 ± 677.43) pg/mL,(1 044.58-± 389.48) pg/mL and (848.70 ± 540.74) pg/mL,respectively.Conclusion There are significant differences in the expression of FAP mRNA among hepatitis,cirrhosis,liver cancer and normal control;as the disease progresses,the expression of FAP is progressive.