中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

2019 Vol. 35, No. 7

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Editorial
Diagnosis and treatment of chronic hepatitis B in women of child-bearing age and strategies for blocking mother-to-child transmission
Han GuoRong
2019, 35(7): 1417-1420. DOI: 10.3969/j.issn.1001-5256.2019.07.001
Abstract:
Women with chronic hepatitis B virus ( HBV) infection face both maternal and child problems during pregnancy. One problem is to prevent hepatitis activities during pregnancy, and the other is to block mother-to-child transmission. Infants born to HBeAg-positive mothers may have a rate of chronic HBV infection of 90% if they do not receive combined immunization in time. The combination of hepatitis B vaccine and hepatitis B immunoglobulin for neonates is a safe and effective measure to prevent mother-to-child transmission of HBV.Although combined immunization is performed, infants born to HBeAg-positive mothers still have a rate of chronic HBV infection of 5%-10%. Changes in the immune system during pregnancy can increase the replication of HBV, and the activation of the immune system postpartum can lead to liver function fluctuation and aggravation of chronic hepatitis B patients. Immune failure in infants becomes the main cause of chronic hepatitis B in children and adults. Therefore, specific detection, intervention, and follow-up measures are worthy of attention and discussion for the special population of women of child-bearing age with chronic HBV infection. This article discusses the management of women of child-bearing age with chronic HBV infection before, during, and after pregnancy, the measures for effective monitoring of pregnant women and infants, and individualized therapy based on disease risk assessment and individual conditions. This article also provides reproductive and health guidance for women with chronic hepatitis B who are ready to give birth.
Discussions by experts
Influence of chronic HBV infection on maternal and neonatal outcomes of women with gestational diabetes mellitus
Xu ChuanLu, Ying Hao
2019, 35(7): 1421-1424. DOI: 10.3969/j.issn.1001-5256.2019.07.002
Abstract:
There are relatively few studies on the association between chronic hepatitis B virus ( HBV) infection during pregnancy and gestational diabetes mellitus ( GDM) , with inconsistent conclusions. A meta-analysis of 23 cohort studies conducted in 2018 showed that HBs Ag-positive pregnant women had a higher risk of GDM, which was consistent across the populations from different geographical regions and studies. Although studies have confirmed the association between HBV infection and GDM, the underlying mechanism remains unclear. This article analyzes the possible mechanism of GDM caused by HBV infection, investigates the influence of chronic HBV infection on maternal and neonatal outcomes of women with GDM, and discusses the challenge for women with HBV infection after the implementation of the“universal two-child policy”. It is still a goal for medical workers to strengthen the monitoring of pregnant women with chronic HBV infection and neonates and reduce the complications of mothers and neonates.
Influence of hepatitis B virus infection on assisted reproductive technology and related prevention measures
Zhu Tong, Li ChengZhong
2019, 35(7): 1425-1429. DOI: 10.3969/j.issn.1001-5256.2019.07.003
Abstract:
Hepatitis B virus ( HBV) infection is prevalent in China. With the rapid development of assisted reproductive technology ( ART) in recent years, more and more couples with infertility and HBV infection choose ART to promote pregnancy. No conclusion has been reached on the influence of HBV infection on ART procedure and the health status of offspring. This article reviews the influence of HBV infection on ART from the aspects of sperm and oocyte function, laboratory environment, pregnancy outcome, and health of offspring and discusses the prevention measures during ART for people with HBV infection, in order to provide a reference for developing scientific management systems and preventing disease transmission.
Influence of pregnancy on the natural history of chronic hepatitis B virus infection
Chen YuXin, Huang Rui, Wu Chao
2019, 35(7): 1430-1434. DOI: 10.3969/j.issn.1001-5256.2019.07.004
Abstract:
Chronic hepatitis B virus ( HBV) infection is still a serious public health problem in China, and the HBsAg carrying rate reaches6. 0%-7. 8% in pregnant women. Maternal immune system is suppressed during pregnancy, which may affect the natural history of HBV infection. At present, no consensus has been reached on the influence of pregnancy on the natural history of HBV infection. The article reviews the research advances in the influence of pregnancy on the natural history of HBV infection from the aspects of maternal immunosuppression during pregnancy and the effect of pregnancy on viral replication, HBeAg seroconversion, liver function, and liver disease progression. Pregnant women with chronic HBV infection should be closely monitored in clinical practice in terms of virological examination and liver function examination during pregnancy and postpartum.
Early diagnosis of liver disease during pregnancy should be taken seriously
Zheng YiShan
2019, 35(7): 1435-1438. DOI: 10.3969/j.issn.1001-5256.2019.07.005
Abstract:
Adaptive physiological changes during pregnancy lead to increased fragility of the liver, impaired buffer capacity, and rapid disease progression, and such changes may weaken the signals or clinical manifestations of liver diseases, which increases the difficulties in early diagnosis and treatment. However, severe liver disease is a dynamic process, and timely identification of early signs of liver disease during pregnancy and establishment of early diagnosis and disease severity scoring system based on big data are the basis for determining the diagnosis and treatment of liver disease during pregnancy and deciding the timing and mode of delivery, as well as the key to improving the cure and reducing the mortality rate of liver disease during pregnancy.
Role of cholestatic liver disease-related genes in intrahepatic cholestasis of pregnancy
Kan YanTing, Yang YongFeng
2019, 35(7): 1439-1443. DOI: 10.3969/j.issn.1001-5256.2019.07.006
Abstract:
Intrahepatic cholestasis of pregnancy ( ICP) is the most common liver disease during pregnancy. ICP usually occurs in late pregnancy, with main manifestations of pruritus, jaundice, and increases in serum levels of total bile acid and aminotransferases found by laboratory examination. ICP has great impact on the fetus and may lead to preterm birth, stillbirth, and deformity. ICP has complex etiologies, and studies have shown that genetic, metabolic, immunological, and hormonal factors may contribute to the onset of ICP. The genes associated with cholestasis, such as ABCB11, ABCB4, ATP8 B1, and FXR, are associated with the genetic susceptibility of ICP. This article reviews the association between cholestasis-related genes and ICP.
Guidelines
Guidelines for the diagnosis and treatment of liver fibrosis in integrative medicine practice (2019)
Liver Disease Committee, Chinese Association of Integrative Medicine
2019, 35(7): 1444-1449. DOI: 10.3969/j.issn.1001-5256.2019.07.007
Abstract(1072) PDF (284KB)(1070)
Abstract:
Clinical practice guidelines for laparoscopic hepatopancreatobiliary surgery
Development Committee of Clinical Practice Guidelines for Laparoscopic Hepatopancreatobiliary Surgery
2019, 35(7): 1450-1458. DOI: 10.3969/j.issn.1001-5256.2019.07.008
Abstract(1459) PDF (1949KB)(1148)
Abstract:
Clinical practice guidelines for robotic hepatopancreatobiliary surgery
Development Committee of Clinical Practice Guidelines for Robotic Hepatopancreatobiliary Surgery
2019, 35(7): 1459-1471. DOI: 10.3969/j.issn.1001-5256.2019.07.009
Abstract:
An excerpt of ASGE guideline on the role of endoscopy in the evaluation and management of choledocholithiasis (2019)
Lin Chuan, Li JiaSu, Liu Feng
2019, 35(7): 1472-1475. DOI: 10.3969/j.issn.1001-5256.2019.07.010
Abstract:
Updated key points and clinical pathway for NCCN clinical practice guidelines in oncology: Pancreatic adenocarcinoma (Version2. 2019)
Meng ZhangTing, Li XiaoQing
2019, 35(7): 1476-1484. DOI: 10.3969/j.issn.1001-5256.2019.07.011
Abstract:
Guideline Interpretation
Updated key points of Guidelines for the diagnosis and management of hepatic encephalopathy in cirrhosis ( 2018)
Li XiaoKe, Wang Shan, Li ZhiGuo, Gan DaNan, Ye YongAn
2019, 35(7): 1485-1488. DOI: 10.3969/j.issn.1001-5256.2019.07.012
Abstract:
In 2018, Chinese Society of Hepatology, Chinese Medical Association, issued Guidelines for the diagnosis and management of hepatic encephalopathy in cirrhosis, which gives recommendations for the clinical diagnosis and treatment of hepatic encephalopathy including minimal hepatic encephalopathy and has important guiding significance. Compared with Consensus on the diagnosis and treatment of hepatic encephalopathy in China ( Chongqing, 2013) and Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver, the updated guidelines have several new points in the classification, diagnosis, and treatment of hepatic encephalopathy. This article summarizes the updated key points in the guidelines, so as to understand the effect of the guidelines in guiding clinical treatment and improve diagnosis and treatment.
Original articles_Viral hepatitis
Current status of hepatitis B virus infection among pregnant women in Shaanxi Province, China and risk factors for mother-to-infant transmission
Yu Qiang, Wang Jing, Liu JinFeng, Yan TaoTao, Feng YaLi, He YingLi, Dai XiaoMin, Chen TianYan, Zhao YingRen, Zhu YaGe
2019, 35(7): 1489-1492. DOI: 10.3969/j.issn.1001-5256.2019.07.013
Abstract:
Objective To investigate the hepatitis B virus ( HBV) infection rate among pregnant women in Shaanxi Province, China and the high-risk population of mother-to-infant transmission ( MTIT) . Methods A survey was performed for 13 451 pregnant women in 18 hospitals in Shaanxi Province to investigate the status of HBV infection, and combined immunization was performed for the infants born to HBsAg-positive women. Univariate and multivariate logistic regression analyses were used to investigate the risk factors for MTIT. The t-test or the Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. Results The prevalence rate of HBsAg was 7. 07% among the pregnant women in Shaanxi Province, and the rate reached as high as 9. 40% in southern Shaanxi. The MTIT rate of HBV was 5. 21%. The univariate analysis showed that HBsAg titer, HBeAg titer, positive HBeAg, and HBV DNA load in mothers were associated with HBV infection in infants, and the multivariate analysis showed that HBV DNA load in mothers is an independent risk factor for MTIT ( relative risk = 1. 586, 95% confidence interval: 1. 020-2. 465, P = 0. 041) . Among the pregnant women with HBV infection and MTIT, 84. 62% had positive HBe Ag and an HBV DNA load of > 106 IU/ml; among the infants with MTIT, 15. 38% were the infants born to the HBe Ag-negative pregnant women. For the pregnant women with positive HBe Ag and HBV DNA > 106 IU/ml, the relative risk of MTIT in infants was 1. 210 ( 1. 129-1. 297) ; for the pregnant women with negative HBe Ag, HBV DNA > 2 × 103 IU/ml, and HBs Ag > 104 IU/ml, the relative risk of MTIT in infants was 26. 062 ( 2. 633-258. 024) . Conclusion There is a high HBV infection rate among pregnant women in Shaanxi Province. Pregnant women with positive HBeAg and a high HBV DNA load have a high risk of MTIT. Although the infants born to HBeAg-negative mothers have a low HBV infection rate, there is still a high risk of MTIT when the mother has an HBV DNA load of > 2 × 103 IU/ml and an HBsAg level of > 104 IU/ml.
Clinical effect of tenofovir disoproxil in treatment of chronic hepatitis B and its effect in blocking mother-to-child transmission of chronic hepatitis B during early pregnancy
Chen ChuanYing, Chen Fang, Cheng QuanHong, Tu XiangLin, Dai Ying, Lin Xue
2019, 35(7): 1493-1495. DOI: 10.3969/j.issn.1001-5256.2019.07.014
Abstract:
Objective To investigate the antiviral effect of tenofovir disoproxil ( TDF) in women with chronic hepatitis B ( CHB) and its effect in blocking mother-to-child transmission of CHB during early pregnancy. Methods A total of 164 pregnant women who were diagnosed with CHB in Nanchang Ninth Hospital from July 2014 to December 2016 were enrolled, and their neonates were also enrolled as subjects. According to their will, the patients were divided into treatment group with 80 patients and control group with 84 patients. The patients in the treatment group were given TDF 300 mg/d during early pregnancy, followed by antiviral therapy for CHB after delivery, and those in the control group did not receive antiviral therapy. All neonates were given hepatitis B immunoglobulin and hepatitis B vaccine after birth.The changes in liver and renal function, electrolytes, myocardial zymogram, routine blood and urine test results, HBV serum markers, and HBV DNA were observed, and adverse reactions were recorded. HBsAg and HBV DNA were measured for infants at birth and at 6 and 12 months after birth; HBV infection, growth and development, and complications were evaluated, and Apgar score was determined. The t-test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between groups. Results There were significant differences between the treatment group and the control group in alanine aminotransferase ( ALT) normalization rate, and HBV DNA clearance rate at 18, 24, and 36 weeks of pregnancy ( ALT normalization rate: χ2= 19. 145, 24. 990, and 36. 414, all P < 0. 001; HBV DNA clearance rate: χ2= 75. 526, 107. 412, and 38. 138, all P < 0. 001) . The infants were evaluated at birth and at 6 and 12 months, and there were significant differences between the treatment group and the control group in HBsAg positive rate ( χ2= 6. 089, 5. 074, and 5. 074, all P < 0. 05) and HBV DNA positive rate ( χ2= 5. 074, P < 0. 05) . There was no significant difference in Apgar score between the two groups ( P > 0. 05) , and their growth and development indices were within normal ranges. Conclusion TDF administration in early pregnancy can help with the recovery of liver function and is safe and effective in blocking the mother-to-child transmission of HBV.
Original articles_Liver fibrosis and liver cirrhosis
Effect of Xiaozhang plaster in treatment of cirrhotic ascites and its influence on the renin-angiotensin-aldosterone system
Li Shuang, Tao YanYan, Xing Feng, Zhao Qiang, Liu ChengHai
2019, 35(7): 1496-1500. DOI: 10.3969/j.issn.1001-5256.2019.07.015
Abstract:

Objective To investigate the effect of Xiaozhang plaster in the treatment of cirrhotic ascites and its influence on the renin-angiotensin-aldosterone system. Methods A total of 220 patients with cirrhotic ascites who were hospitalized in Department of Gastroenterology in Shanghai Baoshan Integrated Traditional Chinese and Western Medical Hospital from March 2015 to March 2016 were enrolled and divided into routine treatment group with 60 patients, Xiaozhang plaster group with 60 patients, and terlipressin group with 100 patients. The patients in the routine treatment group received the routine treatment of cirrhotic ascites with a limitation of the dose of diuretics, those in the Xiaozhang plaster group were treated with Xiaozhang plaster in addition to the routine treatment, and those in the terlipressin group were treated with terlipressin in addition to the routine treatment. The three groups were observed in terms of related outcome measures ( depth of ascites, 24-hour urine volume, abdominal circumference, body weight, and Child-Pugh score) , symptoms and signs ( abdominal distension, diet, passage of gas by anus, and defecation) , hepatic and renal function, electrolytes, routine blood test results, coagulation function, portal vein diameter, glomerular filtration rate, and vasoactive substances [plasma renin activity ( PRA) , angiotensin Ⅱ ( AngⅡ) , and aldosterone ( ALD) ]. An analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for comparison within each group. Results There were significant differences between the three groups in depth of ascites, urine volume, abdominal circumference, Child-Pugh score, AngⅡ level, and ALD level on days 14 and 28 of treatment ( day14: F = 6. 566, 16. 236, 10. 856, 5. 727, 41. 860, and 20. 845, all P < 0. 05; day 28: F = 169. 311, 67. 686, 13. 521, 39. 721, 159. 256, and 80. 400, all P < 0. 05) . There were significant differences between the three groups in body weight and PRA level on day 28 of treatment ( F = 5. 068 and 0. 012, both P < 0. 05) . There were also significant differences between the three groups in the scores of abdominal distension, passage of gas by anus, and defecation on days 7, 14, and 28 of treatment ( day 7: F = 38. 311, 33. 405, and 33. 996, all P < 0. 05; day 14: F = 64. 414, 39. 481, and 52. 455, all P < 0. 05; day 28: F = 57. 596, 23. 041, and 47. 576, all P < 0. 05) . Conclusion Both Xiaozhang plaster and terlipressin can reduce ascites volume in patients with cirrhotic ascites, but they may have different action characteristics. Xiaozhang plaster is superior to terlipressin in the treatment of cirrhotic ascites and can significantly improve clinical symptoms, possibly by reducing the levels of PRA, AngⅡ, and ALD.

Predictive factors for third-generation cephalosporin-resistant spontaneous bacterial peritonitis
Zhu LongChuan, Gan DaKai, Hu QingQing, Xiong MoLong
2019, 35(7): 1501-1504. DOI: 10.3969/j.issn.1001-5256.2019.07.016
Abstract:

Objective To investigate the predictive factors for third-generation cephalosporin-resistant spontaneous bacterial peritonitis ( SBP) . Methods A retrospective analysis was performed for the clinical data of 206 patients with liver cirrhosis who were hospitalized in the Ninth Hospital of Nanchang from January 2010 to December 2018, and all patients had SBP with positive bacteria based on ascites culture. According to drug susceptibility results, the patients were divided into third-generation cephalosporin-resistant SBP group ( 101 patients with third-generation cephalosporin-resistant pathogenic bacteria in ascites) and control group ( 105 patients with pathogenic bacteria sensitive to third-generation cephalosporin) . Electronic medical records were reviewed to collect related information. The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of data with skewed distribution between groups. The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. A dichotomous logistic regression analysis was used for multivariate analysis, and the Forward: LR method was used for the screening of independent variables. Results There was a significant difference in the composition of pathogenic bacteria between the two groups ( P <0. 001) . The univariate analysis showed that a history of broad-spectrum antibiotic exposure in the past three months ( χ2= 12. 351, P <0. 001) , non-first-time onset of SBP ( χ2= 14. 427, P < 0. 001) , blood creatinine ( χ2=-2. 537, P = 0. 011) , and blood bicarbonate ( χ2=-4. 592, P < 0. 001) were candidate predictive factors with statistical significance between the two groups, and further multivariate analysis showed that a history of broad-spectrum antibiotic exposure in the past three months ( odds ratio [OR]= 2. 376, 95% confidence interval [CI]: 1. 009-5. 598, P = 0. 048) , non-first-time onset of SBP ( OR = 2. 841, 95% CI: 1. 133-7. 122, P = 0. 026) , and blood bicarbonate ( OR = 0. 892, 95% CI: 0. 818-0. 973, P = 0. 010) had an independent predictive value for third-generation cephalosporin-resistant SBP. Conclusion A history of broad-spectrum antibiotic exposure in the past three months, non-first-time onset of SBP, and a low level of blood bicarbonate are independent predictive factors for third-generation cephalosporin-resistant SBP, and third-generation cephalosporins should be used with caution in SBP patients with these features.

