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Table of Content

    31 October 2021, Volume 26 Issue 10
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    Guideline and Consensus
    Expert consensus on antiviral therapy for HBV/HCV-related hepatocellular carcinoma:A 2021 update
    Liver Cancer Study Group,Chinese Society of Hepatology,Chinese Medical Association
    2021, 26(10):  1057-1068. 
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    With the development of anti-HBV and HCV therapy,experts in related fields organized by the Liver Cancer Study Group,Chinese Society of Hepatology,Chinese Medical Association updated “Experts Consensus on Antiviral Therapy for HBV/ HCV-related Hepato-cellular Carcinoma”.On the basis of previous expert recommendations/ consensus and the new evidence in recent years,this new consensus was developed,and the relevant recommendations are provided to hepatologists,epidemiologists,medical doctors and specialists working in community service centers and primary health care institutions for guidance of hepatocellular carcinoma antiviral treatment.
    Liver Cancer
    Efficacy of systemic drug therapy for postoperative recurrence of HBV related hepatocellular carcinoma
    ZHANG Yuan-jing, LI Ming-long, WANG Jun-xue, XIE Ying
    2021, 26(10):  1082-1086. 
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    Objective To investigate the efficacy and prognosis of systemic drug therapy in patients with tumor recurrence after radical resection of HBV-related liver cancer, and analyze its influencing factors. Methods For 43 patients who relapsed after radical resection of liver cancer were finally included, baseline demographic data and clinical data were collected. After receiving systemic drug treatment, the curative effect was evaluated based on the RECIST 1.1 standard; the COX regression model was used to analyze the PFS and PFS of HCC patients. Influencing factors of OS, the survival curve was drawn by Kaplan-Meier method. Results The curative effect evaluation results of the entire group of patients showed that there were 7 patients with PD, 10 patients were PR, and the remaining 26 patients were SD. Univariate analysis showed that HBV DNA-positive patients and patients with tumor stage BCLC C stage affected PFS (P<0.05). OS-based analysis showed that ascites HR (95% CI): 2.700 (1.058~6.889), P=0.038; HBV DNA positive HR (95% CI): 2.873 (1.030~8.012), P=0.044; AFP highly expressed HR (95% CI): 4.753 (1.404~16.086), P=0.012; tumor stage BCLC stage C HR (95% CI): 7.753 (2.365~25.414), P=0.001; these factors all reduce the patient's survival . Among them, patients with BCLC stage C before surgery have the worst prognosis and are independent risk factors. Conclusion Patients with ascites, HBV DNA-positive, and late preoperative tumor staging often indicate a poor prognosis for systemic drug therapy, suggesting that such patients should be actively treated with comprehensive systemic treatment after radical surgery to improve their prognosis.
    A clinical controlled study on RFA combined with hyperthermic perfusion TACE in the treatment of primary hepatocellular carcinoma
    JIANG Fu-qiang, LU Wei, YANG Jian, YANG Chao, DU Peng
    2021, 26(10):  1087-1090. 
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    Objective To investigate the efficacy of radiofrequency ablation (RFA) combined with transcatheter arterial chemoembolization (TACE) in the treatment of primary hepatocellular carcinoma (HCC). Methods Patients with HCC were randomly divided into observation group (treated with RFA combined with hyperthermic perfusion TACE) and control group (treated with RFA combined with conventional TACE). The serum levels of liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), tumor markers alpha fetoprotein (AFP), carbohydrate antigen 199 (CA199), angiogenesis factor hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), apoptosis molecules soluble factor associated suicide (sFas), soluble Fas ligand (sFasL) were detected before and 3 days after the operation, respectively. Results The serum levels of ALT, AST, GGT, sFas and sFasL increased, while the serum levels of AFP, CA199, HIF-1α, VEGF and bFGF decreased in both groups after operation (P<0.05). The serum levels of ALT (64.49 ± 12.72) U/L, AST (70.39 ± 11.38) U/L, GGT (128.69 ± 21.28) U/L of the observation group were not significantly different from those of the control goup, which the serum levels of ALT (66.12 ± 13.27) U/L, AST (71.12 ± 10.93) U/L, GGT (126.78 ± 25.82) U/L, (P>0.05). The serum levels of AFP (83.12 ± 13.82) ng/mL, CA199 (41.29 ± 8.14) U/L, HIF-1α (313.32 ± 62.39) pg/mL, VEGF (201.25 ± 42.94) pg/mL, bFGF (4.58 ± 0.72) pg/mL of the observation group were significantly lower than those of the control group, which the serum levels of AFP (113.28 ± 19.48) ng/mL, CA199 (58.35 ± 9.35) U/L, HIF-1α (394.58 ± 77.24) pg/mL, VEGF (262.44 ± 51.38) pg/mL, bFGF (6.51 ± 0.84) pg/mL. The serum levels of sFas (59.19 ± 9.44) ng/mL and sFasL (73.12 ± 12.57) ng/mL in observation group were higher than those in control group, which the serum levels of sFas (40.27 ± 8.15) ng/mL and sFasL (50.38 ± 9.24) ng/mL, (P<0.05). Conclusion The killing effect on tumor cells of RFA combined with hyperthermic perfusion TACE is better than that of RFA combined with conventional TACE in the treatment for HCC. The molecular mechanisms are inhibiting angiogenesis and promoting apoptosis.
    Therapeutic effect of lenvatinib combined with PD-1 inhibitor on unresectable large hepatocellular carcinoma after stereotactic body radiotherapy
    WANG Guo-xue, ZHANG Ai-min, WANG Quan, SUN Jing, LI Wen-gang, DUAN Xue-zhang
    2021, 26(10):  1091-1095. 
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    Objective To investigate the short-term efficacy and side effects of lenvatinib combined with PD-1 inhibitor in the treatment of unresectable large hepatocellular carcinoma (LHCC) after stereotactic body radiotherapy (SBRT). Methods Clinical data of 10 LHCC patients treated with lenvatinib combined with PD-1 inhibitor after SBRT were collected. Modified response evaluation criteria in solid tumors (mRECIST) was used to evaluate the therapeutic efficacy, and progression-free survival (PFS) was selected as the main endpoint of the study. Results Ten patients (100%) were responsive to the treatment, 7 (70%) achieved partial response, objective response rate (ORR) was 70%, and disease control rate reached 100%. No typical radiation-induced liver damage occurred, and Child-Pugh score increased in 6 cases (60%). Conclusion After SBRT, lenvatinib combined with PD-1 inhibitor has an ideal short-term efficacy in the treatment of unresectable LHCC, and the toxic and side effects are controllable.
