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    31 March 2023, Volume 28 Issue 3
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    Frontier, Exploration and Controversy Liver Cancer
    Expression of ESPL1 gene in hepatocellular carcinoma tissue and its role in the prognosis assessment
    HU Bo-bin, WANG Rong-ming, LIANG Heng-kai, WEI Lu, LI Qing-mei, SU Tu-mei, YIN Qian-bing, JIANG Jian-ning
    2023, 28(3):  285-289. 
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    Objective To investigate the expression of Extra spindle poles-like 1 protein (ESPL1) gene in hepatocellular carcinoma (HCC) tissues and its influence on clinical prognosis of HCC, and preliminarily analyze the variation and molecular biological function of ESPL1. Methods ESPL1 expression data and clinical information of HCC patients were obtained from the TCGA database. The expression levels of ESPL1 in cancer, paracancerous, and normal tissues were compared. The COX regression was used to investigate the risk factors of the prognosis in HCC patients, and the Kaplan-Meier method was used to investigate the relationship between the high and low ESPL1 expression level and the prognosis of HCC patients. According to the median ESPL1 expression level, the data were divided into high-expression group and low-expression group, and the log rank test was used to analyze the survival differences between the 2 groups. cBioPortal online software was used to analyze the mutation of ESPL1. The ESPL1 protein interaction network was plotted through the STRING database, and its molecular biological functions were analyzed by GO|KEGG enrichment. Results The ESPL1 expression level of liver cancer tissues was higher than that of paracancerous and normal tissues (0.894 ± 0.643 vs 0.337 ± 0.34, 1.908 ± 1.079 vs 0.912±0.77, P＜0.05), and the level of ESPL1 in hepatitis B-related liver cancer was higher than that of non-hepatitis B-related liver cancer (2.159 ± 1.17 vs 1.747 ± 0.983, P＜0.05). ESPL1 expression level was related to gender, age, body mass index (BMI), primary tumor stage, and alpha fetal protein (AFP) level (P＜0.05). Primary tumor stage and ESPL1 expression level were independent risk factors for the prognosis of HCC patients. The expression of ESPL1 was negatively correlated to the prognosis (HR=1.72, 95%CI: 1.21-2.41, P＜0.05). The mutation rate of ESPL1 in HCC patients was about 1%, and the prognosis of mutants was poor (P＜0.05). The enrichment results show that ESPL1 was mainly involved in cell cycle, mitosis, chromosome segregation and other biological functions. Conclusion ESPL1 expression level is upregulated in HCC tissues. It is highly expressed and specific in hepatitis B-related liver cancer. Patients with HCC have high ESPL1 expression level and ESPL1 mutations can lead to poor prognosis. ESPL1 can be used as a potential marker for poor prognosis in patients with HCC.
    Clinical features of primary liver cancer associated with Wilson's disease
    GUO Dan-dan, ZHANG Ying-hua, GAO Wen-feng, SHENG Shou-peng, ZHANG Yong-hong
    2023, 28(3):  290-292. 
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    Objective To investigate the clinical features of primary liver cancer associated with Wilson's disease (WD). Methods Patients with primary liver cancer admitted to our hospital were retrospectively enrolled. The clinical manifestations, laboratory tests, diagnosis and treatments were collected. Results Among the 12 patients with primary liver cancer associated with WD, 5 cases were males and 7 were females. All cases were combined with liver cirrhosis, 8 cases were Child-Pugh B/C. Four patients with alpha fetoprotein (AFP) negative, while 8 patients with AFP positive. There were 4 cases in BCLC stage A, 1 case in stage B, 4 cases in stage C and 3 cases in stage D. One patients received conservative treatment, 5 patients treated by transcatheter arterial chemoembolization (TACE), 2 patients received TACE combined with ablation and 4 patients received liver transplantation. Conclusion WD-associated primary liver cancer is rare clinically, and most of them are in middle or late BCLC stage. The occurrence of liver cancer should be closely followed up in patients with WD-associated cirrhosis, in order to improve the early diagnosis rate.
    Consistency analysis of major signs of small liver cancer LI-RADS (2018 edition)
    LI Peng, WANG Wei-wei, CAI Jian-ming, DONG Jing-hui
    2023, 28(3):  293-295. 
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    Objective To investigate the concordance of the main signs in small hepatocellular carcinoma (HCC) (< 3 cm) LI-RADS (2018 edition) among different cases. Methods A total of 193 cases who underwent dynamic enhanced magnetic resonance imaging 1 week to 1 month before surgery and treated by small HCC resection in our hospital from May 2018 to October 2022 were collected. Two doctors will determine whether the patient's lesion exhibits the main signs of the 2018 version of LI-RADS, and the consistency between the them was compared. Results Among the 193 patients, kappa values of the major signs of the 2018 version of LI-RADS judged by 2 observers ranged from 0 to 0.747, and the consistency between observers was positively correlated to the lesion size. Conclusion The consistency between observers of the major signs of 2018 LI-RADS is positively correlated with lesion size.
    Viral Hepatitis
    Clinical study on the efficacy and safety of oral nucleos(t)ide analogues in HBV mother-to-infant obstruction of pregnant women with high viral load
    LIANG Heng-kai, WEI Lu, SU Ming-hua, LIANG Huan, HU Bo-bin, HUANG Jian-fang, CHEN Yan-hong, JIANG Jian-ning
    2023, 28(3):  296-298. 
