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    30 April 2024, Volume 29 Issue 4
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    Liver Cancer
    The relationship between central obesity and hepatocellular carcinoma: a Mendelian randomization study
    XU Shan-shan, QIU Li-xia, LIU Ya-li, ZHANG Jing
    2024, 29(4):  387-390. 
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    Objective The relationship between central obesity and hepatocellular carcinoma (HCC) is not completely clear. This study aimed to explore the potential causal associations between central obesity and HCC using Mendelian randomization analysis. Methods Two-sample Mendelian randomization analysis was conducted on the collected data in this study. Genome wide association study (GWAS) data with waist circumference, waist circumference adjusted by body mass index (WCadjBMI), hip circumference, hip circumference adjusted by BMI (HCadjBMI), waist-to-hip ratio and waist-to-hip ratio adjusted by BMI (WHRadjBMI) were obtained from a large-scale database containing 224,459 samples. The visceral fat volume dataset was derived from a European database which included information of 9,275,407 single nucleotide polymorphism (SNP) sites in 32,860 European subjects. The data set for HCC was drawn from the UK Biobank (UKB) database and included aggregated data from 372,184 European subjects. Results Inverse variance weighting (IVW) analysis showed that WCadjBMI increased the risk of HCC (OR=1.001, 95%CI (1.000, 1.001), P=0.024). This was confirmed by weighted median (WM) analysis (OR=1.001, 95%CI (1.000, 1.002), P=0.020), but not by MR-Egger regression analysis (OR=1.002, 95%CI (0.999, 1.004), P=0.135). Other indicators of central obesity were not associated with HCC. Conclusion There exists difference in the abilities of different central obesity indicators to impact on HCC. WCadjBMI may contribute to HCC development, suggesting that in a relatively thin population, central obesity is associated with HCC development with a causal relationship.
    The value of perfluorobutane contrast-enhanced ultrasound for the diagnosis of hepatocellular carcinoma
    LIU Ting, YANG Jin-yu, LIU Qian-yu, YANY Qing
    2024, 29(4):  391-394. 
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    Objective To investigate the diagnostic performance and clinical application value of perfluorobutane contrast-enhanced Ultrasound (CEUS) for hepatocellular carcinoma (HCC). Methods The imaging data of high-risk patients with liver cancer who underwent perfluorobutane CEUS from October 2021 to July 2023 were retrospectively analyzed. The enhancement pattern, regression time and degree of the lesions in vascular phase, and the regression of the lesions in Kupffer phase were observed. In this study, HCC was diagnosed by the following two methods: (1) Arterial phase hyperenhancement (APHE) with delayed /mild washout, which was defined by the 5 categories criteria of contrast-enhanced Ultrasound Liver Imaging Reporting and Data System (CEUS LI-RADS); (2) Hypoenhancement in posterior vascular phase was taken the place of delayed or mild washout, and hyperenhancement in arterial phase (APHE) with hypoenhancement in posterior vascular phase was used as the diagnostic criteria. With the pathological results and imaging follow-up as the golden standard. The diagnostic efficacy of the two methods for diagnosing HCC was analyzed. Results There were 65 malignant lesions in 84 patients, including 55 HCC lesions. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value and Youden index of CEUS LR-5 category for HCC were 76.3%, 93.1%, 82.1%, 95.5%, 67.5% and 0.695, respectively. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value and Youden index of APHE combined with hypoenhancement of posterior vascular phase were 81.8%, 93.1%, 85.7%, 95.7%, 73.0% and 0.749, respectively. The sensitivity of APHE combined with Kupffer phase was significantly increased (χ2=11.58, P<0.05). Compared with the golden standard, the differences between the two diagnostic methods were statistically significant (P<0.05). Conclusion The combination of high arterial phase enhancement (APHE) and low vascular phase enhancement has a higher sensitivity for the diagnosis of HCC. The unique Kupffer phase of perfluorobutane may improve the detection rate of early HCC and provide more information in non-invasive diagnosis of HCC.
    An evaluation on the efficacy and safety of carrilizumab on tumor progression of unresectable hepatocellular carcinoma after DTACE surgery
    CHANG Dong-dong, YIN Rong-hua, ZHANG Yan, ZHOU Rui
    2024, 29(4):  395-399. 
