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    31 January 2023, Volume 28 Issue 1
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    Liver Failure
    Malignant hematological diseases with liver failure as the primary manifestation: a report of 7 cases
    LAI Man, WANG Su-dan, SHEN Lin, LIU Hai-xia
    2023, 28(1):  33-36. 
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    Objective To investigate the clinical features of malignant hematological diseases with liver failure as the initial manifestation. Methods The clinical data including clinical symptoms, laboratory markers, imaging features of 7 malignant hematological cases with acute or subacute liver failure as the initial manifestation diagnosed at our hospital from January 1, 2017 to January 1, 2022 were analyzed retrospectively. Results All the 7 patients were female, with an average age of 7-65 years. They all had typical symptoms and signs of liver failure. Seven cases had fever in the course of the disease, 4 patients had rash, 4 patients had lymphadenopathy, and 6 patients had splenomegaly. During the course of the disease, leukopenia, anemia or thrombocytopenia occurred in 7 cases. Imaging findings were lymphadenopathy, splenomegaly, bone invasion and so on. Bone marrow cytology indicated hemophagocytic syndrome, lymphoma cell.Conclusion Liver failure might be the initial manifestation of patients with hematological malignancies. There is a high misdiagnosis rate in these patients because of the nontypical clinical representations. Cytological examination of bone marrow should be performed as soon as possible in suspicious patients.
    The effects of cirrhosis and related complications on the prognosis of ACLF
    ZHAI Qing-hui, LIU Wan-shu, TIAN Hua, LI Dong-ze, XIN Shao-jie
    2023, 28(1):  37-40. 
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    Objective To investigate the effects of cirrhosis and acute-on-chronic liver failure (ACLF) related complications on the prognosis of patietns with ACLF. Methods A total of 1409 patients with ACLF were enrolled and followed up. Kaplan Meier method and Cox regression were used to analyze the survival rates and risk factors among the groups. Spearman correlation analysis was used to investigate the correlation between the occurrence of complications and ACLF staging. Results The 28-day and 360-day survival rates of ACLF in the cirrhosis group were 57.93% and 24.96%, in the non-cirrhosis group were 81.74% and 66.88%, respectively (χ2=13.618, 58.631, P<0.001). The survival curve showed that the 360-day mortality of non-cirrhosis group was significantly higher than that of cirrhosis group [log rank (mantel Cox) χ2=113.090, P<0.001]. The number of complications was significantly associated with the prognosis of ACLF [log rank (mantel Cox) χ2=268.642, P<0.001]. Cox multivariate regression showed that cirrhosis and 3 or more complications were the independent risk factors for death in patients with ACLF [HR 1.817 (95%CI: 1.460-2.260), 1.753 (95%CI: 1.379-2.229), P<0.001]. The number of complications of patients with ACLF was positively correlated with the type of ACLF, ACLF stage and MELD-Na score (Correlation coefficients were 0.319, 0.340 and 0.472 respectively, P<0.001) and negatively correlated with the prothrombin time activity (Correlation coefficient was -0.358, P<0.001).Conclusion Cirrhosis and complications are the main risk factors affecting the prognosis of ACLF, with a negative correlation. The liver cirrhosis and severity of liver decompensation are the important risk factors for ACLF complications.
    Predictive value of COSSH-ACLFⅡ score for short-term prognosis in patients with acute-on-chronic liver failure
    SHEN Zhou-ming, CHEN Wei-jie, LIU Yi-cun, ZHANG Li, XUE Hong, BIAN Zhao-lian
    2023, 28(1):  41-45. 
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    Objective To investigate the predictive value of COSSH-ACLFⅡ score in the short-term prognosis of patients with acute-on-chronic liver failure (ACLF). Methods A total of 73 patients with ACLF admitted to our hospital from January 2020 to January 2022 were collected, they were divided into survival group and death group according to the survival status during the 90-day follow-up. The χ2 test was used to compare the enumeration data between the 2 groups. The t test or the Mann-Whitney U test was used to compare the measurement data between the 2 groups. The clinical data between the 2 groups were compared, and the receiver operating characteristic (ROC) curve was used to analyze the clinical efficacy of COSSH-ACLFⅡ, MELD, MELD-Na, iMELD and CTP scores in predicting the prognosis of patients with ACLF, and the optimal cutoff of COSSH-ACLFⅡ score was calculated. The Kaplan-Meier method was used to draw survival curves. Results There were significant differences in age (50.84 ± 12.49 vs 63.00 ± 12.47, t=-3.910, P＜0.01), hepatic encephalopathy (16.33% vs 37.50%, χ2=4.043, P=0.044), gastrointestinal bleeding (6.22% vs 