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临床与转化肝病杂志（英文版）
临床与转化肝病杂志（英文版）

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临床与转化肝病杂志（英文版）/Journal Journal of Clinical and Translational Hepatology
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    Sending an SOS: Healing the Liver with the Bone Marrow

    Gustavo AyaresJuan Pablo ArabAshwani K.Singal
    1-3页
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    MAFLD Not NAFLD is Associated with Impairment of Health-related Quality of Life

    Dina AttiaNadia Abdel AtyAhmed ShawketEbada Said...
    4-5页
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Comparing the Diagnostic Criteria of MAFLD and NAFLD in the Chinese Population: A Population-based Prospective Cohort Study

    Cheng YuMinzhen WangShan ZhengMiao Xia...
    6-16页
    查看更多>>摘要：Background and Aims: Metabolic dysfunction-associ-ated fatty liver disease (MAFLD) is a new concept, pro-posed in 2020; however, its applicability in Asia populations has yet to be evaluated. Therefore, we aimed to compare the difference in epidemiological and clinical characteris-tics between MAFLD and non-alcoholic fatty liver disease (NAFLD) among Asian populations. Methods: Based on the Jinchang cohort, 30,633 participants were collected. The prevalence and incidence of MAFLD and NAFLD were used to analyze the epidemic characteristics and its overlapping effects. In addition, the corresponding clinical character-istics of the two diagnostic criteria populations were com-pared. Results: The prevalence rates of MAFLD and NAFLD were 21.03％ and 18.83％, respectively. After an average 2.28-year follow-up, the incidence densities of MAFLD and NAFLD were 41.58 per 1,000 person-years and 37.69 per 1,000 person-years, respectively. With the increase of baseline age, body mass index (BMI), and waist circumfer-ence (WC) levels, the prevalence and incidence of MAFLD and NAFLD were on the rise (all ptrend<0.05). Among the total patients diagnosed at baseline or follow-up, most pa-tients had both MAFLD and NAFLD, accounting for 78.84％ and 82.88％, respectively. Compared with NAFLD, MAFLD patients had greater proportions of males and metabolic diseases (diabetes, dyslipidemia), and had higher BMI, WC, liver enzymes, blood glucose, and lipid levels in the base-line diagnosis patients (p<0.05). Additionally, lean MAFLD patients had higher metabolic disorders than lean NAFLD patients (p<0.05). Conclusions: Compared with NAFLD, the newly proposed definition of MAFLD is more practical and accurate, and it can help identify more fatty liver pa-tients with high-risk diseases.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Gut Microbiota Dysbiosis Strengthens Kupffer Cell-mediated Hepatitis B Virus Persistence through Inducing Endotoxemia in Mice

    Wenqing ZhouJinzhuo LuoXiaohong XieShangqing Yang...
    17-25页
    查看更多>>摘要：Background and Aims: Change of gut microbiota com-position is associated with the outcome of hepatitis B virus (HBV) infection, yet the related mechanisms are not fully characterized. The objective of this study was to investigate the immune mechanism associated with HBV persistence induced by gut microbiota dysbiosis. Methods: C57BL/6 mice were sterilized for gut-microbiota by using an antibi-otic (ABX) mixture protocol, and were monitored for their serum endotoxin (lipopolysaccharide [LPS]) levels. An HBV-replicating mouse model was established by performing HBV-expressing plasmid pAAV/HBV1.2 hydrodynamic injec-tion (HDI) with or without LPS, and was monitored for se-rum hepatitis B surface antigen, hepatitis B e antigen, HBV DNA, and cytokine levels. Kupffer cells (KCs) were purified from antibiotic-treated mice and HBV-replicating mice and analyzed for IL-10 production and T cell suppression ability. Results: ABX treatment resulted in increased serum LPS levels in mice. The KCs separated from both ABX-treated and LPS-treated HBV-replicating mice showed significantly increased IL-10 production and enhanced ability to suppress IFN-γ production of TCR-activated T cells than the KCs sep-arated from their counterpart controls. HDI of pAAV/HBV1.2 in combination with LPS in mice led to a delayed HBV clear-ance and early elevation of serum IL-10 levels compared to pAAV/HBV1.2 HDI alone. Moreover, IL-10 function blockade or KC depletion led to accelerated HBV clearance in LPS-treated HBV-replicating mice. Conclusions: Our results suggest that dysbiosis of the gut microbiota in mice leads to endotoxemia, which induces KC IL-10 production and strengthens KC-mediated T cell suppression, and thus fa-cilitates HBV persistence.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    High Frame Rate Contrast-enhanced Ultrasound Helps Differentiate Malignant and Benign Focal Liver Lesions

