查看更多>>摘要:Background and Aims: Microvascular invasion (MVI) af-fects recurrence after treatment of small hepatocellular car-cinoma (sHCC) of ≤3 cm in size. The present study aimed to investigate whether abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and intermuscular adi-pose tissue (IMAT) are associated with MVI in patients with sHCC. Methods: A total of 124 patients with pathologically-confirmed sHCC diagnosed on surgical resection at the First Hospital Affiliated to Army Military University were recruited and divided into two groups according to MVI classification criteria (i.e., MVI-positive or MVI-negative). The SAT, VAT, and IMAT areas at the lumbar 3 vertebral level were imaged with abdominal computed tomography and measured using ImageJ software. Their association with MVI in sHCC was analyzed. Results: Of the 124 patients with sHCC, 67 were MVI-positive and 57 were MVI-negative. Univariate analy-sis revealed a significant difference in the abdominal VAT and SAT between the MVI-positive and MVI-negative groups (p<0.05), with an area under the receiver operating charac-teristic curve of 0.76 and 0.65, respectively. Conclusions: The results of this study suggest that the areas of abdominal SAT and VAT are of significant clinical value because they can effectively predict the MVI status in patients with sHCC.
查看更多>>摘要:Background and Aims: Irreversible electroporation (IRE) is an emerging local ablation therapy which may be effec-tive for unresectable tumors. This study aimed to evaluate the safety and efficacy of percutaneous IRE in the treat-ment of hepatocellular carcinoma (HCC) abutting the dia-phragm. Methods: A total of 26 participants with 39 tu-mors abutting the diaphragm were prospectively evaluated between July 2015 and September 2018. Complications associated with IRE were recorded, and the survival benefit of IRE was analyzed. The factors associated with time to local tumor progression (LTP) were analyzed using univari-ate and multivariate Cox regression models. Results: No major complications or treatment-related deaths occurred. The technical success rate was 96.2% (25/26) and com-plete ablation rate was 92.3% (36/39). The median follow-up period was 16.7 months (range: 3.0–43.0 months), the LTP occurred in 15.2% of tumors and median time to LTP was 20.4 months. Overall, tumor size (hazard ratio: 1.24 [95% confidence interval: 0.38, 3.81], p=0.03) was the only factor associated with time to LTP. Conclusions: This study shows for the first time that percutaneous IRE is a safe and effective ablation technology for HCC abutting the diaphragm.
Max ShenAnna LeeJay H.LefkowitchHoward J.Worman...
197-206页
查看更多>>摘要:Background and Aims: Vibration-controlled transient elastography (VCTE) is a noninvasive tool that uses liv-er stiffness measurement (LSM) to assess fibrosis. Since real-life data during everyday clinical practice in the USA are lacking, we describe the patterns of use and diagnostic performance of VCTE in patients at an academic medical center in New York City. Methods: Patients who received VCTE scans were included if liver biopsy was performed within 1 year. Diagnostic performance of VCTE in differen-tiating dichotomized fibrosis stages was assessed via area under the receiver operating characteristics (AUROC). Fi-brosis stage determined from VCTE LSM was compared to liver biopsy. Results: Of 109 patients, 49 had nonalcoholic fatty liver disease, 16 chronic hepatitis C, 15 congestive hepatopathy, and 22 at least two etiologies. AUROC was 0.90 for differentiating cirrhosis (stage 4) with a positive predictive value (PPV) range of 0.28 to 0.45 and negative predictive value range of 0.96 to 0.98. For 31 (32%) pa-tients, VCTE fibrosis stage was at least two stages higher than liver biopsy fibrosis stage. Thirteen of thirty-five pa-tients considered to have cirrhosis by VCTE had stage 0 to 2 and 12 stage 3 fibrosis on liver biopsy. Conclusions: VCTE has reasonable diagnostic accuracy and is reliable at ruling out cirrhosis. However, because of its low PPV, caution must be exercised when used to diagnose cirrho-sis, as misdiagnosis can lead to unnecessary health care interventions. In routine practice, VTCE is also sometimes performed for disease etiologies for which it has not been robustly validated.