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    Objective To investigate the efficacy and safety of carrellizumab on tumor progression in patients with unresectable hepatocellular carcinoma (HCC) after the treatment of drug-loaded microspheres of hepatic artery chemoembolization (DTACE) and sorafenib. Methods Fifty-six advanced patients with unresectable HCC treated with DTACE in combination with sorafenib from January 2020 to December 2021 in Haian People’s Hospital and Wuhan Fourth Hospital were selected and randomly divided into an observation group and a control group. The control group continually received DTACE treatment in combination with sorafenib. The observation group was additionally treated with carrilizumab. All with intolerable TRAE, or disease re-progression, or follow-up till deadline as the course of treatment. Both groups of patients were observed and compared about their objective response rate (ORR) and disease control rate (DCR) in 3 months after treatment, their overall survival (OS) and progression-free survival (PFS) at follow-up deadline, the changes in tumor markers and liver function indicators before and after the treatments, and the incidence of chemotherapy-related adverse events (TRAE). Results In three months after treatment, the conversion operation rate, ORR, DCR, OS and PFS in the observation group were 17.86%, 57.14%, 82.14%, 13.83±2.24 months and 8.38±1.56 months, respectively, which were higher than those of 7.14%, 35.71%, 60.71%, 9.75±1.79 months and 6.36±1.27 months in the control group, with statistical significance (χ2=4.039, 3.853, 3.481, t=8.273, 8.015, all P<0.05). After 3 months of treatment, the serum levels of alpha-fetoprotein anisoplast 3 (AFP-L3), α-L-fucoidase (AFU) and tumor-specific growth factor (TSGF) in the observation group were 47.19±11.84 mg/L, 34.39±5.08 U/L and 52.30±5.84 U/mL, respectively, which were significantly lower than those of 80.35±16.72 mg/L, 51.46±7.35 U/L and 63.47±6.37 U/mL in the control group (t=9.514, 8.392, 8.315, all P<0.05). Serum alanine aminotransferase (ALT), γ-glutamyl transpeptidyase (γ-GT) and total bilirubin (TBil) were 59.46±5.28 U/L, 61.69±5.47 U/L and 19.26±3.05 μmol/L, respectively, which were significantly lower than those of 74.08±6.04 U/L, 76.25±6.29 U/L and 24.41±3.83 μmol/L in the control group (t=7.416, 7.395, 6.735, all P<0.05). The TRAE in both groups were level 1~2, and there was no significant difference between the two groups (P>0.05). Conclusion Carrilizumab can improve the efficacy of DTACE in combination with sorafenib treatment to prevent tumor progression in patients with unresectable HCC, which benefits the patients with safety and controllability.
    The Construction and Validation of a Prognostic Signature Linked to Endocytosis in Hepatocellular Carcinoma
    XU Yun-fei, YAO Xiang-qing, LUO Mei-di
    2024, 29(4):  400-407. 
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    Objective Efferocytosis is linked to a variety of disease progression, yet its role in cancer remains under-researched. This study aims at investigating the genes associated with efferocytosis in hepatocellular carcinoma (HCC) and to evaluate their significance in prognosis. Methods Transcriptomes and clinical data for HCC were sourced from TCGA and GEO databases. “Limma” R package was used for differential expression analysis. An efferocytosis-based prognostic signature was created with LASSO Cox regression analysis method, followed by a validation with GEO data. A prognostic nomogram was also developed by incorporating TNM stages and clinical factors. Results Thirty-three efferocytosis-related differentially expressed genes were identified. Within them, six key genes (i.e., ALDH2, C3, ANXA2, CD5L, IL33, and HAVCR1) were significantly correlated with the survival of HCC patients (P<0.01). The signature built on these genes was accurate and stable after validation in different datasets, which may serve as an independent overall survival predictor for HCC (P<0.01). The AUCs of the nomogram for predicting the 1, 3, and 5-year survival of HCC patients were 70.7%, 70.4%, and 70.1%. respectively. Conclusion Key efferocytosis genes were identified in this study to build a prognostic signature of HCC with an high accuracy, which provide new insight in HCC treatment and warrant further validation.    
    The effect and mechanism of Sulfiredoxin-1 on ferroptosis in hepatocellular carcinoma cells
    XU Xing-wen, JIA Jin-tang
    2024, 29(4):  408-413. 
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    Objective To investigate the effect and mechanism of Sulfiredoxin-1 (SRXN1) on ferroptosis in hepatocellular carcinoma cells. Methods Cultured HepG2 cells were divided into the following three groups: negative control group (NC group, treated with dimethyl sulfoxide), eristin group (treated with 10 μM eristin, a ferroptosis inducer ), and si-SRXN1 group (si-SRXN1 group, treated with small interfering RNA of SRXN1 and erasin). The iron content of each group was assayed by the iron content assay kit; The reactive oxygen species (ROS) and MDA levels of each group was detected with enzyme-linked immunosorbent assay (ELISA); The mRNA expression level of SRXN1, GPX4, SLC7A11, ACSL4, and LPCAT3 genes was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR); The expression level of SRXN1 protein was evaluated by Western-blot. Results Compared with the NC group, the cellular iron content [(8.46±0.60) vs (13.64±0.37)], ROS and MDA levels [(132.04±15.21) vs (203.82±13.17), and (97.35±9.58) vs (209.32±8.78)], the mRNA expression levels of ACSL4 and LPCAT3 [(1.00±0.06) vs (2.15±0.03), (1.00±0.02) vs (1.58±0.02)], as well as the expression levels of SRXN1 mRNA [(1.00±0.05) vs (2.94±0.16)] and protein [(0.88±0.02) vs (1.18±0.03)] were all significantly enhanced in the eristin group (P<0.01), whereas the expression of GPX4 and SLC7A11 were both prominently diminished in the eristin group [(1.00±0.03) vs (0.33±0.02), (1.00±0.08) vs (0.33±0.01)] (all P<0.0001). When compared with the eristin group, the cellular iron content [(13.64±0.37) vs (20.91±0.96)], ROS and MDA levels [(203.82±13.17) vs (261.38±16.92), (209.32±8.78) vs (293.86±7.65)], mRNA expression levels of ACSL4 [(2.15±0.03) vs (2.70±0.09)] and LPCAT3 [(1.58±0.02) vs (1.86±0.08)] were all substantially ascended (all P<0.01), but the mRNA expression levels of GPX4 [(0.33±0.02) vs (0.10±0.01)] and SLC7A11 [(0.33±0.01) vs (0.14±0.001)], as well as the expression levels of SRXN1 mRNA [(2.94±0.16) vs (0.48±0.02)] and protein [(1.18±0.03) vs (0.64±0.06)] were all dramatically declined in the si-SRXN1 group,(P<0.01). Conclusion Knocking-down SRXN1 elevates cellular iron content, promotes oxidative stress response, and aggravates ferroptosis in hepatocellular carcinoma cells induced by eristin, which may be related to an inhibition of GPX4 and SLC7A11 genes expression, therefore attenuate antioxidant capacity and activating the expression of ACSL4 and LPCAT3 genes to promote the formation of lipid peroxidation.