    Xiang FeiPeng HanBo JiangLianhua Zhu...
    26-33页
    查看更多>>摘要：Background and Aims: This study aimed to evaluate the diagnostic performance of high frame rate contrast-en-hanced ultrasound (H-CEUS) of focal liver lesions (FLLs). Methods: From July 2017 to June 2019, conventional con-trast-enhanced ultrasound (C-CEUS) and H-CEUS were per-formed in 78 patients with 78 nodules. The characteristics of C-CEUS and H-CEUS in malignant and benign groups and the differences between different lesion sizes (1–3 cm, 3–5 cm, or >5 cm) of C-CEUS and H-CEUS were examined. The diagnostic performance of C-CEUS and H-CEUS was ana-lyzed. The chi-square test or Fisher's exact test was used to assess inter-group differences. The receiver operating characteristic curve was plotted to determine the diagnostic performance of C-CEUS and H-CEUS. Results: There were significant differences in the enhancement area, fill-in direc-tion and vascular architecture between C-CEUS and H-CEUS for both benign and malignant lesions (all p=0.000–0.008), but there were no significant differences in washout results (p=0.566 and p=0.684, respectively). For lesions 1–3 cm in size, the enhancement area, fill-in direction, and vascular architecture on C-CEUS and H-CEUS were significantly dif-ferent (all p=0.000), unlike for lesions 3–5 cm or >5 cm in size. For differentiation of malignant from benign FLLs in the 1–3 cm group, H-CEUS showed sensitivity, specific-ity, accuracy, and positive and negative predictive values of 92.86％, 95.0％, 96.3％, 90.48％ and 93.75％, respectively, which were higher than those for C-CEUS (75.0％, 70.0％, 77.78％, 66.67％ and 72.91％, respectively). Conclusions: H-CEUS provided more vascular information which could help differentiate malignant from benign FLLs, especially for lesions 1–3 cm in size.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Added Value of Quantitative Apparent Diffusion Coefficients for Identifying Small Hepatocellular Carcinoma from Benign Nodule Categorized as LI-RADS 3 and 4 in Cirrhosis

    Xi ZhongHongsheng TangTianpei GuanBingui Lu...
    34-41页
    查看更多>>摘要：Background and Aims: Correct identification of small hepa-tocellular carcinomas (HCCs) and benign nodules in cirrhosis remains challenging, quantitative apparent diffusion coeffi-cients (ADCs) have shown potential value in characterization of benign and malignant liver lesions. We aimed to explore the added value of ADCs in the identification of small (≤3 cm) HCCs and benign nodules categorized as Liver Imag-ing Reporting and Data System (LI-RADS) 3 (LR-3) and 4 (LR-4) in cirrhosis. Methods: Ninety-seven cirrhosis patients with 109 small nodules (70 HCCs, 39 benign nodules) of LR-3 and 4 LR-4 based on major and ancillary magnetic resonance imaging features were included. Multiparametric quantitative ADCs of the lesions, including the mean ADC (ADCmean), min-imum ADC (ADCmin), maximal ADC (ADCmax), ADC standard deviation (ADCstd), and mean ADC value ratio of lesion-to-liv-er parenchyma (ADCratio) were calculated. Regarding the joint diagnosis, a nomogram model was plotted using multivariate logistic regression analysis. The performance was assessed using the area under the receiver operating characteristic curve (AUC). Results: The ADCmean, ADCmin, ADCratio, and ADCstd were significantly associated with the identification of small HCC and benign nodules (p<0.001). For the joint diagnosis, the LI-RADS category (odds ratio [OR]=12.50), ADCmin (OR=0.14), and ADCratio (OR=0.12) were identified as independent factors for distinguishing HCCs from benign nodules. The joint nomogram model showed good calibration and discrimination, with a C-index of 0.947. Compared with the LI-RADS category alone, this nomogram model demon-strated a significant improvement in diagnostic performance, with AUC increasing from 0.820 to 0.967 (p=0.001). Con-clusions: The addition of quantitative ADCs could improve the identification of small HCC and benign nodules catego-rized as LR-3 and 4 LR-4 in patients with cirrhosis.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Hepatic Ischemia-reperfusion Injury in Mice was Alleviated by Rac1 Inhibition – More Than Just ROS-inhibition

