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    30 June 2023, Volume 28 Issue 6
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    Liver Fibrosis & Cirrhosis
    A prospective study of the efficacy of entecavir combined with carvedilol in the treatment of hepatitis B cirrhosis combined with esophagogastric varices
    AN Bao-yan, GUO Qing, FENG Ming-yang, XU Yu-min, CAI Wei, XIE Qing, WANG Hui
    2023, 28(6):  646-648. 
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    Objective To investigate the efficacy of entecavir combined with carvedilol in the treatment of hepatitis B virus (HBV) related cirrhosis complicated with esophagogastric varices (EGV). Methods Patients with HBV related cirrhosis complicated with EGV admitted to our hospital from April 2018 to May 2020 were selected. After enrollment, 35 patients continued entecavir antiviral therapy and were given carvedilol 10 mg orally daily.. Liver function, blood routine test, liver stiffness (LS) and gastroscope were examined at baseline, 48 weeks and 104 weeks respectively. Results The levels of alanine aminotransferase (ALT) were 33.71±11.18 IU/mL at baseline, 27.93±8.71 IU/mL at 48 weeks, and 25.57±7.18 IU/mL at 104 weeks, the differences were statistically significant (P<0.05). Similarly, aspartate aminotransferase (AST), alkaline phosphatase (ALP), glutamine transferase (GGT), baseline were significantly different from 48 weeks or 104 weeks (P<0.05). The level of platelet at baseline was not significantly different from 48 week and were significantly different from 104 week (P<0.05). The LS of patients at baseline, 48 weeks and 104 weeks were 18.24±8.73 kPa, 13.95±5.69 kPa and 12.12±4.20 kPa, respectively. There were significant differences between baseline and 48 weeks, baseline and 104 weeks (P<0.05). The degree of EGV was significantly improved at 48 weeks and 104 weeks compared to baseline (P<0.05). Conclusion Long-term antiviral therapy with entecavir combined with carvedilol significantly improved the degree of liver cirrhosis and prevented esophageal and gastric varices bleeding.
    Predictive value of hepatic venous pressure gradient on the prognosis of patients with decompensated liver cirrhosis
    WEI Feng, WANG Jian, SHI Jian, WEI Jue
    2023, 28(6):  649-653. 
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    Objective To investigate the role of hepatic venous pressure gradient (HVPG) in the prognosis of patients with decompensated cirrhosis. Methods A total of 51 patients with decompensated cirrhosis admitted to our hospital from September 2016 to December 2020 were selected. The HVPG was measured by vascular intervention. The area under receiver operating characteristic curve (AUROC) method was used to analyze the accuracy of HVPG in predicting prognosis. X-tile software was used to derive optimal cutoff values for continuity variables. The overall survival rate was analyzed by Kaplan-Meier method. A Cox regression model was established to evaluate the risk ratio of independent predictors. Results The value of HVPG in patients with decompensated cirrhosis was 20.68 ± 9.02 mmHg. The AUROC of total mortality predicted by HVPG was 0.729. The overall mortality of patients with decompensated cirrhosis was significantly different. Patients with decompensated cirrhosis with HVPG ≤ 19 mmHg had a significantly lower mortality rate than those with HVPG>19 mmHg (P=0.005). In univariate COX variable analysis, bilirubin, alanine aminotransferase (ALT), Child-Turcotte-Pugh (CTP) score, HVPG (HR: 1.051; 95%CI: 1.093-1112; P=0.026), and model for end-stage liver disease (MELD) score were significantly correlated with long-term mortality in patients with decompensated cirrhosis. In multivariate Cox regression analysis, only HVPG (HR: 1.079; 95% CI: 1.009-1.15; P=0.027) and bilirubin were significantly correlated with long-term mortality. Conclusion HVPG has a good predictive value for the prognosis of patients with decompensated liver cirrhosis.
    Predictive value of serum IL-15, pro-ADM and MDH1 for bacterial infection in patients with cirrhosis combined with upper gastrointestinal bleeding
    ZHUANG Xiao-lei, ZOU Hong-rui, HOU Jing-yue
    2023, 28(6):  654-659. 