    Liver Fibrosis & Cirrhosis
    The application of MRI-ideal-iq technique combined with serological indexes in staging hepatic fibrosis in chronic hepatitis B patients
    LIU Jing, GUO Fei, WU Lu-lu, LI He
    2024, 29(4):  414-418. 
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    Objective To explore the application value of MRI least square estimation and asymmetric echo iterative lipography (MRI-ideal-iq) in combination with serological indicators in the staging of hepatic fibrosis (HF) in patients with chronic hepatitis B. Methods 100 patients with hepatitis B admitted to our hospital from January 2021 to January 2023 were selected in this study. According to the guidelines and liver biopsy results, 100 patients were divided into stage S0-S1 group (n=41), stage S2 group (n=28), stage S3 group (n=17), and stage S4 group (n=14). The IDEAL-IQ parameters, serum indicators such as hyaluronic acid (HA), type IV collagen (CIV), laminin (LN), and liver function parameters including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin were compared among the four groups of patients. The value of IDEAL-IQ parameters combined with serological indicators in predicting early liver cirrhosis (S4 stage) was evaluated by receiver operating characteristic curve (ROC) method. The relationship between IDEAL-IQ parameters, serological indicators, and HF were evaluated by Correlation analysis. Results The FF, R2* value, HA, and CIV levels were (1.51±0.33)%, (54.58±8.15)Hz, (139.05±60.57)μg/L, and (88.24±24.78)ng/mL in S0 to S1 group, respectively; (2.01±0.42)%, (69.07±7.44)Hz, (337.56±113.24)μg/L, and (106.04±30.21)ng/mL in S2 group; (3.07±0.46)%, (94.55±10.53)Hz, (416.08±124.51)μg/L, and (134.07±38.76)ng/ml in S3 group; (4.32±0.53)%, (111.14±11.42)Hz, (583.76±150.54)μg/L, and (190.06±42.83)ng/mL in S4 group. There was a statistically significant difference between the four groups (F=188.442, 178.839, 75.985, 38.451, P<0.05); There was no significant difference in serum levels of LN among the four groups (P>0.05). By ROC analysis it was shown that the areas under the curves of FF, R2* value, serum HA and CIV levels for predicting early cirrhosis were 0.777, 0.782, 0.819, and 0.744, respectively, with the optimal cutoff values of FF≥3.560%, R2* value≥102.950 Hz, HA≥517.210 μg/L, and CIV≥173.895 ng/mL, all P<0.05. The area under the curve of a combined prediction for early liver cirrhosis was 0.832, with a sensitivity of 0.786, both were higher than those of the single indicators. The levels of ALT, AST, and albumin were (134.65±37.85) U/L, (74.22±20.57)U/L, and (45.15±3.76)g/L in S0-S1 group, respectively, (192.08±47.52)U/L, (100.25±30.16)U/L, and (43.45±3.01)g/L in S2 group, (214.12±55.63)U/L, (127.13±38.53)U/L, and (40.35±5.24)g/L in S3 group, (159.14±43.71]U/L, (101.54±33.48) U/L, (37.42±3.65)g/L in S4 group, The differences between the four groups were statistically significant (F=18.341, 14.667, 16.786, P<0.05). By correlation analysis, it was found that FF, R2* values, serum HA and CIV levels were positively correlated with HF staging (P<0.05); There was no significant correlation between serum LN levels and HF stagings (P>0.05). Conclusion The FF, R2* values, as well as serum HA and CIV levels show significant differences in patients with different HF stages, which may reflect the degree of HF. Moreover, the combination of them has high sensitivity in diagnosing early cirrhosis.    
    Quantitative evaluation of blood flow state in patients with hypersplenism based on multi-slice spiral CT whole liver perfusion imaging
    ZHANG An-lin, XU Jie, TANG Jie, CHEN De-li
    2024, 29(4):  419-422. 