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    Objective To investigate the effect and safety of nucleos(t)ide analogues (NAs) in hepatitis B virus (HBV) mother-to-infant obstruction of pregnant women with high viral load, and to provide real-world clinical data for interrupting mother-to-child transmission of HBV. Methods A total of 411 pregnant women with HBV DNA≥1×106 copies/mL were retrospectively selected from the follow-up cohort of chronic HBV infection in our hospital, and they were divided into preventing group (256 cases) and control group (155 cases) according to the oral administration of NAs during pregnancy. All infants were vaccinated with hepatitis B vaccine and hepatitis B immunoglobulin as standard after birth. The levels of HBV DNA, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the preventing group were compared at baseline. before delivery and 3 months after delivery. The levels of HBV DNA before delivery and hepatitis B surface antigen (HBsAg) positive rate in infants from 7 months to 1 year were compared between 2 groups. Results The levels of DNA, ALT and AST before delivery were lower than baseline in the preventing group [(3.16 ± 1.05) log10 copies/mL vs. (7.09 ± 0.77) log10 copies/mL, P＜0.01; (21.90 ± 12.00) U/L vs. (66.08 ± 89.35) U/L, P＜0.01; (29.16 ± 9.16) U/L vs. (52.12 ± 54.97) U/L, P＜0.01]. The level of HBV DNA before delivery and the positive rate of HBsAg of infants in the preventing group were lower than those in the control group [(3.16 ± 1.05) log10 copies/mL vs. (6.96 ± 0.78) log10 copies/mL, P＜0.01; 0.00% vs 9.68%, P＜0.01]. No perinatal adverse events were reported in both groups. The levels of HBV DNA, ALT and AST in parturients who stopped taking NAs after delivery were higher than those who continued taking NAs [(6.70 ± 1.39) log10 copies/mL vs. (2.24 ± 0.54) log10 copies/mL, P＜0.01; (54.19 ± 50.00) U/L vs. (34.62 ± 20.04) U/L,P＜0.01; (42.50 ± 28.04) U/L vs. (33.40 ± 11.66) U/L, P＜0.01]. Conclusion The combination of oral NAs, hepatitis B vaccination and HBIG during pregnancy for pregnant women with high viral load and continued antiviral treatment for postpartum patients can successfully interrupt mother-to-child transmission of HBV and ensure the safety of mother and child during pregnancy and postpartum.
    Influence on chronic hepatitis B combined with nonalcoholic fatty liver disease on the development of hepatocellular carcinoma and all-cause mortality: A meta-analysis
    SU Pei-hua, WEI Meng-ping, ZHAO Cai-yan
    2023, 28(3):  299-304. 
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    Objective To investigate chronic hepatitis B (CHB) combined with nonalcoholic fatty liver disease (NAFLD) on hepatocellular carcinoma (HCC) and all-cause mortality. Methods Literature search was conducted in CNKI, Wanfang Chinese Database, China Biomedical Literature Database (CBM), VIP Chinese Database and Pubmed, Cochrane, Embase English Database from the establishment of the database to December 2021, as well as the related literatures supplemented by manual reference search. RevMan5.3 and Stata16.0 were used for meta-analysis. Statistical analysis was performed for all the included studies. The random effect model was used if the heterogeneity was significant; The fixed effect model was used if the heterogeneity was not significant. The relative risk (RR) and its 95% confidence interval (95%CI) were used to investigate the association of NAFLD with the development of HCC and all-cause mortality in CHB patients, and the publication bias test and sensitivity analysis were carried out. Results A total of 9 literatures were included, 8 were about the influence of NAFLD on the risk of HCC in CHB patients and 3 were about the influence of NAFLD on all-cause mortality in CHB patients. The results showed that compared with the CHB group, the CHB combined with NAFLD group had a higher risk of HCC (RR=1.93, 95%CI: 1.05-3.55, P=0.04), but the risk of all-cause mortality in the two groups (RR=1.38, 95%CI: 0.34-5.69, P=0.65) was not significantly different. Conclusion In CHB patients, NAFLD increases the risk of HCC, but has no significant effect on the risk of all-cause mortality. More large-sample, high-quality, multicenter cohort studies are needed in the future.
    Application of retrospective follow-up in improving diagnosis and treatment of hepatitis C virus in hospitalized patients
    HAO Shuai, YAN Hong-lin, KONG Fan-jiao, ZHANG Xiao-ying, HAN Yang, GUO Fei-hu, HE Na
    2023, 28(3):  305-308. 