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    Objective To investigate the predictive value of serum interleukin-15 (IL-15), adrenomedullin precursor (pro-ADM), and malate dehydrogenase 1 (MDH1) for bacterial infection in patients with cirrhosis and upper gastrointestinal bleeding. Methods A total of 118 patients with liver cirrhosis and upper gastrointestinal bleeding admitted to our hospital from June 2018 to June 2021 were selected as the research subjects.They were divided into infection group (33 cases) and non-infection group (85 cases) according to whether bacterial infection occurred during hospitalization. The clinical data including the levels of serum IL-15, pro-ADM and MDH1 between the 2 groups were compared, and the predictive value of various serum indicators for bacterial infection in patients with cirrhosis with upper gastrointestinal bleeding were analyzed. Results Serum IL-15 (262.59±36.52) ng/mL, pro-ADM (13.14±4.22) nmol/L and MDH1 (627.36±201.78) mU/mL in the infected group were higher than those in the uninfected group [(224.83±27.94) ng/mL, (8.97±2.81) nmol/L, (445.21±142.30) mU/mL], (P<0.05). Serum IL-15 (246.15±32.85) ng/mL, pro-ADM (10.99±3.09) nmol/L, MDH1 (531.10±114.36) mU/mL in patients with Child-Pugh classification B or C were higher than those in patients with class A [(212.73±23.59) ng/mL, (8.35±2.26) nmol/L, (422.58±102.45) mU/mL], (P<0.05). Serum IL-15 (248.28±29.67) ng/mL, pro-ADM (11.19±2.58) nmol/L, MDH1 (571.57±137.48) mU/mL in patients with moderate to severe upper gastrointestinal bleeding were higher than those in patients with mild bleeding [(221.60±21.51) ng/mL, (9.02±2.13) nmol/L, (415.44±113.29) mU/mL], (P<0.05). Serum IL-15 (251.83±31.42) ng/mL, pro-ADM (11.48±2.97) nmol/L, MDH1 (563.57±148.22) mU/mLin patients with APACHE II score >21 were higher than those in in patients with score ≤21 [(212.24±20.66) ng/mL, (8.26±2.05) nmol/L, (401.21±109.63) mU/mL], (P<0.05). The results of pearson correlation analysis showed that serum IL-15, pro-ADM, and MDH1 were positively correlated with Child-Pugh classification, severity of upper gastrointestinal bleeding, and APACHE II score (P<0.05). The rusults of logistic regression analysis showed that serum IL-15, pro-ADM, and MDH1 were independently associated with bacterial infection in patients with cirrhosis with upper gastrointestinal bleeding before and after correction for other factors (P<0.05). In ROC curve analysis, the AUC of the combination of serum IL-15, pro-ADM and MDH1 in predicting bacterial infection in patients with cirrhosis and upper gastrointestinal bleeding was 0.931 (95% CI: 0.869-0.970, specificity 90.91%, sensitivity 80.95%), which was better than the predictive value of each index alone 0.844 (95% CI: 0.765 to 0.904), 0.737 (95% CI: 0.648 to 0.814) and 0.744 (95% CI: 0.655 to 0.820). Conclusion Serum IL-15, pro-ADM, and MDH1 can be used as predictors of bacterial infection in patients with cirrhosis and upper gastrointestinal bleeding, and the combined predictive value is more reliable and can provide effective information for clinical prevention and treatment of concurrent bacterial infection in such patients.
    Liver Cancer
    Expression and clinical significance of key genes of iron death pathway in liver cancer
    WANG Xiao, ZHANG Ling-yun
    2023, 28(6):  660-664. 
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    Objective To investigate the expression and prognostic value of key iron death pathway genes in liver cancer and their correlation with the immune microenvironment by bioinformatics. Methods GEPIA online database was used to analyze the expression ferroptosis-related key genes in liver cancer. cBioPortal online database was used to analyze the gene mutation of ferroptosis-related key genes. Kaplan-Meier survival analysis was used to analyze the relationship between ferroptosis-related key genes and prognosis. The TIMER database and the TIDE database were used to analyze the correlation between key genes of the iron death pathway and the immune environment. Results The mRNA expression of ACSL4 was found to be significantly higher in liver cancer tissues than in normal tissues through the GEPIA database (P<0.05). cBioPortal database analysis revealed genetic alterations in key genes of iron death pathway in hepatocellular carcinoma, mainly including gene amplification, deletion mutations, missense mutations and in-frame mutations. Kaplan-Meier survival analysis showed that high GPX4 expression was associated with good prognosis (PFS:HR=0.68, P=0.014) and high expression of SLC7A11 was associated with poor prognosis (OS:HR=2.41, P=5.3e-07; PFS: HR=1.79, P=0.00043). TIMER database analysis showed that SLC7A11 and Nrf2 were positively correlated with infiltration of B cells, CD8+T lymphocytes, CD4+T lymphocytes, neutrophils, macrophages and dendritic cells. Conclusion Iron death pathway key genes are significantly correlated with prognosis and immune cell infiltration in patients with liver cancer, and are potential targets for treatment with important clinical value.
    Correlation between the plasma levels of interleukin-33 and hepatocellular carcinoma, thermal ablation therapy
    GUO Dan-dan, QIN Ling, GAO Weng-feng, YUAN Chun-wang, ZHANG Ying-hua, ZHANG Yong-hong
    2023, 28(6):  665-667. 
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    Objective To investigate the correlation between the plasma levels of interleukin-33 (IL-33) and hepatocellular carcinoma (HCC), thermal ablation therapy. Methods A total of 30 HCC patients, 25 patients with liver cirrhosis patients and 10 healthy adults admitted to our hospital from January 2018 to December 2020 were enrolled. The plasma IL-33 levels were detected by enzyme-linked immunosorbent assay (ELISA). The plasma IL-33 levels were detected in 22 patients treated with complete ablation in HCC at 1 week postoperatively and 4 weeks postoperatively. The plasma IL-33 levels in HCC group before therapy, LC group and healthy control group were compared, and the dynamic changes of plasma IL-33 levels in HCC patients treated with complete ablation before ablation, week 1 and week 4 after ablation were analyzed. Results Compared with the HCC group, LC group and the healthy control group, the preoperative plasma IL-33 level in HCC group was significantly higher than that in healthy control group [19.08 (12.02-31.91) pg/mL vs (9.62+2.65) pg/mL], the difference was statistically significant (P=0.001). There was no significant difference between HCC group and LC group, between LC group and healthy control group (P＞0.05). The plasma IL-33 level in patients with middle and advanced stage (Barcelona clinic liver cancer, BCLC-B/C) was higher than that in patients with early stage (BCLC-0/A) [27.69 (16.06-34.90) pg/ml vs 17.18 (11.16-25.85) pg/mL], the difference was statistically significant (Z=2.031, P=0.043). The level of IL-33 at week 4 after complete ablation was significantly lower than that before treatment and 1 week after the operation [12.02 (9.23, 12.89) pg/mL vs 14.17 (11.16, 22.81) pg/mL, 15.46 (13.74, 18.05) pg/mL], with statistical significant (P=0.029, P<0.001). Conclusion Imbalance of IL-33 expression may be one of the important mechanisms in the development of HCC. Ablation therapy can change IL-33 levels and promote the return of IL-33 to normal.
