Table of Content

31 January 2022, Volume 27 Issue 1

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Drug-Induced Liver Injury

Study on clinicopathological characteristics of polygonum multiflorum-induced liver injury

HUANG Jia-min, ZHAO Xia, SUN Yi-kang, LI Wan-ying, GOU Ji-zhou, ZHOU Guang-de, HE Qing

2022, 27(1):  20-22. 

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Objective To investigate the clinicopathological features of Polygonum multiflorum-associated drug induce liver injury (PM-DILI) and provide pathological evidence for clinical diagnosis and treatment.Methods Eight PM-DILI patients with complete clinical data including liver function, autoimmune antibody tests, clinical epidemiological investigations and other lab tests were enrolled. Liver biopsy was performed in all subjects. The pathological features of hepatic tissue were observed by ematoxylin-eosin staining, reticular fiber staining, Masson’s trichrome staining, special staining of iron and copper, and immunohistochemical staining.Results The male to female ratio of the patients was 1∶1, and the average age was 43. Six cases were diagnosed as acute PM-DILI and 2 were diagnosed as chronic PM-DILI. Serological abnormalities at admission mainly included elevated transaminases levels (87.5%, 7/8) and cholestasis (87.5%, 7/8). The main histopathological changes were focal necrosis (100%, 8/8), interface hepatitis (62.5%, 5/8) and confluent necrosis (50%, 4/8). Confluent necrosis mainly occurred in the acinar zone 3, without or with a few inflammatory cell infiltration. Cholestasis (62.5%, 5/8) mainly occurred in the acinar zone 3, without or with a few inflammatory cell infiltration, and centralphlebitis (37.5%, 3/8). Liver fibrosis or even cirrhosis (25.0%, 2/8) might occur in those with a long disease duration.Conclusion There are some certain histopathology features in PM-DILI, acute cholestasis and hepatocyte necrosis in the acinar zone 3 are the main histological manifestations. Vascular injury such as phlebitis may occur in severe cases. Liver biopsy is helpful for diagnosing PM-DILI and evaluating the severity.

Influence of comorbidity on severity and prognosis of patients with DILI

WU Ting, WANG Yan, LIU Li-wei, LI Ke-xin, WANG Yu, OU Xiao-juan, JIA Ji-dong, ZHAO Xin-yan, MA Hong

2022, 27(1):  23-27. 

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Objective To investigate the influence of comorbidity on severity and prognosis of patients with drug-induced liver injury (DILI).Methods DILI patients admitted to our hospital from January 2016 to December 2019 who met the inclusion criteria were enrolled. According to Charlson Comorbidity Index (CCI), they were divided into significant comorbidity group (CCI≤2) and none or mild comorbidity group (CCI > 2). The clinical characteristics, severity and prognosis between the 2 groups were analyzed by chi-square or non-parametric test.Results A total of 313 DILI patients were included, with an average age of 54±14 years, 227 of them were females (72.5%). There were 272 patients with mild or without comorbidity (86.9%) and 41 patients with significant comorbidity (13.1%). Compared with patients with mild or without comorbidity, patients with significant comorbidity were significantly older (63±8 vs 52±14), and had higher body mass index (24.2±5.2 vs 23.1±3.6) , higher gamma-glutamyl transferase (GGT) level [initial value: 283.0 (159.0-404.0) vs 189.0 (100.0-325.0), higher peak value [335.0 (239.0-582.0) vs 219.0 (131.0-360.0) ] (all P<0.05. There was no significant difference in severity and clinical classification between 2 groups. In this cohort, 250 (79.9%) patients were fully recovered, whereas 41 (13.1%) patients developed to chronic DILI and 22 (7.0%) patients underwent liver transplantation or death. Compared to none or mild comorbidity group, the all-cause mortality and non-liver related mortality were significant higher in significant comorbidity group (19.5% vs 3.7%; 12.2% vs 0.7% all P<0.01).Conclusion Patients with significant comorbidity had poor prognosis, the leading cause of death is non-liver related.

Establishment and validation of an automatic monitoring and prediction model for DILI induced by cefuroxime

HUI Lei, LI Ying-ning, LUO Jing-jing, WU Xin-an

2022, 27(1):  28-32. 

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Objective To investigate the risk factors of drug-induced liver injury (DILI) induced by cefuroxime, and to construct the related prediction model.Methods Two hundred and seventy-one patients treated with cefuroxime sodium injection in our hospital from October 2019 to October 2020 were retrospectively selected through automatic monitoring system. The patients were divided into training group (n=203) and validation group (n=68) by cluster random grouping method. The risk factors of DILI caused by cefuroxime in training group were analyzed by univariate analysis and multivariate logistic regression analysis. The related nomogram prediction model was also established.Results Age ≥ 60 years (OR=3.497, 95%CI: 1.177~10.391), BMI ≥ 28 kg/m² (OR=3.333, 95%CI: 1.207~9.202), alcoholism (OR=3.399, 95%CI: 1.129~10.234) ), hypoalbuminemia (OR=3.272, 95%CI: 1.088~9.837) and dosage > 2.25 g/d (OR=9.045, 95%CI: 3.397~24.083) were independent risk factors of DILI caused by cefuroxime (P<0.05). A nomogram model was established to predict the DILI induced by cefuroxime based on the risk factors, and the model was also validated. The results showed that the C-index of training group and validation group were 0.774 and 0.758, respectively. The calibration curve was close to the standard curve. The area under the curve (AUC) of training group and validation group were 0.785 (95% CI: 0.0735-0.834) and 0.765 (95% CI: 0.707-0.779), indicating that the model had a good prediction ability.Conclusion There are many risk factors for DILI caused by cefuroxime. The nomogram model based on risk factors can accurately predict the incidence of DILI induced by cefuroxime.

Improvement effect of polygoni multiflori radix praeparatac in PD-1 knockout mice with liver injury induced by anti-CTLA-4

WANG Yu, ZHANG Chun-pan, WANG Yan, LIU Li-wei, LI Ke-xin, MA Zi-kun, JIA Ji-dong, WANG Jia-bo, ZHAO Xin-yan

2022, 27(1):  33-37. 