    Zhilin ShaYajie YangRuling LiuHaili Bao...
    42-52页
    查看更多>>摘要：Background and Aims: Reducing reactive oxygen species (ROS) production has proven an effective way for allevi-ating oxidative stress during ischemia-reperfusion injury (IRI). Moreover, inhibition of Rac1 could reduce ROS pro-duction and prevent oxidative stress injury. Previous stud-ies have suggested a positive interactivation feedback loop between Rac1 and hypoxia-inducible factor (HIF)-1α, the latter being up-regulated early during ischemia. The posi-tive inter-activation between Rac1 and HIF-1α would ag-gravate ROS production, thereby promoting IRI. This study was designed to verify the effects of Rac1 inhibition on he-patic IRI both at animal and cellular levels and to explore the interaction between Rac1 and HIF-1α during hepatic IRI. Methods: C57B/6 mice and AML-12 cells were used for the construction of hepatic IRI animal and cell models. Rac1 inhibition was achieved by NSC23766 (a specific Rac1 inhibitor). Lentiviral vectors were used for Rac1 knock-down. At designated time points, serum and liver tissues were collected from the mice and treated cells were col-lected for further analysis. Results: NSC23766 treatment significantly alleviated the hepatic IRI in mice, manifesting as lower vacuolation score and less apoptosis cells, lower ROS and serum/liver alanine aminotransferase/aspartate aminotransferase levels, and fewer activated inflammatory cells. IRI of AML-12 was also alleviated by 50 µM NSC23766 or Rac1-knockdown, manifesting as reduced cell apoptosis, less extensive interruption of mitochondrial membrane po-tential, down-regulation of apoptosis, and effects on DNA damage-related proteins. Interestingly, Rac1 knockdown also down-regulated the expression level of HIF-1α. Con-clusions: Our study supports a protective effect of Rac1 inhibition on hepatic IRI. Aside from the classic topics of reducing ROS production and oxidative stress, our study showed an interaction between Rac1 and HIF-1α signaling during hepatic IRI.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    CEACAM-1 Induced CSF3-receptor Downregulation in Bone Marrow Associated With Refractory Neutropenia in Advanced Cirrhosis

    Chhagan BihariSukriti BawejaSeggere Murlaikrishna ShasthryDeepika Lal...
    53-62页
    查看更多>>摘要：Background and Aims: Cirrhosis patients exhibit cyto-penia, and, at times refractory neutropenia to granulocyte colony-stimulating factor (G-CSF), which acts through the CSF3-receptor (CSF3R), and changes in CSF3R can affect the response. We conducted this study to assess the CSF3R status and its relevance in cirrhotic patients. Methods: Cirrhotic patients (n=127) and controls (n=26) with clini-cally indicated bone marrow (BM) examination were stud-ied. BM assessment was done by qRT-PCR and immunohis-tochemistry (IHC) for CSF3R. Circulating G-CSF, CSF3R, and carcinoembryonic antigen cell adhesion molecule-1 (CEACAM1) were measured. BM hematopoietic precursor cells and their alterations were examined by flow cytom-etry. The findings were validated in liver cirrhosis patients who received G-CSF for severe neutropenia. Results: The mean age was 48.6±13.4 years, and 80.3％ were men. Circulatory CSF3R reduction was noted with the advance-ment of cirrhosis, and confirmed by qRT-PCR and IHC in BM. CSF3R decline was related to decreased hematopoietic stem cells (HSCs) and downregulation of CSF3R in the re-maining HSCs. Cocultures confirmed that CEACAM1 led to CSF3R downregulation in BM cells by possible lysosomal degradation. Baseline low peripheral blood-(PB)-CSF3R also predisposed development of infections on follow-up. Decreased CSF3R was also associated with nonresponse to exogenous G-CSF treatment of neutropenia. Conclu-sions: Advanced liver cirrhosis was associated with low CSF3R and high CEACAM1 levels in the BM and circula-tion, making patients prone to infection and inadequate response to exogenous G-CSF.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Associating Preoperative MRI Features and Gene Expression Signatures of Early-stage Hepatocellular Carcinoma Patients using Machine Learning