Original articles_Liver neoplasms
Clinical significance of the management of adverse events and symptom cluster associated with advanced hepatocellular carcinoma after lenvatinib treatment
An LinJing, Zhang Xin, Yang Ying, Sha HuaYan, Huang Shun, Wang YaDong
2019, 35(7): 1505-1508. DOI: 10.3969/j.issn.1001-5256.2019.07.017
Abstract:
Objective To investigate the symptoms and symptom clusters in patients with advanced hepatocellular carcinoma ( HCC) receiving molecular-targeted therapy with lenvatinib, as well as the clinical significance of the management of symptoms and symptom clusters in reducing lenvatinib-related grade 3 or above adverse events ( AEs) and AEs leading to treatment termination. Methods A total of 98 patients with advanced HCC who were treated with lenvatinib in The Fifth Medical Center of Chinese PLA General Hospital from May 2017 to December 2018 were enrolled. The AEs associated with lenvatinib were observed according to National Cancer Institute Common Toxicity Criteria, and the primary endpoint was the number of cases with a reduced dose or interruption of lenvatinib or treatment termination due to lenvatinib-related AEs after the management of symptoms or symptom clusters. Results All 98 patients completed the whole procedure.As for the lenvatinib-related AEs with an incidence rate of > 20%, hypertension had the highest incidence rate of 42. 9%, followed by diarrhea ( 33. 6%) , hepatic encephalopathy ( 30. 6%) , anorexia ( 30. 6%) , proteinuria ( 25. 5%) , fatigue ( 25. 5%) , hand-foot syndrome ( 22. 4%) , hoarseness ( 20. 4%) , and weight loss ( 20. 4%) . The incidence rate of grade 3 or 4 AEs was 55. 1% ( 54/98) ; the most common grade 3 AEs were hypertension ( 8. 2%) and hepatic encephalopathy ( 6. 1%) , and grade 4 AE was observed in 1 patient ( 1%) . The most common symptom clusters included hypertensive proteinuria ( 56. 1%) , digestive tract syndrome ( 50%) , and pain syndrome ( 36. 7%) . Among the 98 patients, 41 ( 41. 8%) had a reduced dose or interruption of lenvatinib due to lenvatinib-related AEs after the management of symptoms and symptom clusters and 4 ( 4. 1%) experienced treatment termination, which was lower than the percentages of 52. 9% and 8. 8% in the REFLECT study. Conclusion Hypertension and diarrhea are common AEs associated with lenvatinib. Hypertensive proteinuria, digestive tract syndrome, and pain syndrome are the main symptom clusters. Symptom cluster management is an effective means to reduce lenvatinib-related AEs leading to treatment termination.
Clinical effect of transarterial chemoembolization with ultra-liquid iodized oil combined with drug-eluting beads in treatment of Barcelona Clinic Liver Cancer stage B/C hepatocellular carcinoma
Tang HaoHuan, Zhu XiaoLi, Wang WanSheng, Li WanCi, Zhou LinFeng, Du Hang
2019, 35(7): 1509-1513. DOI: 10.3969/j.issn.1001-5256.2019.07.018
Abstract:
Objective To investigate the clinical effect and safety of transarterial chemoembolization ( TACE) with ultra-liquid iodized oil combined with drug-eluting beads in the treatment of Barcelona Clinic Liver Cancer ( BCLC) stage B/C hepatocellular carcinoma ( HCC) .Methods A retrospective analysis was performed for the clinical data of 51 patients with BCLC stage B/C HCC who underwent TACE with ultra-liquid iodized oil combined with drug-eluting beads in The First Affiliated Hospital of Soochow University from May 2016 to September 2018. Liver function was observed before treatment and at 3 days, 7 days, and 1 month after treatment, and adverse events and complications were recorded in detail. Modified Response Evaluation Criteria in Solid Tumors was used to evaluate clinical outcome at 1 and 3 months after surgery. The t-test was used for comparison of continuous data between two groups. Results Superselective TACE procedure was completed in all 51 patients. At 1 month after surgery, the target lesions had a disease remission rate of 70. 6% and a disease control rate of 96. 1%, while at 3 months after surgery, the target lesions had a disease remission rate of 64. 0% and a disease control rate of88. 0%. Of all 51 patients, 5 ( 9. 8%) experienced acute liver injury at 3 days after surgery, and there were significant changes in alanine aminotransferase ( ALT) , aspartate aminotransferase, total bilirubin ( TBil) , and albumin ( Alb) ( t =-5. 454, -3. 997, -5. 346, and7. 212, all P < 0. 001) . There were also significant changes in ALT, TBil, and Alb at 7 days after surgery ( t =-3. 177, -3. 665, and3. 194, all P < 0. 05) . Of all 51 patients, 35 ( 68. 6%) experienced grade 1 or 2 adverse events at 1 month after surgery, and no complications of liver failure, liver abscess, bile tumor, and gastrointestinal bleeding were observed. One patient died of multiple organ failure due to tumor progression on day 61 after surgery. Conclusion TACE with ultra-liquid iodized oil combined with drug-eluting beads is safe and effective in the treatment of BCLC stage B/C HCC, and further studies are needed to observe long-term efficacy and survival benefit.
Value of combined measurement of alpha-fetoprotein and alpha-fetoprotein L3% in the diagnosis of hepatocellular carcinoma
Guan GuiWen, Yao MingJie, Qian XiangJun, Zhai XiangWei, Yan XiaoTong, Zhao JingMin, Lu FengMin, Chen XiangMei
2019, 35(7): 1514-1519. DOI: 10.3969/j.issn.1001-5256.2019.07.019
Abstract:
Objective To investigate the value of combined measurement of alpha-fetoprotein ( AFP) and AFP-L3% in the diagnosis of hepatocellular carcinoma ( HCC) . Methods A retrospective analysis was performed for serological parameters and clinical data of 1208 patients with chronic hepatitis, 1967 patients with liver cirrhosis, and 1569 patients with primary HCC who attended The Fifth Medical Center of Chinese PLA General Hospital from January 2010 to December 2017. The distribution of serum AFP and AFP-L3% was analyzed, and AFP alone, AFP-L3% alone, and AFP combined with AFP-L3% were compared in terms of sensitivity, specificity, and area under the receiver operating characteristic curve ( AUC) . The correlation of AFP with AFP-L3 level and AFP-L3% was also analyzed. A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. The Spearman rank correlation test was used for correlation analysis of continuous data, the Delong test was used for comparison of AUC, and logistic regression was used to establish the model of AFP combined with AFP-L3% for the diagnosis of HCC. Results The HCC group had significantly higher serum levels of AFP and AFP-L3 than the liver cirrhosis group and the chronic hepatitis group ( H = 1107. 3 and 1076. 9, both P < 0. 01) . The HCC group had a significantly higher positive rate of AFP-L3% than the liver cirrhosis group and the chronic hepatitis group ( 30. 9% vs 3. 0%/2. 8%, P < 0. 01) . The HCC group had a significantly higher level of AFP-L3 than the liver cirrhosis group and the chronic hepatitis group ( 3. 3 ( 0-13. 4) % vs 0/0, H = 1034. 1, P <0. 01) . The correlation analysis showed that serum AFP was significantly correlated with AFP-L3 level ( r = 0. 91, P < 0. 01) , and there was no correlation between AFP-L3% and AFP ( r = 0. 04, P > 0. 05) . With specificity remaining the same, AFP combined with AFP-L3% had a significantly higher sensitivity in the diagnosis of HCC than AFP alone ( 26. 6% vs 18. 4%, P < 0. 01) or AFP-L3% alone ( 36. 6% vs 30. 9%, P < 0. 01) . The subgroup analysis showed that for the samples with AFP ≥10 μg/L, AFP combined with AFP-L3%had a significantly higher AUC in the diagnosis of HCC than AFP alone ( 0. 745 vs 0. 701, P < 0. 01) ; for the tumor with a diameter of >2 cm or hepatitis B-related liver cancer, AFP combined with AFP-L3% had a significantly higher sensitivity than AFP alone ( 27. 6% vs18. 0%/27. 7% vs 19. 1%, both P < 0. 01) or AFP-L3% alone ( 37. 0% vs 30. 3%/36. 9% vs 31. 8%, both P < 0. 01) . For the group with a tumor diameter of ≤2 cm and the group without hepatitis B-related liver cancer, there was no significant difference in sensitivity between AFP combined with AFP-L3% and AFP or AFP-L3% alone in the diagnosis of HCC ( all P > 0. 05) . Conclusion AFP combined with AFP-L3% can significantly improve the sensitivity of HCC diagnosis and has a good clinical value in the diagnosis of hepatitis B-related liver cancer and liver cancer with a tumor diameter of > 2 cm.
Establishment of Nomogram model of postoperative recurrence of primary hepatocellular carcinoma with reference to inflammatory cytokines
Gao SuHua, Gan HongYing, Wang Jun
2019, 35(7): 1520-1524. DOI: 10.3969/j.issn.1001-5256.2019.07.020
Abstract:
Objective To establish the Nomogram model of postoperative recurrence of hepatocellular carcinoma ( HCC) by collecting the data on clinical indices and inflammatory cytokines. Methods A total of 314 patients with HCC who were admitted to Wuhan Central Hospital from January 2014 to January 2016 and underwent hepatectomy for the first time were enrolled, and according to follow-up results, these patients were divided into non-recurrence group and recurrence group. General data were collected, and liver function parameters and inflammatory cytokines were measured. The chi-square test was used for comparison of categorical data between two groups, and the Mann-Whitney U test was used for comparison of ranked data between two groups. The receiver operating characteristic ( ROC) curve was used to obtain the optimal cut-off values of continuous data. The multivariate Cox proportional hazards model was used to investigate the independent risk factors for recurrence. The Nomogram model was established according to the results of the multivariate Cox proportional hazards model and was validated by internal data, and the consistency index ( C-index) was calculated. Results The follow-up time ranged from1 month to 40 months, with a median follow-up time of 13 months. Of all patients, 140 had no recurrence, and 174 experienced recurrence. The median recurrence-free survival time was 19 months, and the half-, 1-, and 2-year recurrence-free survival rates were68. 2%, 57. 3%, and 45. 9%, respectively. There were significant differences between the two groups in age, maximum tumor diameter, body mass index ( BMI) , interleukin-2, interleukin-6, interleukin-8, interleukin-17 ( IL-17) , neutrophil-lymphocyte ratio, tumor necrosis factor α ( TNF α) , C-reactive protein, alanine aminotransferase ( ALT) , aspartate aminotransferase, and total bilirubin ( TBil) ( all P < 0. 05) . The Cox proportional hazards model showed that age > 63 years ( hazard ratio[HR]= 2. 391, P < 0. 05) , maximum tumor diameter > 6 cm ( HR = 1. 851, P < 0. 05) , BMI > 27. 17 kg/m2 ( HR = 1. 546, P < 0. 05) , IL-17 > 10. 8 pg/m L ( HR = 1. 556, P <0. 05) , TNF α > 11. 8 ng/L ( HR = 1. 562, P < 0. 05) , ALT > 42 U/L ( HR = 1. 624, P < 0. 05) , and TBil > 15. 6 μmol/L ( HR = 1. 534, P < 0. 05) were independent risk factors for postoperative recurrence in patients with HCC. Validation by internal data showed a C-index of0. 724 ( 95% confidence interval: 0. 668-0. 824) . Conclusion The Nomogram model established in this study can accurately predict the recurrence of HCC patients after first-time hepatectomy, but more clinical studies are needed to confirm this result.
Influence of monoacylglycerol lipase on growth of nude mice xenograft tumor of human hepatocellular carcinoma and related mechanism
Yu JiaJian, Zhang JunYong, Fan DeQing
2019, 35(7): 1525-1531. DOI: 10.3969/j.issn.1001-5256.2019.07.021
Abstract:
Objective To investigate the role and mechanism of action of monoacylglycerol lipase ( MAGL) on the growth of nude mice xenograft tumor of human hepatocellular carcinoma ( HCC) . Methods The transplanted SMMC-7721 cells were divided into SMMC-7721 WT group ( without treatment) , SMMC-7721 MAGL-KDgroup ( with MAGL silencing) , SMMC-7721 MAGL-OEgroup ( with MAGL overexpression) , and SMMC-7721 Vectorgroup ( transfected with empty vector) . A total of 27 male BALB/c nude mice were randomly divided into group A ( 12 mice injected with the cells in the SMMC-7721 WTgroup) , group B ( 5 mice injected with the cells in the SMMC-7721 MAGL-KD group) , group C ( 5 mice injected with the cells in the SMMC-7721 MAGL-OEgroup) , and group D ( 5 mice injected with the cells in the SMMC-7721 Vectorgroup) . The mice in group A were further divided into groups A1 ( control group) , A2 ( treated with high-fat diet and JZL184, a specific inhibitor of MAGL) , and A3 ( fed with high-fat diet) , with 4 mice in each group. The four groups were compared in terms of the change in tumor volume and the expression of proliferating cell nuclear antigen ( PCNA) , metal matrix proteinase-2 ( MMP-2) , lysophosphatidic acid ( LPA) , and prostaglandin E2 ( PGE2) in tumor. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the SNK-q test was used for further comparison between two groups. Results There was a significant difference in the relative protein expression of MAGL between the SMMC-7721 WTgroup, the SMMC-7721 MAGL-KDgroup, and the SMMC-7721 MAGL-OEgroup ( 0. 377 ± 0. 026 vs 0. 182 ± 0. 055 vs 0. 689 ± 0. 019, F = 33. 382, P < 0. 001) ; compared with the SMMC-7721 WTgroup, the SMMC-7721 MAGL-KDgroup had significantly lower protein expression of MAGL and the SMMC-7721 MAGL-OEgroup had significantly higher expression ( P < 0. 05) . There was a significant difference in the size of subcutaneous xenograft tumor between groups A, B, C, and D ( 4236. 125 ± 1284. 283 mm3 vs 1883. 375 ± 552. 977 mm3 vs 10 146. 061 ± 1842. 264 mm3 vs 4307. 452 ± 2070. 708 mm3, F= 6. 804, P = 0. 023) . Group C had a lower growth rate of subcutaneous xenograft tumor than group A ( P < 0. 05) , and group B had a higher growth rate than group A ( P < 0. 05) . There were significant differences between groups A, B, and C in the levels of PCNA ( 25 843.821 ± 4201. 310 vs 17 426. 95 ± 5139. 202 vs 39 753. 103 ± 5721. 444, F = 21. 482, P < 0. 001) and MMP-2 ( 52 841. 621 ± 4339. 253 vs35 511. 451 ± 8251. 423 vs 68 274. 731 ± 6418. 594, F = 11. 526, P < 0. 001) ; group B had significantly lower levels of PCNA and MMP-2 than group A ( P < 0. 05) , and group C had significantly higher levels than group A ( P < 0. 05) . There was a significant difference in tumor volume between groups A1, A2, and A3 ( 23 476. 289 ± 483. 872 mm3 vs 18 593. 851 ± 1385. 805 mm3 vs 37 703. 198 ± 2925. 254 mm3, F = 47. 371, P = 0. 004) . Compared with group A1, group A3 had a significantly higher growth rate of subcutaneous xenograft tumor ( P < 0. 05) and group A2 had a significantly lower growth rate ( P < 0. 05) . There was a significant difference in the level of PGE2 between groups A1, A2, and A3 ( 0. 109 ± 0. 023 μmol/L vs 0. 056 ± 0. 010 μmol/L vs 0. 168 ± 0. 024 μmol/L, F = 16. 492, P < 0. 001) ; group A3 had a significantly higher level of PGE2 than group A1 ( P < 0. 05) , and group A2 had a significantly lower level than group A1 ( P < 0.05) . There was a significant difference in the level of PGE2 between groups B, C, and D ( 0. 069 ± 0. 025 μmol/L vs 0. 175 ± 0. 023 μmol/L vs 0. 096 ± 0. 019 μmol/L, F = 31. 550, P < 0. 001) ; group B had a significantly lower level of PGE2 than group D ( P < 0. 05) , and group C had a significantly higher level than group D ( P < 0. 05) . Conclusion MAGL can promote the growth of subcutaneous xenograft tumor of HCC by regulating PGE2, suggesting that MAGL might become a potential target for HCC treatment in future.
Role of D-bifunctional protein in promoting the growth of hepatocellular carcinoma in rats and nude mice
Lu Xin, Liu Ying, Jia Lei, Kong LingYu, Liu DianQing
2019, 35(7): 1532-1535. DOI: 10.3969/j.issn.1001-5256.2019.07.022
Abstract:
Objective To investigate the expression of D-bifunctional protein ( DBP) in hepatocellular carcinoma ( HCC) tissue in rats and the growth of DBP-induced HCC in nude mice. Methods A total of 22 male Sprague-Dawley rats were randomly divided into normal control group with 8 rats and model group with 14 rats treated with intraperitoneally injected diethylnitrosamine to induce HCC, and Western blotting, immunohistochemistry, and RT-PCR were used to measure the expression of DBP. A total of 14 specific pathogen-free male BALB/c-nu mice were randomly divided into two groups. HepG2 cells were transfected with empty plasmid or DBP overexpression plasmid and were then injected subcutaneously into nude mice. There were 8 mice in the empty plasmid control group and 6 mice in the DBP high-expression plasmid group, and tumor size was measured for both groups. The t-test was used for comparison of continuous data between groups. Results The rats with HCC had significantly higher protein and mRNA expression of DBP in liver tissue than normal rats ( protein:1. 10 ± 0. 35 vs 0. 67 ± 0. 12, t =-7. 48, P < 0. 05; mRNA: 3. 70 ± 0. 85 vs 1. 17 ± 0. 72, t =-20. 46, P < 0. 05) . The DBP high-expression plasmid group had a significantly higher tumor volume than the empty plasmid group [ ( 7590. 50 ± 1867. 97) mm3 vs ( 1663. 78 ±420. 24) mm3, t =-39. 78, P < 0. 01]. Conclusion Highly expressed DBP can promote the progression of HCC in rats and thus provides a new target for the treatment of HCC and the research and development of inhibitory drugs.
Original articles_Pancreatic diseases
Association between dyslipidemia and acute pancreatitis: A prospective cohort study
Ji RuiGeng, Zhu GuoLing, Zhang Bing, Sun Qiu, Zhao Li, Li GuangJian, Cao LiYing
2019, 35(7): 1536-1540. DOI: 10.3969/j.issn.1001-5256.2019.07.023
Abstract:

Objective To investigate the influence of dyslipidemia and number of items conforming to the diagnostic criteria for dyslipidemia on new-onset acute pancreatitis ( AP) . Methods A prospective cohort study was performed for 99 695 on-the-job or retired workers of Kailuan Group who underwent the first physical examination from 2006 to 2007. According to the number of items conforming to the diagnostic criteria for dyslipidemia in the first physical examination, they were divided into G0 group with 69 465 workers who did not meet the diagnostic criteria for dyslipidemia, G1 group with 23 921 workers who met one item of the diagnostic criteria for dyslipidemia, G2 group with5791 workers who met two items of the diagnostic criteria for dyslipidemia, G3 group with 500 workers who met three items of the diagnostic criteria for dyslipidemia, and G4 group with 18 workers who met four items of the diagnostic criteria for dyslipidemia. New-onset AP cases were collected once every year during follow-up, and a multivariate Cox proportional hazards regression model analysis was used to analyze the influence of dyslipidemia on new-onset AP cases. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to calculate the cumulative incidence rate of AP in each group, and the log-rank test was used for comparison of cumulative incidence rate between groups. Results The total follow-up time of all 99 695 workers was 782 395 person-years, and since no new-onset AP cases were observed in G4 group, G4 group was combined with G3 group for analysis. The incidence rates of AP in G0, G1, G2, and G3 groups were 1. 61, 2. 05, 2. 59, and 7. 72 per thousand person-years, respectively, and the cumulative incidence rates of AP in these four groups were 1. 76‰, 2. 40‰, 3. 12‰, and 8. 39‰, respectively. The log-rank test showed a significant difference in cumulative incidence rate between groups ( χ2= 15. 18, P = 0. 004 3) . After adjustment for the other risk factors, the Cox model showed that the hazard ratio ( 95%confidence interval) for AP was 1. 23 ( 0. 88-1. 73) in G1 group, 1. 58 ( 1. 09-2. 10) in G2 group, and 4. 90 ( 1. 81-13. 37) in G3 group. Conclusion Dyslipidemia is a risk factor for new-onset AP, and the risk of AP increases with the increase in the number of items conforming to the diagnostic criteria for dyslipidemia.