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Objective To investigate the effects of the polygoni multiflori radix praeparata (PMRP) in programmed-cell-death-1 (PD-1) knockout mice with liver injury induced by anti-cytotoxic-T-lymphocyte-associated protein-4 (anti-CTLA-4) and its immunological mechanisms.Methods C57BL/6-PD-1^-/- mice (n=10) were divided into the control group (n=4) and the PMRP group (n=6). Anti-CTLA-4 was injected intraperitoneally 3 days before experiment, 1 day before experiment and once a week after the experiment started. Normal saline and PMRP were respectively given to the control group and PMRP group with gastric infusion for 42 days. Blood and liver samples were collected on the 43th day, then hematoxylin-eosin (H&E), staining, immunohistochemical stains (IHC) and flow cytometry were performed.Results Compared with the control group, the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the PMRP group showed a decreased tendency (43.2±15.5 vs 32.8±6.7, P=0.216 and 32.3±7.5 vs 23.8±14.1, P=0.315, respectively). Pathological features of the control group were the existence of multiple inflammatory necrotic foci, macrophages and CD4⁺ T cells were the main infiltrating cells. The number of inflammatory necrotic foci in the PMRP group [121.5(104.0,147.3) vs 24(17.5,61.5), P=0.014] was significantly lower, the numbers of macrophages and CD4⁺ T cells were also significantly decreased. Compared with control group, flow cytometry showed that the proportions of macrophages (2.39±0.77% vs 1.37±0.28%, P=0.028) and neutrophils (0.58±0.11% vs 0.34±0.14%, P=0.025) were significantly decreased in PMRP group. The proportion of neutrophils secreting TNF-α significantly decreased in PMRP group (30.15±10.69% vs 11.56±6.05%, P=0.012). Compared with control group, the proportions of CD4⁺ T and CD8⁺ T cells did not change significantly, however the proportions of activated CD4⁺ T cells and CD8⁺T cells which secreted granzyme B significantly decreased in the PMRP group (26.20±3.47% vs 16.74±6.95%, P=0.044 and 77.05±4.23 % vs 59.70±10.81%, P=0.020, respectively).Conclusion PMRP can improve liver function in PD-1^-/- mice with liver injury induced by anti-CTLA-4, the mechanisms are inhibiting macrophages recruitment, neutrophils and effective T cells activation.

Viral Hepatitis

An analysis of the influence of informationized follow-up and intervention on the compliance of patients with HBV infection

WANG Yu-guang, LIU Zhi-wei

2022, 27(1):  38-41. 

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Objective To compare and analyze the influence of informationized follow-up and intervention on the medication compliances of patients with chronic hepatitis B (CHB).Methods A total of 264 eligible patients were included From October 2014 to October 2017 who were diagnosed as CHB and hepatitis B related cirrhosis in outpatient and inpatient departments of Huizhou Sixth People's Hospital were collected, of which 42 were diagnosed as cirrhosis. The patients were divided into three groups by stratified random sampling method, with 87 cases in WeChat+telephone follow-up group (group A), 88 cases in telephone follow-up group (group B) and 89 cases in control group (group C). All patients were followed-up for 2 years and compared for liver functions, the number of patients with liver cirrhosis, and the time of discontinuing anti-viral treatment of enticavir between the groups.Results After follow-up for two years, there was a significant difference in the numbers of lost visitors among these three groups. The levels of ALT (Z=-3.218, P=0.02), AST(Z=-2.749, P=0.03), Alb(Z=1.746, P=0.04), hepatitis B virus DNA (ALB) were statistically different between group A and group B. The levels of ALT(Z=-11.089, P<0.001), AST(Z=-9.247, P=0.01), TBil(Z=-7.623, P=0.01), APRI (Z=-4.81,P=0.02), hepatitis B viral DNA (Z=-10.078, P< 0.001) between group A and group C were significantly different, but there was no difference in FIB-4 index. The comparison between group B and group C showed that ALT(Z=-1.275, P=0.04), AST(Z=-2.045,P=0.03), TBil(Z=-3.762, P=0.02), APRI (Z=-1.466,,P=0.04) were statistically different. After 2-years’ follow-up, there were 12 cirrhotic patients in group A, 16 cirrhotic patients in group B and 24 cirrhotic patients in group C. There is no significant difference between group A and B (χ²=0.945, P=0.408), and group B and C (χ²=2.741, P=0.103), but there is significant difference between group A and group C (χ²=6.843, P=0.013). Within two years, 15 patients in group A, 28 patients in group B and 61 patients in group C stopped using entecavir. There were significant differences among these three groups (χ²=25.061, P< 0.001).The results of Kaplan-meier analysis showed that entecavir use in group A patients was longer than that in group B (83.0% vs 68.5) P=0.016) and group C (83.0% vs 33.7%, χ²=61.601, P< 0.001), while group B patients took enticavir longer than that of group C (63.5% vs 33.7%, χ²=32.451, P< 0.001).Conclusion Informationized intervention may increase the compliance of CHB patients to antiviral treatment and therefore reduce the incidence of liver function abnormalities and liver cirrhosis.

Clinical value of serum Tim-3 combined with gamma-glutamyl transpeptidase to cholinesterase ratio in CHB patients with normal or slightly elevated transaminase

LI Ni, HUANG Yu-lin, MA Shi-he

2022, 27(1):  42-46. 

