Table of Content

30 November 2020, Volume 25 Issue 11

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Viral Hepatitis

An investigation of the adherence to nucleos(t)ide analogue treatment in patients with chronic hepatitis B and analysis of affecting factors

HAN Zong-ru, MIN Xiao-chun, SHEN Qi-gang, YIN You-kuan, WANG Sen

2020, 25(11):  1148-1152. 

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Objective To evaluate the adherence of patients with chronic hepatitis B (CHB) to nucleos(t)ide analogues (NAs) and relative affecting factors.Methods This study is a cross-sectional study which collected clinical data of CHB patients taking NAs and investigated their compliance.Logistic regression analysis was used to evaluate the effect of different factors on medication adherence.Results 113 CHB patients were enrolled in this study.35 (31.0%) patients reported that they missed more than one dose in the past three months.Multivariate logistic regression analysis showed that patients younger than 30 years old (P=0.034),self-paid drugs (P=0.031),combined with 2 or more chronic diseases (P=0.021),and patients who did not insist on regular follow-up in the same clinic is more likely to have poor adherence (P=0.012).For patients with poor adherence,the one-year HBV DNA conversion rate was significantly lower than patients with good adherence (51.4% vs.79.4%,P=0.004),and the incidence of virological breakthrough was significantly higher than that with good adherence (14.3% vs.2.6%,P=0.017).Conclusion Our study found that certain factors such as age less than 30 years old,self-financed drugs,combined with other chronic diseases,and failure to adhere to regular follow-up in the same clinic were associated with poor medication adherence in CHB patients.We also confirmed that the poor adherence is directly related to the antiviral therapy effect of HBV infection.These findings can help medical staff to intervene and guide patients to improve the overall adherence of antiviral therapy,and ultimately improve the therapeutic effect.

The clinical significance of high-sensitive HBV DNA and HBsAg quantitative detection for chronic hepatitis B patients with low viral load

ZHANG Xiao-man, HE Cai-ting, ZHANG Chun-yu, XU Zheng-ju

2020, 25(11):  1153-1157. 

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Objective To investigate the clinical significance of high-sensitive detection of HBV DNA,in combination with quantitative detection of hepatitis B surface antigen (HBsAg) and serum level of alanine aminotransferase (ALT) for chronic hepatitis B (CHB) viral infected patients.Methods Six hundred and fifty-four CHB patients were retrospectively analyzed for their clinical data and parameters including highly sensitive HBV DNA,HBsAg,hepatitis B e antigen (HBeAg),ALT,and Golgi protein 73 (GP73).The patients were divided into HBV DNA load <20,20~499,500~2 000,and >2 000 IU/mL groups based on a highly sensitive HBV DNA detection by real-time quantitative fluresence polymerase chain reaction.Results Among the 654 CHB patients,82.41% had HBV DNA<2 000 IU/mL and 65.29% had HBV DNA<500 IU/mL.Abnormal rates of ALT and GP73,positive rate of HBeAg and HBsAg were significantly different among the four groups (All P<0.05).HBsAg content was significantly different between the groups of <20 IU/mL,20~499 IU/mL and 500~2 000 IU/mL (all P<0.001).There was a significant curve correlation (P<0.001) between positive and highly sensitive HBV DNA viral load and ALT,GP73 and HBsAg levels,and the correlation coefficients R were 0.394,0.369 and 0.415,respectively.In HBeAg (-) patients,the abnormal rate of ALT in the HBV DNA 20~499 IU/mL group was significantly higher than that in the <20 IU/mL group (P=0.048).In HBeAg (+) patients,the abnormal rates of ALT and GP73 were not significantly different between these two groups (P=0.366,0.120).The HBV DNA positive rate,ALT abnormal rate and antiviral treatment duration of 427 patients with HBV DNA<500 IU/mL were significantly negatively correlated (P=0.001,<0.001).There was no significant trend correlation between the abnormal GP73 rate and the positive HBeAg rate and the treatment time (P=0.165,0.367).The abnormal rate of ALT in the untreated group was significantly different from that of the treatment duration of 1 to 2 years,2 to 3 years,and more than 3 years (P=0.023,0.009,0.001).There were statistically significant differences between the HBV DNA positive rate and the treatment duration of 2 to 3 years and >3 years in patients with abnormal ALT in the untreated group (P=0.028,0.010).Conclusion The combination of high-sensitivity HBV DNA detection with HBsAg quantification is more accurate in reflecting the viral replication status.For patients with HBV DNA<500 IU/mL under antiviral therapy,dynamic and high-sensitive monitoring of HBV DNA may help in controling liver damage caused by persistent low-level of viral replication,which is of great significance for guiding clinical treatment and prognosis.

A follow-up observation on hepatic biochemical indexes of pregnant women with chronic hepatitis B virus infection after discontinuing antiviral treatment during delivery

ZHOU Gui-sheng, SU Jing, GONG Ping

2020, 25(11):  1158-1160. 