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    Objective To investigate the variations in blood flow status and changes in the internal diameter of hepatic and splenic vessels in patients with different degrees of hypersplenism. Methods A total of 36 patients diagnosed with liver cirrhosis and hypersplenism were enrolled between June 2018 and September 2022. Additionally, 40 healthy individuals who underwent examinations at our hospital during the same period were selected as the control group. Clinical data, imaging features of the liver and spleen, as well as liver perfusion parameters were compared between patients with hypersplenism and the healthy control group. Results The comparative analysis of clinical data revealed that patients diagnosed with hypersplenism exhibited significantly elevated levels of ALT, AST and GGT, with values of 87.6(34.3,378.7) U/L, 75.6(39.3,361.2) U/L and 65.7(31.3,83.6) U/L, respectively. These levels were notably higher compared to the healthy control group, which had values of 16.2(12.6,25.1) U/L,18.0(12.0,24.8) U/L and 16.3(11.6,24.0) U/L(P<0.05). Upon evaluation of imaging parameters,, it was discovered that the diameter of the splenic artery, splenic vein, portal vein, and spleen volume in patients with hypersplenism were significantly elevated compared to those of the healthy control group. Specifically, they measured approximately (7.2±1.3) mm, (13.5±2.5) mm, (16.9±2.4) mm and (1842±859.4) cm3, respectively, while the healthy control group were (5.6±0.8) mm, (10.0±1.6) mm, (14.3±1.8) mm and (398.5±149.8) cm3(P<0.05). Additionally, the measurements of splenic artery, splenic vein, portal vein and spleen in the group with moderate hypersplenism were (8.0±1.2) mm, (14.9±1.4) mm, (17.8±2.0) mm and (2361.8±894.0) cm3, respectively. In contrast, the severe hypersplenism group displayed measurements of (7.0±0.8) mm, (14.1±2.5) mm, (17.9±2.2) mm and (1994.4±783.7) cm3, which were significantly higher than those observed in the mild hypersplenism group [(6.4±1.0) mm, (11.9±1.9) mm, (15.9±1.8) mm and (1253.4±582.6) cm3(P<0.05)]. In terms of liver perfusion parameters, the PVP and TLP parameters for the caudate lobe, left lateral lobe, left medial lobe, right anterior lobe and right posterior lobe in hypersplenism group were (46.3±15.5) ml/min and (54.9±21.0) ml/min, (40.7±14.5) ml/min and (49.6±15.1) ml/min, (37.6±13.9) ml/min and (49.7±13.2) ml/min, (41.8±13.6) ml/min and (47.5±15.3) ml/min, (44.7±14.5) ml/min and (56.3±10.0) ml/min. These values were significantly lower when compared to the healthy control group [(80.4±52.7) ml/min and (91.6±56.8) ml/min, (87.8±39.4) ml/min and (98.6±51.3) ml/min, (78.0±46.5) ml/min and (87.7±48.4) ml/min, (79.2±51.1) ml/min and (87.0±42.1) ml/min, (73.1±39.3) ml/min and (85.0±37.1) ml/min(P<0.05) ]. The HPI parameters in the hypersplenism group were (18.5±12.7) %, (20.6±12.0) %, (23.6±14.8) %, (13.8±11.5) % and (20.6±7.5) %, which were significantly higher than those in the healthy control group [(12.4±6.8) %, (14.2±8.2) %, (11.7±9.0) %, (12.2±9.6) % and (12.9±7.4) %]. Conclusion Patients with hypersplenism exhibited dilated splenic, with more pronounced dilation observed in those with moderate and severe hypersplenism. Additionally, hepatic blood perfusion was reduced in patients with hypersplenism.
    Evaluation of esophageal varices in patients with chronic hepatitis B by real-time tissue elastography
    LIU Yun, XU Yun, HAN Liang, QIAN Yi, TAN Bi-bo
    2024, 29(4):  423-428. 
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    Objective To evaluate the effectiveness of real-time elastography (RTE) in the diagnosis of esophageal varices (EVs) in patients with chronic hepatitis B. Methods We conducted a retrospective analysis of the clinical data, abdominal ultrasound, RTE and upper gastrointestinal endoscopy (EDG) results of 127 patients with chronic hepatitis B. The relationship between LF index and different grades of EVs was investigated. The AUROC was used to compare the diagnostic performance of various non-invasive markers for identifying patients with EVs and those at high-risk EVs. Results Among the 127 patients, EDG revealed EVs in 55 (43.3 %). Mild EVs were observed in 33 (26.0 %), moderate EVs in 11 (8.7 %), and severe EVs in 11 (8.7 %). Patients with EVs had lower PLT counts and higher levels of γ globulin, APRI, FIB-4, and LF index (P<0.001). A significant positive correlation was found between the LF index and the grade of EVs (P<0.001, r=0.802). The AUROC values for PLT, γ globulin, APRI, FIB-4, and LF index in diagnosing EVs were 0.296, 0.770, 0.797, 0.801 and 0.891, respectively. The optimal cut-off value for LF index was determined as 2.71, with corresponding sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and diagnostic accuracy of 92.7%, 70.8%, 76.4%, 90.7%, 3.2, 0.1 and 81.8%, respectively. For the diagnosis of high-risk EVs, the AUROC values of PLT, gamma globulin, APRI, FIB-4, and LF index were 0.262, 0.858, 0.862, 0.897 and 0.935, respectively. The optimal cut-off value of LF index was 3.28, with corresponding sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and diagnostic accuracy of 86.6%, 90.5%, 90.3%, 87.1%, 9.1, 0.1, and 88.6%, respectively. Conclusion Real-time liver tissue elastography’s LF index displays strong diagnostic efficacy in detecting EVs in patients with chronic hepatitis B.
    The effect of Fuzheng Huayu Capsules (FZHY) on the development of hepatic fibrosis
    HUANG Xin, MENG Xiang-jun, WU xin
    2024, 29(4):  429-431. 