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    Objective To investigate the status of diagnosis and treatment in inpatients with positive hepatitis C antibody through retrospective follow-up, and to educate the knowledge of hepatitis C, so as to improve the awareness of hepatitis C virus (HCV) in high-risk patients. Methods A total of 364 inpatients with anti-HCV positive admitted to our hospital from July 1, 2021 to February 15, 2022 were followed up. Including understand the basic situation of the patients and conduct specific education according to whether they were aware of anti-HCV positivity and the current status of diagnosis and treatment of hepatitis C. Before the end of the follow-up visit, consulted the patients about their willing of the medical knowledge education and whether they were willing to further confirm the diagnosis and treatment. Results Among the 364 patients, 38.5% were aware of hepatitis C, 42.3% were unaware, and 19.2% were loss to follow up. Among the informed patients: 12.9% were undiagnosed patients and 28.5% were diagnosed and untreated patients. Among the unaware patients: 79.0% were unaware that they had hepatitis C, 10.8% were unaware that hepatitis C could be cured, 7.7% were unaware that the price of drugs had been reduced and that health insurance was available, and 2.6% were informed but unaware of both the cure and the price reduction. After educating patients about hepatitis C knowledge, the patients' awareness rate of the disease, the rate of willingness to further diagnose and the rate of willingness to treat all increased significantly, and 76.3% (184/241) of the patients expressed their willingness to treat and test very positively, 11.6% of patients refused treatment and testing. Conclusion Retrospective follow-up of anti-HCV positive inpatients and education on hepatitis C knowledge and health insurance policies are not only an important means to raise awareness of hepatitis C among high-risk groups, but also an effective complementary measure to eliminate hepatitis C in hospitals, which is of great significance to fully improve the diagnosis and treatment rates of hepatitis C.
    Analysis on risk factors of osteoporosis in chronic hepatitis B patients treated with nucleos(t)ide analogues
    XIE Shuang-shuang, CHENG Wen-jin, JIAO Jun-xia, LIU Xiao-yan, LIU Li
    2023, 28(3):  309-312. 
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    Objective To investigate the incidence and risk factors of osteoporosis (OP) in chronic hepatitis B (CHB) patients treated with nucleos(t)ide analogues (NAs). Methods A total of 1000 cases (male 600 cases, female 400 cases) of CHB patients admitted to our hospital from January 2019 to June 2021 were divided into 3 groups according to the diagnostic criteria of based on the measurement T and Z values of bone density in the middle and distal 1/3 of the ulnar radius of the non-stressed side of the forearm: normal bone group, osteopenia group and osteoporosis group. The general data and related factors of OP were recorded. The risk factors of OP were analyzed with multivariate logistic regression analysis. Results Among the 1000 CHB patients, 36.8% had osteopenia, and 18.2% had OP. The results of multivariate logistic regression analysis showed that age (OR=1.06, 95%CI:1.02-1.11, P=0.005), female (OR=1.37, 95%CI: 1.56-2.13, P=0.015), low body mass index (BMI) (OR=0.88, 95%CI:0.81-0.97, P=0.015), creatinine level (OR=1.45, 95% CI: 1.97-2.03, P=0.025) and taking adefovir dipivoxil or tenofovir dipivoxil (OR=1.00, 95%CI: 1.14-7.45, P=0.028) were correlated with bone mineral density. The blood phosphorus levels of patients treated with adefovir or tenofovir were lower. Conclusion CHB patients treated with NAs are more likely to have osteopenia and OP. The risk of osteopenia and OP is positive correlated with age, gender, low BMI, elevated creatinine level and taking adefovir dipivoxil or tenofovir dipivoxil antiviral therapy. Early prevention and detection should be done to reduce or delay the occurrence of OP.
    Predictors associated with functional cure in HBeAg-negative chronic hepatitis B patients treated with pegylated interferon α-2b
    GU Lin-lin, HU Rui, DOU Yu-ming, XIAO Li
    2023, 28(3):  313-319. 
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    Objective To explore the predictors for functional cure in HBeAg-negative chronic hepatitis B [HBeAg (-)CHB] patients treated with pegylated interferon α-2b (PEG-IFN α-2b). Methods A retrospective study was conducted on HBeAg (-)CHB patients treated with PEG-IFN α-2b from August 2016 to December 2020 in Taizhou People's Hospital, and they were divided into cured group and uncured group. Univariate and logistic multivariate analyses were used to screen out the predictors for the functional cure. ROC-AUC was used to evaluate the predictive efficacy. Patients were grouped according to the cut-off values of predictors derived from ROC-AUC, the accumulated rate of HBsAg seroclearance was estimated by Kaplan-Meier survival curves, and the Log-rank test was used to compare the differences. Results A total of 116 HBeAg (-)CHB patients were included. Median follow-up was 124.93(109.61～140.11)weeks, and the rate of functional cure was 31.03% (36/116). Univariate analysis found that the factors which had statistical differences included the baseline HBsAg level(Z=-6.283, P<0.001), the proportion of cirrhotic patients at baseline(χ2=8.344, P=0.004), HBsAg decline at week 12 and week 24(Z=-3.922 and -5.144 respectively, P<0.001 for all)and the peak value of transient ALT elevation during the treatment (Z=-6.081, P<0.001). Logistic multivariate regression analysis suggested that the baseline HBsAg levels(P=0.001), the magnitude of HBsAg decline at week 24 (P=0.001)and the peak value of transient ALT elevation (P=0.019)were independently associated with functional cure. The cut-off values of the baseline HBsAg, the decline of HBsAg at week 24 and the peak value of transient ALT elevation were 1.68 lg IU/mL, 1.28 lg IU/mL and 110.50 U/L, respectively. The AUCs of the above three factors alone and combined for predicting functional cure were 0.802, 0.855, 0.833 and 0.963, respectively. There were significant differences in the accumulated rate of HBsAg seroclearance between the groups with baseline HBsAg≤1.68 lg IU/mL and ＞1.68 lg IU/mL, the decline of HBsAg≥1.28 lg IU/mL and ＜1.28 lg IU/mL at week 24, the peak value of transient ALT elevation≥110.50 U/L and ＜110.50 U/L during the treatment (χ2=30.966, 42.925,28.463 respectively, P<0.001 for all). Conclusion For HBeAg (-)CHB patients with lower baseline HBsAg levels, the treatment of PEG-IFN α-2b could achieve a higher HBsAg seroclearance rate. Moreover, the functional cure rate could also elevate in patients with a significant HBsAg decline at week 24 and a higher peak value of transient ALT elevation during the treatment.