41.67%, χ2=11.583, P＜0.01), total bilirubin [229.10 (113.80,363.40) vs 294.45 (241.88,366.30), U=-2.243, P=0.025], international normalized ratio (1.67±0.49 vs 1.94 ± 0.56, t=-2.117, P=0.038), serum creatinine (64.14 ± 18.20 vs 94.51±40.60, t=-3.497, P=0.020) and blood urea nitrogen [4.68 (3.12,6.55) vs 6.82 (4.05,10.44), U=-2.178, P=0.029] between the survival group and the death group (P<0.05). The COSSH-ACLFⅡ (6.58 ± 0.95 vs 7.78 ± 0.86, t=-5.238, P＜0.01), MELD (20.46 ± 6.52 vs 24.28 ± 3.76, t=-2.653, P＜0.01), MELD-Na (21.40 ± 9.45 vs 26.15 ± 8.01, t=-2.120, P=0.038), iMELD (40.73 ± 8.64 vs 51.81 ± 14.92, t=-4.019, P＜0.01) and CTP (10.00 ± 1.74 vs 11.00 ± 1.47, t=-2.416, P=0.018) scores in the death group were higher than those in the survival group, and the differences were statistically significant (P<0.05). The ROC curve analysis showed that the area under the curve (AUC) of different scoring systems for predicting acute-on-chronic liver failure were: COSSH-ACLFII (AUC = 0.826,95% CI: 0.727~0.925), MELD (AUC = 0.688, 95% CI: 0.565~0.811), iMELD (AUC = 0.765, 95% CI: 0.684~0.882), MELD-Na (AUC = 0.651, 95% CI: 0.521~0.780) and CTP score (AUC=0.640,95% CI: 0.504~0.775). The AUC of the COSSH-ACLFIIs model was higher than that of other models. The optimal cutoff value of COSSH-ACLFII was determined by the Youden index at 7.02, Kaplan-Meier analysis showed that the cumulative survival rate of patients in COSSH-ACLFⅡ > 7.02 group was significantly lower than that in COSSH-ACLFⅡ ≤ 7.02 group, Log-Rank=19.97, and the difference was statistically significant (P<0.0001).Conclusion The COSSH-ACLFⅡ score model performs better than MELD score, MELD-Nascore, iMELD score and CTP score in predicting the short-term survival rate of patients with ACLF. COSSH-ACLFⅡ > 7.02 indicates poor prognosis.
    Analysis of etiology, clinical outcome and influencing factors of 58 cases of acute liver failure
    ZHAO Zi-yu, NIU Yao-fei, WANG Ming-qiang
    2023, 28(1):  46-49. 
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    Objective To investigate the etiology, clinical outcome and influencing factors of 58 cases with acute hepatic failure (AHF) were reviewed. Methods A total of 58 patients with AHF (27 males and 31 females) admitted to our hospital from January 2015 to December 2020 were included, with an average age of 45 (28, 66) years. According to the clinical outcome, they were divided into survival group and death group. The clinical data of the two groups were compared and analyzed by multiple factors. Results According to the medical history information of patients, 44 cases with known causes and 14 cases with unknown causes. Etiology included drug sources, viral hepatitis and other causes. Drug sources included Chinese herbal medicine (10 cases, 17.4%), acetaminophen (7 cases, 12.1%), antibacterial drugs (4 cases, 6.9%), anti-tuberculosis drugs (2 cases, 3.4%), anti-tumor chemotherapy drugs (1 case, 1.7%) and anticoagulant drugs (phenylpropyl coumarin) (1 case, 1.7%). Viral hepatitis included 5 cases of hepatitis B virus (HBV) (8.6%), 2 cases of hepatitis E virus (HEV) (3.4%) and 1 case of hepatitis A virus (HAV), cytomegalovirus and EB virus (1.7%), respectively. There were 3 cases of extrahepatic malignant tumor metastasis (5.2%), 2 cases of alcoholism (3.4%), 2 cases of severe biliary tract infection (3.4%), 1 case of Budd-Chiari syndrome and 1 case of heart failure (1.7%). Comparing the clinical data, the age of survival group [40 (28, 58) years] was significantly lower than that of death group [47 (36, 66) years, Z=-2.205, P<0.05]. In the survival group, the numbers of hepatic encephalopathy in stage ≤2 and stage > 2 were 19 cases (86.4%) and 3 cases (13.6%), while in the death group, the numbers were 9 cases (25.0%) and 27 cases (75.0%), the difference was statistically significant (χ2=20.592, P<0.05). In the survival group, platelet (PLT), low density lipoprotein (LDH), prothrombin activity (PTA), international normalized ratio(INR) and arterial blood ammonia were 120 (88, 225) ×109/L, 260 (124, 443) U/L, 30 (24, 61)%, 1.8 (1.2, 2.3) and 71 (60, 92) μmol/L, compared with the death group [86 (70, 148 ) ×109/L, 382 (227, 593) U/L, 16 (12, 46)%, 3.4 (2.5, 3.83) and 152 (116, 170) μmol/L], the differences were statistically significant (Z=7.052,-9.450,15.600,-23.634 and -25.466, P<0.05). Logistic regression analysis showed that age, stage of hepatic encephalopathy, INR and arterial blood ammonia were independent risk factors for death of AHF patients (P<0.05).Conclusion Etiology of patients with AHF mainly includes drug-induced and viral hepatitis, with Chinese herbal medicine and HBV as the most common causes. In addition, age, stage of hepatic encephalopathy, INR and arterial blood ammonia are independent risk factors for death of AHF patients.
    Liver Fibrosis & Cirrhosis
    Effect of ascites discharge on intra-abdominal pressure and renal perfusion in patients with cirrhosis
    GUO He-bing, WANG Xue-mei, LIU Jing-yuan
    2023, 28(1):  50-54. 