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Objective To investigate the clinical value of T cell immunoglobulin mucin 3 (Tim-3) combined with gamma-glutamyl transpeptidase to cholinesterase ratio (GCR) in chronic hepatitis B (CHB) patients with normal or slightly elevated transaminase.Methods The clinical data of 109 CHB patients with normal or slightly elevated transaminase were retrospectively analyzed. The receiver operating characteristic (ROC) curve was used to analyze the value of serum Tim-3 and GCR in evaluating the liver inflammation stage and liver fibrosis grade of CHB patients with normal or slightly elevated transaminase.Results Among 109 CHB patients, the numbers of inflammation stages 1, 2, 3 and 4 were 40, 30, 26 and 13; the numbers of fibrosis stages 1, 2, 3, and 4 were 44, 32, 20 and 13. The serum Tim-3 level and GCR in CHB patients with different liver inflammation stages were significantly different (F=24.581, P=0.002; F=12.495, P=0.013). The serum Tim-3 level and GCR of patients in G2 [(16.09±3.57) ng/L, (1.04±0.29)] were higher than those of patients in G1 [(14.28±2.43) ng/L, (0.86±0.17)] and lower than those of patients in G3 [(18.65±4.81) ng/L, (1.26±0.38) ng/L], (P<0.05). The serum Tim-3 level and GCR of patients in G4 [(21.14±5.92) ng/L, (1.41±0.47) ng/L] were higher than those of patients in G3 [(18.65±4.81) ng/L, (1.26±0.38) ng/L], (P<0.05). ROC curve analysis showed that both Tim-3 and GCR could predict liver inflammation stages. The area under the curve (AUC) of Tim-3 combined with GCR was the largest (P<0.05). The serum Tim-3 level and GCR of CHB patients with different liver fibrosis stages were significantly different (F=22.165, P=0.008; F=11.388, P=0.018). The serum Tim-3 level and GCR of patients in S2 were higher than those of patients in S1 (P<0.05) and lower than those of patients in S3 (P<0.05). The serum Tim-3 level and GCR of patients in S4 were higher than those of patients in S3 (P<0.05). ROC curve analysis showed that both Tim-3 and GCR can predict liver fibrosis stages (P<0.05). The AUC of Tim-3 combined with GCR was the largest (P<0.05).Conclusion Both Tim-3 and GCR can predict liver inflammation and fibrosis stages of CHB patients with normal or slightly elevated transaminase. Tim-3 combined with GCR has the highest diagnosing value.

Liver Fibrosis & Cirrhosis

Analysis on risk factors of ischemic hepatitis in patients with liver cirrhosis complicated with esophageal and gastric varices bleeding

ZHANG Xin, LV Dan, LIU Dan-yang

2022, 27(1):  47-50. 

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Objective To investigate the incidence rate, mortality and risk factors of ischemic hepatitis secondary to esophageal and gastric varices bleeding (EGVB).Methods The clinical data of 102 patients with EGVB admitted to our hospital from January to August 2020 were retrospectively analyzed. The patients were divided into observation group and control group according to the occurrence of ischemic hepatitis. The general data, laboratory results, auxiliary examination results and clinical situation were analyzed by univariate analysis, and the statistically significant indexes were selected (P<0.05). The significant indexes were analyzed by multivariate logistic regression analysis, the incidence rate, mortality rate and risk factors of ischemic hepatitis secondary to EGVB were evaluated.Results Among 102 patients with EGVB, 14 of them complicated with ischemic hepatitis (transaminase level > 10 times the upper limit of normal value) were included in observation group, and the remaining 88 patients were included in control group. The mortality of observation group was 35.7%, which was 4.46 times higher than that of control group. The peak values of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in observation group mostly appeared on the second day after admission, which were 791.00 (555.25, 1657.5) U/L and 2541.50 (1480.50, 4594.00) U/L respectively. Univariate analysis showed that there were significant differences in ALT, AST, gamma-glutamyltranspeptidase (GGT), lactate dehydrogenase (LDH), total bilirubin (TBIL), white blood cell (WBC), platelet count, spleen length, splenic portal vein, portal vein trunk diameter, portal vein thrombosis, mortality, complicated with hepatic encephalopathy, complicated with sepsis, Child-Pugh score and ascites situation between the 2 groups (all < 0.05). Multivariate logistic regression analysis showed that liver cancer (P=0.000), white blood cell count(P=0.014), GGT (P=025), Child-Pugh grade ( P=0.050) were significantly correlated with the incidence of ischemic hepatitis secondary to EGVB.Conclusion The incidence rate of ischemic hepatitis secondary to EGVB is 13.72%, and mortality rate is 35.7%. Liver cancer (B = 4.055, OR=57.675), WBC count (B = 0.263, OR=1.300) and Child-Pugh grade (B = 1.774, OR=5.893) were the risk factors of patients with EGVB complicated with ischemic hepatitis. The incidence of ischemic hepatitis is not significantly correlated with shock (P=0.215) or anemia (P=0.280).

Application of ultrasonic measuring the diameter of vein in differentiating between schistosomiasis cirrhosis and hepatitis B cirrhosis

XIAO Kun, LIU Ai-hua, LIU Kun

2022, 27(1):  51-53. 

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Objective To investigate the application value of venous diameter measured by ultrasound in differentiating between schistosomiasis cirrhosis and hepatitis B cirrhosis.Methods A total of 78 patients with liver cirrhosis admitted to our hospital from August 2019 to August 2021 were included. Thirty-three cases were diagnosed as schistosomiasis cirrhosis and 45 cases were diagnosed as hepatitis B cirrhosis. Another 39 healthy volunteers who underwent physical examination in our hospital during the same period were also selected. Patients with schistosomiasis cirrhosis, patients with hepatitis B liver cirrhosis (before treatment) and healthy controls were all scanned by Siemens Acuson Sequoia 512 color Doppler ultrasound diagnostic apparatus to measure diameter of portal vein (DPV), diameter of splenic vein (DSV), diameter of superior mesenteric vein (DSMV). The DPV, DSPV and DSMV values of patients with schistosomiasis cirrhosis, patients with hepatitis B cirrhosis and healthy controls were compared. The value of DPV in diagnosing schistosomiasis cirrhosis and hepatitis B cirrhosis were analyzed by receiver operator characteristic (ROC) curve.Results The values of DPV, DSPV and DSMV in healthy controls were (10.4±1.8) mm, (7.1±1.1) mm, (6.9±2.4) mm, respectively. The values of DPV, DSPV and DSMV in patients with schistosomiasis cirrhosis were (11.9±2.6) mm, (9.3±2.2) mm, (10.7±2.0) mm, respectively. The values of DPV, DSPV and DSMV in patients with hepatitis B cirrhosis were (14.8±3.3) mm, (9.4±2.4) mm, (10.8±2.3) mm, respectively. The values of DPV, DSPV and DSMV of patients with schistosomiasis cirrhosis and patients with hepatitis B cirrhosis were significantly higher than those of healthy people (P<0.05). The DPV value of patients with schistosomiasis cirrhosis was significantly lower than that of patients with hepatitis B cirrhosis (P<0.05). ROC analysis showed that the area under the curve (AUC) of DPV in diagnosing schistosomiasis cirrhosis was 0.734, the standard error was 0.056, the 95% IC was 0.624 to 0.845, the best cutoff value was 10.750, the sensitivity was 0.822, the specificity was 0.590 (P<0.05). ROC analysis showed that the AUC of DPV in diagnosing hepatitis B cirrhosis was 0.825, the standard error was 0.053, the 95% IC was 0.722～0.928, the best cut-off value was 12.300, the sensitivity was 0.727, and the specificity was 0.923 (P<0.05).Conclusion Compared with healthy people, the DPV, DSPV and DSMV values of patients with schistosome cirrhosis and patients with hepatitis B cirrhosis are significantly higher. The DPV value between patients with schistosome cirrhosis and patients with hepatitis B cirrhosis is significantly different. ROC analysis confirmed that DPV can help diagnosing and differentiating the 2 diseases when the best cutoff values are 10.750 mm and 12.300 mm.

