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

2019 Vol. 35, No. 9

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Editorial
Further strengthen the clinical and basic research on liver failure
Han Tao, Liu Lei
2019, 35(9): 1897-1899. DOI: 10.3969/j.issn.1001-5256.2019.09.001
Abstract:
Liver failure is a severe clinical syndrome of liver disease with high mortality. Although great achievements have been made in the research on liver failure in recent years, there are still controversies over many issues including the classification, diagnostic criteria, and treatment of liver failure. The pathogenesis of liver failure needs to be further clarified, and innovative strategies for diagnosis and treatment need to be further explored. Therefore, the clinical and basic research on liver failure should be further strengthened to improve the comprehensive diagnosis and treatment level of liver failure and continuously reduce the mortality rate of liver failure.
Discussions by experts
Establishment of the diagnostic criteria and hierarchical diagnosis and treatment system for acute-on-chronic liver failure based on high-quality Chinese evidence
Li Hai
2019, 35(9): 1900-1902. DOI: 10.3969/j.issn.1001-5256.2019.09.002
Abstract:
Establishment of a hierarchical diagnosis and treatment system for patients with acute exacerbation of chronic liver diseases based on Chinese clinical evidence and development of the diagnostic criteria for acute-on-chronic liver failure ( ACLF) in HBV epidemic areas based on high-quality Chinese evidence provide great opportunities for China to make breakthroughs in the field of severe liver diseases and utter the Chinese voice around the world. Whether the same diagnostic criteria for ACLF can be used in patients with liver diseases as primary diseases with ( liver cirrhosis and nonalcoholic steatohepatitis) or without ( non-cirrhotic chronic hepatitis B) systemic organ injury is the key to the development of the diagnostic criteria for ACLF in HBV epidemic areas. This article introduces the global cooperation between EASL-CLIF Consortium, South America CLIF Consortium, and Chinese CLIF Consortium.
Differences in the diagnostic criteria for acute-on-chronic liver failure between the East and the West
Yang LingLing, Li Jun
2019, 35(9): 1903-1908. DOI: 10.3969/j.issn.1001-5256.2019.09.003
Abstract:
Acute-on-chronic liver failure ( ACLF) is a serious threat to global public health, with a mortality rate of as high as 50%-90% after comprehensive medical treatment, and early diagnosis and treatment are of vital importance to reducing the mortality rate of ACLF. Due to the difference in major etiologies of ACLF between the East and the West, there are still no universally accepted diagnostic criteria for ACLF, with controversies over whether the underlying disease of liver cirrhosis should be one of the diagnostic criteria for ACLF.This article reviews the latest research advances in the definition, diagnostic criteria, predisposing factors, and pathogenesis of ACLF, in order to provide a theoretical basis for the development of new treatment strategies and international guidelines.
Non-bioartificial liver in liver failure: Clinical application and research advances
Li Shuang, Liu Jing, Chen Yu
2019, 35(9): 1909-1915. DOI: 10.3969/j.issn.1001-5256.2019.09.004
Abstract:
Artificial liver is one of the most important methods for the treatment of liver failure. At present, there are many types of non-bioartificial liver used in clinical practice, with different mechanisms and indications, and the severity of the disease varies greatly among patients. Therefore, an individualized treatment regimen should be developed based on patients' conditions, features of each type of artificial liver, and actual situation. This article introduces the non-bioartificial liver systems commonly used in clinical practice, discusses their therapeutic effects, and elaborates on how to choose the appropriate artificial liver according to the clinical manifestations of patients with liver failure, in order to provide a reference for clinicians.
Clinicopathological basis of liver failure
Jiang LiNa, Zhao JingMin
2019, 35(9): 1916-1919. DOI: 10.3969/j.issn.1001-5256.2019.09.005
Abstract:
Liver failure is a group of hepatocyte dysfunctions caused by severe synthetic and metabolic disorders and has a high mortality rate. Histopathology has great clinical significance in the diagnosis, classification, and prognostic evaluation of liver failure. Extensive hepatocyte death and hepatocyte regeneration run through the whole clinicopathological process of liver failure, and necrosis is the major type of cell death in liver failure and is often accompanied by other types such as apoptosis, pyroptosis, and autophagy. Each type of liver failure has its own pathological features. Acute liver failure emphasizes consistent massive or submassive necrosis caused by one hit; subacute liver failure has the features of submassive or massive liver necrosis due to new and old lesions caused by multiple hits; acute-on-chronic live failure shows extensive hepatocyte necrosis caused by one or multiple hits on the basis of chronic liver disease; chronic liver failure has the histological features of liver cirrhosis with small nodules or mixed large-small nodules, compact and wide fibrous septa mainly composed of collagen type I, Laennec stage ( mainly F4 c) , significant reductions in the number and function of liver parenchymal cells, and marked intrahepatic vascular structural abnormalities and blood circulation disorders, as well as liver inflammatory lesions. Hepatocyte death triggers the recruitment of a large number of inflammatory cells and the overactivation of Kupffer cells and stimulates immune-mediated liver injury and systemic inflammatory response syndrome caused by inflammation activation, which are the main pathophysiological mechanisms of multiple organ failure caused by liver failure.
Role of endoplasmic reticulum stress in the pathogenesis of liver failure
Zhang XiangYing, Ren Feng
2019, 35(9): 1920-1923. DOI: 10.3969/j.issn.1001-5256.2019.09.006
Abstract:
Liver failure is a severe liver disease with a complex pathological process, rapid disease progression, and a high mortality rate, and in-depth studies are needed to explore its pathogenesis. Early and mild endoplasmic reticulum stress ( ERS) can maintain the stability of intracellular environment through unfolded protein reaction, while persistent and severe ERS may promote inflammatory response and apoptosis and cause cell death, and therefore, ERS plays a key role in the development and progression of liver failure. This article elaborates on the role of ERS and related signaling pathways in the pathogenesis of liver failure, so as to provides new ideas for the treatment of liver failure.
Guidelines
Multidisciplinary expert consensus on the diagnosis and treatment of hepatic hemangioma (2019 edition)
International Hepato-Pancreato-Biliary Association, China Branch, Hepatic Hemangioma Professional Committee
2019, 35(9): 1928-1932. DOI: 10.3969/j.issn.1001-5256.2019.09.008
Abstract:
An excerpt of acute-on-chronic liver failure: Consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL) 2019 update
Chen Jing, Su HaiBin, Hu JinHua
2019, 35(9): 1933-1936. DOI: 10.3969/j.issn.1001-5256.2019.09.009
Abstract:
An excerpt of British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis (2019)-An excerpt of British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis (2019)
Wang Lu, Han Ying
2019, 35(9): 1937-1941. DOI: 10.3969/j.issn.1001-5256.2019.09.010
Abstract:
Original articles_Viral hepatitis
Expression and significance of cytokines in children with acute hepatitis A
Wei XinHuan, Liu YaLi, Zhang Jing, Lin Wei
2019, 35(9): 1942-1945. DOI: 10.3969/j.issn.1001-5256.2019.09.011
Abstract:
Objective To investigate the clinical significance of cytokines in children with acute hepatitis A. Methods The children with acute hepatitis A who were hospitalized in the Specialized Hospital of Infectious Diseases in Hotan, Xinjiang, from September 2014 to January 2015 were enrolled as acute hepatitis A group, and healthy children matched for age and sex were enrolled as control group. The serum levels of related inflammatory cytokines were measured, including interleukin-6 ( IL-6) , interleukin-8 ( IL-8) , interleukin-10 ( IL-10) , interleukin-1β ( IL-1β) , and tumor necrosis factor-α ( TNFα) . Clinical indices such as liver function, coagulation function, and presence or absence of ascites were monitored, and the correlation between the serum cytokines and clinical features was analyzed.The two-independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The chi-square test was used for comparison of categorical data between two groups. A Spearman correlation analysis was used to investigate correlation. Results A total of70 children with acute hepatitis A and 30 healthy children were enrolled. The serological test showed that the acute hepatitis A group had a significantly higher serum level of IL-10 than the control group [19. 60 ( 15. 50-32. 08) pg/ml vs 5. 00 ( 5. 00-10. 30) pg/ml, Z =-6. 79, P < 0. 01]. In the children with acute hepatitis A, the serum level of IL-10 was positively correlated with alanine aminotransferase ( r = 0. 24, P = 0. 04) , total bilirubin ( r = 0. 32, P < 0. 01) , and prothrombin time ( r = 0. 29, P = 0. 01) . In addition, the serum level of IL-10 was 23. 20 ( 18. 04-45. 00) pg/ml in children with jaundice hepatitis and 18. 40 ( 14. 84-24. 80) pg/ml in those with non-jaundice hepatitis, and there was no significant difference between the two groups of children ( Z =-2. 30, P = 0. 02) . The children with ascites had a significantly higher serum level of IL-10 than those without ascites [42. 60 ( 19. 15-73. 35) pg/ml vs 19. 02 ( 15. 13-27. 33) pg/ml, Z =-2. 42, P = 0. 02]. There were no significant differences between the acute hepatitis A group and the control group in the ser-um levels of IL-6 ( Z =-0. 95, P = 0. 34) , IL-8 ( Z =-0. 97, P = 0. 33) , IL-1β ( Z =-1. 33, P = 0. 18) , and TNFα ( Z =-0. 34, P = 0. 73) , and there were also no significant differences in these cytokines between the children with jaundice hepatitis and those with non-jaundice hepatitis, as well as between the children with ascites and those without ascites ( all P > 0. 05) . Conclusion There is a significant increase in the serum level of IL-10 in children with acute hepatitis A, especially in those with jaundice hepatitis or ascites, suggesting that IL-10 plays an important role in immunologic injury induced by acute hepatitis A virus infection.
Measurement and clinical significance of activating transcription factor 6 level in peripheral blood in patients with chronic HBV infection
Pan GaoFeng, Li GuoYun, Ji XueLiang, Fu MaoYing
2019, 35(9): 1946-1949. DOI: 10.3969/j.issn.1001-5256.2019.09.012
Abstract(1129) PDF (204KB)(239)
Abstract:
Objective To investigate the level of activating transcription factor 6 ( ATF6) in peripheral blood and its association with clinical indices in patients with chronic HBV infections. Methods A total of 20 chronic asymptomatic HBV carriers ( ASCs) , 20 patients with chronic hepatitis B ( CHB) , and 20 patients with hepatitis B liver cirrhosis ( LC) , who were treated in The First People's Hospital of Kunshan from March 2016 to February 2019, were enrolled, and 20 healthy individuals who underwent physical examination during the same period of time were enrolled as normal control group ( NC group) . Quantitative real-time PCR was used to measure the mRNA expression of ATF6 in peripheral blood leukocytes for all patients, and its correlation with clinical indices was analyzed. ELISA was used to measure the serum level of ATF6 protein for healthy controls and CHB patients. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the independent samples t-test was used for comparison between two groups. Results The ASC, CHB, and LC groups had significantly higher mRNA expression of ATF6 in peripheral blood leukocytes than the NC group ( 1. 99 ± 0. 70/2. 12 ± 0. 75/1. 97 ± 0. 85 vs 0. 71 ± 0. 26, all P <0. 05) . There were no significant differences in the mRNA expression of ATF6 between the individuals with different levels of HBsAg, HBV DNA, aminotransferases, and total bilirubin and with the presence or absence of HBeAg in each group ( all P > 0. 05) . The CHB group had a significantly higher serum level of ATF6 protein than the NC group ( 7. 66 ± 1. 94 ng/ml vs 3. 29 ± 0. 30 ng/ml, t =-9. 971, P <0. 001) . Conclusion ATF6 has a higher expression level in peripheral blood in patients with chronic HBV infection. It may be involved in the course of chronic HBV infection.