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    Objective To investigate the effect of Fuzheng Huayu Capsules (FZHY) on the progression of hepatic fibrosis. Methods The impact of FZHY on the activity of LX-2 cells was evaluated using the CCK-8 assay. The expression levels of α-SMA in TGF-β-transfected LX-2 cells were assessed using RT-qPCR and Western blot analysis after treatment with or without FZHJ. A total of 80 patients with chronic hepatitis B undergoing antiviral treatment at Shanghai Ninth People's Hospital between January 2022 and December 2022 were enrolled in the study and divided into a control group and a treatment group. The treatment group received 1.5 g of Fuzheng Huayu Capsules three times daily, and liver elasticity F-value were measured using transient elastography before and after treatment in both groups. Results The inhibitory effect of FZHY on LX-2 cells growth was significantly dose-dependen (P<0.05). Overexpression of TGF-β significantly inceased α-SMA mRNA level (57.14 ± 4.81) compared to the control group (P<0.001). Treatment with 10% or 20% FZHY resulted in a reduction in α-SMA mRNA levels (37.42 ± 3.65 and 21.79 ± 0.496) compared to the TGF-β group, with significant differences (P<0.05, P<0.001). Western blot analysis demonstrated that FZHY partially reversed the upregulated expression of α-SMA induced by TGF-β. While the liver elasticity F value decreased in the treatment group after therapy, but there was no statistically significant difference (P>0.05). Conclusion FZHY exhibits antifibrotic effects by influencing LX-2 cell proliferation and modulating α-SMA expression.
    Expression of CD14+ monocytes and CD163+ macrophages in patients with chronic hepatitis C and their relationship with the severity of liver fibrosis
    HE Yu, ZHANG Zhi-hong, OUYANG Hui, LU Shi
    2024, 29(4):  432-435. 
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    Objective To investigate the expression of CD14+ monocytes and CD163+ macrophages in patients with chronic hepatitis C and their relationship with the severity of liver fibrosis. Methods A total of 83 patients with chronic hepatitis C and 64 healthy subjects were selected between April 2018 and November 2022. The clinical features, the expression of CD163 in liver tissue, the concentration of serum CD163, the proportion of CD14+ cells and the proportion of CD14+ cells expressing different kinds of cytokines were compared. Results The level of ALT and AST of chronic hepatitis C group were (84.6±9.1) U/L and (69.3±7.2) U/L, which was significantly higher than that in healthy control group [(28.4±1.7) U/L and (22.5±6.9) U/L] (P<0.05). The concentration of serum CD163 and the proportion of CD14+ cells, the number of CD163+ cells, concentration of serum CD163+ and CD14+ cell proportion of F<2 patients were 38.2±4.7, (73.6±2.1) μg/L and (73.7±3.2) %, which was significantly higher than that in healthy control group [12.5±1.3, (50.1±2.6) ?g/L and (61.0±8.4) %] (P<0.05). The number of CD163+ cells, concentration of serum CD163+ and CD14+ cell proportion of F≥2 patients were 74.9±8.0, (95.4±9.8) μg/L and (79.2±5.5) %, which was significantly higher than that in healthy control group and F<2 patients. CD14+ cells expressing IL-2, IL-4, IFN-γ, IL-6, IL-8 and TNF-α of F<2 patients were (4.2±1.2) %, (3.8±1.1) %, (3.8±1.0) %, (3.7±1.3) %, (4.0±1.4) % and (6.7±3.6) %, which was significantly higher than that in healthy control group [(0.9±0.1) %, (1.1±0.2) %, (1.8±0.4) %, (1.6±0.6) %, (1.7±0.7) % and (4.6±2.1) %] P<0.05). CD14+ cells expressing IL-2, IFN-γ, IL-8 and TNF-α of F≥2 patients were (2.2±0.8) %, (2.1±0.5) %, (5.6±2.0) % and (6.9±3.2) %, which was significantly higher than that in healthy control group. CD14+ cells expressing IL-8 was (5.6±2.0) %, which was significantly higher than that in F≥2 patients. Conclusion CD14+ monocytes and CD163+ macrophages are involved in the process of liver fibrosis in patients with chronic hepatitis C.
    Viral Hepatitis
    Study on the IL-21 participate in the immunopathogenesis of HBeAg-positive chronic hepatitis B
    CAI Yun, ZHAO Kai, PAN Liang, ZHOU Xin
    2024, 29(4):  436-439. 
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    Objective To investigate the involvement of Interleukin-21 (IL-21) in the immune response of individuals with HBeAg positive chronic Hepatitis B (CHB). Methods 45 HBeAg-positive CHB patients, 20 CHB patients in the immune tolerant (IT) phase, and 20 HBeAg-negative CHB patients in the inactive carrier (IC) phase were enrolled in this study. Levels of HBV serum markers, such as HBeAg, HBsAg, Anti-HBs、Anti-HBe、Anti-HBc, as well as ALT, HBV DNA levels, IL-21 cocentration, frequencies of IL-21+CD4+T cells, and frequencies of IL-21R+CD4+T cells were assessed before and after 48 weeks of antiviral therapy. Additionally, 15 healthy volunteers were included as a control group and were assessed during the same period. Results The serum concentration of IL-21 in the CHB group (82.21±22.32 pg/mL) and IC groups (72.32±25.26 pg/mL) was significantly higher compared to IT group (20.24±15.56 pg/mL, P<0.001). The frequency of IL-21+CD4+T cells (7.42±2.34)% and IL-21R+CD4+T cells (6.46±1.55)% in the IC group was higher compared to the CHB group (P<0.001). No correlation was observed between serum ALT levels and IL-21 concentration (r=0.136, P=0.20). Furthermore, the IL-21 level (92.58±25.76 pg/mL), as well as the frequency of IL-21+CD4+T cells (7.89±2.05)% and IL-21R+CD4+T cells (7.01±1.51)%, were significantly higher in the peripheral blood of HBeAg-positive CHB patients who achieved HBeAg serologic conversion after antiviral therapy compared to those who did not (P<0.01). Conclusion IL-21 plays a significant role in the immunopathogenesis of HBeAg-positive chronic hepatitis B.