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Objective To explore the changes of liver function of pregnant women with chronic hepatitis B virus (HBV) infection after discontinuing antiviral treatment during delivery.Methods A retrospective study was carried out in 110 pregnant women with chronic HBV infection.They were divided into antiviral group (n=55) and control group (n=55).Patients in the antiviral group had received antiviral treatment,whereas patients in the control group remained untreated.The changes of blood routine test,including white blood cell count (WBC),platelet (PLT) and neutrophil,and the levels of HBV DNA,Creatinine (Cr),Total bilirubin (TBil),Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) were measured before antiviral treatment,prenatal and 8 weeks after delivery.The changes of liver function were analyzed.Results The cesarean section rate,postpartum hemorrhage rate and adverse pregnancy rate of the antiviral group were 60.00%,25.45% and 9.09%,respectively.There was no difference compared with 56.36%,21.82% and 10.91% of the control group (P>0.05).The HBV DNA quantity,Cr,TBil,ALT,AST in the antiviral group were lower than those in the control group before and 8 weeks after delivery (P<0.05).Conclusion The discontinuing of antiviral drugs during delivery in pregnant women with chronic HBV infection was not associated with abnormal liver function in 8 weeks after delivery,indicating that it was safe to temperately discontinue antiviral treatment during dilivery.

The analisis of the correlation between serum fibrinogen-like protein 1 and HBV DNA load in patients with chronic hepatitis B

XIE Ming-rong, ZHANG Chuan

2020, 25(11):  1161-1164. 

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Objective To observe the serum level of fibrinogen-like protein 1 (FLP1) and hepatitis B virus-deoxyribonucleic acid (HBV DNA) load in patients with chronic hepatitis B (CHB),and analyze the correlation between them.Methods 204 patients with chronic hepatitis B were divided into S0 group (N=42 cases),S1 group (N=39 cases),S2 group (N=46 cases),S3 group (N=38 cases) and S4 group (N=39 cases) according to their gradings of liver fibrosis stages by liver biopsies.The serum FLP1 level,the logarithmic value of the copy numbers of HBV DNA load,and the positive rate of HBV DNA were compared among the five groups.According to the logarithmic value of HBV DNA copy numbers,the patients were divided into <3 group,3~4 group,5~6 group,>6 group.The serum FLP1 levels in these four groups were compared.Moreover,the correlation between serum FLP1 level and HBV DNA load in patients with chronic hepatitis B was analyzed by bivariate linear correlation test.Results With the progression of liver fibrosis in patients with chronic hepatitis B,the serum FLP1 level decreased,whereas the logarithmic value of HBV DNA copy numbers increased,accompanied by an increased positive detection rate of HBV-DNA (P<0.05);With the increase of the logarithmic value of HPV DNA load,the serum FLP1 level showed a downward trend with statistically significant differences (P<0.05);By bivariate pearson linear correlation test it was showed that serum FLP1 levels of patients with chronic hepatitis B were negatively correlated with the logarithmic value of HBV DNA copy numbers (r=-0.584,P<0.001).Conclusion The serum level of FLP1 in chronic hepatitis B patients decrease with the increment of logarithmic value of HBV DNA load and the positive detection rate.There is a negative correlation between serum FLP1 level and HBV DNA load in CHB patients.Serum FLP1 level may therefore be considered as a clinical parameter to monitor the viral replication.

Analysis on the genotypes and resistance gene mutation of chronic hepatitis B virus in Sichuan

LIN Rui, CHEN Zhu, CHEN Yan, WANG Li, CHEN Xiong

2020, 25(11):  1165-1167. 

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Objective To observe the genotypes and resistance gene mutation of chronic hepatitis B virus in Sichuan to provide reference for antiviral therapy.Methods The index including HBV genotype,resistance gene mutation,liver function,HBeAg and HBV-DNA load of 489 patients with repeated abnormal liver function,who infected with chronic hepatitis B virus (CHB),in our hospital from Jan.2017 to Dec.2018 were examined.Results In our study,the age of patients were 11 to 82,the average was 40.31±7.64,and the number of male was more than female (332 men,67.89%).The main HBV genotype was type B (68.30%,334/489) and type C (27.61%,135/489),and there were 228 patients were founded drug-resistant mutation (58.90%,288/489),age from 13 to 75 (the average was 40.78±8.62).We found that the single site resistance gene mutation was 98 cases (34.03%,98/288),including the rtM204I(V) site mutation (36 cases),rtL180M mutation (31 cases) and rtN236T mutation (31 cases).The two sites mutation was totally 112 cases (38.89%,112/288),in which the most common mutation was rtL180M combined with rtM204I(V) (76 cases,67.86%,76/112).The three sites mutation was 78 cases (37.08%,78/288),which was based on rtL180M,rtM204 I(V) sites combined with rtN236T,rtA181V,rtA194T,rtS202 or rtM250.The drug resistance rate of type B was significantly higher than that of type C and other genotypes (χ²=10.38,P=0.005 6).Conclusion The main genotypes of HBV in Sichuan are type B and type C.Clinicians should be alert to the possibility of drug-resistant mutations in patients with repeated abnormal liver function and formulate individualized antiviral treatment plans according to the drug-resistant mutations.

The relavance of the polymorphism level of IL-17 gene and the prognosis of chronic hepatitis B virus infection

ZHANG Xiao-fang, LIU Xian-jin

2020, 25(11):  1168-1170. 