    The utility of liver imaging report data system version 2018 in the diagnosis of small hepatocellular carcinoma ( ≤ 3 cm)
    LIANG Xu, LIU Yuan-yuan, YANG Xue-gang, REN Jing
    2021, 26(10):  1096-1098. 
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    Objective To investigate the efficiency of liver imaging report data system version 2018(LI-RADSv2108)in the diagnosis of small hepatocellular carcinoma (sHCC) and the consistency between LI-RADSv2108 and radiologists. Methods One hundred and fifteen patients admitted to our hospital from June 2017 to July 2020 were selected, including 89 HCC patients, 9 non-HCC malignant tumors and 17 benign lesions. The images were analyzed retrospectively with blind evaluation by 2 radiologists, and all the lesions were classified according to standard of LI-RADSv2108. The consistency of the conclusion drawn by the 2 radiologists was analyzed by Kappa statistic. Taking the postoperative pathological results as gold standard, the sensitivity, specificity and accuracy of the diagnositic conclusions drawn by the 2 radiologists using LI-RADSv2108 were calculated. McNemar test was performed for the differences. Results The consistency of the diagnositc results between the 2 radiologists was substantial, Kappa value was 0.748 (95% CI: 0.692-0.876). Using LR-5 as a predictor of sHCC, the sensitivity, specificity and accuracy of the diagnositic conclusion drawn by the 2 radiologists respectively using LI-RADSv2108 were 61.8%, 96.2%, 69.6% and 58.4%, 88.5%, 65.2%, respectively, with no significant difference (P>0.05); Using LR 4/5 as a predictor of sHCC, the sensitivity, specificity and accuracy were 78.8%, 80.8%, 79.1% and 78.8%, 65.4%, 75.6%, respectively, with no significant difference (P>0.05). Conclusion LI-RSDSv2018 has moderate sensitivity and high specificity in diagnosing sHCC and the consistency between LI-RADSv2108 and radiologists is good.
    Analysis on the value of contrast-enhanced ultrasonography in the diagnosis of hepatocellular carcinoma with portal vein thrombosis
    LIU Jia, HAO Li-jun, JIANG Wei, WANG Zhen-qi
    2021, 26(10):  1099-1102. 
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    Objective To evaluate the diagnostic value of contrast-enhanced ultrasound (CEUS) in hepatocellular carcinoma (HCC) patients with portal vein thrombosis (PVT). Methods Fifty-two HCC patients combined with PVT (35 males and 17 females) admitted to our hospital from January 2015 to September 2020 were retrospected, with an average age of (59.5 ± 8.6) years old. Thirty-eight were malignant PVT (malignant PVT group), including 32 males and 6 females, 14 were benign PVT (benign PVT group), including 9 males and 5 females. Measurement data were analyzed by t-test or Kruskal-Wallis H test; counting data were analyzed by chi-square test. Results The ages of malignant PVT group and benign PVT group were 58.0 ± 9.2 years and 63.1 ± 5.2 years, respectively, with statistical significance (t=4.104, P<0.05). The AFP levels of the 2 groups were 176.4 (13.8, 2150.4) ng/dl and 4.8 (2.2, 146.8) ng/dl, respectively, with statistical significance (Z=-40.146, P<0.05). The diameters of HCC lesions of the 2 groups were (8.8 ± 4.6) cm and (5.2 ± 4.7) cm, with statistical significance (t=-12.745, P<0.05). However, there was no significant difference in Child-Pugh score, number and location of HCC lesions between the two groups (P>0.05). The times to peak of the 2 groups were (48.3 ± 25.8) s and (80.6 ± 52.4) s, with statistical significance (t=17.540, P<0.05). The peak intensities of the 2 groups were (17.4 ± 5.0) dB and (12.5 ± 5.1) dB, with statistical significance (t=-11.745, P<0.05). The area under the curve (AUC) of the 2 groups were (2130.8 ± 721.6) dB/s and (1114.3 ± 816.7) dB/s, with statistical significance (t=-18.005, P<0.05). The rising times of the 2 groups were (16.6 ± 8.4) s and (8.6 ± 6.4) s, with statistical significance (t=-21.126, P < 0.05). The enhancement on arterial phase of the 2 groups were 36 cases (94.7%) and 8 cases (19.5%), with statistical significance (χ2=-11.107, P<0.05). The wash-out on delay phase of the 2 groups were 32 cases (84.2%) and 1 case (7.1%), with statistical significance (χ2=-26.205, P<0.05). The sensitivity, specificity and accuracy of CEUS in diagnosing malignant PVT were 89.5% (34/38), 100% (14/14) and 92.3% (48/52), respectively. Conclusion CEUS performs well in the differential diagnosis of PVT in HCC patients, which is worth promoting clinically.
    Enhanced CT findings and tumor diameter in patients with microvascular invasion of hepatocellular carcinoma
    SHENG Bao-hua, BI Teng-fei, WANG Hua-yu
    2021, 26(10):  1103-1106. 
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    Objective To investigate the enhanced computer tomography (CT) findings and tumor diameter in patients with microvascular invasion (MVI) of hepatocellular carcinoma (HCC). Methods The clinical data of 68 patients with HCC who received surgical treatment in our hospital from October 2017 to October 2020 were retrospectively analyzed. They were divided into invasion group (n=35) and non invasion group (n=33) according to whether complicated with vascular invasion. Enhanced CT findings (edge enhancement, tumor capsule, tumor classification, intratumoral artery, tumor number) and tumor diameter were compared between two groups. The differences between the 2 groups were included in the logistic regression analysis model to evaluate CT findings and tumor diameter and find risk factors of MVI in patients with HCC. Results The proportion of the existence of tumor capsule (66.67% vs 40.00%), single tumor focus (66.67% vs 22.86%), no intratumoral artery (60.61% vs 31.43%) and tumor diameter < 5 cm (66.67% vs 28.57%) of non invasion group were significantly higher than those of invasion group (P<0.05). Logistic regression analysis showed that the risk factors of MVI in patients with HCC were non-capsule or incomplete tumor capsule (β=1.864, P=0.034, 95%CI=1.154 ~ 36.073), non single tumor focus (β=0.984, P=0.022, 95%CI=1.154 ~ 6.196), intratumoral artery (β=1.494, P=0.040, 95%CI=1.074 ~ 18.488) and tumor diameter ≥5 cm (β=1.908, P=0.026, 95%CI=1.258~36.122). Conclusion Enhanced CT scan and tumor diameter observation have a high value in diagnosing MVI of patients with HCC before operation.