The clinical characteristics of HBV related acute on chronic liver failure patients with hepatitis B after withdrawal of nucleoside (acid) analogues

HU Da-shan, LIU huan, XUAN Ji

2022, 27(1):  54-57. 

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Objective To analyze the clinical characteristics of acute on chronic liver failure (ACLF) patients with hepatitis B after stopping anti-viral drugs, and to emphasize the awareness of standardized medication.Methods Forty ACLF patients with chronic hepatitis B (CHB) and CHB related liver cirrhosis (CHB-cirrhosis) who stopped taking oral nucleoside (acid) analogues were selected in this study. The association between the types of withdrawal drugs and the occurrence of ACLF, and the prognosis of these patients after active comprehensive treatment were analyzed.Results Among the types of withdrawal drugs resulting in ACLF, the proportion of entecavir was the highest (52.5%). In CHB group, the proportion of entecavir discontinuation associated ACLF was the highest (65.2%). In CHB- cirrhosis group, the proportion of adefovir dipivoxil withdrawal associated ACLF was the highest (41.2%). In 40 patients who had stopped taking anti-viral medicine, the levels of cholinesterase (CHE) (7 235±825.2 U/L) and α-fetoprotein (AFP)(156.7±34.0 ng/L) in hepatitis B group were significantly higher than those of CHE (5 534±900.4 U/L) and AFP (30.8±12.6 ng/L) in CHB-cirrhosis group (P<0.05). The levels of total bile acid (TBA) (52.7±11.4 μmol/L), total bilirubin (TBil) (95.6±17.5 μmol/L), direct bilirubin (DBil)(62.7±8.6 μmol/L) and prothrombin time (PT)(14.7±9.5s) in CHB group were significantly lower than those of TBA (67.5±15.5 μmol/L), TBil (349.7±62.2 μmol/L), DBil (214.0±18.7 μmol/L), PT (30.5±12.9 s) in CHB-cirrhosis group (P<0.05). The levels of ALB (30.3±7.2), CHE (7 005±890.4 U/L) and AFP (139.5±28.7 ng/L) in the effective treatment group were significantly higher than those of ALB (25.3±9.4), CHE (5 021±976.4 U/L) and AFP (29.8±4.7 ng/L) in the ineffective treatment group (P<0.05). The levels of TBA (40.7±18.2 μmol/L), TBil (96.5±15.3 μmol/L), DBil (53.5±7.2 μmol/L), PT (15.4±8.9 s) in the effective treatment group were significantly lower than those of TBA (50.9±20.4 μmol/L), TBil (350.6±50.8 μmol/L), DBil (218.0±20.7 μmol/L), PT (29.7±11.4 s) in the ineffective treatment group (P<0.05). In the CHB group and the CHB- cirrhosis group, the difference in the prognosis between effective and the ineffective treatment groups was statistically significant (P<0.05).Conclusion ACLF occurs after withdrawal of nucleoside (acid) analogues in CHB and CHB-cirrhosis patients and imposes a great impact on their prognosis. Cautious should be taken for discontinuing anti-viral agents.
   

The predictive value of CTP-MELD scores combined with serum M30 and M65 levels for the short-term prognosis of patients with hepatitis B-related acute-on-chronic liver failure

CUI Da-guang, XIAO Ling-yan, LIU Yong-fu, SHI Dong-yang, Yang kai, ZHENG Yi-shan

2022, 27(1):  58-62. 

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Objective To explore the predictive value of Child-Turcotte-Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores in combination with serum M30 and M65 levels for the short-term prognosis of patients with hepatitis B-related acute-on-chronic liver failure (HBV-ACLF).Methods One hundred and six HBV-ACLF patients admitted to our hospital from January 2017 to January 2020 were selected in this study. They were divided into a survival group (n=51) and a death group (n=55) according to their 90-day’s prognosis. The general conditions and indicators of laboratory test were compared between the patients in these two groups. Serum M30 and M65 levels were detected and CTP and MELD scores were evaluated. The receiver operating characteristic curve (ROC) was used to analyze the value of CTP and MELD scores, and serum M30 and M65 levels in predicting the short-term prognosis of HBV-ACLF patients.Results The CTP and MELD scores of the death group were (23.02±5.18) points and (31.18±5.89) points, respectively, which were significantly higher than those of (10.49±1.05) points and (13.21±1.34) points of the survival group (P<0.05); the serum levels of M30 and M65 in the death group were (1685.12±413.32) U/L and (2799.41±712.05) U/L, respectively, which were significantly higher than those of (1001.40±316.49) U/L and (1808.85±669.43) U/L of the control group (all P<0.05).The AUC of CTP, MELD, M30, and M65 that individually predicted 90-day mortality were 0.624 (95%CI: 0.525~0.716), 0.804 (95%CI: 0.716~0.875), 0.750 (95%CI: 0.656~0.829), and 0.887 ( 95%CI: 0.810~0.940); The AUC of a combination of these four items was 0.919 (95%CI: 0.850~0.963), which was significantly better than CTP, MELD, M30 in individual evaluation (P<0.05), and higher than M65 individual evaluation but no statistical significant difference (P>0.05).Conclusion CTP and MELD scores and serum M30 and M65 levels can predict the short-term prognosis of patients with HBV-ACLF. The combination of these four items is of better predictive value.