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Objective To study the relationship between the level of interleukin-17 (IL-17) gene polymorphism and the outcome of patients with chronic hepatitis B virus (HBV) infection.Methods Fifty-four cases of chronic hepatitis B from June 2017 to June 2018 were included as the observation group and 54 cases of asymptomatic chronic HBV infection were as the control group.The level of serum IL-17 was compared between the two groups.The HBV DNA content was quantitatively detected by PCR and fluorescent probe,and the distribution of IL-17 rs763780 gene polymorphism was detected by PCR amplification instrument.The incidence of progression to cirrhosis in different genotypes within one year was compared.Results The serum IL-17 of the observation group was significantly higher than that of the control group,and the incidence of HBV DNA content >1×10³ was higher than that of the control group (P<0.05).There were significant difference in the frequency distribution of IL-17 rs763780 genotype and allele between the two groups (P<0.05).The incidence of cirrhosis in TT genotype of IL-17 rs763780 were significantly higher than those in CC genotype and CT genotype (P<0.05).Conclusion The polymorphism of IL-17 gene is closely related to HBV infection.The patients with TT genotype and T allele of IL-17 rs763780 locus are more likely to have chronic HBV infection,and the incidence of cirrhosis is higher.

Liver Cancer

The correlation between the location of vascular embolization and bile duct injury after interventional embolization therapy of liver cancer

ZHAN Qiang, REN Wei, HAN Wei-qing

2020, 25(11):  1171-1174. 

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Objective To explore the correlation between the site of vascular embolization and bile duct injury after transcatheter arterial chemoembolization (TACE) therapy in liver cancer patients.Methods 108 cases of liver cancer patients underwent TACE were divided into three groups according to the location of embolization:tumor supply vascular group (group A,n=35),left hepatic artery group (group B,n=22),right hepatic artery group (Group C,n=25),and hepatic proper artery group (Group D,n=26).The incidence of bile duct injury was compared among the four groups,and the location of bile duct injury was analyzed.The risk factors of bile duct injury were analyzed by logistic linear regression model.Results The incidence of bile duct injury in group A,B,C and D was 14.29% (5/35),9.09% (2/22),8.00% (2/25) and 11.54% (3/26),respectively,without difference among the four groups (P>0.05).Among the 108 patients,a total of 12 had bile duct injuries,and the number of bile duct injuries was 21.The number of injuries in groups A,B,C and D was 8 (38.09%),3 (14.29%),4 (19.05%),and 6 (28.57%),respectively.In group A,4 injury sites were close to the tumor and 1 wasn't.In group B,all injury sites were located at segment I.In group C,all injury sites were located at segment V.In group D,all injury sites were located at hilum.Logistic multivariate analysis suggested that low blood supply and TACE site proximity to bile duct were risk factors for bile duct injury after TACE (P<0.05).Conclusion Interventional embolization at tumor supply vessels,left hepatic artery,right hepatic artery and proper hepatic artery of liver cancer patients weren't associated with the risk of bile duct injury.However,the risk of bile duct injury increased if the embolization site was close to the bile duct.

Effect of different concentrations of iodine contrast agent on the blood perfusion parameters of primary liver cancer measured by 64-row multidetector computed tomography

YANG Yun-fei, XIE Yi, JIAO Cheng-wen

2020, 25(11):  1175-1177. 

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Objective To analyze the effects of different concentrations of iodine contrast agent on the blood perfusion parameters of primary hepatocellular carcinoma (HCC) measured by 64-row multidetector computed tomography (MDCT),and provide further refined imaging diagnosis of primary liver cancer and references for the safety of iodine contrast agent.Methods Eighty-four patients with HCC were selected by case sampling method.Informed consent was obtained from all patients and their families.Equal numbers of patients were randomly assigned to different concentrations of iodine contrast agent groups,with 300 mg I/mL (1.90 mL/kg) in group A and 380 mg/mL (1.50 mL/kg) in group B.Multi-slice spiral CT (MSCT) was performed in both groups of patients.The association between the CT imaging results as measured by different concentrations of iodine contrast agent and the blood flow dynamic parameters of HCC were analyzed.Results The detection sensitivity of The CT values of hepatic parenchymal portal phase,aortic arterial phase,and portal vein phase and the arterial phase of group A patients were significantly higher,whereas the liver perfusion parameters including hepatic blood flow (BF),blood volume (BV),and hepatic artery perfusion (HAP) were significantly lower than those in group B (both P<0.05).Conclusion when detecting primary liver cancer with 64-row MDCT,using a higher concentration of iodine contrast agent [380 mg I/mL (1.50 mL/kg)] has better sensitivity,corresponding to relative lower values of hepatic artery and portal vein pressure in the blood flow perfusion parameters.The causal relationship warrants further validation.

Application of contrast-enhanced ultrasonography in the diagnosis of alpha-fetoprotein negative and positive hepatocellular carcinoma

HU Jian, LIU Ming-chun, WANG Yu, HUAI Yu-shui

2020, 25(11):  1178-1180. 