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    Objective To investigate the characteristics of ultrasonic renal perfusion indexes in patients with cirrhotic ascites and relationship between intra-abdominal pressure and renal resistance index. To investigate the influence of ascites discharge on intra-abdominal pressure, systemic hemodynamics and renal perfusion. Methods Patients with cirrhotic ascites and intra-abdominal hypertension were included, with an average age of 18-70 years. Patients with chronic renal failure and other causes that interfered with abdominal ultrasonography were excluded. A total of 21 cases were included in the study. Color Doppler ultrasonography was used to measure the renal blood perfusion index. Direct peritoneal puncture manometry was used to measure peritoneal pressure. Intra-abdominal pressure, systemic hemodynamic indexes, and renal blood perfusion parameters were recorded and analyzed at 4 time nodes: before discharging ascites, cumulative release of ascites 2500 ml, 5000ml and 7500ml, respectively. Pearson correlation analysis was used to analyze the relationship between intra-abdominal pressure and the renal resistance index. Self-control design was used to analyzed the effect of massive ascites drainage on systemic hemodynamics and renal perfusion. Results Abdominal hypertension was obvious in patients with cirrhosis and ascites. The median intraperitoneal pressure was 18 (15.5-21) cmH2O. Renal artery resistance index (RI) generally increased, the median intraperitoneal RI was 0.727 (0.72-0.755). There was a moderate correlation between the intra-abdominal pressure and the renal resistance index (r=0.491, P＜0.001). Intraperitoneal pressure could be significantly reduced after ascites discharge. The median intraperitoneal pressure before discharging ascites and cumulatively discharging ascites 7500 mL were 18 (15.5-21) cmH2O and 12 (9.5-13.5) cmH2O, H=26.584, P＜0.001. As intra-abdominal pressure decreases, there was a downward trend for the mean arterial pressure. The mean arterial pressure before discharging ascites and cumulatively discharging ascites 7500 mL were 81 (77-90) mmHg and 76 (75-81) mmHg, H=8.767, P=0.033. The renal resistance index decreased significantly with the decrease of intra-abdominal pressure. The average RI before discharging ascites and cumulatively discharging ascites 7500 mL were 0.727 (0.72-0.755) and 0.641 (0.623-0.66), H=64.104, P＜0.001.Conclusion There is a correlation between intra-abdominal pressure and the renal resistance index. Discharging ascites can improve peritoneal hypertension and the renal artery resistance index in cirrhotic patients with ascites.
    Risk factors of rebleeding in cirrhotic patients with esophageal gastric variceal bleeding after endoscopic treatment
    HE Qing-lian, YU Bao-ping, XIAO Yong
    2023, 28(1):  55-60. 
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    Objective To investigate the risk factors for rebleeding within 180 days after endoscopic treatment in cirrhotic patients with esophageal gastric variceal bleeding (EGVB), and to compare the risk factors with child-Turcotte-Pugh (CTP) score, model for end-stage liver disease (MELD), MELD-Na, and integrated MELD (iMELD) and cirrhosis acute gastrointestinal bleeding (CAGIB). Methods A total of 142 cirrhotic patients with EGVB in our hospital from November 1, 2019 to November 31, 2021 were retrospective included, they were divided into rebleeding group and no bleeding group. The baseline data differences between the 2 groups were compared by t-test and non-parameter test. Univariate and multifactor Cox proportional risk regression was used to determine independent predictors of rebleeding. The performance of the Cox multifactor predictive model and CTP, MELD-Na, and CAGIB on the probability of rebleeding at 180 days was evaluated by the receiver operating characteristic (ROC). The area under the receiver operating characteristic (AUROC) was compared among prediction models through the DeLong method. Results During the 180-day follow-up period, rebleeding occurred in 61 (43.0%) patients, and 81 (57.0%) patients without rebleeding. Cox univariate regression analysis showed that the etiology (HR=1.970, 95%CI: 1.155~3.362, P<0.013), portal vein thrombosis (HR=2.605, 95%CI: 1.102~3.869, P=0.024), ApoA1 (HR=2.009, 95%CI: 1.196~3.374, P=0.008), fibrinogen (HR=2.683, 95%CI: 1.558~4.621, P<0.001) were associated with rebleeding; Cox multivariate regression analysis showed that the etiology (HR=3.922, 95%CI: 1.843~8.346, P<0.001), portal vein thrombosis (HR=2.798, 95%CI: 1.385~5.652, P=0.004), ApoA1 (HR=2.207, 95%CI: 1.122~4.340, P=0.022), fibrinogen (HR=2.729, 95%CI: 1.405~5.300, P=0.003) were independently associated with rebleeding within 180 days. ROC curve analysis showed that the predictive value of Cox multivariate hybrid models (AUROC 0.773, P<0.001) was better than MELD (AUROC 0.602, P=0.0388), iMELD (AUROC 0.620, P=0.0145), MELD-Na (AUROC 0.618, P=0.0166), CTP score (AUROC 0.688, P<0.001) and CAGIB (AUROC 0.625, P=0.0108).Conclusion The performance of combined model composed of etiology of cirrhosis, portal vein thrombosis, ApoA1 and fibrinogen had better predictive value for rebleeding in cirrhotic patients with EVGB after endoscopic treatment.
    Clinical outcome of liver cirrhosis patients with different complications treated by TIPS
    YAO Yong, FENG Lei, LIU Tian-yu, LIU Jie, PAN Jin
    2023, 28(1):  61-64. 