Value of real-time elastography in predicting the risk of pancreatic fistula after pancreaticoduodenectomy
Wu YanBin, Zhu HuaMin, Wang XueWen, Niu HongKai, Cheng Yu
2019, 35(7): 1541-1545. DOI: 10.3969/j.issn.1001-5256.2019.07.024
Abstract:
Objective Objective To investigate the value of pancreatic elasticity based on shear wave elastography ( SWE) in predicting the risk of pancreatic fistula, to measure pancreatic hardness by determining the SWE level of the pancreatic body, and to reduce the development of pancreatic fistula after pancreaticoduodenectomy. Methods A retrospective analysis was performed for the clinical data of 53 patients who were admitted to The Affiliated Hospital of Binzhou Medical University from October 2017 to February 2019 and underwent pancreaticoduodenectomy ( PD) . The 53 patients were divided into pancreatic fistula group with 10 patients who developed pancreatic fistula after PD and non-pancreatic fistula group with 43 patients who did not develop this disease after PD. The elasticity value of the pancreatic body measured by SWE was used to reflect the tissue elasticity of the pancreas and evaluate the hardness of the pancreas. The t-test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between groups. A logistic regression analysis was used for univariate analysis, and the Spearman's correlation coefficient was used to investigate the correlation between SWE and other laboratory data. Results Body mass index ( BMI) ( t = 1. 321) , preoperative total bilirubin ( t = 1. 347) , diameter of the main pancreatic duct ( t = 1. 385) , maximum SWE value ( t = 1. 728) , mean SWE value ( t = 1. 634) , and intraoperative pancreatic hardness ( χ2= 4. 983) were risk factors for pancreatic fistula ( all P < 0. 05) . Maximum SWE value and mean SWE value were negatively correlated with age and time of operation ( maximum SWE value: r =-0. 329 and-0. 260, both P < 0. 05; mean SWE value: r =-0. 282, and-0. 282, both P < 0. 05) and positively correlated with BMI ( r = 0. 275 and 0. 350, both P < 0. 05) . Conclusion SWE level is an independent risk factor for pancreatic fistula after pancreaticoduodenectomy, and the SWE level of the pancreatic body has a high predictive value and guiding significance in surgical treatment.
Original articles_Others
Clinical effect of glucocorticoids versus pentoxifylline in patients with severe alcoholic liver disease: A Meta-analysis
Yang Jun, Hu ZhongJie, Zhu YueKe, Yu HongWei, Li Juan, Hou Wei, Ning QiQi
2019, 35(7): 1546-1550. DOI: 10.3969/j.issn.1001-5256.2019.07.025
Abstract:

Objective To systematically review the clinical effect of glucocorticoids used alone or in combination with pentoxifylline in patients with severe alcoholic liver disease. Methods PubMed, Embase, Chinese Scientific Journal Full-Text Database, CBM, China Scientific Journal Database, and Chinese Medical Association Digital Journal Database were searched for related articles published up to November 2018, and related journals and collected papers from conferences were searched manually. The clinical effect of glucocorticoids versus placebo, glucocorticoids versus pentoxifylline, and glucocorticoids combined with glucocorticoids versus glucocorticoids alone was analyzed.The effect of glucocorticoids and pentoxifylline used alone or in combination on 28-day survival rate and hepatorenal syndrome in patients with severe alcoholic liver disease was assessed. Odds ratio ( OR) and 95% confidence interval ( CI) were used to evaluate outcome indicators. RevMan 5. 3 software was used for data analysis. Results A total of 22 studies were included, with 1956 patients in total. The glucocorticoid group had a significantly lower 28-day mortality rate than the control group ( 25. 12% vs 30. 67%, OR = 0. 71, 95% CI: 0. 55-0. 93, P = 0. 01) . Subgroup analysis showed that there was a significant difference in 28-day mortality rate between the glucocorticoid group and the pentoxifylline group ( OR = 0. 68, 95% CI: 0. 48-0. 97, P = 0. 03) , while there was no significant difference between the glucocorticoid + pentoxifylline group and the glucocorticoid group ( OR = 0. 92, 95% CI: 0. 66-1. 29, P = 0. 64) . Compared with the glucocorticoid group, the glucocorticoid + pentoxifylline group had a significantly lower incidence rate of hepatorenal syndrome ( 3. 94% vs8. 03%, OR = 0. 45, 95% CI: 0. 24-0. 83, P = 0. 01) . Funnel plots showed no publication bias. Conclusion Glucocorticoids combined with pentoxifylline can reduce the incidence rate of hepatorenal syndrome in patients with severe alcoholic liver disease.