    Correlation between VEGFR expression level and therapeutic effect of TACE therapy in patients with advanced primary liver cancer
    YIN Xiao-dong, HOU Bo, LI Hai-yang, ZHANG Ming-lei
    2021, 26(10):  1107-1111. 
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    Objective To investigate the relationship between serum vascular endothelial growth factor receptor 2 (VEGFR-2), vascular endothelial growth factor receptor 3 (VEGFR-3) and curative effect in patients with advanced primary liver cancer of transcatheter arterial chemoembolization (TACE) therapy. Methods Seventy patients with advanced primary liver cancer who received TACE therapy from January 2017 to January 2019 in our hospital were selected. The serum VEGFR-2, VEGFR-3 expression levels of patients were detected 1 day before TACE and 7 days after TACE therapy, The relationship among VEGFR-2, VEGFR-3 and short-term efficacy, overall survival (OS) were analyzed. Results The reduction rates of VEGFR-2 (59.52%) and VEGFR-3 (57.14%) in patients with remission were higher than those in patients without remission (32.14%,57.14%, P<0.05). The rate of Child-Pugh B (77.8%), the rate of liver cirrhosis (55.6%), the tumor maximum diameter (4.69 ± 1.58) cm, the serum alpha fetoprotein (AFP) level [489.8 (452.9) μg/mL], and vascular endothelial growth factor (VEGF) level [(335.7 ± 55.8) pg/mL] of patients whose serum VEGFR-2 levels did not reduce were higher, compared with those of the patients whose serum VEGFR-2 levels reduced [47.1%, 26.5%, (3.89 ± 1.46) cm, 428.6 (389.5) μg/mL, (248.9 ± 46.9) pg/ml, the differences were statistically significant, P<0.05]. The rate of Child-Pugh B (85.3%), the rate of liver cirrhosis (55.9%), the tumor maximum diameter [(4.71 ± 1.67) cm], the serum AFP level [488.6 (462.0) μg/mL] and VEGF level [(322.9 ± 56.1) pg/mL] of patients whose serum VEGFR-3 levels did not reduce were higher, compared with those of the patients whose serum VEGFR-3 levels reduced (41.7%, 27.8%, (3.91 ± 1.39) cm, 431.5 (391.2) μg/mL, (253.6 ± 51.0) pg/mL, the differences were statistically significant, P<0.05). Patients were followed up from 15 to 34 months (23.9 ± 3.8 months on average), but 6 cases were lost. Kaplan-Meier method and Log-rank test showed that patients with reduced VEGFR-2 or VEGFR-3 had a higher cumulative OS rate than those without reduction (the differences were statistically significant, P<0.05). Receiver operator characteristic (ROC) curve showed that the serum levels of VEGFR-3 and VEGFR-2 had high value in predicting the survival of patients with primary liver cancer (area under the curve = 0.84, P=0.000, 95%CI=0.77-0.94), with a specificity of 72.3% and a sensitivity of 86.9%. Conclusion The changes on the preoperative and postoperative levels of VEGFR-2 and VEGFR-3 are related to prognosis in patients with advanced primary liver cancer treated by TACE. The serum levels of VEGFR-2 and VEGFR-3 can be used to predict the survival of patients and may become prognostic markers for advanced primary liver cancer.
    The predictive value of CT combined with CTCs and AFP in diagnosing microvascular invasion in hepatocellular carcinoma
    LI Chen-guang, DOU Wen-guang, FU Yi-bin, WU Qing-wu, YUE Jun-yan
    2021, 26(10):  1112-1114. 
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    Objective To investigate the value of computer tomography (CT) combined with circulating tumor cells (CTCs), and serum alpha fetoprotein (AFP) in predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Methods Ninety-two HCC patients who underwent radical resection in our hospital were selected, they were divided into MVI group (34 cases) and non MVI group (58 cases) according to postoperative pathological results. The clinical data of the 2 groups were compared. All patients underwent CT before operation, and the imaging data of the 2 groups were analyzed. The levels of CTCs and AFP were detected before operation. Risk factors of MVI in HCC patients were analyzed by multivariate analysis. Results The proportions of tumor diameter ≥ 5 cm, multinodular type, CTCs positive, serum AFP > 400 μg/L in MVI group were significantly higher than those in non MVI group, and the proportion of tumor capsule integrity was significantly lower than that in non MVI group (P<0.05); tumor diameter, nodule type, tumor capsule, CTCs and serum AFP levels were independent risk factors for MVI in HCC patients (P<0.05). Conclusion Tumor diameter, nodule type, tumor capsule, CTCs and serum AFP are independent risk factors for MVI in HCC patients. Therefore, CT combined with CTCs and AFP can be used to predict the presence of MVI in HCC patients before operation.
    Effects of 125I seed implantation combined with TIPS in the treatment of intrahepatic cholangiocarcinoma complicated by main portal vein tumor thrombus and portal hypertension
    LIU Nian, LIU Jing-wu
    2021, 26(10):  1115-1118. 