    The application of hemihepatic blood flow occlusion combined with intermittent Pringle method in the resection of giant liver cancer
    HONG Han, XU Min-hui, JIN Zheng-kang, LI Gao-chao, XU Xiao-yong
    2023, 28(6):  668-672. 
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    Objective To explore the application effect of hemihepatic blood flow occlusion combined with intermittent Pringle method in the resection of giant liver cancer. Methods From January 2019 to December 2021, seventy-eight patients with liver cancer who underwent giant liver cancer resection were selected from Suzhou Hospital affiliated to Nanjing Medical University. They were divided into a semihepatic group and an experimental group with thirty-nine cases in each group. The semihepatic group was treated with half hepatic blood flow occlusion, and the experimental group was treated with half hepatic blood flow occlusion in combination with intermittent Pringle method. The perioperative indicators of the experimental group and the semihepatic group were compared. The relevant indicators of liver function before operation and at 1 day, 3 days and 5 days after operation were detected and analyzed. The complications and quality of life within 3 months after operation [Quality of life measurement scale for liver cancer patients (QLI-LC score)] were counted. Results Compared with the semihepatic group, the experimental group had less intraoperative bleeding [(163.28±26.47) ml vs 198.24±34.15) ml] and shorter hospital stay [(8.15±1.20) d vs (9.58±1.36)d](P<0.05). The liver function indicators of the two groups increased at 1 day, 3 days and 5 days after operation and decreased thereafter (P<0.05). However, there was no difference in liver function parameters between the two groups at each time point (P>0.05). The incidence of complications in the experimental group was 7.69%, which was significantly lower than that of 25.64% in the semihepatic group (P<0.05). When compared the QLI-LC score at three and a half months after operation, the physical function (12.87±3.21), symptoms and signs (10.09±2.21), psychological function (7.09±1.92), and social function (9.27±1.04) in the experimental groups was lower than those of (21.38±4.98), (17.87±3.76), (13.15±2.03), and (14.28±2.75) respectively, in the semihepatic group (P<0.05). Conclusion The application of hemihepatic blood flow occlusion combined with intermittent Pringle method in the resection of giant liver cancer can reduce intraoperative bleeding, promote postoperative recovery, improve the quality of life with high safety, without aggravating the occurrence of liver injury and complications.
    Application of MRI Dual Lava early and late arterial phases combined with portal phase contrast-enhanced scanning in the diagnosis of liver cancer
    YANG Li-yue, YANG Xiao-liang, YIN Hui-kang
    2023, 28(6):  673-675. 
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    Objective To investigate the value of magnetic resonance imaging (MRI) Dual liver volume rapid three-dimensional imaging (Lava) early and late arterial phases combined with portal phase contrast-enhanced scanning in the diagnosis of liver cancer. Methods The clinical data of 393 patients with liver space-occupying lesions who underwent MRI examination in the hospital from January 2021 to December 2021 were retrospectively analyzed. Pathological examination results were recorded. The MRI imaging findings were compared with the pathological findings. The imaging features of MRI imaging in patients with liver disease were observed. The diagnostic value of MRI Dual Lava arterial early and late arterial phases combined with portal phase contrast-enhanced scanning technology for liver cancer was analyzed by Receiver operating characteristic curve (ROC) method. Results Among the 393 lesions, 55 lesions were diagnosed as liver cancer by pathological examination, and the detection rate was 13.99%. A total of 358 lesions were detected by MRI Lava early and late arterial phases combined with portal venous phase contrast-enhanced scanning, with a detection rate of 91.09%, including 46 liver cancers and 312 benign liver lesions. Dual Lava showed marked enhancement in arterial phase, decreased signal in portal venous phase and delayed phase, and "pseudocapsule" signs were seen. The positive detection rate of Dual Lava arterial phase in MRI scan results of liver cancer patients was higher than those of T1W1, T2W1, delayed phase, and protal venous phase (=4.398, 8.731, 7.566, 11.210, P=0.036, 0.003, 0.006, 0.001). The sensitivity of MRI Dual Lava technology for diagnosing liver cancer was 83.63% (95%CI: 70.69%~91.79%), the specificity was 92.30% (95%CI: 88.80%~94.82%), and the accuracy was 91.09% (95%CI: 87.72%~93.64%), the area under the curve (AUC) was 0.850 (95%CI: 0.842~0.915). Conclusion MRI Dual Lava arterial early and late phases combined with portal venous phase contrast-enhanced scanning has high diagnostic value for liver cancer.
    An evaluation of serum biochemical indexes, pathological characteristics and surgical treatment efficacy of sarcomatoid hepatocellular carcinoma
    MA Bo-heng, WANG Xia, WU Ying
    2023, 28(6):  676-679. 