Interaction between Helicobacter pylori infection and polymorphisms of PPAR-γ2 gene Pro12Ala and GPx-1 gene Pro198Leu and its association with nonalcoholic fatty liver disease
Zhang ChaoXian, Guo LiKe, Zhang LiLi, Li GuangYan, Chang TingMin
2019, 35(7): 1551-1559. DOI: 10.3969/j.issn.1001-5256.2019.07.026
Abstract:

Objective To investigate the interaction between Helicobacter pylori infection and polymorphisms of PPAR-γ2 gene Pro12 Ala and GPx-1 gene Pro198 Leu and its association with nonalcoholic fatty liver disease ( NAFLD) . Methods A total of 750 patients with nonalcoholic fatty liver ( NAFL) , 750 patients with nonalcoholic steatohepatitis ( NASH) , and 750 patients with nonalcoholic fatty hepatic cirrhosis ( NAFHC) who were treated or hospitalized in The First Affiliated Hospital of Xinxiang Medical University from March 2011 to July2015 were enrolled, and 750 individuals who underwent physical examination were enrolled as control group. Peripheral blood leukocytes were collected for each group, and PCR-RFLP was used to detect the polymorphisms of Pro12 Ala and Pro198 Leu. The14 C-urea breath test was used to measure disintegration per minute ( DPM) of Helicobacter pylori binding to14 C, in order to evaluate the degree of Helicobacter pylori infection. A face-to-face questionnaire survey was performed for each subject. The t-test was used for comparison of continuous data between two groups, the chi-square test was used for comparison of categorical data between groups. The multivariate logistic regression model was used for data analysis. The adjusted odds ratio ( OR) and 95% confidence interval of Pro12 Ala polymorphism, Pro198 Leu polymorphism, and Helicobacter pylori infection for the risk of NAFLD were calculated, and the interaction between Helicobacter pylori infection and polymorphism of PPAR-γ2 gene Pro12 Ala and GPx-1 gene Pro198 Leu was analyzed. Results The patients with the genotypes of Pro12 Ala ( PA) , Pro12 Ala ( AA) , Pro198 Leu ( PL) , and Pro198 Leu ( LL) had a significant increase in the risk of NAFLD ( OR = 5. 732 4, 5. 973 2, 6. 360 5, and 6. 165 7, all P < 0. 01) . The combined analysis of the polymorphisms showed positive interactions between Pro12 Ala ( PA) and Pro198 Leu ( PL) , between Pro12 Ala ( PA) and Pro198 Leu ( LL) , between Pro12 Ala ( AA) and Pro198 Leu ( PL) , and between Pro12 Ala ( AA) and Pro198 Leu ( LL) ( all γ > 1) . The Helicobacter pylori infection patients with 100≤DPM < 500 or DPM≥500 had a significant increase in the risk of NAFLD ( 100≤DPM < 500: ORNAFL= 2. 064 1, ORNASH= 4. 448 5, ORNAFHC= 10. 969 5;DPM≥500: ORNAFL= 3. 130 5, ORNASH= 8. 024 6, ORNAFHC= 21. 461 4) , and the patients with DPM≥500 had a significantly higher risk of NAFLD than those with 100 ≤ DPM < 500 ( P < 0. 01) . There were positive interactions between Helicobacter pylori infection and Pro12 Ala ( PA) , Pro12 Ala ( AA) , Pro198 Leu ( PL) , and Pro198 Leu ( LL) ( all γ > 1) . Conclusion The carriers of Pro12 Ala ( PA) , Pro12 Ala ( AA) , Pro198 Leu ( PL) , and Pro198 Leu ( LL) genotypes may have a high risk of NAFLD, and the interaction between these genotypes and Helicobacter pylori infection promotes the development and progression of NAFLD. Therefore, effective prevention measures including Helicobacter pylori eradication and gene expression regulation should be adopted to prevent NAFLD.

Value of combined measurement of urinary insulin-like growth factor-binding protein 7 and tissue inhibitor of metalloproteinases-2 in predicting acute kidney injury associated with HBV-related acute-on-chronic liver failure
Li Ming, Chen RuLi, Wu ZhenPing, Cheng XiaoYu, Mei Qing, Zhang LunLi, Li XiaoPeng
2019, 35(7): 1560-1564. DOI: 10.3969/j.issn.1001-5256.2019.07.027
Abstract:

Objective To perform dynamic measurement of urinary insulin-like growth factor-binding protein 7 ( IFGBP7) and tissue inhibitor of metalloproteinases-2 ( TIMP-2) in patients with HBV-related acute-on-chronic liver failure ( HBV-ACLF) , and to investigate the value of combined measurement of urinary IFGBP7 and TIMP-2 in early prediction of acute kidney injury ( AKI) associated with HBV-ACLF. Methods A total of 61 patients with HBV-ACLF who were admitted to the First Affiliated Hospital of Nanchang University from September 2015 to January 2016 were enrolled, and according to the presence or absence of AKI, they were divided into AKI group with 15 patients and non-AKI group with 46 patients. A total of 21 hospitalized patients with chronic hepatitis B were enrolled as control group. Urine samples were collected at 8∶ 00 and 20∶ 00 every day since the day of admission. For the AKI group, the urine samples collected within 5 days before a confirmed diagnosis of AKI was made were used for analysis, and for the non-AKI group and the control group, the urine samples collected within 5 consecutive days during the same period of time were used for analysis. ELISA was used to measure the levels of IFGBP7 and TIMP-2 in urine, and serum creatinine ( SCr) and estimated glomerular filtration rate ( eGFR) were recorded during the same period of time. The Kruskal-Wallis rank sum test was used for comparison of continuous data between multiple groups; and pairwise compared was made by Wilcoxon test; the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups; the receiver operating characteristic ( ROC) curve and the area under the ROC curve ( AUC) were used to evaluate the efficiency of combined measurement of IFGBP7 and TIMP-2 in the diagnosis of AKI. Results For HBV-ACLF patients, the levels of IFGBP7 and TIMP-2 gradually increased from 48 hours before the diagnosis of AKI to the time of diagnosis, and there were significant differences in the levels of IFGBP7 and TIMP-2 between the control group/the non-AKI group and the AKI group at 48 hours to 12 hours before the diagnosis of AKI to the time of diagnosis ( all P < 0. 05) . With the aggravation of disease conditions in the AKI group, at 36 hours before the diagnosis of AKI and at the time of diagnosis, SCr was significantly higher, eGFR was significantly lower than those at baseline ( both P < 0. 05) . The increases in the levels of IFGBP7 and TIMP-2 at 36 hours before the diagnosis of AKI had a high sensitivity in predicting AKI, with an AUC of 0. 896 ( 95% confidence interval: 0. 789-0. 960, P = 0. 043) and a stronger ability of AKI prediction than SCr and eGFR. Conclusion The increases in urinary TIMP-2 and IGFBP-7 can accurately predict AKI in patients with HBV-ACLF.

Effect of recombinant human granulocyte colony-stimulating factor on rats with acute liver failure
Ha FuShuang, Han Tao, Liang Ning, Nie XinHua, Zhu ZhengYan
2019, 35(7): 1565-1569. DOI: 10.3969/j.issn.1001-5256.2019.07.028
Abstract:

Objective To investigate the effect of recombinant human granulocyte colony-stimulating factor ( rhG-CSF) on acute liver failure ( ALF) induced by D-galactosamine ( D-GalN) in rats. Methods A total of 105 male Sprague-Dawley rats were randomly divided into healthy control group, liver failure model group, and rhG-CSF group, with 35 rats in each group. A rat model of ALF was established by intraperitoneal injection of D-GalN ( 1400 mg/kg) . Alanine aminotransferase ( ALT) level in the liver, total bilirubin ( TBil) , peripheral blood leukocyte count, and liver pathological changes were observed at 12, 24, 48, 72, and 120 hours after modeling, and survival rate was observed at 120 hours after modeling. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the LST-t test was used for further comparison between two groups. Results Compared with the liver failure model group, the rhG-CSF group had a significantly higher degree of hepatocyte degeneration and necrosis at all time points except 120 hours after modeling, and compared with the liver failure model group at 120 hours after modeling, the rhG-CSF group had better recovery of lobular structure on HE staining. Compared with the liver failure model group, the rhG-CSF group had a tendency of increase in the percentage of cells with positive tumor necrosis factor-α at the five time points after modeling. Compared with the liver failure model group, the rhG-CSF group had significantly higher levels of ALT and TBil at all five time points. Both groups had a significant change in ALT level at 24 hours after modeling ( P < 0. 05) , as well as a significant change in TBil at 24, 48, and 120 hours after modeling ( P < 0. 05) . The rhG-CSF group had a significantly higher peripheral blood leukocyte count than the liver failure model group at all five time points ( all P<0. 120="" .="" there="" was="" no="" significant="" difference="" in="" survival="" rate="" at="" hours="" after="" modeling="" between="" the="" two="" groups="" p="">0. 05) . Conclusion Application of rhG-CSF during the stage of acute inflammatory reaction of ALF may aggravate liver inflammatory response.