    Influencing factors of low-level viremia in patients with chronic hepatitis B treated with Entecavir
    HUANG Yong-xu, CHEN Chao, BAO Zi-hong, ZHOU Xiao-hui
    2023, 28(3):  320-324. 
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    Objective To investigate the current status of low-level viremia(LLV)in Entecavir(ETV)-treated chronic hepatitis B(CHB)patients and explore the related factors of LLV. Methods The study was conducted from April 2021 to December 2021. CHB patients who were treated with ETV over one year in The First Affiliated Hospital of Shantou University Medical College and experienced LLV(HBV DNA <100 IU/mL)were enrolled for high-sensitivity HBV DNA detection(the lower limit of detection: 10 IU/mL). According to the test results, they were divided into virological response(VR)group and LLV group. The demographic data and laboratory findings of patients were collected. Univariate analysis and multivariate logistic regression were used to analyze the related factors of LLV in CHB patients treated with long-term ETV. Results A total of 260 CHB patients were included, 40 in the LLV group and 220 in the VR group. The incidence of LLV was 12.8% (25/195)in males, lower than 23.1% (15/65)in females (χ2=3.939, P=0.047); was 12.6% (30/239)in patients with good compliance, lower than 47.6% (10/21)in patients with poor compliance (χ2=15.640, P<0.001); was 8.8% (8/91)in cirrhotic patients, lower than 18.9% (32/169)in non-cirrhotic patients (χ2=4.675, P=0.031); was 30.0% (27/90)in HBeAg-positive patients, higher than 7.6% (13/170)in HBeAg-negative patients (χ2=22.587, P<0.001). The baseline virus load of the LLV group was higher when compared with the VR group(7.0 log10IU/mL vs. 5.6 log10IU/mL, Z=-4.458, P<0.001). Multivariate logistic regression analysis showed that poor medication compliance(OR=2.927, 95%CI: 1.078～7.949, P=0.035), positive HBeAg (OR=2.473, 95%CI: 1.064-5.747, P=0.035)and high HBV DNA load (OR=1.441, 95%CI: 1.068-1.943, P=0.017)before treatment were independent risk factors for LLV in CHB patients treated with ETV. Conclusion Even after long-term entecavir treatment, 15.4% (40/260)of CHB patients with HBV DNA < 100 IU/mL still had LLV. In clinical practice, poor compliance, positive HBeAg and high viral load are risk factors for LLV.
    Diagnostic value of liver stiffness combined with spleen stiffness detected by transient elastography for pathological stage of liver fibrosis in chronic hepatitis B patients
    LU Qiu-yan, LU Yan-hui, XU Cheng-run
    2023, 28(3):  325-329. 
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    Objective To evaluate the diagnostic value of liver and spleen stiffness measured by transient elastography (FibroScan)regarding pathological stages of liver fibrosis in patients with chronic hepatitis B. Methods The clinical data of 317 patients with chronic hepatitis B who received liver biopsy from January 2018 to December 2021 in the No.909 Hospital of the joint logistics support unit were retrospectively analyzed. ROC curve was used to analyze the relationship between liver stiffness measurement (LSM)and spleen stiffness measurement (SSM)measured by FibroScan and fibrosis diagnosed by liver pathology. Logistic regression was used to construct a fibrosis grading stage model based on LSM and SSM. Results There were 79 (24.92%)cases of S0-S1, 102 (32.18%)cases of S2, 87 (27.44%)cases of S3 and 49 (15.46%)cases of S4. There were 31 (9.78%)cases of G1, 109 (34.38%)cases of G2 and 128 (40.34%)cases of G3; G4 was 49 (15.46%). The best LSM values for the diagnosis of significant fibrosis (≥ S2), severe fibrosis (≥ S3)and liver cirrhosis (S4)were 7.4 kPa (AUC = 0.861), 9.8 kPa (AUC = 0.909)and 16.6 kPa (AUC = 0.915), and the SSM values were 36.2 kPa (AUC = 0.817), 42.4 kPa (AUC = 0.913)and 49.1 kPa (AUC = 0.930), respectively. The predictive liver pathological diagnosis model based on LSM and SSM was constructed according to logistic regression, and R = LSM + SSM was obtained after optimization. The diagnostic model was more consistent with the pathological diagnosis than LSM or SSM alone (P<0.001). The AUCs of significant fibrosis, severe fibrosis and liver cirrhosis were 0.913, 0.962 and 0.991, respectively. Conclusion The detection of LSM combined with SSM based on transient elastography can improve the diagnostic efficiency of liver fibrosis in patients with chronic hepatitis B.
    Liver Failure
    The characteristics of acute kidney injury in patients with acute-on-chronic liver failure and its impact on prognosis
    LI Peng-peng, DONG Qi-gang, XU Jun
    2023, 28(3):  330-333. 