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    Objective To review the clinicopathological data and surgical treatment efficacy of sarcomatoid and high-grade hepatocellular carcinoma (HCC) cases, so as to provide clinical information for sarcomatoid HCC. Methods The data of sarcomatoid and high-grade HCC patients who underwent surgery from January 2007 to March 2018 were reviewed. Edmondson-Steiner pathological grade III ~ IV cases were defined as high-grade HCC. A total of 21 cases of sarcomatoid HCC and 74 cases of high-grade HCC patients with followed-up data were included in the final analysis. Clinicopathological data, and survival conditions of sarcomatoid and high-grade HCC patients were compared. Results There were significant differences in sex, HBsAg(+) and AFP between sarcoma-like and high-grade HCC patients (P<0.05), but there were no significant differences in age, HCV-Ab, liver cirrhosis, ALT, TBil, Alb and INR (P>0.05). The tumor diameters of sarcomatoid and high-grade HCC patients were 8.3 (1.6, 24.5) cm and 5.4 (1.3, 17.0) cm, the difference was statistically significant (P<0.05). Sarcoma-like HCC had tumor envelope, tumor necrosis, adjacent organ invasion and lymph node metastasis in 5 cases (23.8%), 17 cases (80.9%), 5 cases (23.8%) and 6 cases (28.6%), which were compared with high-grade HCC [37 cases (50.0%), 26 cases (35.1%), 6 cases (8.1%) and 4 cases (5.4%), respectively, the difference was statistically significant (P<0.05). The median OS of sarcomatoid HCC patients was shorter than that of high-grade HCC patients [10.4 months vs 48.0 months, P<0.05]. The 1-year, 3-year and 5-year OS rates of sarcomatoid HCC were 52.4% (11/21), 19.0% (4/21) and 14.3% (3/21), while those of high-grade HCC were 85.1% (63/74), 54.0% (40/74) and 40.5% (30/74), respectively, the difference was statistically significant (P<0.05). The median RFS of sarcomatoid HCC patients was shorter than that of high-grade HCC patients [5.5 months vs 16.5 months, P<0.05]. The half-year, one-year and three-year RFS rates of sarcomatoid HCC were 47.6% (10/21), 23.8% (5/21) and 9.5% (2/21), respectively, which were significantly lower than those of high-grade HCC [82.4% (61/74), 59.4% (44/74) and 33.8% (25/74), respectively], the difference was statistically significant (P<0.05). Conclusion Compared with high-grade HCC, sarcomatoid HCC has a lower AFP level, more frequent tumor invasion and lymph node metastasis, and a poorer prognosis. The high invasiveness of sarcomatoid HCC may be mediated by specific cancerous components.
    A comparison between HCV-related hepatocellular carcinoma patients with or without direct acting antivirals treatment
    JIN Zhi-en, XU pan, YUAN Hong-wei, XU Jing-jiang
    2023, 28(6):  680-682. 
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    Objective To compare the hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) in patients with or without receiving direct antiviral antivirals (DAAs). Methods Seventy three cases of HCV-related HCC enrolled from March 2018 to June 2021 were reviewed, including 58 males and 15 females, aged 56 (44, 76) years. They were divided into a DAAs group and a non-DAAs group according to whether DAAs treatment had been applied or not. The diagnosis of the disease met the requirements. The baseline data, oncological features and tumor stages (BCLC stage, TNM stage and CLIP score) of HCV-related HCC cases were collected and compared. Results There were 21 cases in DAAs group and 52 cases in non-DAAs group respectively. Abdominal pain, ascites, lower limb edema, jaundice and fatigue in DAAs group were 16 cases (76.2%), 2 cases (9.5%), 1 case (4.8%), and 1 case (4.8%), respectively, which were significantly different with those of 1 case (4.8%), 17 cases (32.7%), 15 cases (8.8%), 11 cases (21.1%), 9 cases (17.3%), 0 case (0) in non-DAAs group (P<0.05). There were 10 cases (47.6%) of portal vein thrombosis in DAAs group, which were significantly higher than those of 12 cases (23.1%) in non-DAAs group (P<0.05). There were 6 cases (28.6%) of Lymph node metastasis in DAAs group, which were significantly higher than those of 3 cases (5.8%) in non-DAAs group [ P<0.05]. The BCLC stages (0, A, B, C, D) in DAAs group were 2 cases (9.5%), 2 cases (9.5%), 3 cases (14.3%), 9 cases (42.8%) and 5 cases (23.8%) in each stage, while those in non-DAAs group were 6 cases (11.5%), 19 cases (36.5%), 16 cases (30.8%), 4 cases (7.7%), and 7 cases (13.5%), respectively, the difference was statistically significant (P<0.05). The TNM stages (Ⅰ, Ⅱ, Ⅲ, Ⅳ) in DAAs group were 2 cases (9.5%), 3 cases (14.3%), 10 cases (47.6%) and 6 cases (28.6%) in each stage, while those in non-DAAs group were 27 cases (51.9%), 12 cases (23.1%) and 8 cases (15.4%), respectively, the difference was statistically significant (P<0.05). The CLIP scores (0, 1, 2, 3, 4~6) of DAAs group were 2 (9.5%), 5 (23.8%), 2 (9.5%), 3 (14.3%) and 9 (42.8%), while those of non-DAAs group were 12 (23.1%), 15 (28.8%), 11(21.1%), 13(25.0%), and 1(1.9%), respectively, the difference was also statistically significant (P<0.05). Conclusion Chronic hepatitis C patients need long-term HCC monitoring even after DAAs treatment.
    Viral Hepatitis
    Characteristics and clinical significance of peripheral blood lymphocyte subsets in patients with chronic hepatitis C
    QIN Yuan-feng, SHI Hai-yan, HUANG Zhong-qiang
    2023, 28(6):  683-687. 