Clinical characteristic and prognostic analysis of HBV-related acute on chronic liver failure in AIDS patients

DENG Hao-hui, LOU Yan, GAO Hong-bo, CHEN Wei-lie

2022, 27(1):  63-67. 

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Objective To analyze the clinical characteristic and prognosis of HBV-related acute on chronic liver failure (HBV-ACLF) in patients with acquired immune deficiency syndrome (AIDS).Methods A total of 61 HBV-ACLF patients hospitalized from June 2012 to October 2020 in Guangzhou Eighth People’s Hospital were enrolled in this study, including 22 HBV-ACLF patients with AIDS and 39 patients with isolated HBV-ACLF. Clinical data were compared between these HBV-ACLF patients with AIDS and HBV-ACLF patients. In addition, the clinical data were further analyzed between treatment improve patients and treatment failure patients with HBV-ACLF and AIDS.Results (1) The baseline characteristics did not differ between HBV-ACLF patients with AIDS and isolated HBV-ACLF patients (P>0.05), All of these patients did not receive antiviral therapy before enrolled. Serum alanine aminotransferase (Z: -2.478, P=0.013) was significantly lower in HBV-ACLF patients with AIDS compared to that of HBV-ACLF patients, whereas HBV DNA (t: 3.778, P<0.001) level was significantly higher in HBV-ACLF patients with AIDS. However, the mortality rate did not differ between these two groups of patients (54.6% vs. 46.1%, P=0.529). Among the treatment failure HBV-ACLF patients with AIDS, 2 patients (16.7%) were died of severe pulmonary infection and 10 patients (83.3%) were died of liver failure or related complications. (2) The preliminary analysis results of the clinical data in HBV-ACLF patients with AIDS showed that age (Z=-2.574, P=0.009), Meld score (t: -2.206, P=0.042) and CD4⁺T cell counts (Z=-2.374, P=0.017) were significantly lower in treatment improve patients compare to those of treatment failure patients, and alpha fetoprotein (Z=-2.317, P=0.020) was significantly higher in treatment improve patients.Conclusion The ratio of treatment failure in HBV-ACLF patients with AIDS was high, and the severity of hepatic inflammation and the prognosis may be associated with the immunity status of the patients. Effective antiviral therapy should be given to HIV/HBV co-infected patients prior to HBV-ACLF occurred.

An analysis of the prognosis and influencing factors on bleeding events in patients with hepatitis B virus-related acute on chronic liver failure

LI Xu-dong, FAN Xi-wei, WANG Li, GUO Zhen-kai

2022, 27(1):  68-71. 

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Objective To analyze the prognosis and influencing factors of bleeding events in patients with hepatitis B virus-associated acute on chronic liver failure (HBV-ACLF).Methods One hundred and fifty-six patients with HBV-ACLF (119 males and 37 females) with an average age of (49.2±10.3) years were collected in this study From January 2017 to January 2021. Within them, 51 cases suffered from bleeding events (bleeding group) and 104 cases weren’t bleeding (non-bleeding group). Clinical data of these two groups of patients were compared. Measurement data were analyzed with T test. Counting data were analyzed with Chi-square test. The survival rates were compared by Log-Rank test.Results There were 31 cases (60.8%) of liver cirrhosis in the bleeding group and 36 cases (34.3%) of liver cirrhosis in the non-bleeding group, and the difference was statistically significant (P<0.05). Creatinine (Cr) and platelet (PLT) in the bleeding group were (80.6±9.8) mol/L and (70.5±12.4)×10⁹/L, respectively, which were significantly higher than those in the non-bleeding group [(62.4±8.4) mol/L and (102.5±22.7)×10⁹/L, P<0.05]. The fibrinogen, coagulation factors V, VII and VIII in the bleeding group were (1.1±0.2) g/L, (31.6±8.7)%, (32.8±9.2)% and (192.4±32.7)%, respectively, which were significantly higher than those in the non-bleeding group [(1.8±0.6) g/L, (64.8±14.7)%、(84.4±13.8)% and (118.0±26.1)%, respectively, P<0.05]. All patients were followed up effectively for 3 months, and the end-point of follow-up was HBV-ACLF related death. The 1-month survival rates of the bleeding group and the non-bleeding group were 84.3%(43/51) and 93.3%(98/105), respectively, without significant difference (P>0.05). The 3-month survival rates of the bleeding group and the non-bleeding group were 51.0%(26/51) and 73.3%(77/105), respectively, and the difference was statistically significant (P<0.05). After 3 months’ follow-up, 103 cases of HBV-ACLF patients survived (survival group) and 53 cases died (death group). Comparing the complications between these two groups, there were significant differences in hepatic encephalopathy, hepatorenal syndrome, electrolyte disturbance and various complications (P<0.05).Conclusion In HBV-ACLF patients, liver cirrhosis, decreased fibrinogen level and decreased coagulation factor VII activity are related to an increased risk of bleeding, which affect the prognosis of the patients. The occurrences of hepatic encephalopathy, hepatorenal syndrome, electrolyte disturbance and various complications during treatment indicated a poor prognosis.

The value of peripheral blood neutrophil to lymphocyte ratio and neutrophil CD64 in diagnosing secondary infection and predicting short-term prognosis of patients with hepatitis B virus-related chronic and acute liver failure

WANG Xin, ZHANG Guo-min, NIU Xing-jie, LI Ping, ZHANG Bing

2022, 27(1):  72-75. 

