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    31 July 2022, Volume 27 Issue 7
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    Liver Failure
    Effects of obesity on the severity and mortality in patients with HBV-ACLF and decompensated cirrhosis: A retrospective cohort study
    MO Rui-dong, ZHANG Zheng-lan, YIN Rong-kun, ZHOU Yan-mei, WANG Yue, YIN Peng-bo, ZHANG Chen-xi, FU Hao-shuang, QIAN Cong, XIANG Xiao-gang, XIE Qing
    2022, 27(7):  742-747. 
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    Objective To investigate the effects of obesity on short-term mortality in patients with hepatitis B virus-related acute on chronic liver failure (HBV-ACLF) and decompensated cirrhosis.Methods Ninty-three patients with HBV-ACLF and 285 patients with decompensated cirrhosis admitted to our hospital were enrolled. Baseline clinical data and risk factors of metabolism were collected. The 90-day and 180-day mortality of patients was recorded. Survival analysis was performed by log-rank test and Kaplan-Meier method. Multivariate analysis of survival was performed by Cox-regression proportional hazards model.Results Among all the patients, there were 146 (38.6%) cases with obesity, which was the major metabolic comorbidities. In I group (25≤BMI<30), the incidence rate of infection in patients with obesity was significantly than that in patients without obesity (44.1% vs 30.6%, χ2=6.37, P=0.042). The proportion of obesity in non-survival group was significantly higher than that in survival group (55.8% vs 36.4%, χ2=6.05, P=0.014). Multivariate analysis showed that obesity was positively correlated with 180-day mortality (HR 2.07, 95% CI 1.13-3.78, P=0.018). The 90-day mortality and 180-day mortality of obesity group were significantly higher than those of non obesity group (χ2=6.17, P=0.013; χ2=5.16, P=0.023).Conclusion Obesity is a risk factor which positively correlated with short-term mortality in patients with HBV-ACLF or decompensated cirrhosis. Close monitoring and early interventions in this part patients are necessary.
    Influencing factors and prognosis of bacterial infection in patients with hepatitis B virus-related acute-on-chronic liver failure
    ZHONG Xiao-qiang, CHU Xu-dong, CHEN Hai-yan, GAO Tai-jun
    2022, 27(7):  748-751. 
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    Objective To investigate the influencing factors and prognosis of bacterial infection (BI) in patients with hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF).Methods A total of 128 patients (94 males and 34 females) with HBV-ACLF admitted to our hospital from January 2016 to April 2021 were enrolled. The average age was 52 (40,62) years. BI was defined as patients with one of the followings: spontaneous bacterial peritonitis, pulmonary infection, biliary tract infection or urinary tract infection. The clinical data was analyzed and compared by t test, chi-square test or rank sum test; Multivariate logistic regression analysis was used to investigate influencing factors of BI in patients with HBV-ACLF.Results Among 128 patients with HBV-ACLF, 24 of which without BI (non-BI group) and 104 of which with BI (BI group). The numbers of patients with prophylactic antibiotics use, hepatic encephalopathy (HE), varicose bleeding and hyponatremia in non-BI group were 7 (29.2%), 3 (12.5%), 2 (8.3%) and 4 (16.7%) respectively, which were significantly higher than those in BI group [13 cases (15.5%), 42 cases(40.4%), 28 cases(26.9%) and 57 cases (54.8%), P<0.05]. The scores of white blood cell (WBC), platelet (PLT), albumin (Alb), total bilirubin (TBil), creatinine (Cr), serum sodium, international normalized ratio (INR) and model for end-stage liver disease (MELD) in non-BI group were 5.3 (4.3, 6.8)×109/L, 98 (62, 133)×109/L, (29.5±3.4) g/L, 225.4 (139.5, 92.8) μmol/L, 55 (47, 66) μmol/L, 136 (133,138) mmol/L, 1.9 (1.6, 2.2) and (19.0 2.5), which were significantly higher than those in BI group [7.3 (4.8, 10.5)×109/L, 76 (46, 110)×109/L, (27.7±3.0)g/L, 214.0 (120.6, 314.7) μmol/L, 66 (50, 103) μmol/L, 132 (128, 136) mmol/L, 2.1 (1.7, 2.7) and (23.2±3.1) points, P<0.05]. All the indexes with significant differences were taken as independent variables for BI in patients with HBV-ACLF (assignment 0=not complicated, 1=complicated). Logistic regression analysis showed that HE and MELD score were independent risk factors (P<0.05), and preventive antibiotic use was protective factor (P<0.05). Patients with HBV-ACLF and BI were divided into survival group and dead group according to the survival outcome. The clinical data of age, WBC, Alb, TBil, Cr, serum sodium, INR and MELD in survival group were 48 (40,54) years old, 6.2 (4.1, 9.6) ×109/L, (28.7±3.3)g/L, 59 (47, 86) μmol/L, 134 (130,137) mmol/l, 2.0 (1.7, 2.4) and (20.5±4.8) points, which were significantly higher than those in the dead group [54 (45,62) years old, 8.3 (5.6, 12.0) ×109/L, 228.2 (126.7, 364.0) μmol/L, 78 (55, 116 ) μmol/L, 132 (127, 134) mmol/l, 2.3 (1.8, 2.9) and (25.2±5.9) points, (P<0.05). There were significant differences in HE, variceal bleeding, mechanical ventilation, shock, hepatorenal syndrome and renal replacement therapy between the 2 groups (P<0.05).Conclusion HE and MELD score are independent risk factors of BI in patients with HBV-ACLF. Preventive antibiotics can effectively improve the prognosis, which has important clinical value.