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    Objective To explore the characteristics and clinical significance of peripheral blood lymphocyte subsets in patients with chronic hepatitis C. Methods Between January 2018 and July 2022, 138 patients with chronic hepatitis C and 72 healthy persons admitted for physical examination in the same period were selected. According to their clinical manifestations, the patients were divided into simple chronic hepatitis C group, early hepatitis C cirrhosis group and decompensated hepatitis C. The general data, peripheral blood lymphocyte subsets count and peripheral blood lymphocyte subsets percentage were compared. Results Comparing the clinical features, the levels of ALT, AST, and total bilirubin were 29.6 (18.2, 47.8) U/L, 33.6 (24.4, 50.1) U/L and 25.5 (18.5, 63.6) μmol/L respectively, which were significantly higher than in control group (21.5 (16.8, 26.5) U/L, 23.5 (15.7, 30.2) U/L and 16.6 (13.6, 26.1) μmol/L) (P<0.05). While the level of Hb was 78.2 (64.2, 105.3) g/L, which was significantly lower than that of control group97.3 [ (78.1, 118.9) ] g/L. Comparing the number of lymphocyte subsets in peripheral blood, the absolute value of CD45+CD3+CD4+ lymphocytes, CD45+CD3+CD8+ lymphocytes, and CD45+CD3-CD16+56+ lymphocytes of simple chronic hepatitis C group were 7058 (4612, 9645) /mL, 5739 (4015, 7462) /mL and 2694 (845, 3512) /mL respectively, which were significantly lower than that of control group [(7962 (5492, 9413) /mL, 6036 (4921, 9687) /mL and 3876 (1694, 4982) /mL)] (P<0.05). The absolute value of CD45+ lymphocytes, CD45+CD3+ lymphocytes, CD45+CD3+CD4+ lymphocytes, CD45+CD3+CD8+ lymphocytes and CD45+CD3-CD16+56+ lymphocytes of hepatitis C early cirrhosis group were 1550 (1256, 1864) /mL, 1126 (826, 1569) /mL, 6342 (5169, 8945) /mL, 5897 (3958, 8521) /mL and 2730 (1398, 4851) /mL respectively, which were significantly lower than in control group [1900 (1659, 2506) /mL, 1420 (913, 1649) /mL, 7962 (5492, 9413) /mL, 6036 (4921, 9687) /mL and 3876 (1694, 4982) /mL] (P<0.05). The absolute value of CD45+ lymphocytes, CD45+CD3+ lymphocytes, CD45+CD3+CD4+ lymphocytes, CD45+CD3+CD8+ lymphocytes and CD45+CD3-CD16+56+ lymphocytes of decompensated hepatitis C cirrhosis group were 1226 (854, 1695) /mL, 953 (562, 1654) /mL, 6095 (4951, 9165) /mL, 3964 (1652, 5984) /mL and 2465 (1245, 3451) /mL respectively, which were significantly lower than in control group [1900 (1659, 2506) /mL, 1420 (913, 1649) /mL, 7962 (5492, 9413) /mL, 6036 (4921, 9687) /mL and 3876 (1694, 4982) /mL] (P<0.05). Compared with the percentage of lymphocytes , the percentage of CD45+CD3-CD19+ lymphocytes and CD4+/CD8+ of hepatitis C early cirrhosis group were 19.8 (9.6, 27.7) and 2.9 (1.4, 3.5), respectively, which were significantly higher than in control group [15.7 (7.5, 21.6) and 2.3 (1.6, 3.1)] (P<0.05). While the percentage of CD45+CD3-CD16+56+ was 15.8 (6.6, 29.8), which was significantly lower than in control group [17.8 (8.6, 27.1)] (P<0.05). The percentage of CD45+CD3-CD19+ and CD4+/CD8+ ratio of decompensated hepatitis C cirrhosis group were 21.5 (6.2, 30.3) and 3.1 (1.3, 4.1), respectively, which were significantly higher than in control group [15.7 (7.5, 21.6) and 2.3 (1.6, 3.1) ] (P<0.05). While the percentage of CD45+CD3-CD16+56+ was 9.6 (3.3, 16.7), which was significantly lower than in control group [17.8 (8.6, 27.1)] (P<0.05). Conclusion During the chronic development of hepatitis C virus infection to the early stage and decompensated stage of liver cirrhosis, the absolute values of CD4+T cells, CD8+T cells and NK cells in peripheral blood decreased, while the percentage of B cells in the peripheral blood and CD4/CD8 ratio both significantly rised.
    Drug Induced Liver Injury
    An analysis on the influencing factors of liver injury caused by immunotherapy in lung cancer patients
    WANG Han, PENG Jin, JIN Hui-ru, WANG Xiao, DAI Jing-jing, Li Jun, JIANG Long-feng
    2023, 28(6):  688-693. 
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    Objective To explore the characteristics and influencing factors of immunotherapy-mediated liver injury in lung cancer patients. Methods The clinical data of lung cancer patients with complete information who received immunotherapy with Immune checkpoint inhibitors (ICIs) from July 2018 to July 2021 were retrospectively analyzed. The patients were divided into non-liver injury group (n=189) and liver injury group (n=81) according to whether they had liver function abnormalities during immunotherapy. Alternatively, they were divided into immunotherapy group (n=25), immunotherapy combined with anti-angiogenic agents group (n=6), and immunotherapy combined with chemotherapy group (n=50) according to different treatment regimes, and the clinical data among all groups were compared. Results The proportion of female patients in the liver injury group was higher than that in the non-liver injury group (30.86% vs 18.52%,P=0.025). The lymphocyte count [1.52 (1.13, 1.94),P=0.010], erythrocyte level [4.29 (3.96,4.67),P=0.004] and hemoglobin level [131.0 0(121.50, 145.00),P<0.001] before immunotherapy in the liver injury group were higher. However, neutrophil count/lymphocyte count [2.62 (1.86, 3.98),P=0.004] and platelet/lymphocyte count [132.39 (92.60,183.27),P<0.001] were lower. Multiple logistic regression analysis showed that gender (P=0.018, OR=2.142, 95%CI 1.137-4.035) was an independent risk factor. Between different immunotherapy regimens, patients in the immunotherapy combined with chemotherapy group showed earlier elevation of transaminase. Conclusion The clinical symptoms of patients with immune-mediated hepatitis are not typical, which is more common in female patients. There is no obvious correlation between the liver injury with age, pathological type, underlying disease, whereas gender is an independent risk factor.