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    Objective To investigate the clinical effect of 125I seed implantation combined with transjugular intrahepatic portosystemic shunt (TIPS) in the treatment of intrahepatic cholangiocarcinoma complicated by main portal vein tumor thrombus (MPVTT) and portal hypertension. Methods Seventy-eight patients with intrahepatic cholangiocarcinoma and MPVTT combined with portal hypertension were selected in this study from January 2016 to December 2018. They were divided into a control group and a test group with 39 cases each by random number method. The patients in the control group was treated with TIPS surgery, while the patients in the test group was treated with 125I seed implantation in combination with TIPS surgery. The two groups of patients were compared for portal pressure before and after the treatment, the standard remission rate and total effective rate, the cumulative survival rate, cumulative restenosis rate of shunts, and symptom recurrence at 6 months, 12 months, and 24 months after surgery. Results After treatment, the portal pressure of the two groups of patients was significantly lower than those before treatment, and the portal pressure of the test group was significantly lower than that of the control group (P<0.05). The standard remission rate and total effective rate of the experimental group were significantly higher than those of the control group (P<0.05). At 6 months, 12 months, and 24 months after operation, the cumulative survival rate of the test group was significantly higher than that of the control group (P<0.05). At 6 months after operation, the cumulative restenosis rate and symptom recurrence rate of the test group were significantly lower than those of the control group (P<0.05). Conclusion 125I seed implantation combined with TIPS may significantly reduce the portal pressure in patients with intrahepatic cholangiocarcinoma and MPVTT and portal hypertension, stabilize tumor thrombus in portal trunk, and prolong the survival time of patients.
    A research on the relevance between Child-Pugh classification and CT perfusion imaging parameters of patients with hepatocellular carcinoma
    JING Changping, HAN Dong, LU Yang
    2021, 26(10):  1119-1122. 
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    Objective To study on the relationship between Computed Tomography perfusion imaging (CTPI) parameters and Child-Pugh classification in patients with hepatocellular carcinoma (HCC). Methods Seventy-six patients with HCC from March 2018 to March 2020 were included as the research objects. All patients underwent CTPI, parameters including hepatic arterial perfusion (HAP), portal venous perfusion (PVP), mean transit time (MTT), hepatic arterial perfusion index (HAPI) were recorded. The relationship between these CTPI parameters and Child-pugh grades of the patients was analyzed. Results In these 76 patients, there were 38 cases with Child-pugh grade A, 24 cases with grade B, and 14 cases with grade C. Significant differences were found in the levels of HAP, PVP, MTT and HAPI in patients with different Child-pugh grades (P<0.05). The HAP and HAPI of grade C patients were significantly higher than those of Grade A and B, while the PVP and MTT were significantly lower than those of Grade A (P<0.05). The Pearson correlation analysis showed that the CTPI parameters such as the HAP and HAPI were positively correlated with child Pugh classification (P<0.05), whereas MTT and PVP were negatively correlated with child Pugh grades (P<0.05). The receiver operator characteristic curve (ROC) analysis showed that the HAP (AUC=0.727, 95%CI=0.562-0.892, P=0.013), PVP (AUC=0.703, 95%CI=0.574-0.832, P=0.026), MTT (AUC=0.747, 95%CI=0.601-0.894, P=0.007), HAPI (AUC=0.694, 95%CI=0.506-0.882, P=0.034) had certain value in judging Child-pugh grade C. The AUC of joint probability to predict Child-pugh C was 0.815 (95%CI=0.689-0.942, P=0.001). Conclusion The CTPI parameters are closely related to Child-pugh classification in HCC patients. CTPI parameters are helpful to predict the Child-pugh classification and provide a basis for clinical intervention.
    The expression and mechanism of α-1,3-fucosyltransferase IV in liver cancer metastasis
    NI Lei, GUO Jian, YU Xue, ZHANG Ning, HAN Yi-ying, YANG Yu-ai, YANG Jian-ren, LI Chun-rui, JIA Juan, LIU Tian-hua
    2021, 26(10):  1123-1127. 
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    Objective To investigate the expression and mechanism of α-1,3-fucosyltransferase IV in liver cancer metastasis. Methods The expression of FUT4 in liver cancer cell lines exhibiting different metastatic potentials was detected by quantitative Real-time PCR (qRT-PCR). The epithelial-mesenchymal transition (EMT) model was established by stimulating human liver cancer cell line MHCC97L with transforming growth factor-β1 (TGF-β1). Morphologic change was observed by phase-contrast microscope. The expression of mRNAs and proteins of EMT markers were detected by qRT-PCR and Western blot, respectively. The expression of FUT4 was detected by qRT-PCR. The expression levels and co-expression genes of FUT4 in primary liver cancer samples with and without metastasis were investigated using Human Cancer Metastasis Database (HCMDB). Enrichment analysis of KEGG pathways was performed by OmicsBean. Results The mRNA expression levels of FUT4 were significantly upregulated in MHCC97H and HCCLM3, two liver cancer cell lines exhibited high metastatic potential, when compared with liver cancer cell line, MHCC97L, which exhibited low metastatic potential (P<0.01), fold changes were 4.99 and 6.08, respectively. After TGF-β1 treatment, MHCC97L cells were spindle-shaped and the mRNA expression of E-cadherin was significantly reduced (P<0.001), however, the mRNA expressions of N-cadherin and vimentin were significantly increased (P<0.001). The proteins' expression of EMT markers were in parallel as the mRNAs' expression. FUT4 was overexpressed in TGF-β1-induced EMT model in MHCC97L when compared with that of the control (P<0.01), the fold change was 1.42. Bioinformatics analysis results further confirmed that mRNA expression level of FUT4 was significantly upregulated in primary liver cancer samples with metastasis compared with those without metastasis (P<0.01), suggesting that FUT4 might participate in the liver cancer metastasis and programmed by the co-expressing genes belonging to KEGG pathways such as transcriptional mis-regulation in cancer, regulation of actin cytoskeleton, and ECM-receptor interaction. Conclusion These findings not only suggest that high-level expression of FUT4 is closely related to EMT and metastasis of liver cancer, but also provide an insight on using FUT4 as a potential biomarker and target for the diagnosis and treatment of liver cancer metastasis.
    The use of contrast-enhanced ultrasound in diagnosing canceration nodules in cirrhotic liver and small hepatocellular carcinoma
    GAO Jie, WANG Ke, ZHANG Na, LIU Xiao-ge
    2021, 26(10):  1128-1131. 