Original articles_Liver fibrosis and liver cirrhosis
Value of FibroScan in the diagnosis of progressive liver fibrosis in patients with chronic hepatitis C and related influencing factors
Chou LiXia, Liang Shan, Fan ZuoPeng, Ma LiXia, Wei XinHuan, Guo HaiQing, Lin Wei, Liu YiRong, Yu HaiBin, Liu YaLi, Zhang Jing
2019, 35(9): 1950-1953. DOI: 10.3969/j.issn.1001-5256.2019.09.013
Abstract:
Objective To investigate the diagnostic efficacy of FibroScan in the diagnosis of progressive liver fibrosis in patients with chronic hepatitis C and related influencing factors. Methods A total of 131 patients with chronic hepatitis C who attended Beijing YouAn Hospital, Capital Medical University from June 2015 to June 2018 were enrolled, and all of them underwent liver biopsy. Fibrosis stage was defined as F1 to F4 stages according to the METAVIR scoring system. General information was collected, and liver stiffness measurement ( LSM) , liver function test, routine blood test, and viral quantification were performed for all patients. Aspartate aminotransferase-to-platelet ratio index ( APRI) and fibrosis-4 ( FIB-4) were calculated according to equations. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous between multiple groups, and the Wilcoxon rank-sum test was used for further comparison between two groups. A Spearman correlation analysis was performed. The receiver operating characteristic ( ROC) curve was used to analyze the value of three noninvasive methods in the diagnosis of liver fibrosis, and STATA was used to investigate whether there was a significant difference between the three methods. Results A total of 131 patients were enrolled, with 60 male patients ( 45. 80%) and 71 female patients ( 54. 20%) , and the mean age was 54. 00 ( 45. 00-58. 25) years. The median values of FibroScan, APRI, and FIB-4 were 7. 80 ( 5. 60-14. 30) kPa, 0. 63 ( 0. 37-1. 28) , and 2. 28 ( 1. 43-3. 60) , respectively. LSM gradually increased with the progression of liver fibrosis, and there was a significant difference between groups ( H = 47. 83, P < 0. 01) . For progressive liver fibrosis ( ≥F3 stage) , FibroScan had a larger area under the ROC curve ( AUC) than APRI and FIB-4, and further analysis based on STATA showed that there was a significant difference in AUC between FibroScan and APRI ( P < 0. 01) , while there was no significant difference in AUC between FibroScan and FIB-4 ( P = 0. 07) . FibroScan was correlated with alanine aminotransferase ( ALT) , aspartate aminotransferase ( AST) , gamma-glutamyl transpeptidase ( GGT) , and platelet count ( r = 0. 271, 0. 507, 0. 444, and-0. 263, all P < 0. 01) . The AUC of FibroScan was not signifi-cantly improved after adjustment for the above influencing factors. Conclusion FibroScan has good diagnostic efficacy in the diagnosis of progressive liver fibrosis in patients with hepatitis C, with better comprehensive diagnostic efficacy than APRI and FIB-4. The accuracy of FibroScan in diagnosis is not affected by the indicators such as ALT, AST, and GGT.
Establishment and evaluation of a predictive model for rebleeding after endoscopic treatment of esophageal and gastric varices
Ai ZhengLin, Hong Shan, Hu JuLong, Li Ping, Zhou YuLing, Liang XiuXia
2019, 35(9): 1954-1957. DOI: 10.3969/j.issn.1001-5256.2019.09.014
Abstract:
Objective To establish a predictive model for rebleeding after endoscopic injection of lauromacrogol combined with tissue adhesive in patients with esophageal and gastric varices, and to investigate its accuracy by cross validation. Methods A total of 180 patients with esophagogastric variceal bleeding who were admitted to Beijing Ditan Hospital from January 2014 to December 2016 were enrolled, and a retrospective analysis was performed for the clinical data of 126 patients, including age, sex, laboratory markers, Child-Pugh score, and degree of esophageal and gastric varices. A logistic regression analysis was used to screen out independent predictive factors for rebleeding and establish a predictive model, and the clinical data of the other 54 patients were used for cross validation of the accuracy of this model.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 two groups. The logistic regression method was used to perform multivariate analysis and establish the predictive model. The receiver operating characteristic ( ROC) curve was used for evaluation of this model and cross validation of its accuracy. Results The 1-year rebleeding rate was 46. 83% in 126 patients, and there were significant differences between the rebleeding group and the non-rebleeding group in platelet count ( t =-7. 488, P < 0. 001) , international normalized ratio ( t = 3. 145, P = 0. 002) , and degree of esophageal varices ( χ2= 8. 841, P = 0. 031) . The multivariate logistic regression analysis showed that sex ( odds ratio [OR]= 3. 366, 95% confidence interval [CI]: 1. 015-11. 166, P = 0. 047) , platelet count ( OR = 0. 922, 95% CI: 0. 893-0. 951, P < 0. 001) , and degree of esophageal varices ( OR = 2. 422, 95% CI: 1. 179-4. 977, P = 0. 016) were independent predictive factors for rebleeding. The predictive model based on the combination of these three factors had an area under the ROC curve of 0. 876, a sensitivity of 86. 0%, and a specificity of 83. 1%.Cross validation based on the clinical data of the other 54 patients showed that this predictive model had an accuracy of 92. 6%. Conclusion Male sex and severe varices are high-risk factors for rebleeding, and platelet count is a protective factor. The predictive model based on thecombination of these three factors has a certain value in predicting rebleeding, with an accuracy of 92.6%.
Effect of Duxiao Ganqing Pill on liver inflammation in rats with cirrhotic endotoxemia: An analysis based on the TLR4/MyD88/NF-κB signaling pathway
Li ShuZhi, Liu TieJun
2019, 35(9): 1958-1964. DOI: 10.3969/j.issn.1001-5256.2019.09.015
Abstract:
Objective To establish a rat model of cirrhotic endotoxemia by CCl4 compound modeling, and to investigate the protective mechanism of Duxiao Ganqing Pill against liver inflammatory injury. Methods A total of 66 rats were selected, among which 17 died during modeling. Among the remaining 49 rats, 3 were selected to measure endotoxin and observe liver structure to determine whether the model was successfully established, and the other 46 rats were randomly divided into normal group with 6 rats, model group with 8 rats, lactulose group with 8 rats, and high-, middle-, and low-dose Duxiao Ganqing Pill ( 223. 4, 111. 7, and 58. 9 mg/kg) groups with 8 rats in each group. CCl4 compound modeling was performed for 8 weeks to establish a rat model of liver cirrhosis. The rats in the normal group and the model group were given distilled water, those in the lactulose group were given lactulose, and those in the Duxiao Ganqing Pill groups were given the drug according to the above doses, once a day for 2 consecutive months. The change in the content of endotoxin was measured. HE staining was used to observe the change in liver tissue, ELISA was used to measure the content of tumor necrosis factor-α ( TNF-α) , interleukin-1β ( IL-1β) , and interleukin-6 ( IL-6) in liver tissue, and Western blot and RT-PCR were used to measure the protein and mRNA expression of TLR4, MyD88, and NF-κB. A one-way analysis of variance was used for data comparison between groups, and the least significant difference t-test was used for further comparison of data with homogeneity of variance between two groups. Results There was a significant difference in serum endotoxin level between these groups ( F = 26. 011, P < 0. 001) ; the model group had a signifi-cantly higher endotoxin level than the normal group ( P < 0. 01) ; after treatment, the lactulose group and high-, middle-, and low-dose Duxiao Ganqing Pill groups had significantly lower serum endotoxin levels than the model group ( P < 0. 01) . There were significant differences in serum levels of IL-6, IL-1β, and TNF-α between these groups ( F = 35. 390, P = 0. 002; F = 38. 271, P = 0. 001; F =40. 241, P < 0. 001) ; the model group had significantly higher serum levels of IL-6, IL-1β, and TNF-α than the normal group ( all P < 0. 01) ; after treatment, the lactulose group and high-, middle-, and low-dose Duxiao Ganqing Pill groups had significantly lower serum levels of IL-6, IL-1β, and TNF-α than the model group ( all P < 0. 01) . There were significant differences in the mRNA and protein expression of TLR4, MyD88, and NF-κB in liver tissue between these groups ( F = 24. 483, 29. 547, 19. 242, 18. 752, 22. 146, and 15. 834, all P < 0. 01) ; the model group had significantly higher mRNA and protein expression of TLR4, MyD88, and NF-κB in liver tissue than the normal group ( all P < 0. 01) ; after treatment, the lactulose group and high-, middle-, and low-dose Duxiao Ganqing Pill groups showed significant reductions in the mRNA and protein expression of TLR4, MyD88, and NF-κB in liver tissue ( all P < 0. 01) , and the middle-and high-dose Duxiao Ganqing Pill groups had significantly greater reductions than the low-dose Duxiao Ganqing Pill group ( all P < 0. 01) . Conclusion Duxiao Ganqing Pill can inhibit the transduction of inflammatory signals by downregulating the TLR4/MyD88/NF-κB signaling pathway in liver tissue, reduce the expression of the cytokines TNF-α, IL-1β, and IL-6, and thus alleviate endotoxemia and exert a protective effect on liver tissue.
Original articles_Liver neoplasms
Short-term clinical effect of cyberknife versus radiofrequency ablation in treatment of small hepatocellular carcinoma
Yang Zhao, Xie Hui, Wang Quan, Zhang Tao, Wang HuaMing, He WeiPing, Duan XueZhang
2019, 35(9): 1965-1969. DOI: 10.3969/j.issn.1001-5256.2019.09.016
Abstract:
Objective To investigate the clinical effect and safety of cyberknife versus radiofrequency ablation in the treatment of small hepatocellular carcinoma. Methods A total of 80 previously untreated patients with small hepatocellular carcinoma who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from October 2017 to March 2018 were enrolled. Among these patients, 35 patients with 41 target lesions received cyberknife, and 45 patients with 47 target lesions received radiofrequency ablation. The two groups were compared in terms of objective response rate ( complete remission + partial remission) , 1-year overall survival rate, 1-year local control rate, and incidence rate of postoperative adverse events. The chi-square test or the continuous calibration chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to calculate local control rate, and the log-rank test was used for survival analysis. Results The patients were followed up for 6. 0-17. 7 months, with a median follow-up time of 13. 5 months. Two patients ( 2. 5%) were lost to follow-up, with one patient from each group. In the cyberknife group, there were 31 lesions with complete remission ( 75. 6%) , 4 lesions with partial remission ( 9. 8%) , 4 lesions with a stable state ( 9. 8%) , and 2 lesions with progression ( 4. 8%) , with an objective response rate of 85. 4%, a 1-year overall survival rate of 100%, and a 1-year local control rate of 94. 3%.In the radiofrequency ablation group, there were 38 lesions with complete remission ( 80. 9%) and 9 lesions with progression ( 19. 1%) , with an objective response rate of 80. 9%, a 1-year overall survival rate of 100%, and a 1-year local control rate of 91. 0%. There were no significant differences in objective response rate and local control rate between the two groups ( both P > 0. 05) . Most postoperative adverse events were mild ( grade 1-2) , and no serious adverse events were observed. Conclusion Cyberknife is as safe and effective as radiofrequency ablation in the treatment of small hepatocellular carcinoma and is one of the options for the treatment of small hepatocellular carcinoma.
Association of Nutritional Risk Assessment 2002 score with recurrence-free survival time and overall survival time in patients undergoing hepatectomy
Tian Tian, Zhang Heng, Jiang Ting
2019, 35(9): 1970-1974. DOI: 10.3969/j.issn.1001-5256.2019.09.017
Abstract:
Objective To investigate the association of Nutritional Risk Assessment 2002 ( NRS-2002) score with recurrence-free survival time and overall survival time in hepatocellular carcinoma ( HCC) patients undergoing hepatectomy. Methods The HCC patients who underwent hepatectomy for the first time in Wuhan Central Hospital from January 2013 to January 2017 were enrolled. The NRS-2002 score was used to evaluate nutritional status before surgery. All patients were followed up, and recurrence-free survival time and overall survival time were recorded. The chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to analyze recurrence-free survival time and overall survival time. The multivariate Cox proportional hazard model was used to investigate the independent risk factors for recurrence and death. Results According to the NRS-2002 score, 72 HCC patients had nutritional risk and 158 patients had normal nutrition before surgery, with an incidence rate of nutritional risk of 31. 3%. The patients were followed up for7-80 months ( mean 46. 14 ± 10. 52 months) . Of all patients, 91 ( 39. 6%) experienced recurrence and 43 ( 18. 7%) died. The 1-, 3-, and 5-year recurrence rates were 10% ( 23/230) , 28. 3% ( 65/230) , and 35. 2% ( 81/230) , respectively, and the 1-, 3-, and5-year mortality rates were 1. 7% ( 4/230) , 12. 2% ( 28/230) , and 16. 1% ( 37/230) , respectively. Among the 72 patients with nutritional risk, 37 ( 51. 4%) experienced recurrence and 20 ( 27. 8%) died, and among the 158 patients with normal nutrition, 54 ( 34. 2%) experienced recurrence and 23 ( 14. 6%) died. The patients with normal nutrition had significantly longer overall survival time and recurrence-free survival time than those with nutritional risk ( P < 0. 05) . The number of tumors ( hazard ratio [HR]= 1. 682, 95% confidence interval [CI]: 1. 161-2. 438) , vascular invasion ( HR = 1. 996, 95% CI: 1. 372-2. 904) , and nutritional risk ( HR = 2. 186, 95% CI:1. 517-3. 150) were independent risk factors for recurrence in HCC patients, and vascular invasion ( HR = 1. 823, 95% CI: 1. 265-2. 627) and nutritional risk ( HR = 2. 068, 95% CI: 1. 431-2. 990) were independent risk factors for death in HCC patients. Conclusion According to the nutritional screening results based on the NRS-2002 score, there is a high proportion of HCC patients with nutritional risk before surgery, which is associated with postoperative recurrence and death.
Screening strategy for primary hepatocellular carcinoma based on different combinations of protein induced by vitamin K absence or antagonist-Ⅱ, alpha-fetoprotein, and alpha-fetoprotein-L3
Xie Fang, Yu LeCheng, Xue Zhu, Li Ping, Sheng YunFeng
2019, 35(9): 1975-1979. DOI: 10.3969/j.issn.1001-5256.2019.09.018
Abstract:
Objective To investigate the sensitivities and specificities of different combinations of serum protein induced by vitamin K absence or antagonist-Ⅱ ( PIVKA-Ⅱ) , alpha-fetoprotein ( AFP) , and alpha-fetoprotein-L3 ( AFP-L3) in the screening for primary hepatocellular carcinoma ( HCC) . Methods Serum samples were collected from 118 patients with HCC and 76 patients with hepatitis or liver cirrhosis who were hospitalized in Liver Disease Center of PLA, General Hospital of Eastern Theater Command, from January 2017 to July 2018, and the serum levels of PIVKA-Ⅱ, AFP, and AFP-L3 were measured. The sensitivities and specificities of each individual indicator and their different combinations in HCC screening were calculated and compared. The Mann-Whitney U test was used for comparison of continuous data with skewed distribution between groups, and the chi-square test was used for comparison of categorical data between groups. The efficiency of PIVKA-Ⅱ, AFP, and AFP-L3 in HCC screening was analyzed, their sensitivities and specificities were calculated, and receiver operating characteristic ( ROC) curves were plotted. Results The HCC group had significantly higher levels of PIVKA-Ⅱ and AFP than the hepatitis/liver cirrhosis group ( Z = 7. 80 and 3. 80, both P < 0. 001) . Compared with the hepatitis/liver cirrhosis group, the HCC group had a significantly higher proportion of patients with positive PIVKA-Ⅱ, AFP, or AFP-L3 ( χ2= 153. 36, 83. 97, and 168. 82, all P < 0. 001) . There was no significant difference between the positive rates of PIVKA-Ⅱ and AFP in the HCC group ( 68. 6% vs 67. 8%, χ2= 0. 02, P > 0. 05) , while a significant difference was observed in the hepatitis/liver cirrhosis group ( 14. 5%vs 51. 3%, χ2= 23. 37, P < 0. 001) . There was a significant difference between the positive rates of PIVKA-Ⅱ and AFP-L3 in the HCC group ( 68. 6% vs 35. 6%, χ2= 25. 83, P < 0. 001) , while no significant difference was observed in the hepatitis/liver cirrhosis group ( 14. 5% vs 9. 2%, χ2= 1. 01, P > 0. 05) . There was a significant difference between the positive rates of AFP and AFP-L3 in the HCC group ( 67. 8% vs 35. 6%, χ2= 24. 50, P < 0. 001) and the hepatitis/liver cirrhosis group ( 51. 3% vs 9. 2%, χ2= 31. 92, P < 0. 001) . In HCC screening, PIVKA-Ⅱ had a significantly larger area under the ROC curve than AFP ( 0. 832 vs 0. 662, P < 0. 01) and AFP-L3 ( 0. 832 vs 0. 656, P < 0. 01) . With PIVKA-Ⅱ > 40 mA U/ml, AFP > 10 ng/ml, and AFP-L3 > 10% as the positive cut-off values for the possibility of HCC, both PIVKA-Ⅱ and AFP had a sensitivity of 67. 8% in the ROC curve, which was significantly higher than the sensitivity of AFP-L3 ( 55%) . PIVKA-Ⅱ had a significantly higher specificity than AFP ( 85. 5% vs 48. 7%) and AFP-L3 ( 85. 5%vs 60%) . In HCC screening, positive PIVKA-Ⅱ, AFP, and AFP-L3 had a sensitivity of 29. 7% and a specificity of 98. 7%; positive PIVKA-Ⅱ and AFP had a sensitivity of 55. 9% and a specificity of 90. 8%; positive PIVKA-Ⅱ and AFP-L3 had a sensitivity of 30. 5%and a specificity of 98. 7%; positive AFP and AFP-L3 had a sensitivity of 34. 7% and a specificity of 93. 4%. Conclusion In the context of no influence from the factors including anticoagulants and cholestasis, elevated serum PIVKA-Ⅱ alone has a better value in HCC screening than elevated AFP or AFP-L3. The increase in PIVKA-Ⅱ or AFP significantly improves the sensitivity in HCC screening, and the increases in all or any two of PIVKA-Ⅱ, AFP-and AFP-L3 can significantly improve the specificity in HCC screening.
Expression of circular RNA FLI1 in patients with hepatocellular carcinoma and its association with prognosis
Tang Ling, Qiu LuDie, Qin Wen, Wu Gang
2019, 35(9): 1980-1984. DOI: 10.3969/j.issn.1001-5256.2019.09.019
Abstract:
Objective To investigate the expression and significance of circular RNA FLI1 ( circ FLI1) in patients with hepatocellular carcinoma ( HCC) . Methods A total of 45 HCC patients who underwent surgical resection in The Affiliated Hospital of Southwest Medical University from January 2013 to January 2018 were enrolled as HCC group, and the samples of cancerous tissue, adjacent tissue, and serum were collected. A total of 45 healthy individuals who underwent physical examination were enrolled as control group, and their serum samples were collected. Human hepatoma cell lines HepG2, SMMC7721, and HB611 were obtained from Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences. qRT-PCR was used to measure the expression of circ FLI1 in hepatoma cells and 45 samples of cancerous tissue and serum. The t-test was used for comparison of continuous data between groups. The Kaplan-Meier method was used to analyze the association between circ FLI1 expression and survival time; the receiver operating characteristic ( ROC) curve was used to evaluate the potential of serum circ FLI1 E2-4 and circ FLI1 E2-5 as the biomarkers for the diagnosis of HCC; univariate and multivariate Cox proportional hazards model analyses were used to investigate the influencing factors for the prognosis of HCC. Results There was high expression of circ FLI1 E2-5 and circ FLI1 E2-4 in the three hepatoma cell lines. Compared with the control group, the HCC group had sig-nificantly higher serum levels of circ FLI1 E2-4 ( 7. 09 ± 0. 26 vs 1. 14 ± 0. 20, t = 19. 970, P < 0. 001) and circ FLI1 E2-5 ( 7. 50 ±0. 25 vs 1. 29 ± 0. 30, t = 16. 640, P < 0. 001) . For the HCC patients, the expression of circ FLI1 E2-4 and circ FLI1 E2-5 in cancerous tissue was significantly higher than that in adjacent tissue ( circ FLI1 E2-4: 7. 62 ± 1. 33 vs 1. 55 ± 0. 32, t = 15. 560, P < 0. 001; circ FLI1 E2-5: 7. 92 ± 0. 35 vs 1. 42 ± 0. 39, t = 21. 170, P < 0. 001) . The patients with high expression of circ FLI1 E2-5 had significantly shorter median progression-free survival time and overall survival time than those with low expression ( median progression-free survival time: 11. 17 ± 0. 49 months vs 23. 35 ± 1. 27 months, χ2= 28. 480, P < 0. 001; overall survival time: 19. 75 ± 0. 76 months vs 37. 44 ± 1. 57 months, χ2= 21. 750, P < 0. 001) . The patients with high expression of circ FLI1 E2-4 had significantly shorter median progression-free survival time and overall survival time than those with low expression ( median progression-free survival time: 10. 29 ± 0. 42 months vs 24.65 ± 1. 58 months, χ2= 19. 620, P < 0. 001; overall survival time: 21. 32 ± 0. 55 months vs 35. 69 ± 1. 74 months, χ2= 19. 730, P < 0.001) . As a serum marker for the diagnosis of HCC, serum circ FLI1 E2-4 had an area under the ROC curve of 0. 910 ( 95% confidence interval [CI]: 0. 621-0. 970, P < 0. 001) , with a sensitivity of 84. 3% and a specificity of 90. 5%. As a serum marker for the diagnosis of HCC, serum circ FLI1 E2-5 had an area under the ROC curve of 0. 760 ( 95% CI: 0. 650-0. 860, P < 0. 001) , with a sensitivity of80. 5% and a specificity of 87. 3%. The multivariate Cox proportional hazards model analysis showed that serum circ FLI1 E2-4 ( hazard ratio [HR]= 3. 060, 95% CI: 1. 630-5. 870, P < 0. 05) and circ FLI1 E2-5 ( HR = 2. 560, 95% CI: 1. 250-6. 460, P < 0. 05) were independent influencing factors for the prognosis of HCC patients. Conclusion Circ FLI1 is highly expressed in the tissue and serum of HCC patients, which is associated with the prognosis of patients. It may be a potential biomarker for prognosis and a therapeutic target for HCC.
Clinical effect of topical application of CpG oligodeoxynucleotide combined with OX40 monoclonal antibody for mouse model of hepatocellular carcinoma
Ma ShiChao, Zhang ChaoQun, Sun DianXing
2019, 35(9): 1985-1989. DOI: 10.3969/j.issn.1001-5256.2019.09.020
Abstract:
Objective To investigate the clinical effect of topical application of CpG oligodeoxynucleotide ( CpG-ODN) combined with OX40 monoclonal antibody in the treatment of hepatocellular carcinoma and its therapeutic effect on distant homologous tumors. Methods H22 single cell suspension was subcutaneously injected into the axilla of the four limbs of BALB/c male mice to establish a tumor-bearing model. After seven days, 30 mice with a similar tumor volume were screened out and randomly divided into model control group, CpG group, and CpG + OX40 group, with 10 mice in each group, and drugs were injected into the tumor in the left lower limb. Ten normal mice in the same batch were selected as normal control group. Tumor volume was calculated, ELISA was used to measure the serum levels of interleukin-12 ( IL-12) and interferon-γ ( IFNγ) , and flow cytometry was used to measure the percentage of CD8+T lymphocytes in the spleen. The three groups were compared in terms of survival after treatment. Repeated measures analysis of variance and one-way analysis of variance were used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. The log-rank test was used to analyze survival rate for the model control group, CpG group, and CpG+ OX40 group, and survival curves were plotted. Results After treatment, the model control group had progressive growth of tumor, with significantly lower serum levels of IL-12 and IFNγ and percentage of spleen CD8+T lymphocytes than the normal control group ( all P <0. 05) . Compared with the model control group, the CpG group and the CpG + OX40 group had a significant reduction in tumor volume after intervention ( all P < 0. 05) . The CpG + OX40 group had a significantly lower growth rate of distant tumor than the CpG group and the model control group ( all P < 0. 05) , but there was no significant difference in distant tumor volume between the CpG group and the model control group ( P > 0. 05) . Compared with the model control group, the CpG group and the CpG + OX40 group had significant increases in serum levels of IL-12 and IFN-γ and percentage of spleen CD8+T lymphocytes ( all P < 0. 05) , which were significantly higher in the CpG +OX40 group than in the CpG group ( all P < 0. 05) . The CpG + OX40 group had a significantly higher survival rate than the model control group and the CpG group ( both P < 0. 05) , while there was no significant difference between the CpG group and the model control group ( P> 0. 05) . Conclusion OX40 monoclonal antibody combined with CpG-ODN can reduce liver tumor volume, effectively slow down the growth of distant tumors, and prolong the survival time of mice.
Original articles_Others
Value of five scoring systems in predicting short-term mortality of patients with acute-on-chronic liver failure
Zhang Jing, Zhou XinMin
2019, 35(9): 1990-1994. DOI: 10.3969/j.issn.1001-5256.2019.09.021
Abstract:

Objective To assess the severity of patients with acute-on-chronic liver failure ( ACLF) using Child-Turcotte-Pugh ( CTP) , Model for End-Stage Liver Disease ( MELD) , integrated MELD ( iMELD) , Chronic Liver Failure-Sequential Organ Failure Assessment ( CLIF-SOFA) , and Chronic Liver Failure-Consortium ACLF ( CLIF-C-ACLF) scores, and to investigate the value of these scoring systems in predicting 28-and 90-day mortality rates. Methods A total of 107 patients with ACLF who were hospitalized in Department of Gastroenterology in Xijing hospital from January 2013 to December 2017 were enrolled, and related laboratory markers on days1, 3-5, and 7-9 after diagnosis were collected. The CTP, MELD, iMELD, CLIF-SOFA, and CLIF-C-ACLF scores were calculated, and the receiver operator characteristic ( ROC) curve was used to compare the clinical value of these scoring systems. The t-test or the Satterthwaite t-test was used for comparison of normally distributed continuous data between groups, the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The chi-square test was used for comparison of categorical data between groups. Results Among the 107 patients, 44 ( 41. 1%) died within 28 days and 55 ( 51. 4%) died within 90 days. The scores of iMELD, CLIF-SOFA, and MELD at the time of diagnosis had an area under the ROC curve ( AUC) of 0. 81, 0. 73, and 0. 75, respectively, in predicting 28-day mortality, as well as an AUC of 0. 73, 0. 68, and 0. 70, respectively, in predicting 90-day mortality.On days 3-5 and 7-9 after diagnosis, there was no significant difference in the AUC for predicting 28-day mortality between MELD/CLIF-SOFA and iMELD ( Z = 0, 0. 15, 3. 08, and 3. 11, all P > 0. 05) , suggesting that the three scores had a similar predictive ability; on days 7-9 after diagnosis, there was no significant difference in the AUC for predicting 90-day mortality between MELD/CLIF-SOFA and iMELD ( Z = 2. 14 and 1. 98, both P > 0. 05) , suggesting that the three scores had a similar predictive ability. At the time of diagnosis and on days 3-5 and 7-9 after diagnosis, iMELD, CLIF-SOFA, and MELD scores had a significantly higher AUC than CLIF-C-ACLF and CTP scores. Conclusion The iMELD scoring system is proved to be an effective predictive system for short-term mortality in patients with ACLF, and dynamic evaluation of iMELD and CLIF-SOFA scores can effectively predict the prognosis of ACLF patients.