    Viral Hepatitis
    Correlation between drug-resistance mutation sites and genotype, as well as cirrhosis in patients with chronic hepatitis B
    ZHENG Jing, PENG Yan-yan
    2022, 27(7):  752-755. 
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    Objective To investigate the correlation between mutation rates in different drug-resistance sites of hepatitis B virus (HBV) gene and genotype as well as cirrhosis.Methods A total of 391 patients with chronic hepatitis B (CHB) treated in our hospital were enrolled. All the patients were treated with nucleoside (acid) analogue (NAs), they were divided into 2 groups according to genotype: B genotype (345 cases) and C genotype (46 cases). Mutation rates of 6 drug-resistance sites (rtL180M, rtM204V, rtM204I, rtV207I, rtA181V, rtN236T) and ratios of multi-mutation types were compared between the 2 groups. The patients were divided into the CHB group and (342 cases) and cirrhosis group (43 cases) according to the existence of cirrhosis, and the mutation rates of 6 drug-resistance sites were compared between the 2 groups.Results The mutation rates of rtL180M (21.7% vs 7.0%) and rtM204V+rtL180M (46.2% vs 16.5%) in C genotype group were higher than those in B genotype group (P<0.05). The mutation rate of rtA181V in cirrhosis group was significantly higher than that in CHB group (7.0% vs 0.3%), (P<0.05).Conclusion Mutation rates of HBV gene at different drug-resistance sites are correlated with different genotypes and cirrhosis. Detection of drug resistance mutation sites in patients with CHB can provide reference for antiviral therapy in clinic.
    HBsAg clearance rate and its influence factors in preschool children with HBeAg negative chronic hepatitis B treated with antiviral therapy
    ZHANG Feng-xiao, ZHANG Jia-wei, BAI Xue-song, HU Chun-xia, ZENG Yan-li
    2022, 27(7):  756-758. 
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    Objective To investigate the clearance rate of hepatitis B surface antigen (HBsAg) in preschool children with hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) treated with antiviral therapy and to analyze the influence factors.Methods Sixty-eight patients with HBeAg negative CHB treated in our hospital were enrolled. All the children received antiviral therapy. The clinical data of HBsAg clearance rate was collected. The general data including serum alanine transaminase (ALT) level, hepatitis B virus (HBV) DNA level, HBsAg level (at baseline and after treatment) were collected. Influencing factors of HBsAg clearance rate were analyzed.Results Twenty children (29.41%) with HBsAg clearance were selected into clearance group and 48 cases (70.59%) without HBsAg clearance were selected into non-clearance group. The average age[(2.86 ± 0.62) years], baseline HBV DNA level [(9.89±2.54) × 106 U/mL] and baseline HBsAg level [(2.62 ± 0.50) lgIU/mL] of the clearance group were significantly lower than those of the non clearance group[(4.84 ± 0.54) years, (11.23 ± 2.10) × 106U/mL, (2.98 ± 0.42) lgIU/ml (P<0.05)], and the decrease level of HBsAg at the 24th week of treatment [(1.60 ± 0.41) lgIU/ml] was significantly higher than that of the non clearance group[(0.84 ± 0.28) lgIU/ml (P<0.05)]. Multivariate logistic regression analysis showed that age (OR=1.520, 95%CI=1.140~2.027), baseline HBV DNA level (OR=1.480,95%CI=1.140 ~ 1.921), baseline HBsAg level (OR=1.654, 95%CI=1.370 ~ 1.997), decreased level of HBsAg at the 24th week of treatment (OR=1.286, 95%CI=1.021 ~ 1.620) were independent influencing factors of HBsAg clearance rate in preschool children with HBeAg negative CHB (P<0.05).Conclusion HBsAg clearance may occur in some preschool children with HBeAg negative CHB after antiviral therapy. Age, baseline HBV DNA level, baseline HBsAg level and the decrease level of HBsAg at the 24th week of treatment are the independent influencing factors of HBsAg clearance rate.
    Analysis on the correlation between IL-17 family cytokines and intestinal flora in patients with chronic hepatitis B
    ZHANG Yi, WANG Zhou, YANG Bin
    2022, 27(7):  759-761. 