    Monocyte subsets and phenotypes in treatment Naive chronic hepatitis C patients treated with daclatasvir and sofosbuvir
    LIU Ya-guang, HU Lian-zhi, DONG Yi-xia
    2024, 29(4):  440-443. 
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    Objective To investigate the alterations in monocyte subsets and phenotypes in treatment-naive chronic hepatitis C patients undergoing daclatasvir and sofosbuvir therapy. Methods A total of 94 treatment-naïve chronic hepatitis C patients were enrolled in this study at our hospital from August 2021 to February 2023, excluding individuals with drug-induced, hereditary, or autoimmune liver diseases. The patients were randomly assigned to either a conventional therapy group or a combination therapy group, with 47 cases in each group. The conventional therapy group received IFNα-2a injections, while the combinaton therapy group was treated with a combination of daclatasvir and sofosbuvir. The levels of TBil, TBA, ALT, AST, GGT, ALP, γ-GT were compared between the two groups, and the expression of CD14+CD16+/CD14+ and CD14+CD16-/CD14+ was assessed using flow cytometry. Adverse events were monitoreded and compared between the two groups for further analysis. Results After treatment, the combination therapy group showed significantly lower levels of TBil and TBA compared to the conventional therapy group (P<0.05). Similarly, the levels of ALT and AST were significantly lower in the combination therapy group (P<0.05). Additionally, the levels of GGT, ALP and γ-GT were significantly reduced in the combination therapy group (P<0.05). Furthermore, the combination therapy group exhibited lower expression of CD14+CD16+/CD14+ and higher expression of CD14+CD16-/CD14+ compared to the conventional therapy group (P<0.05). Conclusion Combination therapy with daclatasvir and sofosbuvir in treatment-naïve chronic hepatitis C patients may alleviate hepatocyte damage, resulting in improvements in inflammatory and liver function. Additionally, this combination therapy can modulate monocytes, enhancing the immune response in these patients.
    Autoimmune Liver Disease
    Clinical and pathological features of IgG4-related autoimmune hepatitis
    YANG Qiu-xia, HOU Zhuo, ZHOU Qiu-ye, HE Yu-yan, HU Qing-rong, YAO Ying
    2024, 29(4):  444-447. 
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    Objective To investigate the clinical presentations, serological features, and histopathological characteristics of IgG4-related autoimmune hepatitis (IgG4-AIH). Methods We collected and analyzed the clinical presentations and serological characteristics of 38 patients diagnosed with autoimmune hepatitis (AIH) based on liver tissue histopathology. Liver tissue samples were ssubjected to HE staining as well as immunohistochemical staining for IgG4 to evaluate histological features and the extent of IgG4-positive plasma cell infiltration. Results Among the 38 AIH patients, 7 exhibited elevated serum IgG4 levels and positive liver tissue IgG4 staining, thus categorizing them into the IgG4-AIH group. The remaining 31 cases were considered part of the classic AIH group. Common symptoms observed in both groups included jaundice, fatigue, and anorexia, accompanied by liver function abnormalities characerized by elevated levels of ALT and AST. Autoantibody ANA was detected in 85.7% (6/7) of IgG4-AIH patients, and in 83.8% (26/31) of classic AIH patients. The serum IgG level was significantly higher in the IgG-AIH group (33.2±7.2) compared to the classic AIH group (26.5±5.3). Liver histological inflammation in the IgG4-AIH group was predominantly categorized as G3 and G4, while in the classic AIH group, it mainly fell under G1 and G2. The differences observed between the two groups were statistically significant. Conclusion Serum and liver tissue IgG4 levels were notably elevated in IgG4-AIH patients, with more pronounced inflammatory activity observed in liver pathological examination. Nevertheless, there were no significant difference in clinical manifestations and biochemical indicators between IgG4-AIH and classical AIH patients.
    Characteristics of patients with primary biliary cholangitis-autoimmune hepatitis overlap syndrome and diverse anti-mitochondrial antibody in Qinghai region
    WANG Chun-qiu, CHEN Ting, ZHANG Zhen-ying, ZHANG Xiao-fei
    2024, 29(4):  448-452. 
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    Objective To delineate the clinical and pathological characteristics of primary biliary cholangitis-autoimmune hepatitis overlap syndrome(PBC-AIH OS) in Qinghai province, aiming to enhance clinical diagnosis and treatment protocols. Methods In a retrospective study spanning December 2017 to December 2022, 85 patients diagnosed with PBC-AIH OS were analyzed. The cohort was divided into two groups based on Anti-mitochondrial antibody status: 58 in Group A(positive) and 27 in Group B(negative). The study evaluated general clinical features, comorbid conditions, serum biochemical markers, immunological indices, and liver tissue pathology. Date adhering to a normal distribution were presented as c±s and analyzed using the independent sample t-test. Non-normally distributed measurements were expressed as medians(P25, P75) and compared using the Wilcoxon rank-sum test. Categorical data were analyzed using chi-square tests to compare proportions between groups; with a P-value of <0.05 denoting statistical significant. Results In the comparison between the two groups, there were no statistically significant differences observed interms of sex, age, TBil, γ-GGT, ALP, IgG, Ro52 presence, the detection rate of SSA, the prevalence of Sjogren′s syndrome, and the grades of liver inflammation and fibrosis (P>0.05). However, significant differences were noted in the levels of ALT (115.41±76.63 vs. 255.90±244.90) and IgM [4.05 (2.75, 5.43) vs. 1.99 (1.41, 3.51)], as well as in the detection rate of ANA-G(χ2=9.67) and the morbidity rate of autoimmune thyroid disease (AITD) (χ2=5.74), with P＜0.05 indicating statistical significance. Conclusion Patients in Group A exhibited levels of ALT, IgM and ANA-Gr detection rates, whereas the prevalence of AITD was greater in the Group B. The pathological histology for both groups predominantly revealed moderate to severe,inflammation and fibrosis rades, suggesting an insidious onset, prolonged disease course, and advanced stage at diagnosis for these patients. Given these findings, it is advisable for patients diagnosed with PBC-AIH OS to undergo thorough screening for,thyroid disorders.