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    Objective To investigate the efficacy of contrast-enhanced ultrasound (CEUS) in diagnosing canceration nodules (CN) in cirrhotic liver and small hepatocellular carcinoma (sHCC). Methods One hundred and twenty-seven patients with liver cirrhotic nodules from February 2018 to February 2020 were included as the research objects. In all patients pathological evaluation of the liver nodules achieved by ultrasound-guided biopsy were recorded as the gold standard, including CN, low-grade dysplastic nodules (LGDN), high-grade dysplastic nodules (HGDN) and sHCC. The characteristics of CEUS in different pathological stages were compared. The accuracy of CEUS in judging the pathological type of CN canceration and sHCC were analyzed. Results The 127 patients were followed up for 8 to 32 months with an average period of time of (16.6±5.4) months. The liver biopsy results showed that there were 38 cases of CN, 32 cases of LGDN, 26 cases of HGDN and 31 cases of sHCC among the 127 patients. The time to peak (TTP)of CN, LGDN, HGDN and sHCC groups were (44.6±13.2)s, (38.4±10.9)s, (30.5±9.0)s and (23.8±8.5)s, respectively(P<0.05), the mean transit time (MTT) were (141.0±35.4)s, (130.4±29.8)s, (117.3±30.2)s and (109.5±27.4)s, P<0.05, the rise time (RT) were (40.6±11.2)s, (35.4±7.7)s, (31.2±9.3)s and (22.1±8.7)s, P<0.05. The CEUS examination showed that the CN perfusion mode (31 cases in stage IV, 5 cases in stage V, 2 cases in stage VI and 1 case in stage VII), LGDN (4 cases in stage V, 24 cases in stage VI, 3 cases in stage VII and 1 case in stage VIII), HGDN(23 cases in stage VI and 3 cases in stage VII), sHCC (24 cases in stage 1, 2 cases in stage II and 5 cases in stage III). The difference of CEUS perfusion mode were statistically significant in different pathological stages (P<0.05). The ROC analysis showed that the TTP (AUC=0.642, 95%CI=0.526～0.758), MTT (AUC=0.651, 95%CI=0.536～0.766) and RT (AUC=0.716, 95%CI=0.606～0.826) had certain application value in judging sHCC (P<0.05). The AUC of sHCC was 0.802 of joint prediction probability of TTP, MTT and RT (SE=0.047, 95%CI=0.710～0.895, P<0.05), the sensitivity was 0.935 and the specificity was 0.561. Conclusion The CEUS can effectively identify the pathological process of CN, and the CEUS examination is helpful for the early detection of sHCC.
    A study on the expression level of somatostatin in liver cancer-associated fibroblasts and its impact on the prognosis of patients
    ZHENG Qian-jing, LIU Ya-fei, QUE Ying-zhao, YU Wei-hua
    2021, 26(10):  1132-1136. 
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    Objective To investigate the level of somatostatin (SST) in liver cancer-associated fibroblasts (CAFs) and its association with the prognosis of hepatocellular carcinoma (HCC) patients, as well as the underling mechanism. Methods Eight-three HCC patients underwent operation were randomly collected in this study. The levels of α-smooth muscle actin (α-SMA), vimentin and SST in isolated CAFs and normal fibroblasts (NFs) from the HCC and adjacent non-cancerous tissues respectively were detected using quantitative reverse transcription PCR (RT-qPCR). The relationship between SST and clinicopathological parameters and the prognosis of HCC patients was analyzed. After transfection of CAFs with SST overexpression plasmid, the supernatant was taken to co-culture with Huh7, a hepatoma cell line. Cell proliferation, invasion and Wnt/β-catenin pathway-related protein levels of Huh7 cells were determined with CCK-8 assay, Transwell assay, and Western blot, respectively. Enzyme-linked immunosorbent assay (ELISA) was conducted to detect the content of chemokines in the supernatant of CAFs-cultured Huh7 cells medium. Kaplan-Meier method was used to evaluate the association of SST with the survival rate of the HCC patients. Results Compared with NFs, the expression of α-SMA (2.87±0.091) and Vimentin (2.93±0.085) were significantly increased in CAFs, while the level of SST (0.328±0.073) was significantly decreased (t=26.441, P=0.001; t=30.886, P=0.001; t=11.197, P=0.001, respectively). The analysis of clinicopathological features showed that the expression of SST was related to TNM stage, lymph node metastasis and tissue differentiation degree in HCC patients, all of which had statistically significant (χ2=5.562, P=0.001; χ2=24.688, P=0.001; χ2=18.685, P=0.001). The supernatant of culture medium of CAFs significantly promoted the proliferation and invasion of Huh7 cells, whereas the supernatant of culture medium of SST-overexpressed CAFs inhibited the proliferation and invasion of Huh7. ELISA results showed that the levels of chemokine CCL2, CCL5, CXCL21 and CXCL 25 in the supernatant of CAFs were significantly different when compared with those of NFs (98.50±3.98, 78.32±4.21 24.32±5.11, and 20.34±4.77pg/mL, vs. 3.2±5.36, 1.40±4.35, 1.02±4.67, and 1.11±5.01, respectively. F=78.324, P=0.001; F=53.611, P=0.001; F=32.847, P=0.001; F=25.635, P=0.001). After overexpression of SST, the expression levels of these chemokines and proteins related to Wnt/β-catenin signaling pathway were markedly suppressed (F=15.951, P=0.001; F=13.806, P=0.001; F=17.824, P=0.001; F=18.347, P=0.001). The progression-free survival (χ2=4.679, P=0.031) and overall survival (χ2=4.304, P=0.038) rates of HCC patients with high SST expression were higher than those of patients with low SST expression. Conclusion The expression of SST was down-regulated in CAFs and associated with the prognosis of HCC patients. The supernatant of CAFs transfected with pcDNA-SST inhibited the proliferation and invasion of hepatoma cells by inhibiting chemokines secretion and Wnt/β-catenin signaling pathway.
    LncRNA-NEF transcriptionally activates FOXA2 and inhibits epithelial–mesenchymal transition of hepatocellular carcinoma cells by inhibiting β-catenin signaling pathway
    CHE Jun, YANG Liu-qing, SUN Bin, JIA Ze-bo
    2021, 26(10):  1137-1141. 