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    Objective To analyze the clinical features and risk factors of acute kidney injury (AKI) in patients with chronic and acute liver failure (ACLF) and the impact of AKI on the patients' outcomes. Methods A total of 117 ACLF patients admitted to our hospital from January 2019 to July 2022 were selected as the research objects. The patients were divided into ACLF-non-AKI group and ACLF-AKI group according to whether AKI occurred or not. The diagnosis of ACLF and AKI met the diagnostic criteria. The clinical data of ACLF-non-AKI group and ACLF-AKI group were compared, and the risk factors of AKI in ACLF patients were analyzed by multivariate analysis. The patients were followed-up and the clinical outcomes of the ACLF patients with or without AKI were compared. Results A total of 117 patients with ACLF were enrolled, including 73 patients in ACLF-non-AKI group and 44 patients in ACLF-AKI group. Compare the clinical data of the two groups, The age, hypertension, gastrointestinal bleeding, bacterial infection, white blood cells count (WBC), total bilirubin (TBil), international normalized ratio (INR), prothrombin time (PT), serum creatinine (Scr), serum K+, Child-Turcotte-Pugh (CTP) score, Model for End-Stage Liver Disease (MELD) score and 90-day mortality of ACLF-non-AKI group were (49.3±7.9) years, 7 cases (9.6%), 9 cases (12.3%), 8 cases (10.9%), (7.0±1.4) ×109/L, (213.6±69.2) μmol/L, (2.2±0.9), (33.3±2.9) s, (60.6±18.4) μmol/L, (3.8±0.6) mmol/L, (11.0±1.6) points, (17.9±3.7) points and 16 cases (21.9%), respectively, which were significantly lower than those of (52.4±8.3) years,11 cases (25.0%), 13 cases (29.5%), 11 cases (25.0%), (9.0±1.6) ×109/L, (272.1±87.1) μmol/L, (2.4±0.9), (35.5±3.7) points, (106.8±30.0) μmol/l, (4.0±0.7) mmol/l, (11.5±1.8) points, (22.2±4.3) points and 25 cases (55.8%) in the ACLF-AKI group (P<0.05). The albumin (Alb) level, estimated glomerular filtration rate (eGFR) and serum Na+ of ACLF-non-AKI group were (31.4±5.1) g/L, (137.2±43.2) ml/min/1.73 m2 and (134.7±2.8) mmol/L, respectively, which were significantly higher than those of (27.2±5.0) g/L, (104.4±34.2) ml/min/1.73 m2 and (132.1±2.2) mmol/L in ACLF-AKI group (P<0.05). Multivariate analysis showed that age, gastrointestinal bleeding, bacterial infection, TBil and PT increased whereas Alb decreased were risk factors of AKI in ACLF patients. Among the 44 patients with ACLF complicated with AKI, the remission and progress were 27 and 17 cases, respectively. Comparing the clinical data of AKI patients with different outcomes, TBil, INR, Scr, CTP score, MELD score and 90-day mortality of patients with remission were (250.7±73.3) μmol/L, (2.3±1.0), (78.2±15.3) μmol/L, (11.5±1.4) points, (25.9±4.5) points and 10 cases (37.0%), respectively, which were significantly lower than those of (307.2±92.6) μmol/L, (3.0±1.0), (172.3±24.7) μmol/L, (12.4±1.5) points, (31.4±6.2) points and 15 cases (88.2%) in patients with progressive disease, respectively, P<0.05. The serum Na+ levels of patients in remission and progression were (132.4±2.3) mmol/L and (130.0±2.1) mmol/L, respectively, and the difference was statistically significant (P<0.05). There were 2 cases (7.4%), 19 cases (70.4%) and 6 cases (22.2%) of acute tubular necrosis, pre-renal azotemia and hepatorenal syndrome in remission patients, respectively, and the difference was statistically significant compared with those of 5 cases (29.4%), 1 case (5.9%) and 11 cases (64.7%), in progression patients (P<0.05). Conclusion Nearly 40% of ACLF patients will develop AKI. Factors of age, gastrointestinal bleeding, bacterial infection, TBil and PT increase whereas Alb decreases significantly increase the risk of AKI in ACLF patients. ACLF patients with AKI usually have disease progression, and the clinical outcome is worse than that of patients with remission.
    Effects of reduced glutathione combined with plasma exchange and Double plasma molecular absorb system on acute-on-chronic liver failure and the establishment of a prognostic scoring model
    XU Hai-ling, ZHANG Ying, YU Chong, WANG Zhong-cheng, CHEN Lin
    2023, 28(3):  334-339. 