    Other Liver Diseases
    Analysis of autoantibody characteristics and prognostic factors in patients with chronic drug-induced liver injury
    MA Wen-jun, QU Xiang-zhen, ZHOU Jing-ya, MA Wei-na, Li Hong-tao
    2024, 29(4):  453-456. 
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    Objective To analyze the characteristics of autoantibodies in patients suffering from chronic drug-induced liver injury(DILI) and identify the key factors influencing their prognosis. Methods Between March 2019 and March 2022, 358 patients diagnosed with chronic DILI at our institution were retrospectively analyzed and categorized based on their prognosis six months post-treatment into two groups: those with a poor prognosis (108 cases) and those with a good prognosis (250 cases). Autoantibody screening was conducted for all patients, dividing them into autoantibody-positive(145 cases) and autoantibody-negative groups (213 cases). All subjects underwent biochemical therapy. Results In this cohort of 358 patients with chronic DILI, more than ten types of drugs were identified as causes, with traditional Chinese medicine being the most common (31.0%), followed by antipyretic and analgesic drugs (12.3 % ), antitumor drugs (11.7 %), antibiotics (9.2 %), and subsequently hormones, cardiovascular medications, and nutraceuticals. Autoantibody analysis revealed that 42.74 % (153/358) of patients were positive for antinuclear antibodies(ANA). Of the toatl patient cohort, 145 were found to be positive for autoantibodies while 213 were negative. It was observed that the autoantibody-postive group had a higher proportion of females and older individuals compared to the negative group. Furthermore, within the entire cohort of 358 patients, those aged ≥60 years or with non-hepatocellular types of DILI exhibited a significantly higher risk of poor prognosis. Elevated levels of alanine aminotransferase (ALT)[ (519.7±90.6) U/L vs. (330.8±88.9) U/L], aspartate aminotransferase (AST)[(410.4±91.3) U/L vs. (269.7±80.5) U/], total bilirubin (TBil)[ (44.0±11.8) μmol/L vs. (31.9±13.5) μmol/L] , direct bilirubin (DBil)[(33.4±11.8) μmol/L vs. (27.8±9.0) μmol/L] correlated with a poor prognosis, while lower slbumin (Alb) levels[(46.0±14.9) g/L vs. (60.1±18.1) g/L] were indicative of a better prognosis. Further analysis highlighted that, for the entire patient population, being aged ≥60 years, having a non-hepatocellular DILI type, and presenting with elevated ALT, AST, TBil, DBil, and decreased Alb levels were risk factors for a poor prognosis in chronic DILI (OR=1.618, 1.996, 1.632, 1.602, 1.600, 1.747, 1.929, respectively, all P<0.05). Conclusion Identified risk factors for poor prognosis in patients with chronic DILI include being over 60 years of age, having a non-hepatocellular type, and presenting with elevated biochemical markers such as ALT levels≥435.4 U/L, AST levels≥325.2 U/L, TBil levels≥38.6 μmol/L, DBil levels≥29.2 μmol/L, and reduced Alb levels≤52.2 U/L. Given these findings, regular monitoring of these indicators is imperative, Implementing corresponding intervention measures based on these parameters is crucial for enhaning patient outcomes and improving prognosis.
    Causes and clinical characteristics of liver injury in 113 hyperthyroidism patients
    CHEN Zhi-feng, SHAO Hui-ge, XIE Kai-han
    2024, 29(4):  457-460. 