    Xiaoming LiLin ChengChuanming LiXianling Hu...
    63-71页
    查看更多>>摘要：Background and Aims: The relationship between quanti-tative magnetic resonance imaging (MRI) imaging features and gene-expression signatures associated with the recur-rence of hepatocellular carcinoma (HCC) is not well studied. Methods: In this study, we generated multivariable regres-sion models to explore the correlation between the preoper-ative MRI features and Golgi membrane protein 1 (GOLM1), SET domain containing 7 (SETD7), and Rho family GTPase 1 (RND1) gene expression levels in a cohort study including 92 early-stage HCC patients. A total of 307 imaging features of tumor texture and shape were computed from T2-weighted MRI. The key MRI features were identified by performing a multi-step feature selection procedure including the cor-relation analysis and the application of RELIEFF algorithm. Afterward, regression models were generated using kernel-based support vector machines with 5-fold cross-validation. Results: The features computed from higher specificity MRI better described GOLM1 and RND1 gene-expression levels, while imaging features computed from lower specificity MRI data were more descriptive for the SETD7 gene. The GOLM1 regression model generated with three features demon-strated a moderate positive correlation (p<0.001), and the RND1 model developed with five variables was positively as-sociated (p<0.001) with gene expression levels. Moreover, RND1 regression model integrating four features was mod-erately correlated with expressed RND1 levels (p<0.001). Conclusions: The results demonstrated that MRI radiomics features could help quantify GOLM1, SETD7, and RND1 ex-pression levels noninvasively and predict the recurrence risk for early-stage HCC patients.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Single-center Experience in the Diagnosis and Treatment of Hepatic Perivascular Epithelioid Cell Neoplasm

    Junjun JiaJia LuoCheng-Gen PanGuomei Ge...
    72-79页
    查看更多>>摘要：Background and Aims: Perivascular epithelioid cell neo-plasms (PEComas) are a rare type of mesenchymal neo-plasm and their preoperative diagnosis is challenging. In this study, we summarized the experience from a single medical center to study the examinations, clinical presen-tations, and pathological and histological characteristics of PEComas in the liver in order to optimize overall un-derstanding of the diagnosis and treatment of these neo-plasms. Methods: We conducted a retrospective analysis to investigate the clinical and pathological characteristics as well as imaging presentations of 75 patients diagnosed with hepatic PEComa in The First Affiliated Hospital of Zhe-jiang University between April 2010 and April 2020. Re-sults: Among the 75 patients, 52 were women, and the median age was 48 years. Most patients had no specific symptoms, and two were admitted to the hospital for a second time owing to relapse. All patients underwent surgi-cal resection. Histologically, 38 patients had classical angio-myolipoma (AML) and 37 had epithelioid AML. The PECo-mas were accompanied by positive immunohistochemical expression of HMB45, Melan-A, and smooth muscle actin. Follow-up data were obtained from 47 of the total 75 pa-tients, through October 2020. Two patients had metastasis after surgery. Conclusions: AML is the most common type of hepatic PEComa. There are no specific symptoms of he-patic PEComa, and serological examinations and imaging modalities for accurate preoperative diagnosis are lacking. Epithelioid AML should be considered a tumor of uncertain malignant potential; however, the prognosis of PEComa af-ter resection is promising.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普