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Objective To analyze the value of contrast-enhanced ultrasonography in the differential diagnosis of alpha-fetoprotein (AFP) negative and positive hepatocellular carcinoma (HCC) patients.Methods Between January 2017 and December 2019,there were 90 HCC patients (62 males and 28 females) enrolled,with an average age of (53.1±7.9) years.Measurement data (±s) were analyzed by t-test.Count data (%) were analyzed by chi-square test.Results There were 56 patients in AFP-positive (AFP ≥ 20 g/L) group with a total of 74 lesions,34 patients in AFP-negative (AFP <20 g/L) group with a total of 38 lesions.The incidence of hepatitis B virus infection in AFP-negative group (24/34,70.6%) was significantly lower than that in AFP-positive group (51/56,91.1%,P<0.05).There were 29 (85.3%) cases with single focus,5 (14.7%) cases with multiple foci in AFP-negative group,and 37 (66.1%) cases with single focus,19 (33.9%) cases with multiple foci in AFP-positive group.Difference was statistical between the 2 groups (P<0.05).The diameter of lesions in AFP-negative group [(2.9±1.4) cm] was significantly shorter than that in AFP-positive group [(3.8±2.5) cm,P<0.05].In arterial phase,there was no significant difference in the incidences of hypoechoic,isoechoic or hyperechoic lesions between AFP negative and positive groups.In portal phase,there were 9 (23.7%) cases of hypoechoic lesions,25 (65.8%) cases of isoechoic lesions,4 (10.5%) cases of hyperechoic lesions in AFP-negative group,and 44 (59.5%) cases of hypoechoic lesions,30 (40.5%) cases of isoechoic lesions,no cases of hyperechoic lesions in AFP-positive group.Differences were statistically significant (P<0.05).In delayed phase,there were 22 (57.9%) cases of hypoechoic lesions,16 (42.1%) cases of isoechoic lesions,no cases of hyperechoic lesions in AFP-negative group,and 58 (78.4%) cases of hypoechoic lesions,16 (21.6%) cases of isoechoic lesions,no cases of hyperechoic lesions in AFP-positive group.Differences were statistically significant (P<0.05).The peak time in AFP-negative group [(29.0±4.1) s] was significantly longer than that in AFP-positive group [(23.7±3.6) s,P<0.05].The retention time in AFP-negative group [(90.4±7.1) s] was significantly shorter than that in AFP-positive group [(98.7±6.7) s,P<0.05].The area under the receiver operating characteristic curve in AFP-negative group (2158.4±210.6) was significantly less than that in AFP-positive group [(2480.2±215.6),P<0.05].However,the arrival time has no significant difference between the 2 groups (P>0.05).Conclusion In contrast-enhanced ultrasound imaging,both AFP negative and positive HCC patients show fast-in and fast-out enhancement,especially in AFP-positive patients.Contrast-enhanced ultrasound is helpful in distinguishing AFP-negative and AFP-positive HCC.

Effects of sorafenib on proliferation and apoptosis of hepatocellular carcinoma cells and JAK-STAT signaling pathway

CHENG Xiu-lian, HAN Li-feng, TANG Xiu-li, ZHAO Na, LIU Ning-ning

2020, 25(11):  1181-1184. 

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Objective To investigate the effects of sorafenib on the activity and apoptosis of hepatoma cell lines (HepG2,MHCC97-H,QGY-7701,Bel-7404 and SKHep-1) and tyrosine kinase Janus kinase and transducer and activator of transcription (JAK-STAT) signaling pathway.Methods The effects of different concentrations of sorafenib on the inhibition and apoptosis of various cell lines were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry.The messenger RNA (mRNA) and protein expression of tyrosine kinase Janus kinase 2 (JAK2) and transducer and activator of transcription 3 (STAT3) in JAK-STAT signaling pathway were detected by quantitative real time polymerase chain reaction and western blot,respectively.Results MTT showed that the half maximal inhibitory concentrations of sorafenib for HepG2,MHCC97-H,QGY-7701,Bel-7404 and SKHep-1 cell lines were (13.17±0.09) μmol/L,(9.28±0.05) μmol/L,(11.97±0.07) μmol/L,(8.49±0.06) μmol/L and (10.54±0.03) μmol/L,respectively.When the concentration of sorafenib was 20 μmol/L and the incubation time was 72 h,the inhibitory effect was the best.Compared with the control group,sorafenib could promote the cell apoptosis,as well as reduce the mRNA and protein expression of JAK2 and STAT3 in liver cancer cell lines (P<0.01).Conclusion Sorafenib can suppress the activity of liver cancer cells,induce apoptosis of cells,and inhibit the protein expression of JAK-STAT signaling pathway in tumor cells.It is suggested that JAK-STAT signaling pathway may be the target of sorafenib,and the potential target for prevention and treatment of other tumors.

Liver Fibrosis & Cirrhosis

Application value of perioperative multi-slice spiral CT portal venography in cirrhotic patients with esophagogastric variceal bleeding

LIU Wei, LIU Sheng-nan

2020, 25(11):  1185-1187. 

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Objective To analyze the application value of multi-slice spiral computed tomography (CT) portal venography over perioperative period in cirrhotic patients with esophagogastric variceal bleeding.Methods A total of 52 cirrhotic patients with esophagogastric variceal bleeding admitted to our hospital from January 2015 to December 2018 were enrolled.All of these patients were treated with the combination of transjugular intrahepatic portosystemic shunt (TIPS) and left gastric vein embolization.Multi-slice spiral CT portal venography was used for perioperative follow-up,and its application value was evaluated.Results Before operation,48 patients (92.3%) had gastric coronary varices,19 patients (36.5%) had short gastric varices,49 patients (94.2%) had esophageal varices,and 10 patients (19.2%) had paraumbilical varices.Portal pressure decreased from (35.3±2.2) cmH₂O before treatment to (26.1±1.9) cmH₂O after treatment,with significant difference (t=9.837,P<0.001).The follow-up at 6 months and 12 months after operation,varices disappeared and blood flow resumed in 38 patients (73.1%),varices relapsed after the improvement in 12 patients (23.1%),and varices had no improvement in 2 patients (3.8%).Within 12 months after operation,variceal rebleeding occurred in 6 patients (11.5%).Within 6 months after operation,hepatic encephalopathy was observed in 4 patients (7.69%).During 13-23 months after operation,3 patients (5.8%) died of hepatic failure.Conclusion For patients undergoing TIPS and left gastric vein embolization,multi-slice spiral CT portal venography has high clinical value in varicose veins monitoring,treatment guiding,and prognosis assessment.