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    Objective To investigate the correlation between interleukin-17 (IL-17) family cytokines and intestinal microflora in patients with chronic hepatitis B (CHB).Methods Seventy-four CHB patients admitted to our hospital from January 2018 to January 2020 were selected as the observation group, and 80 healthy subjects were selected as the control group during the same period. The levels of IL-17 family cytokines (IL-17A, IL-17B, IL-17C, IL-17D, IL-17E and IL-17F) in serum of the 2 groups were detected 1 day after enrollment. The levels of 9 kinds of intestinal flora in the 2 groups were detected. The correlation between IL-17 family cytokines and intestinal flora levels in CHB patients was analyzed.Results The contents of Enterobacteriaceae, Enterococcus faecalis, Clostridium, Bacteroidetes, Prevotella and Bifidobacterium in the observation group [(7.51±0.87), (8.89±1.16), (9.28±1.08), (11.36±1.92), (9.48±1.62), (6.89±0.91) lg Copies/g] significantly higher than those in the control group [(7.06±0.82), (7.38±0.92), (7.32±0.78), (10.12±1.55), (7.82±1.25), (5.09±0.72) lg copies/g], P<0.05. The levels of IL-17 family cytokines in the observation group [(231.65±33.14), (279.36±41.05), (242.36±32.65), (245.73±35.61), (265.49±34.96), (217.58±26.73) pg/mL] were significantly higher than those in the control group [(58.16±5.62), (68.82±12.15), (65.37±4.02), (67.12±6.23), (62.18±6.25), (50.47±3.51) pg/mL], (P<0.05). The levels of IL-17A, IL-17B, IL-17C, IL-17D, IL-17E and IL-17F were all positively correlated with the levels of Enterobacteriaceae, Enterococcus faecalis, Clostridium, Bacteroidetes, Preverobacteria and Bifidobacteria (P<0.05).Conclusion The IL-17 family cytokines levels are positively correlated with the levels of Enterobacteriaceae, Enterococcus faecalis, Clostridium, Bacteroidetes, Preverobacterium and Bifidobacterium. And there is no significant difference between the levels of IL-17 family cytokines and Lactobacillus, Ruminococcus, Candidella albicans.
    Current situation and influence factors on the nucleic acid detection of HBV infection in voluntary unpaid donors in Baoding area
    HE Jiu-sheng, WANG Hao, HU Su-ling
    2022, 27(7):  762-767. 
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    Objective To investigate the current situation on the nucleic acid detection of hepatitis B virus (HBV) infection in voluntory unpaid blood donors in Baoding area, and to analyze the influencing factors.Methods A total of 207,000 donors with hepatitis B surface antigen (HBsAg) rapid test in our blood center from January 2019 to December 2020 were enrolled. Enzyme-linked immunoassay (ELISA) and viral nucleic acid detection technology (NAT) were performed in all cases. The clinical characteristics and influence factors of HBsAg-negative blood donors with HBV infection were compared and analyzed.Results The ELISA results of 207000 qualified samples showed that HBsAg positive in 949 cases, and the HBV DNA positive rate of HBsAg-negative cases was 0.050% (103/206051). The result of HBV DNA quantitative test in 103 HBsAg(-)/HBV DNA(+) blood donors showed that low viral load was the main reason, and the main serological model was hepatitis B surface antibody (anti-HBs) (+)/hepatitis B e antibody (antibody-HBe) (-)/hepatitis B core antibody (anti-HBc) (-). There was no significant difference in HBV infection rate among all blood donors with negative HBsAg screening at different times (P>0.05). There was also no significant difference in HBV infection rate between male and female (P>0.05). The HBV positive rate of blood donors with a history of intravenous drug use, unsafe sex, and blood transfusion was higher than those without the above-mentioned situation. (P<0.05); Logistic regression model analysis showed that the history of intravenous drug use, unsafe sex, and history of blood transfusion were influencing factors of HBV infection (P<0.05).Conclusion There is a certain rate of voluntary blood donors with HBV infection, and most of carriers with low viral load. Screening of risk factor should be further strengthened on the basis of ELISA screening to reduce the risk of HBV transmission.
    Effect of hepatic steatosis on the efficacy of antiviral therapy and hepatic fibrosis progression in chronic hepatitis B
    YANG Xiu-zheng, YUAN Shu-fang, SE Dong-ming, KE Liu, LI Liang, HE Tang-yan, ZHANG Yue-yuan, LI Xia-rong, DAN Yang-ping
    2022, 27(7):  768-772. 