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    Objective To investigate the underlying causes and delineate the clinical features of injury in patients with hyperthyroidism (HT). Methods A retrospective analysis was conducted on the clinical data of 113 HT patients admitted to the Central Hospital of Nanhua University from May 2019 to May 2023. Patients were categorized into two groups: those with liver injury (66 cases) and those without(47 cases), Comparative analysis covered clinical indicators, liver and thyroid function parameters and complication rates between the groups. Results In this study, the liver injury group showed higher average age (44.7±5.7 years vs. 36.5±5.2 years), longer disease duratic(4.4±1.3 years vs. 2.4±0.7 years) , and elevated basal metabolic rate(33.5±10.5% vs. 26.1±8.8%), with all differences reaching statistical significant (P<0.05). Liver function tests revelaed markedly elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamyltransferase (GGT), alkaline phosphatase (ALP), and total bilirubin (TBiL) in the liver injury group compraed to controls, with values of (96.6±28.4) U/L vs. (43.8±13.5) U/L, (113.2±35.5) U/L vs. (47.8±16.8) U/L, (71.2±9.3) U/L vs. (33.3±7.5) U/L, (162.8±34.3) U/L vs. (75.3±21.7) U/L, (33.5±8.8) μmol/L vs. (17.4±5.3) μmol/L, repectively, indicating significant liver dysfunction (P<0.05). Thyroid fucntion tests also showed significant differences, with free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (TT3), and tetraiodothyronine (T4) levels all higher in the liver injury group[(19.3±6.4) pmol/L vs. 13.7±4.1) pmol/L, (86.7±25.3) pmol/L vs. (35.6±11.2) pmol/L, (7.8±2.1) nmol/L vs. (5.4±1.8) nmol/L, (253.7±19.5) nmol/L vs. (216.8±17.8) nmol/L], highlighting the impact of liver injurt on thyroid fuction(P<0.05). Furthermore, the total complication rate was significantly higher in the liver injury group(33.3%) compared to the uncomplicated liver injury group(14.9%), underscoring the clinical relevance of liver injurt in hyperthyroidism management(P<0.05). Conclusion HT patients, those with prolonged disease duration, and those exhibitaing reduced basal metabolic rates demonstrated a higher susceptibility to liver injury. HT individuals presenting with concurrent liver damgae exhibit notably poorer liver and thyroid functions and face a higher incidence of clinical complications. These findings underscore the importance of early diagnosis and timely intervention, emphasizing the necessity for targeted symptomatic treatment to mitigate the adverse outcomes associated with HT and liver injury.
    Clinical and imaging profiles of congenital intrahepatic portosystemic shunts in pediatrc patients
    MA Lian-jun, HAO Yin, LI Xu-xue
    2024, 29(4):  461-463. 
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    Objective To elucidate the clinical characteristics and imaging findings associated with congenital intrahepatic portosystemic shunts in pediatric patients. Methods From June 2017 to June 2022, we examined the clinical and imaging features of 40 pediatric patients diagnosed with congenital intrahepatic portosystemic shunts at our hospital. Results In our cohort of 40 pediatric patients with congenital intrahepatic portosystemic shunts, a significant proportion(23 cases, 57.5%) had a history of hepatitis B cirrhosis. The predominant clinical classification was type III shunts(23 cases, 57.5%), with the shunt site most commonly identified at the right posterior branch of the portal vein inferior vena cava (17 cases, 42.5%). These patients exhibited alterations in liver function markers, including elevated alanine aminotransferase(ALT), glutamic oxaloacetic aminotransferase(AST), and total bilirubin(TBil) levels. CT imaging revealed that lesions were predominantly located in the right hepatic lobe(25 cases, 62.5%) and the left hepatic lobe(15 cases, 37.5%). A majority(33 cases, 82.5%) showed significant expansion of hepatic veins at the shunt site, whereas 7 cases (17.5%) did not. Ultrasound findings indicated that lesions were situated near the surface or lobe edge within the parenchyma, appearing as tubular, cystic, or irregular shaped structures without echo on two-dimensional ultrasound. Color Doppler ultrasound demonstrated non-pulsatile, alternating red and blue blood flow signals from the portal vein branch to the hepatic vein. Conclusion In pediatric patients, congenital intrahepatic portosystemic shunts exhibit distinct clinical and radiological profiles, often correlated with a history of hepatitis B cirrhosis. Predominatly classified as type III, these shunts frequently occur at the right posterior branch of the portal to the inferior vena cava, eliciting significant alterations in liver function parameters. These diagnostic features and their clinical implications offer valuable reference points for effective management in clinical settings.
    Disseminated tuberculosis involving liver and lymph nodes: a case report and review of the literatures
    CHENG Qi, ZHOU Xian, JIANG Wei-min
    2024, 29(4):  464-467. 
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    Objective To understand the clinical features of hepatic and disseminated tuberculosis. Methods This study analyzes the clinical presentations, laboratory and imaging findings, treatment strategies and prognosis of a patient diagnosed with disseminated tuberculosis involving the liver and lymph nodes by the Department of Infectious Diseases at Huashan Hospital, affiliated with Fudan University. A comprehensive review was conducted of literature form Pubmed and Chinese databases soanning the years 2003 to 2022, focusing on . hepatic tuberculosis and disseminated tuberculosis. Reports pertinent to disseminated hepatic tuberculosis were meticulously screened, and relevant clinical data were extracted and evaluated to underscore patterns, outcomes, and insights into this condition. Results Presented is the case of an elderly male suffering from recurrent epidodes of fever, fatigue, and anorexia, with no response to various anti-infective treatments. Comprensive imaging examinations revealed the presence of multiple abnormal metabolic hypertrophy lesions across the body. The diagnosis of disseminated tuberculosis, including hepatic involvemnt, was ultimately confirmed through biopsy. Subsequent anti-tuberculosis treatment resulted in marked clinical improvement. A literature review, complemented by this case, identified 82 similar patients, with an average age of 39.3 years (1-59 years old), predominantly presenting with fever. Diagnosis was generally established via imaging, culture of lesion pus, or biopsy , and the prognosis post anti-tuberculosis treatment was favorable. Conclusion Hepatic tuberculosis represents an uncommon manifestion of extrapulmonary tuberculosis, characterized by non-specific clinical symptoms, complicating its timely diagnosis. The reliance on imaging techniques and pathological biopsies is crucial for accurate identification. Early detection plays a pivotal role in the management of this condiion. In patient with an allergic constitution, like the case in point, the judicious selection of suitable anti-tuberculosis medications is pivotal for treatment efficay and patient recovery.