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Objective To explore the diagnostic and predictive value of peripheral blood neutrophil to lymphocyte ratio (NLR) and neutrophil CD64 (nCD64) in the secondary infection and short-term prognosis of hepatitis B virus-related chronic and acute liver failure (HBV-ACLF).Methods The clinical data of 85 HBV-ACLF patients admitted between July 2018 and July 2020 was retrospective analyzed. They were divided into an infected group (45 cases) and a non-infected group (40 cases) according to whether they had secondary infection. Patients in the infected group were further divided into an improved group (29 cases) and a non-improved group (16 cases) based on the short-term prognosis of them after 3 months’ treatment. The peripheral blood samples of all patients within 24 hours after admission were collected to detect the levels of NLR and nCD64. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value and short-term prognostic value of the combined detection of peripheral blood NLR and nCD64 for secondary infection in HBV-ACLF patients.Results The levels of peripheral blood NLR [(10.33±3.16)%] and nCD64[(74.41±19.06)%] in the infected group were significantly higher than those in the non-infected group [(6.53±1.14)% vs (43.49±13.27)%] , The difference was statistically significant (P<0.05). ROC curve shows that peripheral blood NLR and nCD64 have a certain diagnostic value for secondary infection in HBV-ACLF patients (AUC=0.756, 0.789, P<0.01), and the combination of the two (AUC=0.837, P<0.01) has a higher diagnostic value. The peripheral blood NLR[(9.24±2.46)%] and nCD64[(72.67±15.71)%] levels of HBV-ACLF patients in the improved group were significantly lower than those in the non-improved group [(11.54±3.11)% vs (85.89±12.43)%], The difference was statistically significant (P<0.05). ROC curve shows that peripheral blood NLR and nCD64 have a certain predictive value for the short-term prognosis of secondary infection in HBV-ACLF patients (AUC=0.784, 0.765, P<0.01), and the combination of the two (AUC=0.823, P<0.01) has a higher predictive value.Conclusion Peripheral blood NLR and nCD64 can be used as indicators for the diagnosis of secondary infection in HBV-ACLF patients, and for the assessment of their short-term prognosis, and the efficacy is higher with a combined detection.

Liver Cancer

An analysis on the influencing factors of post-operative infection after interventional surgery in primary liver cancer patients with diabetes mellitus

WANG Qiu, LIN Chuan

2022, 27(1):  76-80. 

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Objective To analyze the influencing factors of infection after interventional treatment of primary liver cancer patients with diabetes mellitus, so as to establish a prevention and treatment plan for the post-operative infection in the future.Methods The clinical data of 42 patients with primary liver cancer complicated with diabetes mellitus who were infected after interventional therapy from February 2019 to October 2020 were retrospectively analyzed and enrolled into the infection group; the clinical data of 40 patients with diabetes mellitus and primary liver cancer who did not get infection after interventional surgery at the same period of time were collected and enrolled into the non-infection group. Single and multi-variant analyses were performed on the baseline data of these two groups of patients to find out the influencing factors of infection post interventional therapy.Results The binary variables including duration of diabetes, duration of primary liver cancer, radiotherapy and chemotherapy, Child-Pugh classification, perioperative invasive operation, anemia and index of insulin resistance obtained by single variant analysis were taken as independent variables, and the incidence of infection in patients with diabetes mellitus complicated with primary liver cancer after interventional therapy was taken as a dependent variable (1=occurred, 2=not occurred). It was shown that the course of diabetes mellitus, the course of primary liver cancer, radiotherapy and chemotherapy, Child-Pugh classification, perioperative invasive operation, anemia, insulin resistance were the influencing factors of post-operative infection after interventional therapy in primary liver cancer patients with diabetes mellitus(OR=73.667, 85.500,61.667,380.00,74.000,218.667,68.889,P<0.05[gh1]).Conclusion The course of diabetes (≥1 year), the course of primary liver cancer (≥1 year), radiotherapy and chemotherapy (yes), child Pugh classification, perioperative invasive operation (≥ 3 times), anemia (yes), and the existence of insulin resistance were the influencing factors of infection after interventional surgery in primary liver cancer patients with diabetes mellitus. It is important to take protective strategies in these patients for improving their outcome after interventional therapy.

Expression and clinical significance of ACSL1 in hepatocellular carcinoma

LI Jiao-jiao, SHI Dou-dou, HUANG Qi-chao, TAO Mei

2022, 27(1):  81-85. 

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Objective To explore the expression of long-chain acyl-CoA synthetase 1 (ACSL1) in hepatocellular carcinoma (HCC) and its clinical values.Methods 334 paired HCC tissues were collected to detect the expression of ACSL1 by immunochemistry staining. The paper also analyzed the relationship between the expression of ACSL1 protein and the clinicopathological characteristics and prognosis of HCC patients. Lentivirus transfection was used to overexpression ACSL1 in HCC cell line SNU739. Cell proliferation and apoptosis were respectively measured by MTS assay and Flow cytometry. Cell energy metabolism were detected by SeahorseXF24 analyer and Lactate Assay Kit.Results The expression of ACSL1 in HCC tissues was markedly lower than that in adjacent tissues (3.02±2.57 vs 7.60±3.34, t=20.040, P=0.000), and the expression of ACSL1 was related to age of the patients (c2 = 16.472, P=0.000). The level of ACSL1 expression was a risk factor for survival in HCC patient (HR=1.642, P=0.012). ACSL1 was significantly promoted cell apoptosis (t=13.886, P=0.000), mitochondrial basal oxygen consumption rate(F=83.429, P=0.001) and maximal oxygen consumption rate(F=859.792, P=0.000)in SNU739 cell.Conclusion ACSL1 is low experssion in HCC tissues, and the prognosis of HCC patient with low ACSL1 expression is worse. ACSL1 can be used as a potential marker of prognosis in HCC patients, which is expected to be helpful to screen for early HCC and improve the survival rate of HCC patients.
   