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    Objective To explore the molecular mechanism of long-chain non-coding RNA-neighboring enhancer of FOXA2 (lncRNA-NEF) on the epithelial-mesenchymal transition (EMT) process of hepatocellular carcinoma (HCC), a key step in liver cancer metastasis. Methods HCC line Hep3B was treated with transforming growth factor-β (TGF-β) to induce EMT. A pcDNA3.1-FOXA2 overexpression vector was constructed and transduced into another HCC line HepG2 to overexpress FOXA2 and induce mesenchymal-epithelial transition (MET). The EMT-related markers including E-cadherin, Vimentin and Snail were detected and cell invasion assay was performed in these lines with and without relative treatment. The expression of lncRNA-NEF was determined in 10 paired operated liver cancer tissues and adjacent normal tissues, as well as in the HCC lines. Subsequently, the protein expression of factors related to β-catenin signaling pathway before and after EMT or MET transformation in the HCC lines were detected. Results The expression level of lncRNA-NEF in liver cancer tissues and HCC lines was lower than that in normal controls (P<0.05). Compared with the control cells, the cell invasion ability of TGF-β treated HCC cells significantly enhanced (P<0.05), but the cell invasion ability of PCDNA3.1-FOXA2 transduced cells significantly reduced (P<0.05). The expression level of phosphorylated β-catenin (p-β-catenin) in Hep3B cells treated with TGF-β increased significantly when compared with the control cells. On the contrary, the expression level of phosphorylated β-catenin (P-β-catenin) in HepG2 cells transfected with PCDNA3.1-FoxA2 significantly decreased. The level of total β-catenin protein remained unchanged in both HCC lines with and without relative treatment. LncRNA-NEF activated FOXA2 in a cis-acting manner, and inhibited the EMT process of liver cancer cells by inhibiting the β-catenin signaling pathway. Conclusion LncRNA-NEF activates FOXA2 transcription and inhibits the EMT process of liver cancer cells by inhibiting the β-catenin signaling pathway.
    Liver Fibrosis & Cirrhosis
    The effect of optimized antiviral therapy on T cell immunity and cytokines levels in hepatitis B-related cirrhotic patients
    GAO De-yong, LOU Xiao-li, MA Shuang, ZHANG Kun-lun, LIU Liang-ming, LIU Hong-xiang
    2021, 26(10):  1142-1145. 
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    Objective To investigate the effect of optimized antiviral treatment with nucleoside (acid) analog tenofovir disoproxil fumarate on hepatitis B-related cirrhotic patients and its influence on peripheral blood T lymphocyte subsets and cytokines levels. Methods Thirty-six patients with chronic hepatitis B-related liver cirrhosis admitted from January 2017 to December 2018 were selected as the observation group. Thirty cases of healthy physical examination population during the same time period were selected as the control group. Clinical indicators such as liver and kidney function, HBV-DNA load in the observation group before and after treatment were collected and analyzed. The levels of T lymphocyte subsets and cytokines levels including IL-2, IFN-γ, IL-4 and IL-10 were detected and compared between these two groups. Results After antiviral treatment, the level of alanine aminotransferase (ALT) in the observation group was significantly improved than that of before treatment (tALT=13.728, P<0.05), without significant alteration in renal function. The negative change rate of HBV DNA titer was 100%. Although the percentage of CD3+ cells (68.6±12.3) and CD4+ cells (40.6±9.3), and the ratio of CD4+/CD8+ (1.3±0.6) in the observation group after anti-viral treatment were significantly increased (tCD3+=9.382, tCD4+=14.175, tCD4+/CD8+=9.753, P<0.05), the levels were still lower than those of the control group (tCD3+=4.947, tCD4+=6.598, tCD4+/CD8+=7.329,P<0.05); On the contrary, the percentage of CD8+ cells in the observation group (30.3±6.2) was significantly lower than that of before treatment (tCD8+=12.368, P<0.05), but still higher than that in the control group (tCD8+=5.986, P<0.05). Serum anti-Th1 cell cytokines IL-2 (32.24±16.55pg/ml) and IFN-γ (9.08±5.23 pg/ml) levels in patients of the observation group were significantly lower after TDF treatment (tIL-2=7.615, tIFN-γ=18.763, P<0.05), but higher than that of the control group (tIL-2=5.784, tIFN-γ=13.643, P<0.05); The cytokine IL-4 (45.90±18.27 pg/mL) and IL-10 (19.85±5.63 pg/mL) levels of Th2 cells in the observation group were significantly higher than those of before treatment (tIL-4=11.249,tIL-10=17.452, P<0.05), but still significantly lower than that of the control group (tIL-4=10.476, tIL-10=9.415, P<0.05). Conclusion Antiviral therapy with TDF effectively improves liver function and reduces HBV DNA viral load in patients with hepatitis B-related liver cirrhosis. The treatment restores immune function and has a significant impact on the serum levels of immunological cytokines in the patients.
    Prediction of recurrence of esophageal varices after esophageal variceal ligation in patients with hepatitis B cirrhosis by endoscopic ultrasonography
    WU Jing-jing, DONG Jia-zhong, WANG Li-hui
    2021, 26(10):  1146-1149. 
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    Objective Endoscopic ultrasonography (EUS) was used to predict the recurrence of esophageal varices after esophageal variceal ligation (EVL) in patients with hepatitis B liver cirrhosis (LC), so as to effectively evaluate the prognosis of the patients. Methods A total of 116 LC patients treated with EVL from January 2016 to September 2019 were reviewed, including 38 patients with recurrence (29 males and 9 females) and 78 patients without recurrence (52 males and 26 females). T-test was used for measurement data, chi-square test was used for counting data, and Logistic regression analysis was used to explore the influencing factors of EVL recurrence. Results The Child-Pugh scores in EVL recurrent group and non-recurrent group were (8.5±3.2) points and (6.5±3.0) points respectively, and the difference was statistically significant (t=8.980, P<0.05). The EV degrees of F2 and F3 in recurrent group were 20 cases (52.6%) and 18 cases (44.4%), respectively, while those in non-recurrent group were 63 cases (80.8%) and 15 cases (19.2%) respectively, and the difference was statistically significant (χ2=-4.244, P<0.05). The diameters of EV, para-esophageal collateral vein and communicating vein in recurrent group were (10.1±2.5) mm, (9.1±2.4) mm and (3.5±0.6) mm, respectively, compared with those in non-recurrent group [(8.2±2.3) mm, (7.0±1.7) mm and (3.0±0.5) mm], the difference was statistically significant (t=10.548, 10.246, 4.405, P<0.05). There was no significant difference in splenomegaly, PLT and the number of communicating branches between the two groups. The above statistically different indicators were included in multivariate analysis. The results showed that Child-Pugh score, the diameter of para-esophageal collateral vein and the maximum diameter of communicating vein were independent risk factors for the recurrence of EVL, while the degree of EV, gastric varices and EV diameter were not independent risk factors for the recurrence of EVL. The sensitivity, specificity and accuracy of EUS in the diagnosis of EVL recurrence were 81.6% (31/38), 92.3% (72/78) and 88.8% (103/116), respectively. Conclusion EUS could accurately predict the recurrence of LC patients after EVL. For patients with poor Child-Pugh score, abnormal diameter of para-esophageal collateral vein and maximum diameter of communicating vein, it is necessary to pay attention and formulate reasonable treatment strategies.