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    Objective To investigate the clinical outcome of liver cirrhosis patients with different complications treated by transjugular intrahepatic portosystemic shunt (TIPS) and investigate the best indications of TIPS for patients with cirrhosis. Methods A total of 80 patients with liver cirrhosis and portal hypertension treated by TIPS were included, they were divided into refractory ascites (RA) group and variceal bleeding (VB) group according to the complication. Clinical data including age, sex, Child score and the model for end-stage liver disease score (MELD score) were collected and analyzed. The Kaplan Meier method was used to calculate survival rate and log rank test was used to compare the survival condition. Results There was no significant difference of age (VB group: 61.4±10.3 years,RA group: 63.5±10.5 years), sex (male/female in VB group: 32/20, male/female in RA group: 15/13), Child score (level A/ level B/ level C in VB group: 24/26/2, level A/ level B/ level C in RA group: 7/18/3) or MELD score (VB group: 11.35±4.4,RA group: 13.2±5.3) between the 2 groups. The median survival times of RA and VB group were 28 months and 60 months respectively, and the difference was significant (P=0.008). After TIPS implantation, the average survival time of patients without stent occlusion (>60 months) was significantly higher than patients with stent occlusion (50 months), (P=0.025). The average survival time of patients with MELD score≤10 (51.3 months) was significantly higher than patients with MELD score>10 (36.1 months), (P=0.001). Overall survival curve showed there was a gradual decline of postoperative survival rates in patients with liver cirrhosis after the TIPS and survival rate was 45.3% at 60-month follow-up.Conclusion Compared to patients with liver cirrhosis and RA, patients with liver cirrhosis and VB benefit more from TIPS. In addition, stent occlusion and MELD score >10 are influencing factors of the survival time in patients with liver cirrhosis treated by TIPS.
    Visualized analysis on the association of nutrition with end-stage liver disease
    YANG Cheng, YANG Hua-sheng, HU Jian-hua, ZHANG Li-li, XU Chen
    2023, 28(1):  65-69. 
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    Objective To summarize the research progress and trends on the association of nutrition with end-stage liver disease (ESLD) via bibliometric analysis. Methods English literature on liver disease-associated nutrition problems from the core data set of Web of Science from January 30 of 1992 to,2021 were collected. The related literature were visually analyzed through the VOSviewer software, and the distributions of related authors, journals and key words were explored. Results "CLINICAL NUTRITION" magazine has the largest number of publications. The most outstanding researchers are Jenab M and Bamia C. The research hotspots are: non-alcoholic fatty liver disease, liver cirrhosis, liver cancer, malnutrition, lifestyle intervention, etc.Conclusion By visualized analysis on the related data including journals, citations and keywords, a panoramic picture of nutrition research on ESLD was constructed which may provide insight into the clinical work and research.
    The value of serum LPO, APN and TGF-β1 levels in evaluating the severity and prognosis of patients with alcoholic cirrhosis
    SHI Hong, XUE Xiao-chun, WANG De-qin, LV Zhong-mei
    2023, 28(1):  70-74. 
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    Objective To investigate the value of a combined determination with lipid peroxide (LPO), adiponectin (APN) and transforming growth factor -β1 (TGF-β1) for the severity and prognosis of alcoholic cirrhosis (ALC). Methods One hundred and fifty-two patients with alcoholic liver disease (ALD) were divided into alcoholic fatty liver (AFL) group, alcoholic hepatitis (AH) group and ALC group according to the types of their diseases. The ALC group was further divided into A, B and C subgroups according to the modified Child-Pugh grading standard, and mild, moderate and severe subgroups according to the model of end-stage liver disease (MELD) scoring standard. The levels of serum LPO, APN and TGF-β1 in patients of AFL, AH and ALC groups, and in different subgroups of patients in the ALC group were compared. The correlation between the levels of LPO, APN and TGF-β1 and total bilirubin (TBil), Albumin (Alb) and liver hardness (LSM) in ALC group were analyzed by Pearson method. Receiver operating characteristic (ROC) curves were drawn and the diagnostic efficacies of LPO, APN and TGF-β1 for the severity and prognosis of ALC patients were analyzed. Results The levels of LPO and TGF-β1 in ALC group were 7.56±1.68 μmol/L and 287.63±59.52 μg/L, respectively, which were higher than those of AH group (4.92±1.03 μmol/L and 3.46±0.85 μmol/L) and AFL group (215.19±43.87 μg/L and 168.53±32.48 μg/L); APN level was 4.29±1.03 mg/L, which was lower than those of 7.46±1.82 mg/L in AH group and 12.57±3.46 mg/L in AFL group (F=16.736, 13.275, 19.418, P<0.05). The levels of LPO and TGF-β1 in child-Pugh grade C subgroup of ALC group were 9.04±1.85μmol/L and 341.67±70.25μg/L . respectively, which were higher than those of 7.38±1.52μmol/L, 6.13±1.27 μmol/L in grade B, and 279.83±57.46 μg/L, 234.51±48.38 μg/L in grade A subgroups. The APN level in child-Pugh grade C subgroup was 3.37±0.85 mg/L, which was lower than those of 4.42±1.16 mg/L in grade B and 5.76±1.34 mg/L in grade A subgroups (F=13.259, 11.762, 15.386, P<0.05). The levels of LPO and TGF-β1 in the severe subgroup of ALC group were 9.83±1.96 μmol/L and 364.78±76.91 μg/L, respectively, which were higher than those of moderate (7.54±1.61 μmol/L and 5.83±1.14 μmol/L) and mild (290.62±59.73 μg/L and 225.76±45.82 μg/L) subgroups. APN level was 3.08±0.74 mg/L, which was lower than those of moderate (4.26±1.09 mg/L) and mild (5.93±1.42 mg/L) subgroups (F=15.461, 13.628, 17.853, P<0.05). Pearson analysis showed that LPO and TGF-β1 levels of ALC were positively correlated with TBil and LSM levels, but negatively correlated with Alb levels. APN level was positively correlated with Alb level, but negatively correlated with TBil and LSM level (P<0.05). ROC curve analysis showed that the AUC of LPO, APN and TGF-β1 and their combined efficacies on the diagnosis of ALC were 0.806, 0.784, 0.835 and 0.928, respectively, and the combined evaluation efficacy was higher than any individual detection (P<0.05).Conclusion The levels of LPO, APN and TGF-β1 are of high value in evaluating the severity and prognosis of ALC patients, and their combined evaluation is most effective.