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    Objective To explore the effect of reduced glutathione combined with plasma exchange and double plasma molecular absorb system (PE+DPMAS) on liver function of patients with acute-on-chronic liver failure and establish a prognostic scoring model. Methods A total of 84 patients with acute-on-chronic liver failure diagnosed from May 2018 to May 2021 were retrospectively selected. The patients were randomly divided into PE+DPMAS group (group A) and reduced glutathione+PE+DPMAS group (group B), with 42 cases in each group. The 6-month survival status of the patients was recorded. The patients in Group B were further divided into a survival group and a death group. The baseline data, liver function indexes and clinical efficacy after 2 months of treatment between these two groups were compared. The influencing factors of six-month survival were analyzed. The ROC model for predicting 6-month survival was established. Results The INR of group B and group A was 1.82 (1.48-2.20) and 2.18 (1.52-2.87), respectively (Z=-4.350, P=0.003); the level of Cr in group B and group A was 0.63 (0.40-0.71) and 0.78 (0.62～0.85), respectively (Z=-2.256, P=0.006); MELD score of group B and group A was 23.69 (17.85～27.02) and 24.67 (22.37～28.86), respectively (Z=-5.307, P<0.001); The MELD-Na score of group B and group A was 21.25 (16.69-29.95), and 25.66 (21.84-31.67), respectively (Z=-4.892, P<0.001). After 3 months of treatment, the AST level of group B and group A was 42.11±9.85 and 68.02±13.79, respectively (t=9.909, P<0.001); the level of TBIL in group B and group A was 21.55±6.32 and 32.77±6.09, respectively (t=8.285, P<0.001); γ-GT level in group B and group A was 32.55±9.07 and 78.05±15.79, respectively (t=16.193, P<0.001); the ALT level in group B and group A was 45.38±10.73 and 78.05±15.79, respectively (t=7.589, P<0.001). There was no death in both groups, and the total effective rate of 92.86% in group B was significantly higher than that of 76.19% in group A (χ2=4.459, P<0.05). According to the 6-month survival, patients in group B were divided into a survival group (25 cases) and a death group (17 cases). COX multivariate analysis showed that age (OR=1.013, 95%CI: 1.102-1.03), TBil (OR=1.003, 95%CI: 1.024-1.085), INR (OR=1.101, 95%CI: 1.132-2.387), PLT (OR=1.008, 95%CI: 1.092-1.101) were independent risk factors for the patients' survival. According to the COX results, a prediction model (A model) for the prognosis of liver failure in group B treatment was established. In the ROC curve, the AUC area of 0.752 (95%CI: 0.660-0.845) predicted by the A model was larger than that of 0.662 (95%CI: 0.557-0.768) by the MELD scoring model and 0.702 (95%CI: 0.605-0.799) by the MELD-Na scoring model. Conclusion Reduced glutathione+PE+DPMAS can significantly promote the recovery of liver function in patients with acute-on-chronic liver failure. Age, TBil, INR and PLT are independent risk factors for the patients' survival. The new A model is significantly better than traditional MELD score and MELD-Na in predicting the prognosis of patients' survival.    
    Drug-induced Liver Injury
    Analysis of autoantibodies and serum immunological characteristics of drug-induced liver injury and autoimmune hepatitis
    CHEN Ke, GE Li-li
    2023, 28(3):  340-342. 
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    Objective To analyze the differences in autoantibodies and serum immunological characteristics between patients with drug-induced liver injury (DILI)and autoimmune hepatitis (AIH)so as to promote effective diagnosis, therapy, and differentiation. Methods Patients with DILI(Group A)and AIH(Group B)admitted to our hospital from January 2019 to September 2022 were selected. The diagnosis of DILI and AIH met the standard. Clinical data of DILI and AIH were collected for comparison. Results A total of 85 patients were enrolled, including 52 patients with DILI(29 males, 23 females; mean age 51.7 years)and 33 patients with AIH(8 males. 25 females, mean age 49.1 years). There was a significant difference in sex between the two groups (P<0.05). In terms of clinical symptoms, the difference was statistically significant between the two groups regarding fatigue(75.0% vs. 24.4%, P<0.05). Regarding examination indexes, ALT, AST, Alb, PT, APTT, IgA, and IgG differed significantly between the two groups(all P<0.05. Compared with DILI, the ANA titer of AIH patients ≥ 1∶3200 was significantly higher (P<0.05). No significant difference was found in AMA antibody, anti-gp210 and anti-SP100 between the two groups(P>0.05). Compared with DILI, the cases of intrahepatic cholestasis in AIH patients decreased significantly (P<0.05), while the cases of interfacial hepatitis, rose petal formation and bile duct injury increased significantly(P<0.05). Conclusion There are some differences in autoantibodies and immune indexes between patients with DILI and AIH. Moreover, AIH is characterized by interfacial hepatitis, rose petal formation and bile duct injury, while intrahepatic cholestasis is typical of DILI.
    A clinical observation and analysis of 122 cases of acute and chronic drug-induced liver injuries
    GE Wen-jun, LIU Jun, REN Jun
    2023, 28(3):  343-345. 