Protective effect of probiotics in rats with acute-on-chronic liver failure and related mechanism
Zhang YongChao, Bi YanZhen, Fang Xiao, Wang QuanYi, Wang QuanQuan, Tang HuiXin, Kong LingBin, Chen Yu, Duan ZhongPing, Shu ZhenFeng, Hong Feng
2019, 35(7): 1570-1575. DOI: 10.3969/j.issn.1001-5256.2019.07.029
Abstract:

Objective To investigate the effect of probiotics intervention on rats with acute-on-chronic liver failure ( ACLF) and related mechanism. Methods A total of 44 male Sprague-Dawley rats were randomly divided into six groups using a random number table, i. e., control group 1 ( C1 group with 6 rats without any intervention) , model group 1 ( M1 group with 8 rats treated with intraperitoneally injected40% CCl4 oil solution for 10 weeks, followed by phosphate-buffered saline by gavage since week 7 and D-galactosamine acute attack at the end of week 10) , probiotics intervention group 1 ( Y1 group with 8 rats treated with the same modeling method as the M1 group, and probiotics solution was given by gavage) , control group 2 ( C2 group with 6 rats without any intervention) , model group 2 ( M2 group with 8 rats treated with intraperitoneally injected 40% CCl4 oil solution, followed by D-galactosamine acute attack at the end of week 10 and phosphate-buffered saline by gavage at 48 hours after attack, and they were sacrificed at the end of week 12) , and probiotics intervention group 2 ( Y2 group with 8 rats treated with the same modeling method as the M2 group, and probiotics solution was given by gavage) . Body weight, liver function, and liver histopathology were observed before and after intervention. ELISA was used to measure the levels of endotoxin and endocrine immunoglobulin A ( s IgA) in plasma, Western Blot was used to measure the content of the intestinal tight junction protein Occludin, RT-PCR was used to measure the mRNA expression of Occludin and ZO-1, and a selective medium was used to measure the changes in related indices including intestinal flora. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the SNK-q test was used for further comparison between two groups. Results There were significant differences in body weight, liver index, alanine aminotransferase, aspartate aminotransferase, total bilirubin, plasma endotoxin, s IgA, and mRNA expression of Occludin and ZO-1 between the C1, M1, and Y1 groups ( F = 27. 65, 8. 96, 61. 37, 18. 27, 21. 00, 87. 01, 67. 10, 101. 50, and105. 40, all P < 0. 05) , as well as between the C2, M2, and Y2 groups ( F = 14. 04, 12. 85, 14. 02, 11. 39, 35. 80, 19. 14, 15. 37, 25. 02, and 126. 00, all P < 0. 05) . There was no significant difference in the protein expression of Occludin between the C1, M1, and Y1 groups ( F = 16. 40, P < 0. 05) . There were significant differences in the content of Lactobacillus, Bifidobacterium, Enterococcus, and Enterobacter between the C1, M1, and Y1 groups ( F = 77. 95, 66. 61, 25. 63, and 33. 29, all P < 0. 05) , as well as between the C2, M2, and Y2 groups ( F = 21. 50, 22. 62, 6. 71, and 17. 74, all P < 0. 05) . Conclusion Intestinal flora disturbance and intestinal barrier dysfunction are observed in rats with ACLF, and probiotics intervention can remodel the structure of intestinal flora, maintain intestinal barrier function, and promote liver repair.

Value of Gd-EOB-DTPA-enhanced MRI in the assessment of liver function in dogs with acute liver failure
Wang Hao, He Cheng, Chen Hao, Ou YangZhongMin, Liu ZhiQiang
2019, 35(7): 1576-1581. DOI: 10.3969/j.issn.1001-5256.2019.07.030
Abstract:

Objective To investigate the value of Gd-EOB-DTPA-enhanced MRI in the assessment of liver function in dogs with acute liver failure ( ALF) . Methods A total of 16 healthy adult male Beagle dogs were randomly divided into ALF group and blank control group, with 8 dogs in each group. The dogs in the ALF group were given injection of 30% acetaminophen via the saphenous vein of the forelimb and abdominal subcutaneous injection of 40% carbon tetrachloride at a dose of 0. 5 ml/kg, and 12 hours later, 30% acetaminophen and 40% carbon tetrachloride were injected at half of the first dose. Gd-EOB-DTPA-enhanced MRI scan was performed after 24 hours, and after injection of the contrast agent Gd-EOB-DTPA ( 0. 15 ml/kg body weight) , the signal values of high-, medium-, and low-signal regions were measured during plain scan and at 20 and 26 minutes of MRI scan. Liver puncture was performed in different signal regions. Gd-EOB-DTPA-enhanced MRI was performed for the control group, and liver puncture was performed in the corresponding regions. HE staining and electron microscopy were used for tissue examination, and the two groups were compared in terms of signal values and the results of HE staining and electron microscopy. The independent samples t-test was used for comparison of continuous data at each time point between the two groups, and an analysis of variance with repeated measures was used for comparison at different time points within groups; a one-way analysis of variance was used for comparison of signal values at each time point within groups. Results The ALF group had high, medium, and low signals in different time periods after Gd-EOB-DTPA-enhanced MRI scan, and HE staining and electron microscopy showed varying degrees of hepatocyte injury in the high-, medium-, and low-signal regions. The ALF group had significant differences in the levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin at 0, 6, 12, and 24 hours ( F = 54. 909, 148. 238, and 11. 778, all P < 0. 01) . In the ALF group and the control group, the high-, medium-, and low-signal values showed significant changes during plain scan and at 20 and 26 minutes of MRI scan ( ALF group: F = 232. 69, 65. 39, and 24. 91, all P < 0. 01; control group: F = 800. 43, 817. 35, and 795. 71, all P < 0. 01) . In the ALF group, there were significant differences in the high-, medium-, and low-signal values during plain scan and at 20 and 26 minutes of MRI scan ( F = 3. 914, 24. 343, and 22. 424, all P < 0. 05) . There were significant differences between the two groups in the medium-and low-signal values at 20 minutes of MRI scan ( t =-7. 813 and-7. 492, both P < 0. 001) and the high-, medium-, and low-signal values at 26 minutes of MRI scan ( t =-3. 075, -4. 785, and-6. 326, P =0. 008, P < 0. 001, and P < 0. 001) . The reduction in corresponding signals was associated with the degree of hepatocyte injury. Conclusion Gd-EOB-DTPA-enhanced MRI scan is feasible for the assessment of liver function in ALF dogs, and it can also predict the degree of liver pathological damage.

Brief reports
A study of construction strategy for regional clinical pathology center of liver disease based on SWOT analysis
Tang Hong, Xu RongRong, Jiang LiLin, Lu ZhongHua
2019, 35(7): 1582-1584. DOI: 10.3969/j.issn.1001-5256.2019.07.031
Abstract:
Case reports
Cirrhosis with capillary leak syndrome and hypothyroid myopathy: A case report
Zhou Yun, He WenGe, Huang ZhangXing
2019, 35(7): 1585-1587. DOI: 10.3969/j.issn.1001-5256.2019.07.032
Abstract:
Scleroderma with hepatic sarcoidosis: A case report
Zhang Yu, Shao YueMing, Yin Xin, Gao Hui, Xu Fang, Jin QingLong, Wen XiaoYu
2019, 35(7): 1588-1590. DOI: 10.3969/j.issn.1001-5256.2019.07.033
Abstract:
A case of hepatolenticular degeneration with neurological disorders as the prominent symptom
Lu: Jia, Zhao Gang, Sun XueHua, Gao YueQiu
2019, 35(7): 1591-1593. DOI: 10.3969/j.issn.1001-5256.2019.07.034
Abstract:
Low-molecular-weight heparin sodium for the treatment of hepatic sinusoidal obstruction syndrome: A case report
Jiang MinJie, Song LiSha, Xin GuiJie, Gao PuJun
2019, 35(7): 1594-1595. DOI: 10.3969/j.issn.1001-5256.2019.07.035
Abstract:
A case of lymphocytic interstitial pneumonia during corticosteroid treatment for autoimmune hepatitis
Xiong WeiJue, Cao Shan, Zhang GuoYan, Chen GuoDong, Wang ZhiFeng, Liu YuLan
2019, 35(7): 1596-1598. DOI: 10.3969/j.issn.1001-5256.2019.07.036
Abstract:
Primary biliary cholangitis with Sjogren's syndrome and immune thrombocytopenia: A case report
Chen QingLing, Kui YiWen, Zhong Rui, Yang QianQian, Zhang XiaoXue, Wen XiaoYu, Yu ChengNan, Jin QingLong
2019, 35(7): 1599-1600. DOI: 10.3969/j.issn.1001-5256.2019.07.037
Abstract:
Biliary stent implantation for malignant obstructive jaundice through the percutaneous transhepatic biliary drainage pathway: A report of 2 cases
Peng FengHui, Liu Kai, Yang Yang, Liu YaHui, Ji Bo
2019, 35(7): 1601-1603. DOI: 10.3969/j.issn.1001-5256.2019.07.038
Abstract:
Reviews
Mechanism of action of hypoxia-inducible factor 1α in the development and progression of liver fibrosis
Zhou Dan, Zhang LiTing, Li JunFeng, Wang Shan, Xiao Ping
2019, 35(7): 1604-1607. DOI: 10.3969/j.issn.1001-5256.2019.07.039
Abstract:

Liver fibrosis and end-stage liver cirrhosis are often accompanied by liver hypoxia. As a key transcription factor for regulating the body's response to hypoxia, hypoxia-inducible factor 1α ( HIF-1α) plays an important role in the activation of hepatic stellate cells and the development and progression of liver fibrosis. In addition, downregulation of HIF-1α expression can alleviate liver fibrosis and thus HIF-1α is expected to become a new target for the treatment of liver fibrosis. This article reviews the association between HIF-1α and liver fibrosis-related signaling pathways and genes and further discusses the potential of HIF-1α as a new therapeutic target for liver fibrosis.