    Liver Cancer
    Correlation analysis of CD38 expression level and efficacy of PD-1 inhibitors in advanced HCC
    WANG Lu, SUN Xiao-hu, BAI Jing-hui, YU Hong
    2023, 28(1):  75-78. 
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    Objective To explore the correlation between CD38 expression level and the efficacy of PD-1 inhibitor in patients with advanced hepatic cellular cancer (HCC). Methods 60 patients with advanced liver cancer treated with PD-1 inhibitor from 1 January 2019 to 31 December 2020 were selected as the study subjects and clinical information was collected. The tumor tissues of advanced liver cancer patients were selected by liver puncture, and the adjacent normal tissues of HCC cancer treated surgery our hospital at the same time were selected as the control. The relationship of CD38 expression and the prognosis of HCC patients was analyzed by bioinformatics analysis; Follow-up observations of HCC patients treated with PD-1 inhibitors compared the relationship between CD38 expression levels and patient prognosis; Risk factors were selected to influence the outcome of patients with advanced HCC. Results The KM-plotter database showed that in the HCC(HR=0.73,95%CI:0.54~0.98,P=0.036) and advanced HCC(HR=0.51,95%CI:0.26~1.00,P=0.045) samples, higher CD38 expression and longer PFS; CD38 expression was significantly lower in advanced HCC patients than in adjacent normal tissue(χ2=10.126,P=0.006); Patients with high CD38 expression performed better results with PD-1 inhibitors than those with low CD38 expression (χ2=5.833,P=0.016), and some correlation between CD38 expression and the effect of PD-1 inhibitors (Spearman r=-0.404, P<0.001); Patients with high CD38 expression had longer overall survival (OS, 24.19±3.89 vs 29.56±3.35weeks) and progression-free survival (PFS, 14.32±2.13 vs 17.52±3.02weeks) (P<0.05) than patients with low CD38 expression; BCLC stage, Child-Pugh grade, and CD38 expression may be associated with patient PFS (P<0.05).Conclusion CD38 expression was low in advanced HCC patients, CD38 expression was associated with the therapeutic effect of patient PD-1 inhibitor, and high expression of CD38 predicted a better effect of patient PD-1 inhibitor.
    Contrast ultrasonography and CEUS LI-RADS standard classification of DN-HCC and DN patients were observed
    SHI Xu, QIAO Xiang-bin, LIU Jia, XIAO Bao-jun
    2023, 28(1):  79-82. 
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    Objective To investigate the contrast-enhanced ultrasound (CEUS) findings and the standard classification results of CEUS liver image reporting and data system (CEUS LI-RADS) in patients with dysplastic nodules with focal hepatocellular carcinoma (DN-HCC) and dysplastic nodules (DN). Methods 78 patients with hepatic focal lesions (80 lesions, including 12 DN and 68 DN-HCC) admitted to our hospital between October 2019 and October 2021, and all patients underwent CEUS examination. All lesions were classified according to CEUS Li-RADS V2017 criteria. Results The proportion of synchronous enhancement in arterial phase in DN group was 66.7%, which was significantly higher than 13.2% in DN-HCC group (P<0.05); The proportion of high enhancement in arterial phase in DN group was 16.7%, which was significantly lower than 58.8% in DN-HCC group (P<0.05). In the DN group, there were three CEUS enhancement modes in arterial phase and delayed phase, of which low / equal accounted for 25.0%, equal/equal accounted for 66.7%, and high / high accounted for 8.3%;There were six CEUS enhancement modes in dn-hcc group, of which equal/equal accounted for 4.4%, low / low accounted for 5.9%, equal/low accounted for 8.8%, low/equal accounted for 13.2%, high (including local high enhancement) / low accounted for 29.4%, and high (including local high enhancement)/equal accounted for 38.2%. The proportion of LR-3 in CEUS LI-RADS v2017 standard classification in DN group was 100.0%, which was higher than 26.5% in DN-HCC group (P<0.05).Conclusion CEUS arterial phase high enhancement or delayed phase decline has differential significance between DN and DN-HCC, which is worthy of clinical verification.