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    Objective To analyze the clinical features and prognosis of acute and chronic drug induced liver injuries (DILI). Methods A total of 122 patients with DILI from January 2015 to December 2021 were included, including 79 males and 43 females, with an average age of 50 (38, 68) years old. According to the courses of diseases, the patients were divided into acute DILI (n=101) and chronic DILI (n=21) groups. The diagnosis of DILI meets the Chinese guideline for the diagnosis and treatment of DILI. The etiologies, clinical features, and clinical outcomes of acute and chronic DILI patients were compared. Results The causes of acute and chronic DILI were similar. The main causative drugs included Chinese patent medicines (78 cases, 63.9%), antibacterial drugs (15 cases, 12.3%) analgesic and antipyretic drugs (13 cases, 10.6%). Comparing the clinical features of acute and chronic DILI patients, the platelet (PLT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of acute DILI patients were 212 (104, 376) ×109/L, 276 (29, 711) U/L and 168 (18, 643) U/L, which were significantly higher than those of chronic DILI [162 (84, 235) ×109/L, 80 (12, 318) U/L and 114 (10, 307) U/L, P<0.05]. the positive rates of anti-nuclear antibody (ANA) and anti-smooth muscle actin antibody (SMA) in acute DILI patients were 38 cases (37.6%) and 4 cases (4.0%), respectively, which were significantly lower than those in chronic DILI [13 cases (61.9%) and 4 cases (19.0%), P<0.05]. By analyzing the clinical outcomes of acute and chronic DILI patients, the incubation period of acute DILI patients [32 (2, 150) days] was significantly shorter than that of chronic DILI patients [44 (12, 260) days, P<0.05]. 9 cases (8.9%) and 1 case (1.0%) of patients with acute DILI were treated with steroid hormone or steroid plus immunosuppressant, and the difference was statistically significant (P<0.05) when compared with those of 8 cases (38.1%) and 5 cases (23.8%) of chronic DILI. Conclusion The causative drugs for acute and chronic DILI are similar, mainly including Chinese patent medicine, antibacterial drugs, analgesic and antipyretic drugs. Compared with acute DILI, patients with chronic DILI have severe liver enzyme abnormalities and longer latent periods, with requirement of adjuvant treatment by steroids and immunosuppressants to improve the patients' clinical outcome.
    Predictive value of lncRNAs expression level in peripheral blood before chemotherapy on anti-tuberculosis drug induced liver iniury
    LI Xiang, GAO Jing, BAO Hai-yang, ZHU Yan-qiu, CHEN Yan-hui, WANG Xing-hua
    2023, 28(3):  346-350. 
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    Objective To study the predictive value of long non-coding RNAs (lncrnas) expression in peripheral blood before chemotherapy on anti-tuberculosis drug induced liver iniury(ATDILI). Methods From May 2017 to may 2019, patients with newly diagnosed pulmonary tuberculosis in our hospital were selected, the expression level of lncRNAs in peripheral blood before chemotherapy were determined by lncRNAs microarray and fluorescence quantitative PCR. The patients were divided into ATDILI group and non-ATDILI group according to whether ATDILI occured during chemotherapy. ROC curve was used to analyze the predictive value of lncRNAs for ATDILI, and logistic regression model was used to analyze the influencing factors of ATDILI. Results By lncrnas microarray analysis, compared with non-ATDILI group, the expression of 46 lncRNAs in peripheral blood of ATDILI group significantly up-regulated and the 5 most upregulation lncRNAs were lncRNA MALAT1, HNF1α-AS1, H19, XIST and CCAT1. By fluorescence quantitative PCR, the expression of lncRNA MALAT1, HNF1α-AS1, XIST and CCAT1 in peripheral blood of ATDILI group were significantly higher than non-ATDILI group; ROC curve analysis showed that lncRNA MALAT1, HNF1α-AS1, XIST and CCAT1 had predictive value for ATDILI; logistic regression analysis showed that gender, malnutrition, viral hepatitis history, drinking history and lncRNA MALAT1, XIST were the influencing factors of ATDILI. Conclusion The increased expression of lncRNA MALAT1 and XIST in peripheral blood before chemotherapy relates to the occurrence of ATDILI, which can be used as a predictor for ATDILI.
    Other Liver Diseases
    Clinical and histological characteristics of patients with Alagille syndrome
    WU Li-na, SUN Li-ying, ZHU Zhi-jun, WANG Xiao-ming, WANG Yu, OU Xiao-juan, JIA Ji-dong, ZHAO Xin-yan
    2023, 28(3):  351-354. 
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    Objective To find out the clinical characteristics and histological features of patients with Alagille syndrome(ALGS). Methods A total of 27 patients diagnosed with ALGS in Beijing Friendship Hospital from January 2016 to February 2022 were retrospectively enrolled. The demographic characteristics, clinical presentation, liver biochemical tests, gene sequencing, liver histology, and clinical outcomes of the patients were analyzed. Results The common clinical features were growth retardation(16/27, 59.3%), facial features(8/27, 29.6%), cardiovascular involvement(16/27, 59.3%), butterfly vertebrae(10/27, 37.0%), renal involvement(8/27, 29.6%)and posterior embryonic(1, 3.7%). All the cases were accompanied by chronic cholestasis, among which 23(85.2%)cases had splenomegaly. In addition, there were 8 cases (29.6%)of esophageal and gastric varices, 10 cases (37.0%)of ascites, and 3 cases (11.1%)of hepatic lesions. The histological characteristics included ductopenia(16/27, 84.2%), portal inflammation(16/27, 84,2%), interface hepatitis(6/27, 31.6%), ductular reaction(6/27, 31.6%), cholestasis(12/27,63.2%)and cholate stasis(5/27,26.3%). All patients had different degrees of fibrosis. Among them, eight patients suffered from liver cirrhosis (42.1%). Gene sequencing showed that all patients had the JAG1 gene variant. There were 15 cases(68.2%)with spontaneous variants and one with the NOTCH2 gene variant. Conclusion In addition to the characteristic multiple organ involvement and cholestasis, attention should be paid to the role of portal hypertension and its complications in the progression of ALGS; Clinical symptoms combined with histological characteristics should be considered in infants due to the lack of the manifestation of ductopenia.