Value of procalcitonin combined with Infection Probability Score in predicting infection in patients with liver failure
Liu WenHui, Gan JianHe, Qin AiLan
2019, 35(9): 1995-2000. DOI: 10.3969/j.issn.1001-5256.2019.09.022
Abstract:

Objective To investigate the value of procalcitonin ( PCT) combined with Infection Probability Score ( IPS) in predicting the possibility of infection in patients with liver failure. Methods A retrospective analysis was performed for the clinical data of patients with liver failure who were admitted to The First Hospital Affiliated to Soochow University from January 2015 to June 2018. According to the clinical diagnosis, the patients were divided into infection group and non-infection group, and the two groups were compared in terms of clinical features, common laboratory markers, IPS score, and sequential organ failure assessment ( SOFA) score. The t-test and the Wilcoxon rank-sum test were used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. A multivariate logistic regression analysis was performed to analyze the influencing factors for infection and establish a diagnostic model of PCT combined with IPS score. The receiver operating characteristic ( ROC) curve was used to assess the predictive efficiency of PCT combined with IPS score in infection. Results A total of 179 patients with liver failure were enrolled, among whom 123 ( 68. 72%) experienced infection. Among the 123 patients with infection, 99 ( 80. 49%) had pulmonary infection, 49 ( 39. 84%) had abdominal infection, and 40 ( 32. 52%) had infections at 2 or more sites. The multivariate logistic regression analysis showed that PCT ( odds ratio [OR]= 3. 822, 95% confidence interval [CI]: 1. 714-8. 523, P = 0. 001) and IPS score ( OR = 1. 125, 95% CI: 1. 030-1. 230, P = 0. 009) were independent predictive factors for liver failure with infection. The ROC curve analysis showed that PCT combined with IPS score had the strongest predictive efficiency in liver failure with infection with an area under the ROC curve ( AUC) of 0. 857 ( 95% CI:79. 7-90. 5) , with a significantly higher predictive efficiency than IPS alone and PCT alone ( 0. 857 vs 0. 803/0. 802, both P < 0. 05) , and PCT combined with IPS score had a positive likelihood ratio as high as 3. 40 and a negative likelihood ratio as low as 0. 28. Conclusion Both PCT and IPS score can predict infection in patients with liver failure with similar predictive efficiency, while a combination of PCT and IPS score has a better predictive value.

Effect of response at 48 hours of treatment of acute kidney injury on short-term prognosis of hepatitis B virus-associated acute-on-chronic liver failure
Zhai XingRan, Xu Xiang, Chen Jing, Mu XiuYing, Tong JingJing, Su HaiBin, Liu XiaoYan, Guan ChongDan, Wang Yu, Hu JinHua
2019, 35(9): 2001-2005. DOI: 10.3969/j.issn.1001-5256.2019.09.023
Abstract:

Objective To investigate whether response to the treatment of acute kidney injury ( AKI) is achieved at 48 hours and its effect on the 28-and 90-day prognosis of patients with hepatitis B virus-associated acute-on-chronic liver failure ( HBV-ACLF) and AKI.Methods A retrospective analysis was performed for the clinical data of 130 patients with HBV-ACLF and AKI who were hospitalized and treated in The Fifth Medical Center of Chinese PLA General Hospital from December 2012 to December 2014. According to the response to AKI treatment at 48 hours, the patients were divided into response group and non-response group, and the two groups were compared in terms of 28-and 90-day survival rates to screen out the independent influencing factors for 28-and 90-day prognosis. The t-test was used for comparison of normally distributed continuous data between two groups, and the Kolmogorov-Smirnov Z test was used for comparison of non-normally distributed continuous data between two groups. The chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier survival curve was used to analyze survival rate, and the log-rank test was used for comparison. The Cox regression model was used to perform the univariate and multivariate analyses of influencing factors for prognosis. Results There were38 patients ( 29. 2%) in the response group and 92 patients ( 70. 8%) in the non-response group. The non-response group had significantly lower 28-and 90-day survival rates than the response group ( χ2= 16. 91, 23. 28, both P < 0. 01) . The Cox regression analysis showed that response to AKI treatment at 48 hours, age, serum creatinine, serum sodium, international normalized ratio, and hepatic encephalopathy were independent risk factors for 28- ( HR ( 95% CI) = 0. 271 ( 0. 116-0. 631) , 1. 024 ( 1. 001-1. 047) , 1. 002 ( 1. 000-1. 005) , 0. 948 ( 0. 904-0. 993) , 1. 451 ( 1. 139-1. 849, 1. 987 ( 1. 076-3. 670) , all P < 0. 05) and 90-day ( HR ( 95% CI) = 0. 292 ( 0. 151-0. 563) , 1. 024 ( 1. 004-1. 044) , 1. 002 ( 1. 000-1. 004) , 0. 946 ( 0. 909-0. 984) , 1. 473 ( 1. 180-1. 839) , 2. 135 ( 1. 232-3. 700) , all P < 0. 05) mortality in patients with HBV-ACLF and AKI. Conclusion Response to AKI treatment at 48 hours can significantly improve the short-term prognosis of patients with HBV-ACLF and AKI. Early diagnosis and active treatment of AKI should be strengthened in clinical practice to improve patient prognosis.

