Table of Content

15 December 2017, Volume 22 Issue 12

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Evaluation of risk factors for hepatic encephalopathy in patients with acute-on-chronic hepatitis B liver failure using artificial neural network

LIU Bao-rong, FANG Jian-kai, LIN Ming-hua, GAO Hai-bing, PAN Chen.

2017, 22(12):  1085-1089. 

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Objective To investigate the value of artificial neural network (ANN) in evaluating the risk factors of hepatic encephalopathy in patients with hepatitis B virus - related acute-on-chronic liver failure (HBV-ACLF).Methods In this retrospective study, 479 patients with HBV-ACLF were enrolled. Sex, age, diabetes, celiac infection,pulmonary infection, upper gastrointestinal hemorrhage, albumin, globulin, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase, cholinesterase, total cholesterol, potassium, sodium, creatinine, prothrombin time international normalized ratio (INR), white blood cell (WBC), hemoglobin (HGB), platelet(PLT), alpha-fetoprotein and HBV DNA were analyzed with univariate analysis for screening the significant risk factors for hepatic encephalopathy. Then the ANN model and the logistic regression model were used to determine the risk factors by multivariate analysis. The area under the receiver operating characteristic (ROC) curve (AUC) were used to evaluate the value of ANN model and logistic regression model.Results The ANN model indicated that risk factors of hepatic encephalopathy in patients with HBV-ACLF were INR,WBC, HGB, age, sodium, total bilirubin, creatinine, AFP, celiac infection, upper gastrointestinal bleeding and pulmonary infection sequentially in turn. The logistic regression model showed that INR (B=0.45, P<0.001,OR=1.566), WBC (B=0.12, P<0.001,OR=1.125), HGB (B=-0.01, P=0.015,OR=0.987), and age (B=0.02, P=0.026,OR=1.021) were the significant risk factors. The AUC of the ANN model and logistic model were 0.881±0.016 and 0.825±0.020 (P=0.029), respectively.Conclusion ANN model might have a powerful clinic value in evaluating risk factors of hepatic encephalopathy in patients with HBV-ACLF, which revealed that higher INR, higher WBC, lower HGB, and older age were the significant risk factors of hepatic encephalopathy.

The treatment effect of ursodeoxycholic acid combined with S-adenosyl-L-methionine on drug-induced cholestatic liver injury

YE Yan-ju, YU Jian-ping, XU Yu-min, WANG Hui, XIE Qing.

2017, 22(12):  1090-1093. 

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Objective To investigate the efficacy of ursodeoxycholic acid combined with S-adenosyl-L-methionine therapy in drug-induced cholestatic liver injury.Methods A retrospective analysis of 84 patients with drug-induced cholestatic liver injury from January 2013 to May 2015 in our hospital was conducted. Patients were divided into two groups depending on therapeutic regimen, including 46 patients receiving ursodesoxycholic acid and S-adenosyl-L-methionine combination therapy for 4 weeks in treatment group, and 38 patients receiving S-adenosyl-L-methionine in control group. All patients were followed up for 24 weeks, and the clinical outcomes were accessed.Results After 4-week treatment, patients in treatment group had higher response rate than those in control group (97.83% vs 84.21%, P=0.02). Furthermore, the liver function indexes, including total bilirubin, direct bilirubin, alkaline phosphatase and gamma-glutamyl transpeptidase, were all significantly improved in treatment group compared with those in control group (all P<0.05). During 24-week follow-up, two patients in control group were re-hospitalized due to abnormal liver function, including one patient with positive autoantibody and histopathologically diagnosed of drug induced liver injury-associated-autoimmune hepatitis. However, no similar case was observed in treatment group. No adverse effect was observed in both groups during and after treatment.Conclusion Ursodeoxycholic acid and S-adenosyl-L-methionine combination therapy might be more effective than S-adenosyl-L-methionine monotherapy for drug-induced cholestatic liver injury. Ursodeoxycholic acid might putatively contribute to prevention of autoimmune hepatitis, which needs to be further investigated.

The regulatory effect of Fuzhenghuayu capsule on peripheral blood cytokines in hepatitis B-related cirrhosis patients with effectively antiviral therapy

WU Mei, XU Lieming.

2017, 22(12):  1094-1097. 

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Objective To investigate the effect of Fuzhenghuayu (FZHY) capsule on peripheral blood cytokines secretion, liver function and liver cirrhosis in hepatitis B-related cirrhosis patients with effectively antiviral therapy.Methods A total of 63 patients with hepatitis B-related cirrhosis treated with entecavir effectively were enrolled in this study, including 30 cases treated with entecavir combined with FZHY as FZHY group and 33 cases treated with entecavir only as control group. Twenty healthy cases were set as normal group. Liver cirrhosis, liver function [alanine aminotransferase (ALT), aspartate transaminase (AST), albumin (Alb), total bilirubin (TBiL)] and the secretion of peripheral blood cytokines interleukin (IL) -1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-13, monocyte chemotactic protein (MCP)-1, interferon(IFN)-γ, tumor necrosis factor (TNF)-α, TGF-β1) were measured after one-year treatment, respectively.Results After treatment, the levels of ALT and AST decreased significantly in FZHY group (P<0.05, P<0.01). Liver stiffness in FZHY group (P<0.05) and control group were both decreased. Compared with that in control group, the levels of TGF-β1 and IL-13 declined significantly in FZHY group after treatment (P<0.01).Conclusion FZHY capsule could relieve the progress of liver cirrhosis in effectively antiviral patients through inhibiting the secretion of inflammatory cytokines.