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    Objective To retrospectively analyze the clinical data of E antigen positive chronic hepatitis B (CHB) patients admitted from January 2019 to January 2021, and to explore the influence of Controlled Attenuation Parameter (CAP) of fatty liver on the efficacy of antiviral therapy and liver fibrosis progression in CHB.Methods According to the results of CAP determined by transient elastography, the patients were divided into group A (CAP<260 db/m,N=60 cases), group B (CAP between 260 ~ 292 db/m,N=60 cases) and group C (CAP> 292 db/m,N=60 cases). The biochemical, virological and serological responses at 12 weeks, 24 weeks, 48 weeks and 96 weeks after antiviral treatment were retrospectively analyzed. Twenty patients in each group were randomly assigned for hepatological examination to evaluate liver fibrosis.Results There were no differences in age, sex, baseline alanine transaminase (ALT), aspartate transaminase (AST) and HBV-DNA among the three groups. The levels of body mass index (BMI), Triglyceride (TG), total cholesterol (TC) and γ-glutamyl transpeptadase (GGT) in Group C were higher than Group A (P<0.05) and the levels of cholesterol (TC) and triglyceride (TG) in group B were higher than those in group A (P<0.05). Twenty patients in each of the three groups were randomly divided into cirrhotic group and non-cirrhotic group according to the pathological results. Logistics regression analysis showed that there were significant differences in CAP value (P<0.01), BMI and TG between the cirrhotic and noncirrhotic groups (P<0.05). Receiver operator characteristic curve (ROC) analysis showed that the areas under the curve (AUC) of CAP and TG were the largest, which were 0.780 and 0.746. At 12th, 24th, and 48th weeks after entecavir (ETV) antiviral treatment, there were significant differences in the normalization rate of ALT levels, which were 35 cases (58.33%), 60 cases (100%), and 60 cases (100%) in Group A, 22 cases (36.67%), 55 cases (91.67%) and 59 cases (98.33%) in group B, 14 cases (23.33%), 21 cases (35%) and 48 cases (80%) in Group C, respectively, especially in Group A and Group C (P<0.01). The negative conversion rate of HBV DNA gradually increased with time after ETV treatment. At 24 weeks, the negative rates of HBV DNA in these three groups were 96.67% (58 cases), 75% (45 cases) and 63.33% (38 cases), respectively, with significant differences between group A and group B, or group A and group C (P<0.01). At the 48th and 96th week of antiviral treatment, the HBeAg seroconversion rate gradually increased, the HBeAg negative rate were 8.33% (5 cases) and 11.67% (7 cases) in Group A; 1.67% (1 case) and 5% (3 cases) in group B. and 0%, 1.67% (1 case) in Group C, respectively, with a significant difference between group A and group C.Conclusion Low CAP value, TG and BMI are independent indexes related to liver fibrosis progression in patients with CHB complicated with NAFLD. Liver steatosis affects biochemical response, delays early response of antiviral treatment, and affects serological response of HBeAg. Therefore, prevention and treatment of NAFLD in CHB patients complicated with NAFLD is of positive significance to improve antiviral efficacy.
    Liver Cancer
    Imaging manifestations and clinicopathological analysis of sarcomatoid hepatocellular carcinoma
    JIANG Jia-qi, DONG Jing-hui, LIU Yuan, LIU Chang-chun, ZHENG Zeng, REN Hong-wei
    2022, 27(7):  773-777. 
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    Objective The aim of the present study was to retrospectively analysis the imaging manifestations and clinicopathological characteristics of sarcomatoid hepatocellular carcinoma (SHC) patients, in order to improve the efficiency of clinical diagnosis of SHC.Methods The clinical data of 11 patients with pathologically confirmed SHC from January 2012 to March 2021 were collected. The clinical symptoms, Computed tomography (CT) and magnetic resonance imaging (MRI) findings, pathological features, immunohistochemical staining, and other findings during followed-up were retrospectively analyzed.Results Among the 11 patients with SHC, 7 were male and 4 were female, of which 6 patients have single lesions, 5 patients have multiple lesions, and 1 patient was complicated with hepatocellular carcinoma and cholangiocellular carcinoma. One patient underwent CT enhanced scan, 5 patients underwent MRI enhanced scan, and 5 patients underwent CT and MRI enhanced scan. The imaging examination of the SHC lesions showed low-density on CT plain scan, circular or patchy uneven enhancement in the arterial phase of the enhanced scan, and low-intensity in the portal phase and the delayed phase; MR plain scan showed slightly longer T1 and longer T2 signals, and one case of intratumoral hemorrhage showed focal and shorter T1 signals, and the lesion enhancement method was similar to CT findings; Pseudocapsular enhancement was observed in 3 cases. Septal changes were seen in 1 case, with necrotic cystic areas within the tumor. One patient with mixed carcinoma showed delayed enhancement on enhanced scan. Immunohistochemical results showed that Vimentin was positive in 9 patients; Hepa was negative in 8 patients; CK19 was positive in 4 patients; CD34 was positive in 8 patients; Ki67 was positive in 6 patients (Ki67>75%); EMA was positive in 5 patients; SMA was positive in 3 patients. Three patients had metastasis before surgery and 5 patients had recurrence and metastasis after surgery.Conclusion The clinical features and imaging manifestations of SHC are atypical and rare. If a large intrahepatic tumor is found with large necrotic cystic areas within the tumor, ring-shaped, patch-like edge enhancement or uneven enhancement arterial phase lesions shown in enhanced scan, the possibility of SHC should be considered.
    The guiding value of intravoxel incoherent motion diffusion-weighted imaging in the curative effect of argon-helium knife cryotherapy on primary liver cancer
    MA Jun-wei, LIU Ji-qiang, SONG Ran
    2022, 27(7):  778-781. 