Expression and significance of T-cell immunoglobulin and mucin domain-containing molecule 3 in peripheral blood CD3+CD56+ natural killer T cells in patients with hepatitis B virus-related acute-on-chronic liver failure
Gao MengDan, Tan Ling, Sun JianPing, Li Kang, Li Ang, Lou JinLi, Zhang YongHong, Zhao Yan
2019, 35(9): 2006-2010. DOI: 10.3969/j.issn.1001-5256.2019.09.024
Abstract:

Objective To investigate the expression of T-cell immunoglobulin and mucin domain-containing molecule 3 ( TIM-3) in natural killer T ( NKT) cells and its association with liver injury and prognosis in patients with hepatitis B virus-related acute-on-chronic liver failure ( HBV-ACLF) . Methods Peripheral blood mononuclear cells were isolated from 43 patients with HBV-ACLF and 28 patients with chronic hepatitis B ( CHB) who were treated in Beijing YouAn Hospital, Capital Medical University, from September 2016 to June 2018, and flow cytometry was used to measure the number of peripheral blood CD3+CD56+NKT cells and the expression of TIM-3.The t-test was used for comparison of normally distributed continuous data between two groups. The Kruskal-Wallis H test was used for comparision of non-normally distributed continuous data between multiple groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between groups, and the Pearson correlation coefficient was used to investigate correlation. Results Compared with the CHB group, the HBV-ACLF group had significantly higher alanine aminotransferase ( ALT) , aspartate aminotransferase ( AST) , total bilirubin ( TBil) , creatinine, international normalized ratio ( INR) , HBV DNA, TBil/ALT ratio, and Model for End-Stage Liver Disease ( MELD) score, as well as significantly lower albumin and prothrombin time activity ( PTA) ( all P < 0. 05) . Compared with the CHB group, the HBV-ACLF grouphad a significantly higher number of CD3+CD56+NKT cells ( 19. 13% ± 13. 82% vs 26. 75% ± 11. 84%, t = 2. 401, P = 0. 019) and significantly higher expression of TIM-3 in CD3+CD56+NKT cells [5. 53% ( 2. 95%-10. 2%) vs 1. 59% ( 0. 91%-2. 7%) , Z =-5. 260, P < 0. 001]. The expression of TIM-3 in CD3+CD56+NKT cells was positively correlated with ALT ( r = 0. 637, P < 0. 000 1) , AST ( r = 0. 414, P = 0. 006) , INR ( r = 0. 335, P = 0. 031) , and MELD score ( r = 0. 355, P = 0. 021) and was negatively correlated with PTA% ( r =-0. 313, P = 0. 043) . Among the 43 patients with HBV-ACLF, 12 had early-stage HBV-ACLF, 21 had middle-stage HBV-ACLF, and 10 had advanced HBV-ACLF, and there was no significant difference in the number of CD3+CD56+NKT cells between the three groups ( all P > 0. 05) , but with a tendency of increase; the patients with middle-stage or advanced HBV-ACLF had significantly higher expression of TIM-3 in CD3+CD56+NKT cells than those with early-stage HBV-ACLF [6. 5% ( 3. 16%-11. 45%) /8. 56% ( 4%-10. 93%) vs 2. 58% ( 1. 92%-6. 02%) , Z =-2. 284, -2. 641, both P < 0. 05]. Among the 43 patients with HBV-ACLF, the28-day survival group had significantly lower expression of TIM-3 in CD3+CD56+NKT cells than the 28-day liver transplantation/death group [2. 98% ( 1. 94%-6. 88%) vs 8. 56% ( 4. 27%-11. 43%) , Z =-2. 831, P = 0. 005]. Conclusion There is an increase in the expression of TIM-3 in peripheral blood CD3+CD56+NKT cells in patients with HBV-ACLF, which is associated with the degree of liver injury and prognosis.

Influence of interleukin-35 on peripheral CD8+ T cell function in patients with acute-on-chronic liver failure
Gao Yi, Liang ZhiJun, Fu Jian
2019, 35(9): 2011-2016. DOI: 10.3969/j.issn.1001-5256.2019.09.025
Abstract:

Objective To investigate the serum level of interleukin-35 ( IL-35) and its influence on CD8+T cell function in patients with acute-on-chronic liver failure ( ACLF) . Methods A total of 28 patients with ACLF who attended Hainan Provincial People's Hospital from November 2018 to April 2019 and 14 healthy controls were enrolled in this study. ELISA was used to measure the serum level of IL-35. Peripheral CD8+T cells were separated and stimulated with recombinant human IL-35, and real-time quantitative PCR was used to measure the mRNA expression of perforin, granzyme B, and granulysin in CD8+T cells; flow cytometry was used to measure the expression of programmed death-1 ( PD-1) and cytotoxic T-lymphocyte-associated antigen 4 ( CTLA-4) in CD8+T cells. The direct-and indirect-contact co-culture systems were used for the co-culture of HLA-A2-restricted CD8+T cells and HepG2 cells, and after recombinant human IL-35 was added, the percentage of target cell death and the secretion of cytokines were measured to evaluate the changes in the cytolytic and noncytolytic activities of CD8+T cells. The two-independent-samples t test or the paired t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the Spearman correlation analysis was performed to investigate correlation. Results Compared with the health controls, the patients with ACLF had a significant increase in the serum level of IL-35 [72. 32 ( 54. 04-111. 30) pg/ml vs 46. 00 ( 27. 02-82. 29) pg/ml, Z = 2. 184, P = 0. 020]. CD8+T cell exhaustion was observed in ACLF patients, with the manifestations of reductions in the relative mRNA expression of perforin and granzyme B, increases in the percentages of PD-1+or CTLA-4+CD8+T cells, and reductions in the cytolytic ( induction of target cell death) and noncytolytic ( secretion of interferon-γ) functions of CD8+T cells ( all P < 0. 05) . After the stimulation with recombinant IL-35, both ACLF patients and healthy controls had significant reductions in the relative mRNA expression of perforin and granzyme B in CD8+T cells, significant increases in the percentages of PD-1+orCTLA-4+CD8+T cells, and significant reductions in the cytolytic and noncytolytic functions of CD8+T cells ( all P < 0. 05) . Conclusion Elevated IL-35 can suppress the cytolytic activity of CD8+T cells in ACLF patients, suggesting that IL-35 might induce the exhaustion of cellular immune function in ACLF patients.

Expression and clinical significance of CD38 and multiple myeloma oncogene 1 in autoimmune hepatitis
Jiang LiLin, Tang LinXin, Gu Juan, Lu ZhongHua, Tang Hong, Wang RuoFei
2019, 35(9): 2017-2020. DOI: 10.3969/j.issn.1001-5256.2019.09.026
Abstract:

Objective To investigate the expression of the leukocyte differentiation antigen CD38 and multiple myeloma oncogene 1 ( MUM-1) in liver biopsy tissue of patients with autoimmune hepatitis ( AIH) , as well as their roles in the development and progression of AIH. Methods Liver biopsy tissue samples from 46 AIH patients who were admitted to Department of Pathology in Wuxi Fifth People's Hospital from January 2017 to December 2018 were selected as experimental group, and normal liver tissue samples from 30 patients with gallbladder carcinoma who underwent radical treatment were selected as control group. Immunohistochemistry was used to measure the expression of CD38 and MUM-1, and an analysis was performed with reference to patients' clinical and pathological features. The Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups, the chi-square test was used for comparison of categorical data between groups, and a Spearman correlation analysis was also performed. Results The experimental group had significantly higher expression of CD38 and MUM-1 than the control group ( Z =-7. 181 and-7. 484, both P < 0. 001) . The AIH patients with inflammatory activity grade ≥3 and fibrosis stage 4 had significant increases in the expression of CD38 and MUM-1, with significantly higher expression than those with inflammatory activity grade < 3 and fibrosis stage < 4 ( χ2= 10. 085, 15. 769, 14. 988, and26. 966, all P < 0. 05) . The expression of CD38 and MUM-1 was positively correlated with chronic inflammatory activity grade and fibrosis stage ( r = 0. 552, 0. 876, 0. 603, and 0. 934, all P < 0. 001) , and CD38 was also positively correlated with MUM-1 ( r = 0. 932, P <0. 001) . Conclusion CD38 and MUM-1 are involved in the inflammatory activity of AIH and the process of fibrosis formation. There is a synergistic effect between them, which affects the process of liver cirrhosis. Therefore, they may become potential targets for diagnosis and treatment in future.