Clinical value of albumin-bilirubin grade in evaluating the prognosis of hepatocellular carcinoma
Luo Hao, Huang Jun
2019, 35(7): 1608-1612. DOI: 10.3969/j.issn.1001-5256.2019.07.040
Abstract:
Hepatocellular carcinoma ( HCC) is one of the most common primary malignant tumors in the world, and although there are various therapeutic methods for HCC, its prognosis remains unsatisfactory. Albumin-bilirubin ( ALBI) grade is a new clinical index which can be used to evaluate liver function and prognosis of patients with HCC. This article reviews the advances in the application of ALBI grade in surgical treatment, local ablation, transarterial chemoembolization, and drug therapy for HCC. It is pointed out that ALBI grade has a good value in predicting the prognosis of HCC patients undergoing different therapies.
Role of intestinal microflora in the pathogenesis of hepatocellular carcinoma
Zheng Wei, Zhang YongHong, Zhao Yan
2019, 35(7): 1613-1615. DOI: 10.3969/j.issn.1001-5256.2019.07.041
Abstract:
Hepatocellular carcinoma ( HCC) is the most common type of primary liver cancer and is one of the complications of chronic liver diseases. Recent experimental and clinical studies have shown that the gut-liver axis plays a key role in the pathogenesis of chronic liver diseases including HCC. Change in intestinal microflora is considered the key factor for the progression of chronic liver diseases to HCC.This article summarizes the latest research advances in changes in intestinal microflora associated with HCC and discusses the importance of intestinal microflora in the development and progression of HCC.
Expression of vascular endothelial growth factor receptors and invasion and metastasis of hepatocellular carcinoma
Li CunDi, Cao WeiYa, Wang Jian
2019, 35(7): 1616-1620. DOI: 10.3969/j.issn.1001-5256.2019.07.042
Abstract:
Vascular endothelial growth factor receptors ( VEGFRs) consist of three receptor tyrosine kinase ( RTK) superfamily members and two non-RTK superfamily members and bind to the ligand in a non-one-to-one way. VEGFRs mediate various signaling pathways such as Raf1→MAP2 K1/2→ERK1/2 through cell surface receptor internalization and thus promote the proliferation of hepatocellular carcinoma cells, angiogenesis, and lymphangiogenesis. VEGFRs can be highly expressed in local cancerous lesions of liver cancer patients, which is a key factor mediating malignant proliferation, invasion, and metastasis of hepatocellular carcinoma, and the expression of VEGFRs is negatively correlated with progression-free survival. Matrix metalloproteinase-9 and heat shock protein 90β can upregulate VEGFRs to promote the proliferation and metastasis of hepatoma cells, while miR-203 a, miR-378 a, and miR-199 a-3 p can downregulate VEGFR expression and inhibit hepatoma cell infiltration. Targeted drug therapy based on VEGFR can induce the apoptosis of hepatoma cells, block tumor angiogenesis, and delay disease progression.
Research advances in the pathogenesis of nonalcoholic fatty liver disease-related hepatocellular carcinoma
Liu SuTong, Zhao WenXia
2019, 35(7): 1621-1625. DOI: 10.3969/j.issn.1001-5256.2019.07.043
Abstract:
The incidence rate of nonalcoholic fatty liver disease-related hepatocellular carcinoma ( NAFLD-HCC) is gradually increasing.Its pathogenesis is associated with the changes in genetic and epigenetic modifications, metabolism, immunity, intestinal microecology, endocrine pathways, and circadian rhythm. This article summarizes the available data on the pathogenesis of NAFLD-HCC and points out that HCC is caused by the interactions between multiple factors.
Association between chemokines and nonalcoholic fatty liver disease
Chu PeiLing, Wang Qi, Guo XiaoQing, Liu JinChun
2019, 35(7): 1626-1628. DOI: 10.3969/j.issn.1001-5256.2019.07.044
Abstract:
In recent years, the incidence rate of nonalcoholic fatty liver disease ( NAFLD) keeps increasing, and the age of onset tends to become younger. NAFLD has become one of the major public health problems in the 21 st century. This article reviews the research advances in the association between some chemokines ( CCL2, CCL5, CXCL8, and CXCL10) and NAFLD in recent years, in order to provide directions for the research on the pathogenesis and prevention and treatment of NAFLD.
Mechanism of action of microRNA in the regulation of hepatic ischemia-reperfusion injury
Zhang ShiLong, Peng CiJun, Feng ZanJie, Gao WeiDong, Duan YuLing, Fan GuoXin
2019, 35(7): 1629-1631. DOI: 10.3969/j.issn.1001-5256.2019.07.045
Abstract:
Hepatic ischemia-reperfusion injury is one of the most important factors affecting the prognosis of clinical hepatic surgery. Studies have shown that microRNAs can participate in the process of hepatic ischemia-reperfusion injury through multiple pathways. This article reviews the biosynthesis and function of microRNAs and the mechanisms of action of microRNAs in the regulation of hepatic ischemia-reperfusion injury through energy metabolism, apoptosis, autophagy, oxidative stress, and cellular inflammation. It is pointed out that the treatment targeting microRNAs has a promising future in the treatment of hepatic ischemia-reperfusion injury, and further studies are needed in the future.
Research advances in mutation characteristics of the UGT1A1 gene in Gilbert syndrome and its influence on intrahepatic and extrahepatic systems
Liang Chen, Bai Li, Zheng SuJun
2019, 35(7): 1632-1635. DOI: 10.3969/j.issn.1001-5256.2019.07.046
Abstract:
Gilbert syndrome is the most common type of hereditary hyperbilirubinemia with a high incidence rate. This article briefly describes the research advances in epidemiological characteristics of Gilbert syndrome, common UGT1 A1 gene mutation sites, and the influence of Gilbert syndrome on intrahepatic and extrahepatic diseases. It is pointed out that an understanding of these aspects plays an important role in the diagnosis and treatment of Gilbert syndrome and the prevention and treatment of intrahepatic and extrahepatic diseases.
Role of microRNA in the pathogenesis, diagnosis, and outcome evaluation of primary biliary cholangitis
Wang Jing, Zhang BiQing, Pan YunZhi, Zhu ChuanWu
2019, 35(7): 1636-1639. DOI: 10.3969/j.issn.1001-5256.2019.07.047
Abstract:

Primary biliary cholangitis ( PBC) is one of common autoimmune liver diseases, and its pathogenesis remains unclear. This article summarizes the role of microRNA in the pathogenesis, diagnosis, and outcome evaluation of PBC and points out that microRNA may be involved in the development and progression of PBC and may thus be used as a potential biomarker for diagnosis and outcome evaluation.

Value of percutaneous transhepatic choledochoscopic lithotripsy in treatment of hepatolithiasis
Liu XinWen, Cheng Yao, Gong JianPing
2019, 35(7): 1640-1643. DOI: 10.3969/j.issn.1001-5256.2019.07.048
Abstract:
Hepatolithiasis is a common benign biliary disease in China. It is a challenge to treat hepatolithiasis. Some patients with complicated hepatolithiasis fail to achieve satisfactory outcomes after several biliary operations, and therefore, how to improve the treatment outcome of hepatolithiasis is a major problem for biliary surgeons. At present, surgery is still the main treatment method for hepatolithiasis. Percutaneous transhepatic choledochoscopic lithotripsy ( PTCSL) , as a minimally invasive surgical treatment for hepatolithiasis, has been accepted by many biliary surgeons and patients with hepatolithiasis and gradually gains a place in the treatment of hepatolithiasis. This article reviews the research advances in PTCSL in the treatment of hepatolithiasis.
Research advances in perioperative management of hilar cholangiocarcinoma
Jiang Hua, Wang YueHua
2019, 35(7): 1644-1647. DOI: 10.3969/j.issn.1001-5256.2019.07.049
Abstract:
Hilar cholangiocarcinoma ( HCCA) is a common malignant tumor of the biliary system with great difficulties in surgery, and there are still controversies over the standardized diagnosis and treatment system of HCCA. This article reviews the research advances in perioperative management of HCCA, including preoperative diagnosis and evaluation, clinical stage, preoperative preparation, surgical approach, and postoperative management.