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    Objective To explore the guiding role of Intravoxel Incoherent Motion (IVIM) Diffusion-Weighted Imaging (DWI) in the curative effect of argon-helium cryotherapy for patients with primary liver cancer (PLC).Methods A total of 112 patients with PLC admitted to the hospital from February 2016 to July 2019 were selected as the research objects. The patients were all treated with cryotherapy with argon helium knife. The patients were examined by IVIM-DWI at 1 day prior and 1 month after the operation. They were followed up for 1 year and divided into recurrence group and non-recurrence group according to whether their PLC recurred after operation. The clinical data and IVIM-DWI parameters before and after surgery in these two groups were collected and compared. Logistic regression analysis was used to explore the factors affecting the recurrence of PLC. The receiver operating characteristic curve (ROC) was used to determine the predictive value of IVIM-DWI parameters for postoperative recurrence of patients with PLC.Results After a 1-year’s follow-up, 112 patients with PLC received cryotherapy with argon-helium knife. There were 16 (14.29%) cases in the recurrence group and 96 cases in the non-recurrence group. The tumor size of the recurrence group was higher than that of the non-recurrence group (P<0.05). The standard postoperative diffusion coefficient (ADC) and postoperative pure diffusion coefficient (D) of the recurrence group were lower than those of the non-recurrence group (P<0.05). The proportion of cases with TNM staging of stage II in the recurrence group was higher than that in the non-recurrence group (P<0.05). Logistic multivariate regression analysis showed that postoperative ADC value, postoperative D value, and tumor size were all influencing factors for the recurrence of PLC (P<0.05). The ROC analysis showed that the postoperative D and ADC values have a certain diagnostic power in predicting the recurrence of PLC after surgery (P<0.05).Conclusion The D and ADC values of IVIM-DWI parameters of PLC patients at one month post cryotherapy with argon-helium knife cryotherapy have certain efficacies in predicting the recurrence of PLC.
    Beclin 1-mediated inhibitory effect of NS5ATP9 on starving-induced apoptosis in HepG2 cells
    QUAN min, XING Hui-chun
    2022, 27(7):  782-784. 
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    Objective To investigate Beclin 1-mediated inhibitory effect of NS5ATP9 on starving-induced apoptosis in hepatoblastoma cell line HepG2 cells.Methods HepG2 cells were serum starved and collected at different time points. The expression changes of NS5ATP9, Beclin1 and Bax proteins were detected by Western blot. In addition, HepG2 cells were transfected with NS5ATP9 siRNA or its overexpression vector for 48h. The cells were then serum starved for 24 h and collected for detection of bax by Western blot. Moreover, after knockdown of Beclin 1 by siRNA or overexpression of NS5ATP9 by transfected vector, the cells were serum starved for 24 h and collected for the detection of caspase-3/7 activity by chemiluminescence method. The expression of NS5ATP9, Beclin1 and Bax proteins were detected by Western blot.Results (1) the protein expressions of NS5ATP9 and bax in HepG2 cells were increased after 0, 6, 12, 18 and 24 h of serum starvation. The bax protein expression was increased After siRNA knockdown of NS5ATP9 expression. (2) After serum starvation for 24 h, the activity of Caspase-3/7 in HepG2 cells was increased in the Beclin 1 expression-inhibited cells (P=0.001), this was accompanied by a decreased effect of NS5ATP9 on inhibiting caspase-3/7 activity (P=0.000), and a weakened negative regulatory effect of NS5ATP9 on bax.Conclusion Beclin 1 partly mediated the inhibitory effect of NS5ATP9 on starving-induced HepG2 cell apoptosis through down-regulation of bax expression.
    Detection of hepatitis B viral DNA integration in HepG2.2.15 cells by a modified Alu-PCR method
    RUAN Peng, HE Chun-ping, HUANG Chao, ZHOU Rui
    2022, 27(7):  785-788. 
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    Objective To investigate the integration site of hepatitis B viral DNA (HBV DNA) in HepG2.2.15 cells using a modified Alu-PCR method.Methods This study detected the HBV integration site in HepG2.2.15 cells using a simplified Alu-PCR method, followed by a quantitative analysis of the integration site that was found in HepG2.2.15 cells with and without H2O2 treatment by RT-qPCR.Results One HBV integration site was found. The binding junction of the inserted viral fragment was at 1,228nt of HBV DNA with 3 bp (CTG) of microhomology. The viral fragment was inserted into Alu repeats of host DNA in HepG2.2.15 cells. Logarithmically transformed analysis (log10copies/cell) showed that the average copy numbers of this integration site in the cells with H2O2 treatment (-1.13±0.07) were significant higher than those without H2O2 treatment (-2.10±0.82,P<0.001). No significant difference was found between the HBV cccDNA levels in cells with and without H2O2 treatment (-1.94±1.45 and -1.79±1.40,P=0.915). No correlation was found between cccDNA level and the integration site in the cells (P=0.463).Conclusion This study provided a cost-effective, simplified method for the detection of HBV DNA integration by a modified Alu-PCR method.
    Other Liver Diseases
    The impact of past hepatitis B virus infection on biochemical response and prognosis of patients with autoimmune hepatitis
    SU Yu, SUN Xiao-yi, WANG Qian-yi, ZHAO Xin-yan, JIA Ji-dong
    2022, 27(7):  789-794. 