Association of nonalcoholic fatty liver disease with vitamin D and bone mineral density
Qu YuLei, Wang YingChun, Wan JinXin
2019, 35(9): 2021-2025. DOI: 10.3969/j.issn.1001-5256.2019.09.027
Abstract:

Objective To investigate the association of nonalcoholic fatty liver disease ( NAFLD) with vitamin D and bone mineral density.Methods A total of 180 patients with NAFLD who were hospitalized or visited the outpatient service of Zhongshan Hospital Affiliated to Dalian University from May 2018 to March 2019 were enrolled as NAFLD group, and 180 healthy individuals matched for age and sex who underwent physical examination were enrolled as control group. The two groups were compared in terms of vitamin D, bone mineral density, and biochemical markers for bone metabolism [β isomer of C-terminal telopeptide of type I collagen ( β-CTX) , type 1 procollagen amino terminal peptide ( P1 NP) , and osteocalcin ( OC) ]. The independent samples t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data. The chi-square test was used for comparison of categorical data between groups. A Spearman correlation analysis was performed, and a binary logistic regression analysis was used to investigate the risk factors for NAFLD. Results Compared with the control group, the NAFLD group had significantly lower levels of 25 ( OH) D [13. 06 ( 10. 73-19. 77) ng/ml vs 19. 88 ( 12. 56-22. 60) ng/ml, Z =-1. 37, P = 0. 041], L1-4 bone mineral density[0. 87 ( 0. 83-1. 05) g/cm2 vs 1. 05 ( 0. 92-1. 21) g/cm2, Z =-2. 17, P = 0. 034], bone mineral density of the femoral neck ( 0. 76 ±0. 21 g/cm2 vs 0. 84 ± 0. 51 g/cm2, t = 2. 02, P = 0. 015) , P1 NP [45. 40 ( 33. 35-58. 02) ng/ml vs 67. 39 ( 48. 09-87. 49) ng/ml, Z =-0. 83, P = 0. 044], and OC [14. 79 ( 11. 64-18. 87) ng/ml vs 17. 29 ( 15. 16-21. 04) ng/ml, Z =-2. 09, P = 0. 037], as wellas a significantly higher level of β-CTX [354. 75 ( 186. 32-526. 57) pg/ml vs 287. 67 ( 164. 10-497. 76) pg/ml, Z =-1. 04, P =0. 027]. Compared with those with alanine aminotransferase ( ALT) ≤2 × upper limit of normal ( ULN) , the NAFLD patients with ALT >2 × ULN had significantly lower levels of 25 ( OH) D ( 13. 51 ± 3. 20 ng/ml vs 18. 86 ± 3. 70 ng/ml, t = 3. 02, P = 0. 038) , L1-4 bone mineral density ( 0. 75 ± 0. 24 g/cm2 vs 1. 05 ± 0. 31 g/cm2, t = 2. 17, P = 0. 035) , and bone mineral density of the femoral neck ( 0. 71 ± 0. 18 g/cm2 vs 0. 82 ± 0. 21 g/cm2, t = 2. 25, P = 0. 042) . There were no significant differences in 25 ( OH) D, L1-4 bone mineral density, and bone mineral density of the femoral neck between the groups of patients with different degrees of fatty liver disease on CT ( all P > 0. 05) .Bone mineral density was positively correlated with high-density lipoprotein cholesterol ( r = 0. 232, P < 0. 05) and was negatively correlated with body mass index ( BMI) ( r =-0. 271, P < 0. 05) , blood glucose ( Glu) ( r =-0. 242, P < 0. 05) , ALT ( r =-0. 375, P < 0. 05) , aspartate aminotransferase ( r =-0. 312, P < 0. 05) , and low-density lipoprotein cholesterol ( r =-0. 247, P < 0. 05) . The logistic regression analysis showed that 25 ( OH) D ( odds ratio [OR] = 1. 113, 95% confidence interval [CI]: 1. 023-1. 210, P =0. 013) , BMI ( OR = 0. 676, 95% CI: 0. 522-0. 877, P = 0. 003) , and Glu ( OR = 0. 350, 95% CI: 0. 139-0. 882, P = 0. 026) were influencing factors for NAFLD. Conclusion Patients with NAFLD have significantly lower levels of vitamin D and bone mineral density than healthy individuals. An analysis of serum vitamin D and bone mineral density can further clarify the features of bone metabolism in NAFLD, and early screening of NAFLD with osteoporosis should be performed to improve the prognosis and quality of life of patients with NAFLD.

Value of microparticles in the diagnosis of nonalcoholic steatohepatitis
Chen Jun, Li LiangPing, Fu WanZhi
2019, 35(9): 2026-2031. DOI: 10.3969/j.issn.1001-5256.2019.09.028
Abstract:

Objective To investigate the value of plasma levels of microparticles ( MPs) derived from CD14+cells and invariant natural killer T ( iNKT) cells in the diagnosis of nonalcoholic steatohepatitis ( NASH) . Methods A total of 36 patients with nonalcoholic fatty liver disease ( NAFLD) who underwent liver biopsy in Department of Gastroenterology and Department of Hepatobiliary Surgery, Sichuan Provincial People's Hospital, from March to November 2015, were enrolled, and according to the activity score of NAFLD and fibrosis stage, the patients were divided into NASH group with 22 patients and non-NASH group with 14 patients. A total of 15 individuals, matched for age and sex, who underwent physical examination were enrolled as control group. Flow cytometry was used to measure the plasma levels of MPs derived from CD14+cells and iNKT cells in all subjects. The t-test was used for comparison of normally distributed continuous data between groups; the t-test was used for comparison of non-normally distributed continuous data which became normally distributed after logarithmic transformation between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The chi-square test was used for comparison of categorical data between two groups. An analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. The Pearson correlation analysis was used to investigate the correlation between two variables, and the receiver operating characteristic ( ROC) curve was used to evaluate the diagnostic value of MP. Results Compared with the control group, the NAFLD group had significantly higher plasma levels of MPs from CD14+cells ( 5. 92 ± 0. 62 cells/μl vs 4. 52 ± 0. 42 cells/μl, t =7. 160, P < 0. 001) and MPs from iNKT cells ( 4. 38 ± 0. 51 cells/μl vs 3. 79 ± 0. 28 cells/μl, t = 3. 966, P < 0. 001) . Compared with thenon-NASH group, the NASH group had significantly higher plasma levels of MPs from CD14+cells ( 6. 25 ± 0. 48 cells/μl vs 5. 44 ± 0. 49 cells/μl, t = 4. 773, P < 0. 001) and MPs from iNKT cells ( 4. 70 ± 0. 39 cells/μl vs 3. 96 ± 0. 26 cells/μl, t = 6. 544, P < 0. 001) . There were significant differences in the plasma levels of MPs from CD14+cells and iNKT cells between the three groups ( F = 61. 039 and42. 285, both P < 0. 05) ; the NASH group had significantly higher plasma levels of MPs than the non-NASH group and the control group, and the non-NASH group had significantly higher plasma levels of MPs than the control group ( all P < 0. 05) . The plasma levels of MPs from CD14+cells and iNKT cells were positively correlated with NAFLD activity score ( r = 0. 697 and 0. 793, both P < 0. 001) . MPs from CD14+cells had an area under the ROC curve ( AUC) of 0. 886 ( 95% confidence interval [CI]: 0. 750-1. 000, P < 0. 001) in the diagnosis of NASH, with a sensitivity of 90. 9% and a specificity of 85. 6%; MPs from iNKT cells had an AUC of 0. 935 ( 95% CI: 0. 822-1. 000, P < 0. 001) , with a sensitivity of 81. 8% and a specificity of 92. 9%. Conclusion There are increases in the plasma levels of MPs from CD14+cells and iNKT cells in patients with NASH, which are positively correlated with the degree of liver inflammation, and therefore, they can be used as potential noninvasive indices for liver inflammation.