The combined inhibiting effect and related mechanism of Curcumin and ABT-737 on epithelial-mesenchymal transition of human liver cancer cell

ZHENG Rui-nian, SUN Cheng-hui, JIA Yun, LIN Shun-huan, LIN Qin-xiong, LIU Chun, HAO Yan-yan, PAN Xue-bing, HE Yu, SHAO Jun-wei

2022, 27(1):  86-90. 

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Objective To explore the combined inhibiting effect and related mechanism of Curcumin and ABT-737 on epithelial-mesenchymal transition (EMT) of human liver cancer cell.Methods After treatment with 2 μmol/L Curcumin, 5 μmol/L ABT-737 alone or 2 μmol/L Curcumin in combination with 5 μmol/L ABT-737, the morphological change of 7404 cells was observed under an inverted microscope, the cell migration was analyzed by Wound Healing, the expression levels of Vimentin, N-cadherin, ZEB1 and E-cadherin proteins in 7404 cells were detected by Western blotting. The expression levels of p-beta-catenin, p-JNK, Snail and Twist proteins in 7404 cells were also detected by Western blotting. The animal models of liver cancer(Alb-Cre; P53^f/f; Ras)was established. The numbers of metastatic tumor in liver was observed and calculated under hematoxylin eosin stain.Results As compared with the 7404 cells with treatment of 2 μmol/L Curcumin or 5 μmol/L ABT-737, the numbers of 7404 cells that changed shape to spindle-like after treatment with 2 μmol/L Curcumin + 5 μmol/L ABT-737 were obviously reduced (P<0.05), with significantly decline of cell migration ability. Compared with the 2 μmol/L Curcumin or 5 μmol/L ABT-737 group, the expression levels of E-cadherin protein were significantly increased while the expression levels of Vimentin, N-cadherin and ZEB1 protein were significantly decreased in 7404 cells after treatment with 2 μmol/L Curcumin and 5 μmol/L ABT-737 (P<0.05). What’s more, as compared with the 7404 cells treated with the 2 μmol/L Curcumin or 5 μmol/L ABT-737 group,the expression levels of p-beta-catenin and p-JNK protein were significantly increased while the expression levels of Snail and Twist protein were decreased significantly in the 7404 cells after treatment with 2 μmol/L Curcumin + 5 μmol/L ABT-737 (P<0.05). The numbers of metastatic tumor in liver were decreased significantly in the animal models of liver cancer (Alb-Cre; P53^f/f; Ras) after Curcumin and ABT-737 treatment than those in the animal models without any treatment (as a control) (P<0.05).Conclusion The combination treatment of curcumin and ABT-737 may inhibit the epithelial-mesenchymal transition of human liver cancer cell, and JNK-beta-catenin signaling pathway may be involved in EMT.

Other Iiver Diseases

Clinical and imaging features, and curative effect observation of 54 infants with hepatic hemangioma

ZHOU Fei-fei, LIU Yong-gang, LIU Hao, SUN Hao-kai

2022, 27(1):  91-94. 

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Objective To analyze the clinical and imaging features of ultrasound, contrasted enhanced CT (CECT) and contrasted enhanced MRI (CEMRI) in 54 infants with hepatic hemangioma (IHHs), and to evaluate the therapeutic effect of IHH.Methods From January 2005 to March 2018, there were 54 IHHs (19 males and 35 females) with an age of (17.2±8.5) months. Fifty-eight patients with other focal liver lesions under 14 years old were selected in the same period.Results Univariate analysis of clinical data of IHHs (IHH group) and other patients with focal liver lesions (non-IHH group) showed that the ages of IHH group and non-IHH group were (17.2±7.5) months and (42.3±16.5) months, with statistical significance (P<0.05). 41 cases (75.9%) with AFP<20 ng/mL in IHH group, 13 cases (24.1%) with AFP>20ng/ml in non-IHH group, 8 cases (13.8%) with AFP<20 ng/mL and 50 cases (86.2%) with AFP>20 ng/mL had statistical significance (P<0.05). The tumor diameters of IHH group and non-IHH group were (5.6±1.8) cm and (8.4±2.6) cm, with statistical significance (P<0.05). In IHH group, resistance index (RI) was < 0.7 in 43 cases (79.6%), > 0.7 in 11 cases (20.4%), and in non-IHH group, RI was < 0.7 in 16 cases (27.6%), and > 0.7 in 42 cases (72.4%), the difference was statistically significant (P<0.05). Among the 54 IHHs, 43 were focal type (79.6%), 7 were multifocal type (13.0%), and 4 were diffuse type (7.4%). The lesion boundary was clear in 52 cases (96.3%) and unclear in 2 cases (3.7%). There was calcification in 26 cases (60.5%), and all cases were from patients with focal type. On plain CT scan of IHHs, it was showed low-density shadow, and CECT showed obvious enhancement around the lesion in arterial phase and centripetal filling enhancement in portal vein phase. On MRI of IHH lesions, T1-weighted sequence showed lower signal intensity than normal liver parenchyma, and T2-weighted sequence showed higher signal intensity. CEMRI showed the same performance as CECT. 26 cases (48.1%) of 54 IHHs were followed up. 17 cases were treated with drugs because of hepatomegaly and dyspnea, including 8 cases (14.8%) treated with hormone, 7 cases (13.0%) treated with propranolol and 2 cases (3.7%) treated with hormone combined with propranolol. 9 cases were treated with surgical intervention because of unsatisfactory drug treatment effect, including 7 cases (13.0%) with surgical resection and 2 cases (3.7%) with transcatheter arterial embolization. The lesions subsided or cured in 45 cases (83.3%) and significantly reduced in 5 cases (9.2%). All patients were followed up effectively for at least 3 months, 51 cases (94.4%) survived and 3 cases (5.6%) died of heart failure.Conclusion Compared with other focal liver lesions, IHH is younger in diagnosis, lower in AFP level and smaller in tumor diameter. Ultrasound, CECT and CEMRI are effective ways to diagnose IHH. Most IHH patients have a good natural course of disease, and hormone, propranolol and surgical resection of hepatic hemangioma are the effective treatment methods to relieve symptoms.