Effect of microecological preparation on intestinal barrier function in patients with cirrhosis and spontaneous peritonitis

YANG Xiao-dong, YU Ming-li, JIA Ting, ZHANG Xiu-ling, GAO Si-yuan, YU Xiang-qiong, WANG Li-ping, SHI Jun

2020, 25(11):  1188-1190. 

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Objective To investigate the effect of microecological preparation on intestinal barrier function in patients with cirrhosis and spontaneous peritonitis (SBP).Methods A total of 80 patients with cirrhosis and SBP admitted to our hospital from May 2015 to May 2019 were divided into control group and observation group according to random number table.The control group was given routine treatment,the observation group was given microecological preparation in addition to routine treatment,and the course of treatment in both groups was 2 weeks.Clinical efficacy of the 2 groups was compared.Two ml venous blood was collected before and 2 weeks after treatment,respectively.Serum endotoxin (ET),procalcitonin (PCT),hypersensitive c-reactive protein (CRP),and interleukin-6 (IL-6) levels were detected in the 2 groups,to indirectly reflect changes of intestinal barrier function.Results The total effective rate of the observation group was 95.00%,higher than 80.00% of the control group,and the difference was statistically significant (P<0.05).After treatment,the levels of serum ET,PCT,CRP and IL-6 in both groups were lower than those before treatment,and the levels in the observation group were significantly lower than those in the control group (P<0.05).The adverse reaction rate was 7.50% in the observation group and 5.00%in the control group,with no significant difference (P>0.05).The complication rate was 5.00% in the observation group and 10.00% in the control group,with no significant difference (P>0.05).Conclusion Compared with the conventional treatment in patients with cirrhosis and SBP,the addition of microecological agents can promote intestinal barrier function and improve the curative effect,with high value of clinical application.

Characteristics of esophagogastric varices patients with and without hemodynamic response after the intervention of propranolol

CHEN Xiao-yin, KONG Fan-jing, JIAN Wei, NIU Yan-feng, ZHANG Wan-li, LI Fen

2020, 25(11):  1191-1194. 

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Objective To study the hemodynamic response and clinical characteristics of patients with esophageal and gastric varices after the intervention of propranolol.Methods There were 102 cirrhotic patients with esophagogastric varices in our hospital undergoing the measurement of hepatic vein pressure gradient before and 7 days after the administration of propranolol.The patients who successfully completed the 2 tests were followed up to analyze the tolerance of propranolol,hemodynamic status and bleeding.Results There were 96 of 102 patients finally included in the study,and the hemodynamic response rate accounted for 43.75%.In responders,the heart rate,wedged hepatic venous pressure and hepatic venous pressure gradient after short-term administration of propranolol were significantly lower than those before administration (P<0.05).In non-responders,the heart rate and hepatic venous pressure gradient after administration were significantly lower than those before administration (P<0.05).The post-treatment hepatic vein pressure gradient of the responders was significantly lower than that of the non-responders (P<0.05).During the follow-up of 3 years,the incidence of esophageal and gastric variceal bleeding in the whole cohort was 25.00%.The incidence of bleeding in responders was 0,significantly lower than 55.56% in non-responders (P<0.05).Conclusion Patients with cirrhotic esophagogastric varices who received propranolol for a short period of time were probable to have a hemodynamic response.And those with no hemodynamics response had a higher risk of bleeding than responders.

Study on risk factors of third generation cephalosporin resistance in patients with cirrhosis ascites and spontaneous bacterial peritonitis

WU Gang, WANG Lei, LIN Hai, TANG Li

2020, 25(11):  1195-1198. 

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Objective To study the risk factors for third-generation cephalosporin resistant bacteria infection in patients with cirrhosis ascites and spontaneous bacterial peritonitis (SBP).Methods The clinical data of 158 cirrhotic ascites patients with SBP from November 2014 to November 2019 were analyzed retrospectively.According to the results of drug sensitivity,the patients were divided into resistance group (77 cases with third-generation cephalosporin resistant bacteria in ascites) and non-resistance group (81 cases without third-generation cephalosporin resistant bacteria in ascites).The composition of pathogenic bacteria in the 2 groups was investigated.And the independent influencing factors for third-generation cephalosporin resistant bacteria infection in patients with cirrhosis ascites and SBP were analyzed by multivariate logistic regression.Results The types of third-generation cephalosporins involved in drug susceptibility testing included ceftazidime,ceftriaxone,cefoperazone and cefotaxime.Pathogens in the resistance group were resistant to the above 4 drugs,while those in the non-resistance group were sensitive.The proportions of Escherichia coli and Enterococcus faecalis in the resistance group were significantly higher than those in the non-resistance group (P<0.05),while the proportions of Klebsiella pneumoniae,Streptococcus and Corynebacterium were significantly lower than those in the non-resistance group (P<0.05).The proportions of patients with broad-spectrum antibiotics exposure in recent 3 months and reemerging SBP in the resistance group were significantly higher than those in the non-resistance group (P<0.05).The blood creatinine level was significantly higher in the resistance group than that in the non-resistance group (P<0.05),and the blood bicarbonate level was significantly lower in the resistance group than that in the non-resistance group (P<0.05).Broad-spectrum antibiotic exposure in recent 3 months,SBP history and blood bicarbonate were independent influencing factors for the third-generation cephalosporin resistance bacteria infection in patients with cirrhotic ascites and SBP (P<0.05).Conclusion Broad-spectrum antibiotic exposure in recent 3 months,SBP history,and low-level blood bicarbonate are closely related to the infection of third-generation cephalosporin resistant bacteria in patients with cirrhosis ascites and SBP.Selection of third-generation cephalosporin in patients with these characteristics should be with more caution.