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    Objective To explore the impact of past infection of hepatitis B virus (HBV) on the biochemical response and prognosis of patients with autoimmune hepatitis (AIH).Methods Patients diagnosed with AIH from January 2002 to December 2020 at liver research center, Beijing Friendship Hospital, Capital Medical University were included. The clinical characteristics, biochemical response and end-point events such as hepatocellular carcinoma, liver transplantation and death from liver diseases were compared between the AIH patients with and without past HBV infection.Results 114 AIH patients with sufficient baseline and follow-up clinical data were retrieved, of which 74 patients were without past HBV infection and the rest of 40 patients were with HBV infection. The baseline levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly lower in AIH patients with past HBV infection (99.5 vs.178.0, P=0.046; 137.2 vs.161.0, P=0.049, respectively). When compared with AIH patients without past HBV infection, patients with past HBV infection showed higher positivity of antineutrophil cytoplasmic antibody (ANCA) (35.7% vs. 4.8%, P=0.028). No significant difference was shown in the biochemical responsive rate and the incidence of end-point events between these two groups. Past HBV infection was not associated with biochemical response (OR=1.06, 95%CI: 0.03-1.21, P=0.106) and end-point events (HR=1.68, 95%CI: 0.42-6.75, P=0.463). However, the level of globulin (OR=1.06, 95%CI: 1.02-1.11, P=0.030) and the normalization of IgG (OR=3.75, 95%CI: 1.22-11.49, P=0.021) at 3 months of immunosuppressive therapy were independent predictors of complete biochemical response of the AIH patients at 1 year of the treatment. Liver stiffness (HR=1.06, 95%CI: 1.00-1.12, P=0.045) and decompensated cirrhosis (HR=7.54, 95%CI: 1.27-44.72, P=0.026) were risk factors of poor prognosis.Conclusion Compared with AIH patients without past HBV infection, AIH patients with past HBV infection can achieve comparable biochemical response and prognosis once immunosuppressive therapy has been initiated.
    Clinical characteristics of primary biliary cirrhosis with negative serum specific antibodies
    LI Wei- kun , LI Hui-ming, CHANG Li-xian, PENG Dan, LIU Chun-yun, QI Yan-shan, MOU Chun-yan, ZHANG Yin-yuan, XU Dan-qing, LIU Li
    2022, 27(7):  795-799. 
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    Objective Comparing a series of clinical features and pathological manifestations of patients with primary biliary cirrhosis (PBC) with negative and positive anti-mitochondrial antibodies (AMA), in order to provide a theoretical basis for the diagnosis and treatment of AMA-negative PBC patients.Methods From January 2017 to December 2020, patients with abnormal liver function for half a year or more, accompanied by elevated γ-glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) were selected, and the final subjects were obtained according to the inclusion and exclusion criteria. Liver puncture pathological examination was performed on all selected subjects, and they were divided into AMA negative and positive groups. Routine blood, serum biochemical, thyroid function and pathological tests were performed on the two groups. After collecting the clinical data, SPSS25.0 was used for data analysis. The counting data were expressed as (mean±standard deviation), and t test was used for comparison between the two groups. The measurement data was expressed by rate or percentage (%), and chi-square test was used for the comparison of rates between two groups.Results The results showed that the majority of PBC patients with AMA negative (19 cases) and positive (49 cases) were female, and the patients were mainly 50-55 years old. There was no difference in age and sex between the two groups (P<0.05). Laboratory test results showed that there was statistically significant difference between AMA negative (183.27±1.67) and AMA positive (265.67±1.37) in PLT levels of blood routine (P<0.05), and no difference in other indicators. In addition, liver function test results showed that the GGT value of patients in the AMA negative group (444.5±2.72) was higher than that in the AMA positive group (276.33±3.86). For biochemical factors, the results showed that the levels of triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) in AMA negative group were lower than those in AMA positive group [TG: (1.74±0.58) vs (1.97±0.94), P=0.023; LDL-C: (3.57±0.42) vs (4.87±0.7), P=0.016], while the expression of immunoglobulin IgE was opposite. The IgE expression in the AMA negative group was lower that in the AMA positive group [(70.15±0.91) vs (33.67±0.65), P=0.011]. Thyroid function analysis showed that the T4 expression level of AMA negative group was lower than that of AMA positive group [(110.72±10.34) nmol/L vs (122.56±10.88) nmol/L, P<0.05]. Positive results of autoimmunity antibody showed that anti-liver and kidney microsomal antibody 1 (LKM1) was not expressed in PBC, while antinuclear antibody (ANA) and RO52 in AMA negative group were higher than those in AMA positive group (86.36% vs 9.26%, 81.82% vs 14.81%, both P<0.05). Immunohistochemical results of cytokeratin 7 (CK7) and CK19 showed that there was no statistical difference in positive rate between the two groups.Conclusion The clinical features and pathological manifestations of AMA-negative and positive PBC patients are very similar, and equal attention should be paid to AMA-negative patients to improve the diagnosis rate of PBC and the treatment effect.
    Restrospective analysis of clinicopathological features of 46 cases of neonatal cholestasis
    LIU Yin-zhi, YANG Hui, LIAO Zhen-yu, ZHAN Cai-xia, YANG Zhi-ming, YE Hong-qiu, HUANG Rui-wen
    2022, 27(7):  800-802. 