    Clinical analysis of immune-mediated hepatotoxicity induced by immune checkpoint inhibitors in tumor patients
    QIAN Xiang-yun, HUANG Da-bing, WANG Feng
    2023, 28(6):  694-697. 
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    Objective To evaluate the incidence and risk factors of immune-mediated hepatotoxicity (IMH) based on the clinical data of tumor patients treated with immune checkpoint inhibitors (ICIs). Methods A total of 148 tumor patients [115 males and 33 females, aged 67 (41, 82) years] who received ICIs treatment in our hospital from June 2019 to August 2022 were collected, including 67 cases of non-small cell lung cancer, 43 cases of renal cell carcinoma, 25 cases of urothelial carcinoma and 13 cases of malignant melanoma. ICIs included 77 cases of nivolumab, 42 cases of pembrolizumab, 9 cases of durvalumab, 8 cases of atezolizumab, 5 cases of ipilimumab and 7 cases of nivolumab combined with ipilimumab. The CTCAE grade of liver injury ≥2 was used to exclude liver injury caused by other causes, and ALT/AST ratio> 3 times the upper limit of normal value was defined as the IMH group, and the rest were classified as non-IMH groups. Multiple regression analysis was performed to explore the influencing factors of IMH risk increase. Results There were 25 cases in the IMH group and 123 cases in the non-IMH group. The mean time to develop IMH after receiving ICIs treatment was 51 (7, 207) days after ICIs treatment. In IMH group, CTCAE grade =2, 3 and 4 were 9 cases, 11 cases and 5 cases respectively. All cases discontinued ICIs; among them, 5 cases were treated with ursodeoxycholic acid, 11 cases were treated with cortisol, and the remaining 9 cases were treated with a combination of ursodeoxycholic acid and cortisol. All patients in the IMH group were followed up, and their liver function improved. Six patients resumed ICIs treatment after their liver injury improved, while the rest discontinued treatment either due to IMH or other immune-related adverse events (irAEs). In the IMH group, the numbers of cases of non-small cell lung cancer, malignant melanoma, treatment with nivolumab combined with ipilimumab, prior ICIs treatment history, and liver metastasis were 3 cases (12.0%), 12 cases (48.0%), 6 cases (24.0%), 5 cases (20.0%) and 9 cases (36.0%) respectively. When compared with the non-IMH group [64 cases (52.0%), 1 case (7.7%), 1 case (0.8%), 2 cases (1.6%) and 13 cases (10.6%)], the difference was statistically significant (P<0.05). The levels of ALT and AST in the IMH group were significantly higher than those in the non-IMH group(all P<0.05). Multiple regression analysis showed that malignant melanoma [OR (95% CI): 11.3 (3.5, 38.0), P<0.05] and the combination of nivolumab and ipilimumab [OR (95% CI): 60.2 (7.9, 475.3), P<0.05] were independently associated with the increased risk of IMH. 16.9% of tumor patients treated with ICIs had liver injury with CTCAE grade> 2. Conclusion Cortisol therapy can effectively improve liver injury in IMH patients. The occurrence of IMH is related to tumor type and ICIs drugs used, and the risk of IMH is significantly increased in patients with malignant melanoma and those receiving combination therapy of nivolumab and ipilimumab.
    Analysis of influencing factors and prognosis of 32 patients with drug-induced liver injury and liver failure
    WU Ya-ling, YAO Min, QIN Cheng
    2023, 28(6):  698-701. 
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    Objective To explore the risk factors and prognosis of drug-induced liver injury(DILI) and liver failure(DILF). Methods Between January 2015 and December 2022, hospitalized patients in Nantong Cancer Hospital who were diagnosed with DILI or DILF were enrolled. There were 221 patients with DILI[97 males, 124 females; age=46 (37, 60) years] and 32 cases of DILF[17 males, 15 females, age=47 (40, 58) years]. The clinical data of DILI, DILF and DILF patients with different clinical outcomes were compared. Multivariate analysis was used to explore the risk factors and poor prognosis of liver failure. Results The drug use of DILI patients included 120 cases of traditional Chinese medicines/proprietary Chinese medicines (54.3 %), 37 cases of anti-tuberculosis drugs (16.7 %), 29 cases of cold drugs (13.1 %), 11 cases of anti-tumor drugs (5.0 %), 7 cases of hypolipidemic drugs (3.2 %), 5 cases of antithyroid drugs (2.3 %) and neuropsychiatric drugs. The drug use of DILF patients included 14 cases of anti-tuberculosis drugs (43.7 %), 12 cases of traditional Chinese medicine/proprietary Chinese medicine (37.5 %), 2 cases of cold drugs (6.2 %), and 1 case of anti-tumor drugs, immunomodulators, psychotropic drugs and antihypertensive drugs (3.1 %). Univariate analysis showed that the scores of HBV infection, anti-tuberculosis drugs, WBC, AST, TBil, blood ammonia, INR and MELD in patients with DILI were significantly lower than those in patients with DILF, while PLT and PTA in patients with DILI were significantly higher than those in patients with DILF(P<0.05). Excluding indicators that reflect the severity of liver injury such as liver function, coagulation function and other indicators, multivariate analysis showed that HBV infection, increased WBC and decreased PLT were independent risk factors for DILF(P<0.05). After systemic treatment, 14 patients with DILF improved and 18 patients deteriorated. Univariate analysis indicated that the differences in ALT, TBil, Scr, PTA, INR and MELD scores between patients with DILF who improved and those who deteriorated were statistically significant (P<0.05). Multivariate analysis showed that low PTA was an independent risk factor for poor prognosis of DILF patients (P<0.05). Conclusion There are many risk factors for patients with DILF, including increased WBC and decreased PLT. When HBV-infected patients take anti-tuberculosis drugs, traditional Chinese medicine/Chinese patent medicine and other high-risk drugs causing liver injury, they need to be alert to the occurrence of AILF. In addition, patients with AILF often have poor prognoses when they have abnormal coagulation function.