Changes in oxidative stress and ERK signaling pathway during the formation and regression of liver fibrosis

PING Da-bing, CUI Hong-yan, SUN Xin, HUANG Kai, PENG Yuan, TAO Yan-yan, LIU Cheng-hai

2020, 25(11):  1199-1204. 

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Objective To investigate the characteristics of oxidative stress and extracellular signal-regulated kinase (ERK) signaling pathway during the formation and regression of liver fibrosis.Methods Rats were injected intraperitoneally with dimethyl nitrosamine (DMN) to establish the rat liver fibrosis model.Normal rats were used as control group.The activity of superoxide dismutase (SOD)/glutathione S-transferase (GST),reduced glutathione (GSH) content,collagen deposition,hydroxyproline content,α-smooth muscle actin (α-SMA) expression and collagen I messenger RNA (mRNA) level in liver tissue were observed at 1 day,3 days,1 week,2 weeks,3 weeks,4 weeks after the initiation of injection and 1 week (5 weeks),2 weeks (6 weeks),4 weeks (8 weeks) after the last injection.Gelatin zymography was used to determine the activity of matrix metalloproteinase 2/9 (MMP2/9).The protein expressions of MMP2/9,tissue inhibitor of metalloproteinase 1/2 (TIMP1/2),ERK and phosphorylated ERK1/2 (p-ERK1/2) were analyzed by western blot.Results As DMN intoxication continued,the collagen deposition and α-SMA expression in the liver of the model rats increased,with marked fibrous septum and pseudo-lobule formation.After stopping the intoxication,the collagen deposition,fibrous septum,and the positive staining area of α-SMA reduced.Western blot showed that with the formation of liver fibrosis,the activity of MMP2/9 was enhanced,and the expressions of TIMP1/2 and p-ERK protein increased gradually.During the regression of liver fibrosis,the expressions of these proteins decreased,but still maintained a relatively high level.Compared with the normal group (287.12±97.15,8.17±0.59),the trends of SOD activity and GST activity in each model group were consistent,which decreased significantly from the first week (277.81±27.40,8.19±1.26),reached the lowest point at the forth week (121.83±21.69,5.95±2.21),and recovered after stopping exposure (255.69±109.51,6.53±1.67),but remained a relatively low level.The GSH content (53.71±17.07) showed a transient increase on the day 1 and 3 of exposure (63.33±16.94,70.72±21.46),then decreased gradually during exposure,and recovered to the normal level gradually after stopping exposure (42.32±18.25).Conclusion The formation and regression of hepatic fibrosis induced by DMN presents corresponding oxidative stress changes,which are related to ERK signaling pathway.

Liver Injury

Analysis of clinical characteristics in 116 patients with drug-induced liver injury

YIN Jie, LIU Tao-tao, SHEN Xi-zhong

2020, 25(11):  1205-1207. 

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Objective Aim To analyze clinical characteristics of drug-induced liver injury (DILI).Methods Clinical data of 116 patients with DILI in Zhongshan Hospital Affiliated to Fudan University were retrospectively collected from November 2016 to November 2019.Clinical characteristics were analyzed.The continuous data were expressed as median and interquartile range M(P25-P75),and the Mann-Whitney U test was used for comparison between groups.The chi-square test was used for comparison of categorical data between groups.Results Among all 116 patients,there were 69 female patients and most of the patients were aged 40-69 years.Of all patients,23 cases were induced by Western medicine,82 cases had DILI induced by Chinese herbal medicine and healthcare products,11cases may caused by Chinese herbal medicine and Western medicine.The most commonly implicated Chinese herbal medicines were compound preparations or decoctions containing Panax pseudo-ginseng or Radix polygoni multiflori.The most commonly causative Western medicines were antimicrobial agents and non-steroidal anti-inflammatory drugs.The median time from taking medications to the onset of symptoms were 28 days.70.7% cases were presented with hepatocellular injury type.The patients with liver injury induced by Chinese herbal medicine had significantly higher on admission values of ALT,AST and γ-GT than those with liver injury induced by Western medicine (all P<0.05).Liver biopsy was performed in 9 cases,whereas all pathological findings prompted diagnosis of DILI.Only one patient displayed combination with auto immune hepatitis in pathological presentation.Biopsy ratio was significantly different in different clinical classification,while biopsy ratio was highest in mixed type.Fourty-four patients treated with glucocorticoid had higher on admission levels of TBil,DBil,ALP and lower serum albumin than those without glucocorticoid treatment.Of all patients,94.8% of them achieved improvement,and patients with poor responses to treatment had higher values of TBil,DBil,INR and lower serum albumin than patients with good prognosis (all P<0.05).Conclusion DILI is commonly observed in female middle-aged and elderly patients.The most causative drugs were Chinese herbal medicines.The major type of DILI was hepatocellular injury.Liver biopsy was not required for the diagnosis of DILI in our setting.Most DILI patients have good prognosis.