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    Objective To analyze the clinical data of neonatal cholestasis and analyze its difference between different onset time.Methods A total of 46 cases of neonatal cholestasis were retrospectively analyzed from January 2016 to December 2020 at the Department of Neonatology of Hunan Children’s Hospital. According to the onset time of cholestasis, all children were divided into early onset group (onset within 2 weeks after birth) and late onset group (onset after 2 weeks after birth). The general clinical data, biochemical indexes and prognosis of the two groups were observed. The age of onset, gestational age, birth weight, months of recovery, total bilirubin, conjugated bilirubin, total bile acid, alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT) and alkaline phosphatase (AKP) were statistically compared between the two groups by independent sample t-test. Chi-square test was used to statistically compare the sex composition ratio, the proportion of full-term infants, the cure rate, the composition ratio of different etiologies, the incidence of clay colored stool and the proportion of hepatomegaly between the two groups.Results 1. There were no significant differences in sex composition, cure time, proportion of infectious cholestasis, total bilirubin, direct bilirubin, total bile acid, GGT and AKP between two groups (P>0.05). The average disease onset age of early onset group was (5.91±4.61) d and that of late onset group was (36.8±14.1d). The average gestational age of early onset group was higher than that of late onset group [(35.4±2.8) w vs (31.6±2.5) w] . The average birth weight of early onset group was (2001.8±522.2) g, higher than that of late onset group [(1477.3±356.4) g], the difference was statistically significant (t=11.21, 4.325, 3.111, P<0.05). Full term infants accounted for 36.4% in early onset group, and there were all premature infants in late onset group. The cure rate of early onset group (72.3%) was lower than that of late onset group (100%).There were 0 case of venous nutrition-related cholestasis in early onset group, which was significantly lower than that in late onset group (48.6%). The proportion of cholestasis with unknown cause in early onset group (63.4%) was higher than that in late onset group (28.6%). The proportion of clay colored stool in early onset group (36.4%) was higher than that in late onset group (8.6%), and the difference was statistically significant (χ2=13.939, 10.21, 8.475, 4.417, 5.011, P<0.05). The ALT level in the early onset group was (142.3±122.8) IU/L, which was significantly higher than that in the late onset group (77.5±46.4) IU/L, the difference was statistically significant (t=2.625, P=0.012). The mean cure age of all cured children was 3.4 months.Conclusion There are differences in clinical characteristics of cholestasis between the early onset group and the late onset group. The gestational age, birth weight and ALT level of the early onset group are higher than those of the late onset group, and the proportions of unexplained cholestasis, clay colored stool and full term infants are higher, and the prognosis is worse. The late onset group has a higher proportion of venous nutrition-related cholestasis and a better prognosis.
    Prospective study of iPV-LPV and CV-LPV in the treatment of extrahepatic portal hypertension in children
    PENG Qiu, GAO Hai-yan, CHEN Zhi-li, DU Yong, ZOU Bing
    2022, 27(7):  803-806. 
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    Objective To prospectively analyze the clinical efficacy of main portal vein-left portal vein shunt with interposition of portal vessels (iPV-LPV) and gastric coronary vein-left portal vein shunt (CV-LPV) in the treatment of extrahepatic portal hypertension in children.Methods 64 children with extrahepatic portal hypertension admitted to our hospital from March 2016 to 2021 were selected. After admission, they were divided into iPV-LPV group (n=31) and CV-LPV group (n=33) according to different treatment methods. We compared perioperative related indicators of two groups after surgery, including operation time, intraoperative blood loss, first postoperative eating time, first postoperative getting out of bed time and hospitalization time. The hepatic venous blood flow, portal vein blood flow, spleen length spleen thickness, and blood platelet (PLT) count and hemoglobin (Hb) were examined and compared between the two groups at admission and 6 weeks after operation. Finally, the complications during hospitalization were counted and compared between the two groups.Results In the iPV-LPV group, the operation time, intraoperative blood loss, first postoperative eating time, first postoperative getting out of bed time and hospitalization time were (176.9±47.5) min, (54.2±12.8) mL, (27.5±4.1) h, (2.4±0.5) d, (8.1±1.7) d, those in CV-LPV group were (210.4±50.4) min, (59.7±15.7) mL, (27.4±4.0) h, (2.8±0.9) d, (9.8±2.4) d. The operation time, first postoperative getting out of bed time and hospitalization time in the iPV-LPV group were significantly shorter than those in the CV-LPV group (P＜0.05). There was no significant difference between the two groups in intraoperative blood loss and first postoperative eating time (P>0.05). The preoperative hepatic artery blood flow, portal vein blood flow, spleen length, and spleen thickness in the iPV-LPV group were (375.4±72.4) mL/min, (1421.4±304.5) mL/min, (13.5±2.7) cm, (4.5±0.9) cm, and those postoperatively were (514.7±94.8) mL/min, (1104.1±124.8) mL/min, (10.6±2.0) cm, (2.9±0.5) cm. The preoperative hepatic artery blood flow, portal vein blood flow, spleen length, and spleen thickness in the CV-LPV group were (375.6±72.7) mL/min, (1422.0±304.9) mL/min, (13.4±2.7) cm, and (4.4±0.9) cm, respectively, which were (439.8±84.1) mL/min, (1280.4±235.7) mL/min, (11.8±2.3) cm, (3.5±0.7) cm postoperatively. The postoperative hepatic artery blood flow in the iPV-LPV group was significantly higher than that in the CV-LPV group, while the portal vein blood flow, spleen length, and spleen thickness were significantly lower than those in the CV-LPV group after surgery (P＜0.05). The postoperative hepatic artery blood flow in the two groups was significantly higher than that before the operation, while the portal vein blood flow, spleen length, and spleen thickness were significantly less than those before the operation (P<0.05). The preoperative PLT and Hb levels in the iPV-LPV group were (159.1±42.4) × 109 and (92.4±23.4) g/L, respectively, and the postoperative PLT and Hb levels were (224.7±70.6) × 109 and (105.4±26.4) g/L, respectively. The levels of PLT and Hb before operation in the CV-LPV group were (159.3±42.5) × 109 and (92.5±23.5) g/L, respectively, and after operation there were (189.4±67.8) × 109 and (105.6±26.4) g/L, respectively. The postoperative PLT level in the iPV-LPV group was significantly higher than that in the CV-LPV group (P＜0.05). The levels of PLT and Hb after operation in the two groups were significantly higher than those before operation (P<0.05). There was no significant difference in the total incidence of postoperative complications in the iPV-LPV group and CV-LPV group (16.1% vs 18.2%, P>0.05).Conclusion Compared with CV-LPV, IPV-LPV in the treatment of children with extrahepatic portal hypertension can better improve the hepatic venous blood flow, portal venous blood flow, spleen length, spleen thickness and serum PLT, which is more conducive to postoperative recovery of children.