    Liver Failure
    Predictive value of COSSH-ACLF score combined with serum NLR and AFP for short-term prognosis of acute-on-chronic liver failure after artificial liver support therapy
    ZHANG Xue, SONG Jie, SHAO Xue
    2023, 28(6):  702-706. 
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    Objective To investigate the predictive value of COSSH-ACLF score combined with serum neutrophil/lymphocyte ratio (NLR) and alpha-fetoprotein (AFP) in the short-term prognosis of acute-on-chronic liver failure (ACLF) after artificial liver support therapy. Methods 260 patients with ACLF who successfully received artificial liver support therapy in our hospital from February 2020 to January 2022 were selected retrospectively as the treatment group. Based on whether the patients survived 90 days after treatment, the patients in the treatment group were subdivided into survival group (236 cases) and death group (24 cases). In addition, 260 volunteers who underwent physical examination in our hospital at the same time were selected as the control group. COSSH-ACLF score, NLR and AFP levels were recorded for further analysis. Multivariate logistics regression analysis was used to analyze the risk factors affecting the short-term prognosis of ACLF. ROC curve was used to evaluate the predictive value of COSSH-ACLF score, NLR and AFP on the short-term prognosis of ACLF after artificial liver support therapy. Results The scores of COSSH-ACLF, NLR and AFP in the treatment group were higher than those in the control group (P<0.05); COSSH ACLF score, NLR and AFP in the death group were higher than those in the survival group (P<0.05); The short-term prognosis of ACLF after artificial liver therapy was correlated with serum total bilirubin (TBil), creatinine (Cr), international normalized ratio (INR), MELD score, C-reactive protein (CRP), COSSH-ACLF score, NLR and AFP (P<0.05); Multivariate regression analysis showed that TBil, INR, COSSH-ACLF score, NLR, AFP were the risk factors for short-term prognosis of ACLF treated with artificial liver support therapy (P<0.05). ROC curve showed that the combined prediction of COSSH-ACLF score, NLR, and AFP for short-term prognosis of ACLF had an AUC of 0.877, which was greater than the AUC of individual predictions (P<0.05), and AUC of COSSH ACLF score, NLR, AFP were 0.733, 0.798, 0.794, respectively. Conclusion COSSH ACLF score, NLR and AFP are risk factors for short-term prognosis of patients with ACLF after artificial liver support therapy, and their combined detection has certain predictive value for short-term prognosis of patients with ACLF.
    Clinical efficacy of DPMAS combined with PE in the treatment of liver failure
    YANG Hang, LUO Yong-yan, PAN Lu-da, ZHANG Lue-tao, SONG Su-na
    2023, 28(6):  707-710. 
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    Objective To study the curative effect of double plasma molecular adsorption system (DPMAS) combined with plasma exchange (PE) on patients with liver failure. Methods A total of 138 patients with liver failure from October 2018 to May 2022 were enrolled. The patients were randomly divided into DPMAS group(Group A), PE group(Group B) and DPMAS+ PEgroup(Group C) with 46 cases in each group. The changes of liver function indexes (AST, ALT, TBil), the serum cytokines (TNF-α, IFN-γ and IL-6) and coagulation function (PT, INR, PTA) in the 3 groups were collected. Results On the 90th day of treatment, managment in Group C was assessed as markedly effective in 22 cases, effective in 14 cases and ineffective in 3 cases. 7 cases died during the treatment. The intervention outcomes for Group C outperformed those of both Group A(which had 12 effective cases, 19 effective cases, 3 ineffective cases and 12 deaths) and Group B(which had 11 effective cases, 18 effective cases, 3 ineffective cases, 14 deaths) (Z=-2.044, -2.408; P=0.041, 0.016). On the 28th and 90th of treatment, the levels of TBil in Group B[(201.1±77.4) μmol/L and (93.6±28.2) μmol/L, respectively] were significantly higher than those in Group A [(157.9±56.2) μmol/L and (80.2±21.7) μmol/L] and Group C [(162.7±50.2) μmol/L and (78.6±24.6) μmol/L, F=6.630、5.004,P=0.002、0.008]. On the 90th day of treatment, the serum levels of TNF-α, IFN-γ and IL-6 in Group C[(20.6±14.4) pg/mL, (32.4±13.8) pg/mL and (31.7±10.1) ng/L, respectively] were significantly lower than those in group A [(34.2±16.2) pg/mL, (43.2±18.4) pg/mL and (48.7±14.4) ng/L] and group B [(35.7±17.3) pg/mL, (40.6±17.6) pg/mL and (50.0±12.8) ng/L]. F=12.417、5.228、30.406,all P<0.05]. On the 90th day of treatment, PT and INR in Group A[(18.3±3.8) s and (1.23±0.11), respectively] were significantly higher than those in Group B [(15.1±3.6) s and (1.10±0.09)] and Group C [(14.6±3.9) s and (1.07±0.27), F=13.052、10.722,P=0.000、0.000]. Conclusion The DPMAS sequential PE therapy for patients with liver failure effectively leverages the strengths of both DPMAS and PE. It is capable of clearing cytokines, improving coagulation disorder, safeguarding liver function and thereby enhancning the overal therapeutic efficacy.