Analysis of etiology, clinical characteristics and prognosis of 128 children with drug-induced liver injury

CHEN Shu-ping, AN Hong-jun, GAO Shui-ju, LI Wen-li

2020, 25(11):  1208-1211. 

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Objective To explore the etiology,clinical features and prognostic factors of drug-induced liver injury (DILI) in children,and to improve the understanding of DILI in children.Methods From January 2007 to December 2019,128 children (76 males and 52 females) with DILI (<14 years old) were admitted to our hospital.Measurement data were expressed in (±s),t-test was used,counting data was expressed in (%),and chi-square test was used.Results The primary diseases include respiratory tract infection,malignant tumor,drug allergy and local inflammatory diseases.The types of drugs include western medicine and traditional Chinese medicine/proprietary Chinese medicine.Seventy cases (54.7%) of western medicine,including antimicrobials (macrocyclic esters,penicillin,cephalosporins),anti-tuberculosis drugs (isoniazid,rifampicin),antineoplastic drugs (cytarabine,methotrexate,azathioprine),and hormone drugs.Twenty-six cases (20.3%) of traditional Chinese medicine/proprietary Chinese medicine,including traditional Chinese medicine/proprietary Chinese medicine preparation and herbal medicine.Thirty-two cases (25.0%) were used in combination.The youngest patient was 5 months old,the oldest was 14 years old,8 cases were under 1 year old (6.3%),11 cases were 1 to 3 years old (8.6%),68 cases were 4 to 9 years old (53.1%),and 41 cases were 10 to 14 years old (32.0%).According to the clinical classification of DILI,there were 90 cases of hepatocyte type (70.3%),24 cases of cholestasis type (18.7%) and 24 cases of mixed type (18.7%).DILI severity grade was mild in 56 cases (43.7%),moderate in 65 cases (50.8%) and severe in 7 cases (5.5%).The pathological findings of transhepatic puncture (78 cases,60.9%) included inflammatory cell infiltration (such as neutrophils,eosinophils),hepatocyte steatosis,hepatocyte punctate necrosis and/or interface hepatitis.The clinical manifestations of children with DILI were fatigue in 72 cases (56.3%),loss of appetite in 69 cases (53.9%),nausea and vomiting in 25 cases (19.5%),yellow skin or yellow urine in 38 cases (29.7%),and skin pruritus or rash in 16 cases (12.5%).After stopping medication and symptomatic treatment,24 children with DILI were cured (18.8%),90 cases improved (70.3%),14 cases were not cured (10.9%),and there was no death.The cured and improved cases were defined as effective group (n=114),and the uncured cases were defined as ineffective group (n=14).There were significant differences in age,ALT,international standardized ratio (INR) and drug types between the two groups (P<0.05).Conclusion Most of the children with DILI were relieved after stopping treatment,and the prognosis of the children with DILI who were younger and took traditional Chinese medicine/proprietary Chinese medicine was worse than that of the older children who took western medicine.In the process of drug use for children in the future,we should focus on prevention and control of drug use and use it as appropriate,so as to reduce the incidence of DILI.

The treatment mode of hyperthyroid patients with severe liver damage

LV Sa, ZHU Bing, XU Tian-jiao, LI Dong-ze, TIAN Hua, YOU Shao-li

2020, 25(11):  1212-1215. 

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Objective To explore the treatment mode of hyperthyroidism patients with severe liver damage.Methods The clinical data and treatment outcome of 4 patients with severe hyperthyroidism were analyzed retrospectively.Results Among the 4 patients,1 male and 3 female,aged 29-58 years old,with no hyperthyroidism and no antithyroid drugs have been used.Among them,2 cases were subacute liver failure,2 cases were complicated with decompensated cirrhosis of autoimmune liver disease,TBil was higher than 10 × ULN,ALT,AST,ALP and GGT were higher in different degrees.The patients were treated with β-blocker,glucocorticoid and ¹³¹I after plasma exchange.The patients were followed up for 5 months and 3 months respectively.The liver function of patients with subacute liver failure recovered completely.The patients with cirrhosis were stable.Conclusion β-blocker,glucocorticoid and artificial liver should be used as adjuvants in the treatment of hyperthyroidism patients with severe liver damage,and 131I treatment opportunity should be created in time,which can effectively improve the liver function and prognosis.

Other Liver Diseases

Efficacy evaluation of silybin capsule combined with fenofibrate in the treatment of nonalcoholic fatty liver

ZHAI Yu-rong, LI Li, HUANG Ling, DUAN Hua-rong

2020, 25(11):  1216-1219. 