查看更多>>摘要:Background and Aims: Although activation of hepatic stellate cells (HSCs) plays a central role in the development of liver fibrosis, the mechanism underlying the activation of HSCs remains unclear. Keratin 17 (KRT17), a member of the intermediate filament family, can regulate tumor cell proliferation and migration. The current study aimed to elucidate the role of KRT17 in the activation of HSCs and the mechanisms underlying liver fibrosis. Methods: The expression of KRT17 was determined using immunohisto-chemistry in tissue microarray. Western blotting and qRT-PCR assays were used to determine the KRT17 expression in fibrotic liver tissues obtained from human subjects and mice. LX-2 cells were treated with TGF-β1 recombinant pro-tein and adipocyte differentiation mixture (MDI) mix to in-duce and reverse LX-2 cell activation, respectively, in order to explore the correlation between KRT17 and HSC activa-tion. Additionally, cell proliferation and migration abilities of LX-2 cells transfected with KRT17-overexpressing plasmid or small interfering RNA were determined using CCK-8, flow cytometry, Transwell, and wound healing assays. Finally, rescue assay was used to explore the role of KRT17 in HSC activation and epithelial-mesenchymal transition (EMT). Results: The expression of KRT17 was higher in the hu-man and mouse fibrotic liver tissues than in healthy liver tissues, and it was positively correlated with HSC activa-tion. Upregulated KRT17 enhanced proliferation, migration, HSC activation and EMT in LX-2 cells, while knockdown of KRT17 reversed these effects. TGF-β1 recombinant protein accelerated KRT17-mediated EMT, HSC activation and pro-liferation, while TGF-β1 inhibitor counteracted the effect of KRT17 in vitro. Conclusions: KRT17 promoted HSC activa-tion, proliferation and EMT in hepatic fibrosis probably via TGF-β1 signaling, and KRT17 might serve as a therapeutic target for the treatment of liver fibrosis.
查看更多>>摘要:Background and Aims: Previous studies have reported that the single nucleotide polymorphisms (SNPs) of SAMM50-rs738491, PARVB-rs5764455 and PNPLA3-rs738409 are associated with nonalcoholic fatty liver disease (NAFLD). However, no studies have examined the effect of interactions between these three genotypes to affect liver disease severi-ty. We assessed the effect of these three SNPs on nonalcohol-ic steatohepatitis (NASH) and also examined the gene-gene interactions in a Chinese population with biopsy-confirmed NAFLD. Methods: We enrolled 415 consecutive adult individ-uals with biopsy-proven NAFLD. Multivariable logistic regres-sion analysis was undertaken to test associations between NASH and SNPs in SAMM50-rs738491, PARVB-rs5764455 and PNPLA3-rs738409. Gene-gene interactions were ana-lyzed by performing a generalized multifactor dimensionality reduction (GMDR) analysis. Results: The mean ± standard deviation age of these 415 patients was 41.3±12.5 years, and 75.9% were men. Patients with SAMM50-rs738491 TT, PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes had a higher risk of NASH, even after adjustment for age, sex and body mass index. GMDR analysis showed that the combination of all three SNPs was the best model for predict-ing NASH. Additionally, the odds ratio of the haplotype T-A-G for predicting the risk of NASH was nearly three times higher than that of the haplotype G-C-C. Conclusions: NAFLD pa-tients carrying the SAMM50-rs738491 TT, PARVB-rs5764455 AA or PNPLA3-rs738409 GG genotypes are at greater risk of NASH. These three SNPs may synergistically interact to increase susceptibility to NASH.
查看更多>>摘要:Background and Aims: We compared lung function parameters in nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD), and examined the association between lung function parameters and fibrosis severity in MAFLD. Meth-ods: In this cross-sectional study, we randomly recruited 2,543 middle-aged individuals from 25 communities across four cities in China during 2016 and 2020. All participants received a health check-up including measurement of an-thropometric parameters, biochemical variables, liver ul-trasonography, and spirometry. The severity of liver dis-ease was assessed by the fibrosis (FIB)-4 score. Results: The prevalence of MAFLD was 20.4% (n=519) and that of NAFLD was 18.4% (n=469). After adjusting for age, sex, adiposity measures, smoking status, and significant alco-hol intake, subjects with MAFLD had a significantly lower predicted forced vital capacity (FVC, 88.27±17.60% vs. 90.82±16.85%, p<0.05) and lower 1 s forced expiratory volume (FEV1, 79.89±17.34 vs. 83.02±16.66%, p<0.05) than those with NAFLD. MAFLD with an increased FIB-4 score was significantly associated with decreased lung function. For each 1-point increase in FIB-4, FVC was di-minished by 0.507 (95% CI: ?0.840, ?0.173, p=0.003), and FEV1 was diminished by 0.439 (95% CI: ?0.739, ?0.140, p=0.004). The results remained unchanged when the statistical analyses was performed separately for men and women. Conclusions: MAFLD was significantly asso-ciated with a greater impairment of lung function param-eters than NAFLD.