    Application of transcatheter arterial embolization in the treatment of grade Ⅲ, Ⅳ and partial grade Ⅴ traumatic hepatic rupture
    DUAN Jian-feng, LIU Xiao-chen, YANG Fan, DUAN Chang-hu, WU Lin, ZHU Huan, ZHAO Li-fei
    2022, 27(7):  807-809. 
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    Objective To discuss the application of transcatheter arterial embolization (TAE) in the diagnosis, treatment of grade Ⅲ, Ⅳ and partial grade Ⅴ traumatic liver rupture.Methods A total of 168 severe traumatic liver rupture were treated with TAE from July 2014 to December 2020, including 92 cases with grade Ⅲ injury, 67 cases with grade Ⅳ injury and 9 cases with grade Ⅴ injury. Its efficacy and related complications were observed.Results All 168 patients achieved hemostasis after TAE and no re-bleeding events occurred. One patient died. The main complications of liver trauma in the late stage of TAE were perihepatic infection and liver abscess, and pipuncture tube drainage could achieve good efficacy.Conclusion Under the condition that the damage of major blood vessels in the liver are excluded, for liver trauma above grade Ⅲ, even grade Ⅳ and partial grade Ⅴ injuries, as an emergency hemostatic measure, TAE has the advantages of both diagnosis and treatment, less trauma and less impact on the physiological function of the body, which is safe and effective.
    Clinical observation of liver function damage in patients with acute promyelocytic leukemia induced by all-trans retinoic acid combined with arsenious acid
    WANG Yan-qiu, XUE Juan, CHEN Meng-lu
    2022, 27(7):  810-813. 
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    Objective To observe the effect of all-trans retinoic acid (ATRA) combined with arsenious acid (ATO) on liver function damage in patients with acute promyelocytic leukemia (APL).Methods From January 2012 to April 2021, 92 newly diagnosed APL patients (50 males and 42 females), aged 40 (12, 77) years, were reviewed. Among them, 38 cases were induced by ATRA or ATO alone, and 54 cases were induced by the combination treatment. Mann-Whitney U-test was used for measurement data and chi-square test was used for counting data. Kaplan-Meier method was used for survival analysis, and log-rank test was used for difference comparison.Results The complete remission (CR) time of combined induction group and single induction group was 27 (20, 38) days and 35 (25, 50) days, and the difference was statistically significant (P<0.05). There were 36 cases (66.7%) and 14 cases (36.8%) of liver function damage in combined induction group and single induction group respectively, and the difference was statistically significant (P<0.05). There were 23 cases (42.6%) and 5 cases (13.1%) of grade Ⅲ/Ⅳ liver damage in combined induction group and single induction group, and the difference was statistically significant (P<0.05). 87 patients with hematological CR continued to complete consolidation therapy (> 2 cycles), among which 23 patients received ATRA combined with ATO consolidation chemotherapy over 1 cycle, and 3 patients (13.0%) had liver function damage. The incidence of liver damage in ATRA combined with ATO consolidation therapy was significantly lower than that in combined induction therapy (P<0.05). 52 patients who completed consolidation therapy continued to receive ATRA and ATO sequential maintenance therapy, of which 12 patients (23.1%) had liver function damage. The incidence of liver function damage in ATRA and ATO sequential maintenance therapy was significantly lower than that in combined induction therapy (P<0.05). Patients were followed up until April 2021. 70 patients received ATO chemotherapy after induction, consolidation and maintenance treatment, including 28 patients with grade Ⅲ/Ⅳ liver damage. The overall survival (OS) rates of patients with grade Ⅲ/Ⅳ liver damage and non-grade Ⅲ/Ⅳ liver damage were 92.8% (26/28) and 95.2% (40/42), with no significant difference (P>0.05). Event free survival (EFS) rates were 85.7% (24/28) and 90.5% (38/42), with no significant difference (P>0.05).Conclusion ATRA combined with ATO can effectively shorten the time of reaching CR in APL patients, while increases the risk of liver function damage. However, the liver damage of most patients is transient and reversible. Compared with induction period of ATRA combined with ATO, the proportion of liver damage was significantly lower in patients receiving consolidation and maintenance therapy. In addition, liver damage caused by ATO does not affect the prognosis of patients.