    The value of of MSCT and dynamic contrast-enhanced MRI in differential diagnosis of HCC and IHPCC
    YIN Rui, YIN Hui-kang, GENG Cheng-jun
    2023, 28(1):  83-85. 
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    Objective To explore the value of MSCT and dynamic contrast enhanced(DCE)- MRI in differential diagnosis of patients with hepatocellular carcinoma(HCC) and intrahepatic peripheral cholangiocarcinoma(IHPCC). Methods 76 patients with primary liver cancer was selected, both MSCT and DCE-MRI were performed. Results From the study group of 76 patients, 48 patients had HCC and 28 had IHPCC according to histopathological examination. The basic information of HCC patients and IHPCC patients were comparable (P>0.05). The diagnostic coincidence rate of MSCT of 44 cases with HCC was 84.62% (44/52), the diagnostic coincidence rate of MSCT of 13 cases with IHPCC was 54.17% (13/24), and the overall diagnostic coincidence rate was 75.00% (57/76). The diagnostic coincidence rate of MRI of 48 cases with HCC was 92.31% (48/52), the diagnostic coincidence rate of MRI of 16 cases with IHPCC was 66.67% (16/24), and the overall diagnostic coincidence rate was 84.21% (64/76). The results of MSCT combined with MRI, Kappa=0.882, P<0.05, and the combined diagnostic accuracy was 96.05% (73/76).Conclusion Both MSCT and MRI can be used for the differential diagnosis of HCC and IHPCC patients, and the two combined performs better in diagnosis.
    Viral Hepatitis
    Performance comparison of quantitative serum HBsAg and HBV DNA in predicting significant hepatitis activity in patients with HBeAg-positive chronic HBV infection
    LU Wei, ZHANG Zhan-qing, YAN Li, HUANG dan, LIN Wei-jia, ZHOU Xin-lan, DING Rong-rong, WANG Yan-bing, LI Xiu-fen
    2023, 28(1):  86-94. 
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    Objective To comparatively evaluate the performance of serum HBsAg and HBV DNA in predicting significant hepatitis activity in HBeAg-positive patients with chronic HBV infection. Methods 505 HBeAg-positive patients were enrolled. HBsAg and HBeAg were measured in an Abbott Architect I2000 automatic immunoassay system, HBV DNA was measured in a Roche LightCycler 480 qPCR system, and serum ALT was measured in an Abbott Architect C16000 automatic biochemical analysis system. Diagnoses of Liver pathological grade and stage referred to the Scheuer standard. Significant hepatitis activity was divided into three levels, which were successively defined as “ALT≥20 IU/L or (pathological grade>G1 or stage>S1)”, “ALT≥30 IU/L or (pathological grade>G1 or stage>S1)”, and “ALT≥40 IU/L or (pathological grade>G1 or stage>S1)”. Results According to LOESS regression analyses of ALT with HBsAg, HBeAg and HBV DNA, 279 patients were classified as possible high HBV replication population. In the total number of infected, the areas under ROC curve (AUCs) of HBsAg and HBV DNA for predicting the three levels of significant hepatitis activity were successively 0.737 and 0.532, 0.737 and 0.548, and 0.686 and 0.545; in possible high HBV replication population, the AUCs of HBsAg and HBV DNA for predicting the three levels of significant hepatitis activity were successively 0.866 and 0.544, 0.837 and 0.540, and 0.787 and 0.564. In both overall and possible high HBV replication population, the AUCs of HBsAg and HBV DNA for predicting the three levels of significant hepatitis activity were all significantly greater than and all close to the area under diagonal reference line (all P<0.002 and all P>0.150); and the AUCs of HBsAg for predicting the three levels of significant hepatitis activity were all significantly greater than those of HBV DNA (P<0.001). With standard of HBsAg≤4.699 log10 IU/mL, the sensitivity and specificity of HBsAg for predicting significant hepatitis activity with ALT≥20 IU/L, ALT≥40 IU/L of overall population were 86.50% and 56.25%, 89.52% and 43.94%, respectively; and of possible high HBV replication population were 75.37% and 81.82%, 80.51% and 67.44%, respectively.Conclusion HBsAg has good performance and HBV DNA has no value in predicting significant hepatitis activity in patients with HBeAg-positive chronic HBV infection.
    The relationship between single nucleotide polymorphisms of ITPA gene and thrombocytopenia induced by pegylated interferon therapy in chronic hepatitis C and chronic hepatitis B patients
    DENG Hao-hui, LOU Yan, LI Xiao-qiang, QIU Jiu-xiang
    2023, 28(1):  95-99. 