Role of fibroblast growth factor 21 in pathogenesis of alcoholic liver fibrosis

TIAN Shu-xia, RUAN Jun, XIAO Tie-gang, HAN Yong-long, DU Jiang, CHEN Jun-ming.

2017, 22(12):  1098-1102. 

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Objective To observe the dynamic variety of fibroblast growth factor 21 (FGF21) in the development of alcoholic liver fibrosis in rats, and further investigate the role of FGF21 in alcoholic liver fibrosis.Methods Male SD rats weighing 240-280g were randomly divided into blank group, carbon tetrachloride (CCl₄) group and model group. The model was built with 10 mL/kg of alcohol mixture (56 DEG of alcohol: corn oil: pyrazole =5∶1∶10) by gavage daily and 0.3 ml/kg CCl₄ mixture (CCl₄∶olive oil =1∶3) by intraperitoneal injection twice a week for 12 weeks. The rats were sacrificed at week 4, 8, 10 and 12, respectively. Pathological changes in liver tissue were observed. Immunohistochemistry, western blot and fluorescent quantitative polymerase chain reaction (PCR) were used to measure FGF21 expression.Results Compared with blank group, the severity of liver fibrosis in model group was significantly increased. Level of FGF21 was significantly increased at week 4 (1.06±0.10 vs 0.23± 0.01, P<0.05), and then gradually increased till week 10 (1.36±0.16 vs 1.06±0.10, P<0.05), while significantly decreased at week 12 compared with that at week 10 (1.08±0.11 vs 1.36±0.16, P<0.05).Conclusion FGF21 might play a key role in the development of alcoholic liver fibrosis. Level of FGF21 was elevated under stress during liver injury and decreased when fibrosis developed. Therefore, increasing the level of FGF21 might be a potential target for treatment of alcoholic liver fibrosis.

Clinical application of serum PIVKA-Ⅱ in diagnosis of primary liver cancer

QIN Ya-nan, HONG Lei, SONG Zheng-xia, DING Qin

2017, 22(12):  1103-1106. 

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Objective To investigate the clinical value of serum prothrombin induced by vitamin K absence-Ⅱ (PIVKA-Ⅱ) in diagnosis of primary liver cancer.Methods Peripheral venous blood serum was collected from 330 patients from February 2016 to November 2016 in our hospital. Serum PIVKA-Ⅱ and alpha-fetoproteins (AFP) levels were measured using LUMI-PULSE G1200 automated immunoassay analyzer, and further analyzed for evaluating their clinical value in diagnosing and monitoring primary liver cancer.Results Serum levels of both PIVKA-Ⅱ and AFP in primary liver cancer group were higher than those in chronic hepatitis group and liver cirrhosis group (PIVKA-Ⅱ:U=1016, 280.5, 582.5, P=0.00, 0.00, 0.00; AFP:U=3534, 1225, 2849,P=0.00, 0.00, 0.00). The sensitivity of serum PIVKA-Ⅱ (83.19%) and combination of PIVKA-Ⅱ and AFP (89.38%) was higher than serum AFP (66.37%, adjusted χ²=7.60, P=0.006, χ²=16.05, P=0.00) in diagnosing primary liver cancer, respectively. The serum level of PIVKA-Ⅱ was positively correlated with tumor volume (r=0.63, P=0.00), and the sensitivity of detection was positively correlated with tumor size. The serum level of PIVKA-Ⅱ was higher in stage Ⅲ and IV than that in stage I and Ⅱ, respectively (Ⅲ: U=151.00, 173.00, P= 0.00, 0.04; IV: U=238.50, 292.50, P=0.00, 0.02). The serum levels of PIVKA-Ⅱ and AFP had no significant correlation with tumor differentiation. The serum levels of PIVKA-Ⅱ and AFP were significantly increased in early primary liver cancer with portal vein thrombosis, intrahepatic metastasis and lymph node enlargement (U=134.00,183.00, P=0.00, 0.01). The levels of serum PIVKA-Ⅱ and AFP were significantly decreased in patients with primary liver cancer after operation or intervention therapy (Z= -5.08,-4.28, P=0.00, 0.00), and the level of serum PIVKA-Ⅱ (80.13%) decreased more than the level of AFP (57.87%, χ²=4.226, P=0.04).Conclusion PIVKA-Ⅱ detection had a higher sensitivity and specificity for diagnosing primary liver cancer than AFP, which could be used as a tumor marker for clinical detection and prediction of primary liver cancer prognosis.