The case-control study of the association between pre-alcoholic cirrhosis and new-onset non-alcoholic fatty liver disease after liver transplantation

FENG Dan-ni, ZHANG Da-li, HE Xi, ZHANG Xiao-feng, NIU Xiao-feng, LI Zhi-jie, LI Li-xin, LIU Jia, ZHUANG Yun-long, LIU Zhen-wen, WANG Hong-bo

2022, 27(1):  95-97. 

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Objective To explore whether alcoholic cirrhosis before liver transplantation is a risk factor for non-alcoholic fatty liver disease (NAFLD) after liver transplantation.Methods Continuously collected the clinical data of patients with liver transplantation from May 2015 to May 2019 in the Fifth Medical Center of PLA General Hospital. New-onset NAFLD patients were screened, those who met the criteria for new-onset NAFLD were enrolled into the case group, and patients without NAFLD after liver transplantation were grouped into the control group. Analyzed the differences between the two groups of new-onset NAFLD patients and non-NAFLD patients. Logistic regression was used to analyze whether pre-transplant alcoholic cirrhosis was a risk factor for new-onset NAFLD.Results Finally, 136 patients were eligible, 15 of them who diagnosed with NAFLD were grouped into case group, and 121 of them who without NAFLD were into control group. The incidence of new-onset NAFLD at 1 year after liver transplantation was 11.03%. Compared with patients without NAFLD, preoperative median BMI (27.85 vs 23.17, P=0.003), indication for alcoholic cirrhosis (66.7% vs 23.1%, P=0.001), preoperative history of hypertension (33.3% vs 5.4%, P=0.016), and currently ALT level at 1 year after liver transplantation (24.0 U/L vs 21.5 U/L, P=0.012) were statistically significant between the two groups. Logistic regression showed that liver transplantation indications for alcoholic cirrhosis (OR=4.79, 95%CI: 1.35-16.98) and pre-liver transplantation high BMI (OR=1.23, 95%CI: 1.05-1.46) were risk factors for new-onset NAFLD.Conclusion Alcoholic cirrhosis before liver transplantation is a risk factor for new onset NAFLD.

Insulin sensitizers for nonalcoholic steatohepatitis: A meta-analysis of randomized clinical trials

WAND De-he, WANG Yi-qun, ZHOU Pan, YE Min-chao, ZHANG Wei, LI Ying

2022, 27(1):  98-102. 

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Objective To explore and evaluate the histological and serological efficacy of existing?medicine of insulin sensitizers in the clinical treatment and effect of nonalcoholic steatohepatitis (NASH).Methods Chinese and English database were electronically searched for the goal of collecting randomized clinical placebo trials (RCTs) on existing insulin sensitizers in the clinical treatment of NASH. Two different researchers independently screened these studies, collected data from them using the same forms and gave judgment independently of the risk of bias on these chosen clinical studies above. After then, Meta-analysis was performed precisely by RevMan5.3 software on computer.Results A total of 8 articles including 750 qualified researched subjects with NASH were finally chosen. And the results of analysis revealed that insulin sensitizers were able to alleviate liver fibrosis (RR=1.53, 95%CI [1.09, 2.14], P<0.05), steatosis (RR=2.29, 95%CI [1.76, 2.98], P<0.05), hepatocellular ballooning (RR=1.77, 95%CI [1.30, 2.42], P<0.05) and serological ALT (change value MD=-18.42, 95%CI [-29.79, -7.05], terminal value SMD=-1.01, 95%CI [-1.46, -0.56], P<0.05), AST (change value MD=-8.26, 95%CI [-15.12, -1.39], terminal value MD=-15.09, 95%CI [-21.12, -9.07], P<0.05), TG (SMD=-0.46, 95%CI [-0.65, -0.27], P<0.05), FPG (change value SMD=-0.62, 95%CI [-0.98, -0.26], Terminal value SMD=-0.50, 95%CI [-0.93, -0.07], P<0.05), FINS (SMD=-0.77, 95%CI [-1.11, -0.44], P<0.05) indicators, compared with the placebo group, but they could not give a substantial improvement in lobular inflammation (RR=1.53, 95%CI[0.92, 2.54],P>0.05), TC (SMD =-0.21, 95%CI[-0.63, 0.21], P>0.05) and BMI (change value MD=0.06, 95%CI [-1.53, 1.64], terminal value MD=-0.33, 95%CI [-1.44, 0.78], P>0.05) indicators.Conclusion Insulin sensitizer has a certain efficacy in the treatment of NASH, and has a good effect in improving liver histology and serological indicators.

Effect of fenofibrate combined with insulin in the treatment of type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease

LI Zhen-zhen, BAI Yang, HUANG Ting

2022, 27(1):  103-105. 

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Objective To compare the effect of fenofibrate combined with insulin in the treatment of type 2 diabetes mellitus (T2DM) complicated with nonalcoholic fatty liver disease and its influence on liver function, blood glucose content and vascular endothelial function.Methods The clinical data and follow-up data of 150 patients with type 2 complicated with nonalcoholic fatty liver disease were analyzed retrospectively, they were divided into control group (n=70) and observation group (n=80) according to the random number method. The patients in the control group received the guidance of healthy diet and reasonable exercise, and received insulin treatment. The observation group was treated with fenofibrate on the basis of the control group, and both groups were treated for 3 months. The clinical efficacy, liver function, blood glucose content and vascular endothelial function before and after treatment were compared between the two groups.Results The clinical effective rates of the observation group and the control group were 92.50% and 75.71% (P<0.05); compared with those before treatment, ALT, AST, FPG, 2hPG, HbA1c in the two groups were decreased after treatment (P<0.05), and the decline in the observation group was greater than that in the control group (P<0.05). After treatment, ET and TXB2 in the two groups were decreased (P<0.05), and PGF1 and NO were significantly increased (P<0.05) in the observation group. The improvement degree was significantly greater than that in the control group (P<0.05).Conclusion Fenofibrate combined with insulin in the treatment of T2DM patients with nonalcoholic fatty liver disease has significant clinical curative effect, which can improve renal function, reduce blood glucose level and improve vascular endothelial function, which is worthy of further clinical promotion.