    VO2 max is correlated with liver steatosis in male nonalcoholic fatty liver patients
    LIU Xiao-hui, GOU Yu-song, LIANG Shan, REN Hong, LI Qiang, DUAN Wei, ZHANG Jing
    2023, 28(3):  355-359. 
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    Objective To investigate the level of cardiopulmonary fitness (CRF) in NAFLD patients and to evaluate the relationship of CRF with liver steatosis, inflammation and liver fibrosis. Methods Sixty-two patients were enrolled in this study. Maximal oxygen uptake (VO2 max) level was determined to reflect CRF and controlled attenuated parameter (CAP) was tested to reflect liver fat content. Biochemical and body composition indexes were simutaneously detected. The CRF level was graded according to age and gender. The correlation between VO2 max and various fatty liver associated parameters were analyzed. Results Forty cases (64.5%) of the 62 patients were male, and their VO2 max, body weight, CAP, ALT, uric acid and body fat rate were significantly higher than those of female patients (all P<0.05). The levels of CRF were classified into 3 grades, i.e., excellent/good, general/poor and very poor. There were 3 cases, 14 cases and 23 cases in male patients, and 10 cases, 11 cases and 1 case in female patients were classified into each of the 3 grades, respectively, with significant difference between the male and female patients (P<0.001). In male patients, there were 10 cases with mild to moderate fatty liver and 30 cases with severe fatty liver. The BMI [(30.0±3.5) vs. (25.6±3.0)kg/m2], CAP value [(357.2±24.1) vs. (282.3±15.6)dB/m], weight hip ratio [(0.98±0.03) vs. (0.93±0.03)]and body fat rate [(29.7±4.3) vs. (23.9±4.2)%] were higher in patients with severe fatty liver, but their VO2 max [(30.1±3.2) vs. (32.8±3.0)mL/(kg·min)] was significantly lower than that in patients with mild to moderate fatty liver (both P<0.05). By correlation analysis it was shown that VO2 max was negatively correlated with CAP value, body fat rate, visceral fat content, visceral fat area and BMI in male patients, and positively correlated with appendicular skeletal muscle mass (both P<0.05). Conclusion VO2 max is closely associated with the severity of liver steatosis. The cardiopulmonary function and aerobic exercise capacity are low in NAFLD patients, especially in male patients. The results indicated that male patients with NAFLD had poor responsiveness to exercise intervention, and individualized exercise programs should be formulated for them according to their tolerance in clinical treatment.
    An evaluation on the histological characteristics and clinical outcome of non-obese patients with nonalcoholic fatty liver disease
    WANG Wei, GE Liang, YU Ning, XIONG Xiao-yun
    2023, 28(3):  360-363. 
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    Objective To evaluate the histological features and clinical outcomes of non-obese patients with nonalcoholic fatty liver disease (NAFLD). Methods A total of 152 patients (81 males and 71 females) with an average age of (52.1±11.7) years old who were admitted from January 2015 to June 2021 were selected. According to their Body Mass Index (BMI), the NAFLD patients were divided into non-obese type (BMI<25 kg/m2) and obese type (BMI>25 kg/m2). The histological features and clinical outcomes of non-obese and obese NAFLD patients were compared. Results There were 36 cases of non-obese NAFLD patients and 116 cases of obese NAFLD patients. The BMI, waist circumference and diastolic blood pressure of non-obese NAFLD patients were 23.5 (22.4, 24.6) kg/m2, (83.4±7.0) cm and 74 (60, 86) mmHg, respectively, which were significantly higher than those of [28.8 (26.5, 31.5) kg/m2 and (99.2±11.2) cm and 86 (75, 98) mmHg, P<0.05] of the obese patients. The aspartate transaminase (AST) of non-obese and obese NAFLD patients was 25 (18, 31) U/L and 32 (21, 48) U/L, with statistical significant difference (P<0.05). There are 15 cases (41.7%) and 13 cases (36.1%) of non-obese NAFLD with hypertension and metabolic syndrome, respectively, which are significantly different from those of the obese NAFLD [68 cases (58.6%) and 77 cases (66.4%), P<0.05]. The non-obese NAFLD steatosis, NAFLD activity score, hepatocyte ballooning, liver fibrosis stage and liver fibrosis were 35 (16, 52) %, (3.2±1.2) points, 19 cases (52.8%), (1.4±0.6) stage and 20 cases (55.6%), which are significantly different from those of [50 (30, 68) %, (3.8±1.3) points, 85 cases (73.3%), (1.9±0.8) stage and 92 cases (79.3%) of the obese NAFLD patients (P<0.05]. The LSM of non-obese and obese NAFLD patients was 6.2(4.6, 8.3) kPa and 8.4(6.0, 12.8) kPa, with statistical significance (P<0.05). There were no death patients during following-up. The cardiovascular events in non-obese and obese NAFLD patients were 1 case (2.8%) and 18 cases (15.5%), respectively, with statistically significant difference (P<0.05). The liver-related events were 1 case (2.8%) and 4 cases (3.4%), respectively, without statistically significant difference (P>0.05). Conclusion Compared with obese NAFLD patients, non-obese NAFLD patients have lighter histological abnormalities and better clinical outcome, but the long-term prognosis of these patients warrants further studies.