    Viral Hepatitis
    Diagnostic value of serum pregenomic RNA in hepatitis B virus-infected patients with different clinical outcomes
    MA Hai-xia, ZHAO Li-ping, CHEN Wen-jie, HU Wei-hong, ZHANG Shi-kun
    2021, 26(10):  1150-1153. 
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    Objective To assess the diagnostic value of serum pgRNA in patients with different clinical outcomes after HBV infection and its relevance with serum-related parameters. Methods This study recruited 210 HBV-infected patients treated with nucleoside analogues, classified as asymptomatic carriers (ASC), chronic hepatitis B (CHB), and cirrhosis (LC) according to different outcomes, each group with 70 cases. The difference of pgRNA levels among each group was compared and their correlation with HBV DNA and HbsAg was evaluated. Results HBV pgRNA levels were significantly different among these three groups. HBV pgRNA levels were significantly correlated with serum HBV DNA and HBsAg Levels (HBV pgRNA and HBV DNA: R=0.613, P<0.001; HBV pgRNA and HbsAg: R=0.503, P<0.001). Of the patients with HBV DNA levels <500 IU/mL, 72.8% were HBV pgRNA positive and 17.6% of patients were still positive in patients with DNA below 20 IU/mL. Conclusion Serum HBV pgRNA level was a proper marker reflecting viral replication in hepatocytes. HBV pgRNA levels was helpful in the monitor of cccDNA levels.
    Efficacy of ribavirin combined with sofbuvir and dalatavir in the treatment of chronic hepatitis C with low viral load genotype 1b
    ZHOU Jing, LU Yu-hong, WANG Xin
    2021, 26(10):  1154-1156. 
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    Objective To study the efficacy of ribavirin combined with sofbuvir and dalatavir in the treatment of genotype 1b low viral load chronic hepatitis C. Methods From August 2018 to August 2020, 90 patients with chronic HCV infection due to low viral load of genotype 1b in our hospital were randomly divided into group A and group B, with 45 cases in each group, Group A was treated with conventional ribavirin combined with subcutaneous injection of ethylene glycol interferon α, and group B was treated with sothibuvir combined with dalatavir on the basis of conventional ribavirin combined with subcutaneous injection of ethylene glycol interferon α, The levels of alanine aminotransferase (ALT), total bilirubin (TBIL) and aspartate aminotransferase (AST) before and after treatment were compared between the two groups, and the incidence of adverse reactions during treatment was compared between the two groups. Results There was no significant difference in the negative rate of HCV-RNA (62.22%vs66.67%,86.67%vs91.11%,93.33%vs93.33%)and the incidence of SVR(91.11%vs93.33%,84.44%vs88.89%,80.00%vs86.67%) between the two groups at each time point (P>0.05); the negative rate of HCV-RNA(86.67%、93.33%vs62.22,91.11%、93.33%vs66.67%) in the two groups at 8 weeks and 12 weeks of treatment was significantly higher than that at 4 weeks of treatment, and the difference was statistically significant (P<0.05).After treatment, AST [(27.56±4.32)U/L]and ALT[(35.42±6.71)U/L] in group B were significantly lower than those before treatment[(72.58±6.43)U/L、(117.58±15.46)U/L] and the group A[(31.25±5.34)U/L、(42.38±5.47)U/L], the difference was statistically significant (P<0.05); TBil in two groups after treatment[(18.54±2.34)、(18.16±2.54)μmol/L] was significantly lower than that before treatment[(20.46±4.31)、(20.53±4.38)μmol/L], the difference was statistically significant (P<0.05).The total incidence of adverse reactions in group A was 31.11%, which was not significantly different from 46.67% in group B (P>0.05). Conclusion Ribavirin combined with sofbuvir and dalatavir has good clinical efficacy in the treatment of genotype 1b low viral load chronic hepatitis C.
       
    Other Liver Diseases
    Investigation on the prevalence and risk factors of fatty liver disease in 2961 in-service medical staff
    LI Xiao-he, LIU Hui-xin, CHEN Hong-song, RAO Hui-ying
    2021, 26(10):  1157-1162. 
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    Objective To investigate the prevalence, distribution and risk factors of fatty liver disease (FLD) of in-service medical staff. Methods A cross-sectional study was designed to collect the physical examination results of medical staff in a large general hospital in Beijing from July to August 2019. The relationship between age, gender, metabolic factors and FLD were analyzed. Univariate and multivariate logistic regression were used to analyze the influencing factors of FLD. Results Prevalence rate of FLD was 22.32 (661/2961), with 48.09% (290/603) in male and 15.73% (371/2357) in female(χ2=289.98,P<0.001). The prevalence rates of male aged 20-29, 30-39, 40-49 and ≥ 50 years old were 34.5%(35/110), 46.9%(105/224), 55.1% (70/127) and 56.3% (80/142), respectively (χ2=202.30, P<0.001), with significant higher incidence than women in each age group, 5.5% (38/632), 12.0% (110/914), 21.7% (117/538) and 38.8%(106/273), all P value＜0.001. The prevalence of moderate to severe FLD was about 5% (38/632), with male (12.11%, 73/603) more than female (3.18%, 75/2357) (χ2=80.56, P<0.001). Age, gender, overweight/ obesity, FBG ≥ 7.0 mmol/L, dyslipidemia, hypertension and hyperuricemia were all influential factors for FLD (all P<0.05). After stratification for age, overweight/obesity (OR 3.92-13.54) and hypertriglyceridemia (OR 2.91-3.67) were risk factors in all groups of age. Compared with normal level of uric acid populations, staffs with hyperuricemia were at an increased risk for FLD by 7.28 (95%CI: 3.92-13.54) fold and 2.01 (95%CI: 1.34-3.03) fold in group 20-29 and 30-39 years old,respectively. The risk increased about 4.3-and 2-fold in group of 40-49 and ≥50 years old (P<0.01) due to diabetes. Conclusion The prevalence of FLD in serving medical staffs in Beijing was increased with age, and men tend to have a higher prevalence rate than women. Overweight/obesity, hyperuricemia, abnormal glucose metabolism, hypertension and dyslipidemia were major causes of FLD.