查看更多>>摘要:Background and Aims: Chronic kidney disease (CKD) usually occurs during the chronic infection of hepatitis B virus (HBV). However, the risk factors of CKD in an HBV population have not been completely demonstrated. Our present study aimed to investigate the risk factors of CKD in chronic HBV infection using a hospital based cross-sec-tional study in the northern area of China. Methods: Dur-ing January 2013 to December 2017, a total of 94 patients with CKD complicated by chronic HBV infection were con-secutively enrolled in the study, as well as 548 age- and sex-matched hepatitis B patients without CKD who were enrolled as controls. Univariate and multivariate regression analyses were used to determine the effects of each vari-able after adjusting for cofounding factors. Results: Mul-tivariate analysis showed that HBeAg-positive status (odds ratio [OR]=2.099, 95% CI 1.128–3.907), dyslipidemia (OR: 3.025, 95% CI 1.747–5.239), and hypertension (OR: 12.523, 95% CI 6.283–24.958) were independently associ-ated with the incidence of CKD, while duration of HBV in-fection (≥240 months) (OR: 0.401, 95% CI 0.179–0.894), Log10 HBsAg (OR: 0.514, 95% CI 0.336–0.786), and coro-nary heart disease (OR: 0.078, 95% CI 0.008–0.768) were protective factors for the incidence of CKD. Duration of HBV infection, Log10 HBsAg, HBeAg-positive status and dyslipi-demia remained the risk factors for CKD after adjusting for diabetes mellitus, hypertension, and coronary heart dis-ease. Conclusions: Duration of HBV infection, Log10 HB-sAg, HBeAg-positive status and dyslipidemia contributed to the incidence of CKD during chronic HBV infection in a Chinese population.
查看更多>>摘要:Background and Aims: Chronic hepatitis B virus (HBV) infection is a serious health problem worldwide. Evaluating liver injury in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) with detectable HBV DNA and normal alanine aminotransferase (ALT) is crucial to guide their clinical management. We aimed to investi-gate the stages of liver inflammation and fibrosis as well as the predictive accuracy of gamma-glutamyl transpepti-dase-to-platelet ratio (GPR) in these patients. Methods: A total of 184 treatment-na?ve HBeAg-negative CHB pa-tients with detectable HBV DNA and normal ALT were en-rolled. The Scheuer scoring system was used to classify liver inflammation and fibrosis. Results: The distribution of patients with different liver inflammation grades were as follows: G0, 0 (0%); G1, 97 (52.7%); G2, 68 (37.0%); G3, 12 (6.5%); and G4, 7 (3.8%). The distribution of pa-tients with different liver fibrosis stages were as follows: S0, 22 (12.0%); S1, 72 (39.1%); S2, 42 (22.8%); S3, 19 (10.3%); and S4, 29 (15.8%). The areas under the re-ceiver operating characteristic (AUROC) curves of GPR in predicting significant inflammation, severe inflammation, and advanced inflammation were 0.723, 0.895, and 0.952, respectively. The accuracy of GPR was significantly superior to that of ALT in predicting liver inflammation. The AUROCs of GPR in predicting significant fibrosis, severe fibrosis, and cirrhosis were 0.691, 0.780, and 0.803, respectively. The predictive accuracy of GPR was significantly higher than that of aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) in identifying advanced fibrosis and cirrhosis, and it was superior to FIB-4 but comparable to APRI in identifying significant fibrosis. Conclusions: Nearly half of the HBeAg-negative CHB pa-tients with detectable HBV DNA and normal ALT levels had significant liver inflammation or fibrosis. GPR can serve as an accurate predictor of liver inflammation and fibrosis in these patients.