    Other Liver Diseases
    The predictive value of serology combined with MRI in-phase and opposed-phase sequences for fat quantification in nonalcoholic fatty liver disease
    PENG Xiao-lin, GONG Xiu-ru, GUO Ya-xin, ZHU Ting-ting, ZHANG Min-guang, SHU Zheng
    2023, 28(6):  711-715. 
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    Objective To explore a new method for assessing fat content in nonalcoholic fatty liver disease(NAFLD) by combining imaging methods and serological indicators to construct a multiple linear regression prediction model. Methods A total of 220 patients were enrolled from January 2015 to December 2020 in the Radiology Department of The Hospital of Traditional Chinese Medicine affiliated with Shanghai University of Traditional Chinese Medicine, including 86 patients in the non-NAFLD group and 134 patients in the NAFLD group. Furthermore, the NAFLD group was subdivided into mild group, moderate group and severe group, according to the degree of fatty liver. All patients underwent CT and MRI scans at the same time and obtained serological examination including alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamine transpeptidase (γ-GT), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C). The correlation of serology, MRI in-phase and opposed-phase and diffusion-weighted imaging with different degrees of fatty liver was analyzed, and the prediction model of multiple linear regression was established. Results AST levels of the mild, moderate and severe groups were 32.78±23.81 U/L, 37.53±24.87 U/L and 46.10±28.62 U/L, respectively. ALT levels were 37.79±33.64 U/L, 43.60±22.60 U/L and 70.11±57.23 U/L, respectively. TG levels were (2.18±1.09), (2.47±1.75) and (3.00±2.60) mmol/L, respectively. GGT levels were 61.81±86.91 U/L, 108.22±157.38 U/Land 78.80±73.39 U/L, respectively. These serological indicators were significantly higher than the control group(P<0.05). HDL-C of the mild, moderate and severe groups were 1.19±0.35 U/L, 1.10±0.28 mmol/L and 1.11±0.31 mmol/L, respectively, significantly lower than that of the control group (1.32±0.30 mmol/L)(P<0.05). In the diagnosis of the mild group, the optimal cut-off value of HFF was 0.04, AUROC was 0.911 (95%CI 0.873-0.949), sensitivity was 88.1%, specificity was 81.4%; In the diagnosis of the moderate group, the optimal cut-off value was 0.11, AUROC was 0.880 (95%CI 0.815-0.945), sensitivity was 87.2%, specificity was 77.5%. In the diagnosis of the severe group, the optimal cut-off value was 0.18, AUROC was 0.978 (95%CI 0.960-0.996), sensitivity was 100%, and specificity was 88.9%. The final multiple linear regression equation was: liver/spleen density ratio =1.202-0.002AST-2.215HFF (R2=0.690). Conclusion In the initial diagnosis of fat content in patients with NAFLD, AST and HFF have the potential to substitute the ratio of liver/spleen CT value in predicting the fat content of NAFLD.
    Clinical, biochemical and histological features of 82 cases of acute autoimmune hepatitis
    WANG Hui-chi, TIAN Lu, ZHENG Yi, ZHAO Peng, DONG Hai-ling, BIAN Yu-yao
    2023, 28(6):  716-719. 
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    Objective To analyze the clinical, biochemical and histological characteristics of patients with acute autoimmune hepatitis (AAIH). Methods Between January 2010 and October 2022, 82 patients with AAIH who underwent liver biopsy were reviewed, including 13 males and 61 females, aged (53.2±8.7) years. All cases met the diagnostic criteria for AIH and AAIH. Patients were classified into three groups based on their International Normalized Ratio(INR) status and the presence of hepatic encephalopathy: acute non-severe cases(INR<1.5), acute severe cases(INR>1/5, with no hepatic encephalopathy), and fulminate cases(acute severe cases where hepatic encephalopathy occurred within 26 weeks post-jaundice onset). The clinical and pathological data of each group were compared, and the influencing factors of AAIH patients' conditions were discussed by multivariate Logistic regression analysis. Results There were 52 cases of non-severe, 21 cases of acute severe and 9 cases of fulminant AAIH, respectively. The TBil level and prothrombin activity in non-severe cases were 101.6 (28.0, 202.5) μmol/L, 74 (55, 87) %, respectively. Compared with those in acute severe cases [211.6 (150.9, 381.3) μmol/L, 42 (33, 58) %] and fulminant cases [352.2 (215.1, 492.4) μmol/L, 31 (22, 50) %], the differences were statistically significant (P<0.05). There were 49 cases (94.2%), 13 cases (61.9%) and 5 cases (55.5%) of acute non-severe, acute severe and fulminant AAIH patients, respectively, and the difference was statistically significant (P<0.05). Taking the conditions of AAIH patients (assignment 0= acute non-severe, 1= acute severe and fulminant) as dependent variables, and TBil, prothrombin activity and steroid use (assignment 0= used, 1= unused) as independent variables, multivariate Logistic regression analysis showed that TBil, prothrombin activity and steroid use were independent predictors of AAIH patients' condition (P<0.05). There were 15 cases (28.8%), 10 cases (47.6%) and 8 cases (88.9%) of acute non-severe, acute severe and fulminant AAIH patients with cholestasis, and the difference was statistically significant (P<0.05). There were 26 cases (50.0%), 12 cases (23.1%) and 14 cases (26.9%) of non-severe mild, moderate and severe central lobular necrosis, compared with acute severe [4 cases (19.0%), 2 cases (9.5%) and 15 cases (71.4%)] and fulminant [3 cases (33.3%), 0 (0) and 6 cases (66.7%)], and the difference was statistically significant (P<0.05). Conclusion Compared with chronic AIH, AAIH patients have differences in clinical manifestations, laboratory data and histological results. Fulminant hepatitis, cholestasis, TBil and prothrombin activity are risk factors for the prognosis of AAIH patients.