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    Objective To investigate the relationship between single nucleotide polymorphisms (SNP) of inosine triphosphatase (ITPA) gene and thrombocytopenia induced by pegylated interferon (Peg-IFN) therapy in chronic hepatitis C (CHC) and chronic hepatitis B patients (CHB). Methods A total of 92 CHC and 87 CHB patients treated by Peg-IFN α-2a or α-2b for 48 week (w) with complete clinical data collected from January 2011 to December 2016 were enrolled in this study. The SNPs of ITPA gene on rs1127354 site were detected by Sanger sequencing methods. The clinical data (platelets counts and dose adjustments of Peg-IFN) between patients with different SNPs on rs1127354 site at 4w, 8w, 12w, 24w, 36w and 48w after antiviral therapy were compared and analyzed using SPSS 13.0 software. Results Among the 92 CHC patients enrolled in this study, the genotypes of rs1127354 in 55 patients (59.8%) were homozygous CC, 31 patients (33.7%) were heterozygous AC and 6 patients (7.6%) were homozygous AA; among the 87 CHB patients, the genotypes of rs1127354 in 53 patients (60.9%) were homozygous CC, 29 patients (33.3%) were heterozygous AC and 5 patients (5.7%) were homozygous AA. In CHC patients, thrombocytopenia in rs1127354 AA/AC genotypes was more frequent than CC genotype at 4w (F=6.195, P=0.015) and 8w (F=4.304, P=0.042) after Peg-IFN/ribavirin (RBV) therapy. However, the difference in thrombocytopenia was not found between CHB patients with rs1127354 AA/AC and CC SNPs at different time points post antiviral therapy (P>0.05). In addition, the chances of Peg-IFN dose reduction were significantly higher in CHC patients with rs1127354 AA/AC than those with CC SNPs (χ2=4.796, P=0.029), but there was no difference between CHB patients with rs1127354 CC and AA/AC SNPs (χ2=0.051, P=0.822).Conclusion Peg-IFN induced thrombocytopenia is related to the gene polymorphisms of ITPA rs1127354 in CHC patients received Peg-IFN/ RBV therapy, but not to those of CHB patients received Peg-IFN therapy.
    Early efficacy of tenofovir amibufenamide (TMF) in the treatment of patients with chronic hepatitis B: a real-word multicenter clinical study
    LI Ya-ping, CUI Dan-dan, GOU Guo-e, LIN Yong-mei, ZU Hong-mei, XU Guang-hua, GAO Xiao-hong, DANG Shuang-suo
    2023, 28(1):  100-104. 
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    Objective To evaluate the efficacy and safety of tenofovir amibufenamide (TMF) in the treatment of patients with chronic hepatitis B (CHB). Methods In this multicenter, prospective, real-world cohort study, we recruited 91 patients with CHB who attended the outpatient clinic of the Department of Infection of the 4 sites from August 2021 to August 2022 and were treated with TMF antiviral therapy. We collected clinical data, and compared the changes of HBV DNA, alanine transaminase (ALT), hepatitis B virus e antigen (HBeAg) and hepatitis B virus surface antigen (HBsAg) conversion, renal function and lipid metabolism at 12W and 24W. Results A total of 91 CHB patients were enrolled at 24W, 28 patients in treatment-naïve and 63 patients in previously treated. Complete virological response was achieved in 17.4% and 47.9% of treatment-naïve patients at 12W and 24W. The proportion of treated patients achieving complete virological response at 12W and 24W was 48.4% and 58.1%, respectively. HBV DNA [(4.88±0.54) lg IU/mL vs (2.69±0.35) lg IU/mL vs (2.40±0.39 lg IU/mL)] was significantly lower compared to baseline and 12W primary patients (F=24.51, P=0.000); HBV DNA in previously treated patients[(2.67±0.31) lg IU/mL vs (1.70±0.24) lg IU/mL vs (1.49±0.09) lg IU/mL decreased from before (F=5.83, P=0.009). The ALT recurrence rates based on laboratory criteria were 64% and 92% for 12W and 24W, respectively. And the ALT recurrence rates were 38.4% and 78.9% for 12W and 24W using AASLD 2018 criteria. After 24W of antiviral therapy 4.53% of patients had HBeAg conversion, 2.17% of patients had HBeAg seroconversion, 1.09% of patients had HBsAg conversion, no patients have yet had HBsAg seroconversion. In terms of safety, there was no significant change in blood Cr, eGFR and CysC at 24 weeks of antiviral therapy in CHB patients compared with baseline. 33 treated patients who had early kidney injury switched to TMF and continued antiviral therapy for 24W had a significant decrease in urinary α1-MG and urinary NAG and urinary β2-MG compared with baseline, with P values <0.05, which were statistically significant. Compared with baseline, there was a trend of decreasing TG and increasing TC, but the difference was not statistically significant.Conclusion TMF is effective and safe in the treatment of patients with CHB.
    Other Liver Diseases
    Retrospective analysis of 62 children with drug-induced liver injury
    ZHANG Sheng-nan, BAI Chao-hui, LIU Lei, XV Yao
    2023, 28(1):  105-107. 
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    Objective To study the clinical characteristics of drug-induced liver injury (DILI) in children. Methods Data were taken retrospectively from the 62 children with DILI in Henan Children's Hospital, and different variables including age distribution, clinical symptoms, types of drugs causing liver injury, therapeutic drugs, clinical outcome, liver function indexes and the Roussel uclaf causality assessment method (RUCAM) were defined and analyzed. Results Hepatocellular DILI was the most common type based on the R ratio, accounting for 87.1% (54/62). The most affected children were in the 1-3-year-old (33.9%, 21/62) and 3-6 year-old group(41.9%, 26/62). The most prevalent clinical symptom of DILI was loss of appetite (59.7%, 37/62). The drugs causing DILI in children mainly included antibacterial drugs, antipyretic analgesics and Traditional Chinese medicine. There were significant differences in serum ALT, AST and ALP levels among the three types of DILI patients (F=21.357, 12.574, 6.200, all P<0.05) . Outcomes for patients with DILI were excellent after treatment, and the recovery rate was 93.5% (58/62). 51.6% (32/62) of the children with liver injury were “highly likely” to be related to drug causality. RUCAM scale scores of the hepatocellular, cholestatic and mixed types were 5.8±1.9, 6.1±1.7 and 5.2±1.5, respectively. No significant difference among the three groups was found(F=0.240, P=0.787).Conclusion Hepatocellular injury is the main type in children with DILI. Clinical monitoring hepatotoxicity of antibiotics, antipyretic analgesics and Traditional Chinese medicine should be strengthened to reduce the adverse drug reactions to children.