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Objective To explore the clinical efficacy of silybin capsules combined with fenofibrate tablets in the treatment of non-alcoholic fatty liver.Methods One hundred and eighteen patients with non-alcoholic fatty liver treated in our hospital from March 2017 to May 2019 were selected as the research subjects and randomly divided into observation group and control group,with 59 cases in each group.Fifty-nine patients in the observation group were treated with silybin capsules and fenofibrate tablets,and 59 patients in the control group were treated with silybin capsules.After treatment,the clinical efficacy,liver function,blood glucose and blood uric acid,blood lipid,inflammation index,liver and spleen CT ratio,and safety index were used as the evaluation indicators.Results The clinical effective rate of the observation group was 96.61%,which was significantly higher than that of the control group (77.97%).The difference was statistically significant (P<0.05).The serum levels of ALT,AST and GGT in the observation group and the control group were significantly lower than those in the control group,and the observation group was significantly lower than the control group,the difference was significant (P<0.05).After treatment,the FBG,FINS and the control group were compared with the control group.The level of SUA was significantly different from that before treatment,and the observation group was significantly lower than the control group,with significant difference (P<0.05).The serum levels of TC,TG and LDL-C in the observation group and the control group were significantly decreased,and the observation group decreased greater than that of the control group.HDL-C was significantly increased,and the observation group was more significant than the control group.The serum IL-6,TNF-α and NF-κB in the observation group were compared with the control group.The decrease was significantly lower in the observation group than in the control group,and the difference was significant (P<0.05).The CT ratio of the liver and spleen in the observation group and the control group was significantly higher than that before the treatment,and the increase in the observation group was greater than that in the control group,and the difference was significant (P<0.05).There was no significant difference in adverse reactions between the observation group and the control group (P>0.05).Conclusion Silybin capsules combined with fenofibrate tablets in the treatment of non-alcoholic fatty liver can significantly improve clinical efficacy,enhance liver function,improve blood glucose,blood lipid and blood uric acid levels,reduce inflammation levels,and have good safety.It is worthy of clinical promotion.

Quality of life and patient reported outcomes of Primary biliary cholangitis are analyzed and researched

WNAG Jing, REN Li-mei, ZHANG Jing-jie, SU Riguge, SU Qi-hao, DANG Tong, MENG Xian-mei, JIA Yan

2020, 25(11):  1220-1222. 

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Objective To investigate and analysis SF-36 and The General Self-efficacy scale(GSES) which can explore quality of life and clinical outcomes of patients with primary biliary cholangitis (PBC) in different groups.Methods A analysis was performed for 215 patients with PBC who were admitted to The Second Affiliated Hospital of the Baotou Medical College form March 2015 to July 2019.Fourtyfive cases who made physical examination were randomly selected as a control.The patients with PBC who were divided into three groups with the Child classification,and the association between SF-36,GSES and the quality of life,confidence and self-control were analyzed.The t test was used for comparison between two groups.When P<0.05 means there is a difference between the two to be compared,P<0.01 means there are significant differences.Results SF-36 and GSES scores of three groups of patients with PBC compared with normal control group.SF-36,GSES scores of PBC patients in group Child A were higher than the control group,P<0.05.The score of group Child B compared with the control group with no difference,P>0.05.the score of PBC patients in group Child C were lower than the control group,P<0.01.Conclusion Patients with PBC have great mood swings during disease progression.From the Child A group with high mood,to the Child C group's depression,which were all involved in disease development.Mood changes can change the vascular endothelial function involved in the occurrence and development of liver disease,which deserves deeper and more systematic research.We suggested that medical workers may pay more attention to the patients' moods in the clinical work in the future.If the patients were found in high spirits or low spirits,they should be timely guided and corrected,and prevent the disease occuprogress.

Clinical and genotypic characteristics of 6 patients with Citrin deficiency

WANG Cai-hong, ZHUO Zhi-qiang, HUANG Bing-qing, TANG Weng-tao, XIE Xin-bao

2020, 25(11):  1223-1226. 

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Objective To investigate the clinical characteristics and gene mutation of children with Citrin defect.Methods The data including medical history,laboratory examination,gene mutations and treatment of 6 children with Citrin deficiency diagnosed in Xiamen Children's Hospital were retrospectively analyzed.Results Among the six cases,5 of them were admitted to hospital due to cholestasis and delayed development.The age of the cases ranged from 1m7d to 4m.Biochemical results showed that total bilirubin (141.3～231.3 μmol/L) and conjugated bilirubin (41.5～94.9 μmol/L) were increased,AST(49～148 U/L)＞ALT(10～41 U/L),hypoglycemia(2.31～3.5 mmol/L),hypoproteinemia(39.7～60.4 g/L),blood coagulation abnormality(PT 11.2～23.5s). The alpha fetoprotein were significantly increased(＞3 000～15 000 ng/mL),and blood tandem mass spectrometry showed that hyper citrullinemia.Urine mass spectrometry showed that 4-hydroxyphenyllactate,4-hydroxyphenylpropionic acid and 4-hydroxyphenylacetic acid were increased.Five children were treated with lactose free fortified medium chain fatty acid milk powder,ursodeoxycholic acid and fat soluble vitamins for 1-2 months,and jaundice subsided.One child was hospitalized because of the increase of total bile acid for more than 7 years,and had hypoglycemic syncope twice in the morning.Children have special dietary preferences,like high protein and high fat food.Six cases of children underwent full exome gene detection,and analysis revealed five of them with SLC25A13 gene mutations.C.852-855del was a common mutation.In case 6,the SLC25A13 gene mutation and the SLC10A1 gene mutation were detected,and the final diagnosis was Citrin deficiency and NTCP gene deficiency.The child is undergoing dietary treatment and follow-up.Conclusion The clinical manifestations of Citrin deficiency are diverse.In addition to cholestasis in the neonatal period,children with unexplained hypoglycemic syncope and a special diet preference to protein-rich foods should also be alert to Citrin deficiency.Early improvement of hematuria tandem mass spectrometry and genetic testing can help to confirm the diagnosis.Early and accurate management of patients can effectively improve the prognosis of patients.