    Application of PTCD sequential percutaneous nephroscopy in the treatment of refractory liver abscess after interventional therapy
    DUAN Chang-hu, LIU Xiao-chen, DING Jian-long, DUAN Jian-feng
    2021, 26(10):  1163-1166. 
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    Objective To investigate the application of percutaneous transhepatic cholangial drainage sequential percutaneous nephroscope in the treatment of refractory liver abscess after hepatic artery intervention. Methods Retrospective analysis of 5 patients with refractory hepatic abscess after transcatheter arterial chemoembolization (TACE) in our hospital from January 2018 to March 2021 (a case of hepatic abscess caused by TACE in hepatic metastases after pancreaticoduodenectomy, a case of hepatic abscess caused by repeated TACE for massive hepatocellular carcinoma, two cases of hepatic abscess caused by TACE for traumatic hepatic rupture, a case of liver abscess after interventional treatment of metastatic tumor in right lobe of liver after operation of colon cancer). We reviewed the effect of refractory liver abscess by PTCD and sequential percutaneous nephroscope. Results Blood routine, procalcitonin, liver and kidney function, coagulation, blood culture and abdominal enhanced CT were performed in all 5 patients, combined with the clinical manifestations, and the diagnosis of liver abscess was clear. Conventional interventional ultrasound or CT guided puncture catheter irrigation and drainage, combined with sensitive antibiotics anti-infection treatment, the curative effect was not good. Then sequential percutaneous nephroscope was used to remove the necrotic tissue of liver abscess and drainage, 5 cases of refractory liver abscess were cured, the effect was good. Conclusion In view of the refractory liver abscess after interventional operation, when the effect of irrigation and drainage by puncture and catheter is not good, and it is unable or difficult to tolerate surgical operation, PTCD sequential percutaneous nephroscope is an effective alternative for the treatment of liver abscess necrosis tissue removal and drainage.
    Analysis of 80 cases of hepatic echinococcosis treated by radical operation in Tibetan area
    YU Yan-bin, ZHUANG Yun-long, LI Li-xin, WANG Hong-bo
    2021, 26(10):  1167-1169. 
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    Objective To summarize the clinical data of hepatic echinococcosis treated by radical operation, and to provide the corresponding clinical data for improving the treatment level of hepatic echinococcosis. Methods The preoperative, intraoperative and postoperative clinical data of 80 patients with hepatic echinococcosis undergoing radical surgery in Tibetan area from 2016 to 2019 were comprehensively analyzed, and the relevant surgical methods and therapeutic effects were discussed. Results 80 patients were treated with radical operation in our hospital, and good results were obtained. There were 78 cases with preoperative liver function rating of Grade A, accounting for 97.5%, and 2 cases with grade B, accounting for 2.5%. There were 62 cases with the number of lesions ≤ 3, accounting for 77.5%, and 18 cases with multiple lesions, accounting for 22.5%. The incidence of bile duct invasion, vascular invasion, extrahepatic involvement and other organs were 2.5%, 18.75%, 26.25% and 11.25%, respectively. The average operative time was 343 min, the average intraoperative blood loss was 390 ml, the average drainage time was 7.9 d, and the average hospital stay was 27.5 d. The recurrence rate of complications was 21.25%, mainly fat liquefaction (14 cases) and bile leakage (3 cases), which were properly treated in the later stage. Conclusion The radical operation of liver echinococcosis has achieved good clinical effect.
    Factors affecting the clinical outcomes of patients with gynura segetum induced sinusoidal obstruction syndrome
    SHAO You-lin, Zhang Suo-cai, Wu Jian-ming, XIE Jing, LONG Chun-mei, ZHENG Ting-ting, LIU Long-gen
    2021, 26(10):  1170-1175. 
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    Objective To investigate the factors affecting the clinical outcomes of patients with gynura segetum induced hepatic sinusoidal obstructive syndrome (gynura segetum-HSOS). Methods The patients were divided into survival group (n=37) and death group (n=18) according to the 120-day clinical outcomes. The medical history, clinical manifestations, laboratory examinations, iMELD scores and treatments were analyzed. Kalpan-meier survival curve was used to analyze the relationship between the use of low molecular weight heparin sodium and 120-day prognostic of gynura segetum-HSOS patients. Cox regression analysis was used to analyze the affecting factors of patients' 120-day prognostic, and AUROC was used to analyze the predictive power of relevant factors. Results ① The daily dose and durations of patients taking gynura segetum were with huge differences. There was no significant difference between both groups in the length of main complaint, the length of gynura segetum intake and the days from taking gynura segetum to onset. ② The most common symptoms of patients with gynura segetum-HSOS were fatigue (96.36%), loss of appetite (96.36%), abdominal distension (98.18%), and reduced urine output (98.18%), and there was no statistical difference between the two groups. ③ In the death group, serum TBIL, DBIL, TBA, WBC, Hb, INR, D-D dimer levels and iMELD were significantly higher than those in the survival group, but CHOL was lower. ④ Kalpan-meier survival curve analysis showed patients treated with low molecular weight heparin sodium had a higher 120-day survival rate (P=0.0061). ⑤ The results of multivariate analyzed by Cox regression analysis revealed that reduced urine output, liver palm/spider angioma, low molecular weight heparin sodium, CHOL, Hb, iMELD were associated with clinical outcomes in patients with gynura segetum-HSOS. The AUROC of combined predictor which obtained based on the integration of iMELD, Hb, CHOL, low molecular weight heparin sodium and liver palm/spider angioma was 0.91 (95% CI: 0.83-0.99). Conclusion Application of low molecular weight heparin sodium was beneficial for the 120-day survival rate in patients with gynura segetum-HSOS. The combined predictor may be a useful predictor of the 120-day prognosis of patients with gynura segetum-HSOS.