    Comparison of clinical efficacy of ERCP and LBEPS combined with LC in the treatment of gallbladder complicated with common bile duct stones
    WANG Yang, XU Zhen, WANG Zheng, PAN Zhi
    2023, 28(1):  108-111. 
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    Objective To compare the performances of laparoscopic cholecystectomy (LC) combined with endoscopic retrograde cholangiopancreatography (ERCP) and laparoscopic common bile duct exploration (LBEPS) on the patients suffering from gallbladder (GS) and common bile duct stones (CBDS). Methods The clinical data of 82 patients treated for GS and CBDS in our hospital from May 2017 to February 2022 were enrolled and divided into two groups: the LBEPS+LC group(43 cases) and the ERCP+LC group(39 cases ) according to different surgical plans. Between the two groups, quality of life, liver function indexes, pancreatic injury indexes, surgery-related indexes were compared. Results LCBDE+LC group had a shorter mean(SD) postoperative length of stay (11.28±3.45 d vs 14.64±4.27 d, P<0.05) and operation time (86.72±16.54 min vs 112.42±20.57 min, P<0.05). In the LCBDE+LC group the intraoperative blood loss was significantly lower than that in the ERCP+LC group(41.83±7.59ml vs 46.89±9.61ml, P<0.05). There was no significant difference in complications between the two groups (P>0.05). On postoperative day 1(POD1), the LCBDE+LC group showed remarkable increases in serum levels of amylase (AMY) (102.41±11.59 U/L vs 81.53±7.96 U/L), alanine aminotransferase (ALT) (61.28±5.24 U/L vs 35.87±3.21 U/L) and alkaline phosphatase (ALP) (91.59±8.35 U/L vs 75.41±6.92 U/L) than pre-operatively (P<0.05). In the ERCP+LC group, ALT (60.75±5.63 U/L vs 35.49±3.46 U/L), ALP (90.62±8.11 U/L vs 76.83±6.57 U/L), and AMY (110.84±12.43 U/L vs 82.75±7.42 U/L) were also higher than pre-operatively (P<0.05) . There was no significant difference in ALP and ALT between the two groups on POD1 (P>0.05). While serum level of AMY in the LCBDE+LC group was significantly lower than in the ERCP+LC group on POD1(102.41±11.59 U/L vs 110.84±12.43 U/L, P<0.05). At 3 months after operation, the Short- Form Health Survey (SF-36) scores increased in both groups(P<0.05), while no difference was found in the SF-36 scores between the two groups (P>0.05).Conclusion Both protocols have therapeutic effect, but LBEPS combined with LC is more efficacious in ameliorating pancreatic damage, shortening postoperative length of stay and operation time, and reducing surgical trauma.
    GITR-positive effector T cells are involved in AAF/PH mouse liver regeneration
    LI Li, HE Yu, LIU Kai, WANG Ping
    2023, 28(1):  112-116. 
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    Objective To observe the ratio variation of effector T lymphocytes during liver regeneration in 2-acetylaminofluorene/partial hepatectomy (AAF/PH) mouse. Methods After daily intragastric administration of AAF for 5 days, C57BL/6J mice were performed 1/3 hepatectomy followed by daily administration of AAF for 7 days or 14 days. Immune fluorescence staining and western blot were used to detect the activation of hepatic progenitor cells. Collagenase digestion and Percoll-density centrifugation were used to isolate liver non-parenchymal cells, and multi-color immune staining and flow cytometry were used to analyze the percentage of effector T lymphocytes and their glucocorticoid-induced TNF receptor (GITR)-positive ratio. Results On the 7th post-operative day, there was no significant difference with regard to liver weght between the AAF/PH and control groups. Although few inflammatory cells and no significant liver fibrosis were observed in the liver tissue of the AAF/PH group, the liver tissue showed significant inflammatory cell infiltration and extracellular matrix deposition at the portal area on the 14th post-operative day. After partial hepatectomy, the number of Sox9+ hepatic progenitor cells increased time-dependently, and the expression level of Sox9 also enhanced in the liver tissue. Flow cytometry analysis showed that the ratio of CD8+ T lymphocytes to CD3+ T lymphocytes increased after partial hepatectomy, while the ratio of CD8+GITR+ T cells increased at 7 days post-operation, when compared to the control group, but reduced to the level of the control group at 14 days post-operation. Although the ratio of CD4+ T lymphocytes to CD3+ T lymphocytes did not change significantly, the ratio of CD4+GITR+ T lymphocytes reduced significantly at 14 days post-operation compared to the control group.Conclusion AAF/PH activates hepatic progenitor cells in mouse liver regeneration model, and effector T cells are involved in mouse liver regeneration.