Original articles_Analysis and evaluation on journal
An analysis of the bibliometric indicators and academic influence of Journal of Clinical Hepatology in 2011-2018
Gao Ge, Zhu Jing, Li Ri, Lun ZhiJun, Xing XiangYu
2019, 35(9): 2032-2039. DOI: 10.3969/j.issn.1001-5256.2019.09.029
Abstract:
Objective To evaluate the quality and academic influence of Journal of Clinical Hepatology through a statistical analysis of the bibliometric indicators and assessment indices of this journal in 2011-2018. Methods The data for the bibliometric analysis were obtained from CNKI Chinese Citation Database. The search was performed on June 10, 2019, and citations up to December 31, 2018 were included in analysis. Citations and distributions of articles, authors, institutions, and funds were analyzed based on the following indicators: number of published articles, number of citations, citation rate, citation frequency, and average citation frequency per article. The data for the analysis of assessment indices were obtained from Chinese Science and Technology Journal Citation Reports ( Core version) published by Institute of Scientific and Technical Information of China in 2011-2018, and six important assessment indices were extracted, i. e., total citation frequency, core impact factor, overall evaluation score, subject diffusion index, subject impact index, and red point factor, to determine the ranking of Journal of Clinical Hepatology among Chinese Core Journals of Science and Technology and journals in gastroenterology and hepatology. Results In 2011-2018, a total of 2523 articles were published in the regular columns of Journal of Clinical Hepatology ( Original Article, Case Report, and Review) , with 26. 28 articles per issue, and among these articles, 1489 were original articles, accounting for the highest percentage of 59. 02%. As for featured columns ( Commentary/Expert Forum, Guidelines and Standards, and A Brief Introduction of High-quality Articles in Foreign Journals) , 546 articles were published in Commentary/Expert Forum, with 94 in Commentary and 452 in Expert Forum, and the topics of these articles covered internal medicine and surgery for hepatic, biliary, and pancreatic diseases in tradi-tional Chinese medicine and Western medicine; 301 articles were published in Guidelines and Standards, among which Guidelines for the prevention and treatment of chronic hepatitis B ( 2015) had the highest citation frequency of 584; 527 articles were published in A Brief Introduction of High-quality Articles in Foreign Journals, and the excerpts mainly came from top foreign journals in related fields. According to Chinese Science and Technology Journal Citation Reports ( Core version) published in 2011-2018, the total citation frequency of Journal of Clinical Hepatology increased from 626 to 2556 by 308. 31%; the ranking of this journal among Chinese Core Journals of Science and Technology increased from 993 rd to 257 th by 286. 38%, with an average annual increase of 105, and the ranking among the journals in gastroenterology and hepatology increased from 9 th to 1 st. The core impact factor of this journal increased from 0. 35 to 1. 401 by 300. 29%; the total ranking increased 1103 rd to 128 th by 761. 72%, with an average annual increase of 139 places, and the subject ranking increased from11 th to 2 nd. The overall evaluation score of this journal increased from 29. 3 to 69. 2; the total ranking increased from 1292 nd to 155 th by733. 55%, with an average annual increase of 162 places, and the subject ranking increased from 11 th to 2 nd. Conclusion The overall quality of the articles published in Journal of Clinical Hepatology kept increasing in 2011-2018, and the influence of this journal is gradually expanded. This journal ranks in the top places among the core journals in medicine and gastroenterology & hepatology and acts as an important platform for guiding disciplinary development, increasing academic communication, and promoting academic exchange.
Case reports
Atypical multiple cavernous hemangiomas of the liver misdiagnosed as liver cancer: A case report
You LiPing, Zheng Chao, Zhang JingHao, Wu Mei, Sun XueHua
2019, 35(9): 2040-2041. DOI: 10.3969/j.issn.1001-5256.2019.09.030
Abstract:
Primary liver cancer with gastric signet ring cell carcinoma: A case report
Zhu ZeMin, Xie ZhiQin, Zhao ZhiJian, Li HongXia, Wang JinWen, Tang CaiXi
2019, 35(9): 2042-2044. DOI: 10.3969/j.issn.1001-5256.2019.09.031
Abstract:
Primary liver cancer with autoimmune encephalitis: A case report
Zhao Jing, Fang XingGuo, Li GuoYan, Zhang HongFei, Zhong JiangLi, Du ShengQi, Wang Hong
2019, 35(9): 2045-2047. DOI: 10.3969/j.issn.1001-5256.2019.09.032
Abstract:
Severe radiation-induced gastritis after radiotherapy for hepatocellular carcinoma: A case report
Li ShanShan, Chen Yu
2019, 35(9): 2048-2049. DOI: 10.3969/j.issn.1001-5256.2019.09.033
Abstract:
Acute-on-chronic liver failure with severe bone marrow suppression: A case report
Lai ZhangXiang, Wang Fang, Wang Song, Li ZhiYu
2019, 35(9): 2050-2053. DOI: 10.3969/j.issn.1001-5256.2019.09.034
Abstract:
Primary sclerosing cholangitis with elevated IgG4 levels: A case report
Chen QingLing, Zhong Rui, Fang YiNa, Zhang XiaoXue, Feng LiNa, Yang QianQian, Wen XiaoYu, Jin QingLong
2019, 35(9): 2054-2056. DOI: 10.3969/j.issn.1001-5256.2019.09.035
Abstract:
Primary biliary cholangitis with myelofibrosis: A case report
Yang QianQian, Ren TianQi, Xue ShuWen, Chen QingLing, Feng LiNa, Zhang XiaoXue, Wen XiaoYu, Jin QingLong
2019, 35(9): 2057-2058. DOI: 10.3969/j.issn.1001-5256.2019.09.036
Abstract:
Early treatment of PBC-AIH overlap syndrome with histological remission: A case report
Wang Jing, Zhao LiLi, Shi RuiFang, Liu YongGang, Li Jia
2019, 35(9): 2059-2061. DOI: 10.3969/j.issn.1001-5256.2019.09.037
Abstract:
Gleevec for treatment of chronic myeloid leukemia with primary biliary cholangitis: A case report
Wang ZhiYi, Xu ChunFang
2019, 35(9): 2062-2063. DOI: 10.3969/j.issn.1001-5256.2019.09.038
Abstract:
Recurrence of autoimmune pancreatitis with herpes zoster: A case report
Feng LiNa, Zhang XiaoXue, Kui YiWen, Yang QianQian, Chen QingLing, Wen XiaoYu, Jin QingLong
2019, 35(9): 2064-2066. DOI: 10.3969/j.issn.1001-5256.2019.09.039
Abstract:
Reviews
Research advances in the role of oxidative stress in the development and progression of liver fibrosis
Zhao Jie, Qi YongFen, Yu YanRong
2019, 35(9): 2067-2071. DOI: 10.3969/j.issn.1001-5256.2019.09.040
Abstract:
Liver fibrosis is a wound-healing response and is fibrous connective tissue deposition due to chronic liver injury caused by various pathogenic factors, and without timely treatment, it may progress to life-threatening diseases such as liver cirrhosis and even liver cancer. Hepatic stellate cells are transformed into myofibroblasts after activation and then secret a large amount of extracellular matrix, which is the most important pathological feature of liver fibrosis. More and more evidence has shown that oxidative stress plays an important role in the development and progression of liver fibrosis, and oxidative stress is involved in liver fibrosis caused by various diseases. In most cases, oxidative stress interacts with other factors to promote the pathophysiological process of liver fibrosis. Therefore, this article reviews the research advances in the influence of oxidative stress on liver fibrosis and its interaction with other factors such as inflammation, apoptosis, and autophagy.
Role of liver sinusoidal endothelial cells in liver regeneration and the development of liver fibrosis
Yu ZiYue, Lin Xin, Han Ying, Cui LiNa
2019, 35(9): 2072-2074. DOI: 10.3969/j.issn.1001-5256.2019.09.041
Abstract:
As a main population of liver nonparenchymal cells, liver sinusoidal endothelial cells ( LSECs) are thin-layer flattened cells lining the hepatic sinusoid, and the fenestrae on the surface are channels for the exchange of plasma and nutrients between the hepatic sinusoid and hepatocytes. The secretion function of LSECs, especially the Wnt signaling pathway, plays an important protective effect on self-renewal of Axin2+-derived hepatocytes and liver regeneration after partial hepatectomy or liver injury. The structure of LSECs changes during liver injury, including the disappearance of fenestra and the formation of basement membrane, which is also known as hepatic sinusoidal capillarization. Hepatic sinusoidal capillarization is the starting point for liver fibrosis and also promotes the progression of liver fibrosis. The switch of the regulatory effect of LSECs in liver regeneration and liver fibrosis can be realized via signaling pathways under different physiological or pathological conditions. A deep understanding of the mechanism of action of LSECs in liver regeneration and liver fibrosis is expected to provide new therapeutic targets for the prevention and treatment of chronic liver diseases.
Application of serological markers in noninvasive assessment of cirrhotic portal hypertension
Xiao Peng, Zhang YaNan, Ba TaoTao, Ding MengMeng, Gao YanHang
2019, 35(9): 2075-2078. DOI: 10.3969/j.issn.1001-5256.2019.09.042
Abstract:
The most common cause of portal hypertension is liver cirrhosis due to various reasons. When portal venous pressure reaches a certain level, serious clinical complications can endanger patient's life, such as splenomegaly, ascites, hepatic encephalopathy, and esophageal variceal bleeding. Therefore, diagnosis and evaluation of portal hypertension is crucial for the diagnosis of patients with compensated cirrhosis and the treatment and prognosis of patients with decompensated cirrhosis. As the gold standard for the evaluation of portal hypertension, hepatic venous pressure gradient is invasive and highly expensive, and thus noninvasive evaluation of portal hypertension has become a research hotspot in recent years. Noninvasive evaluation of portal hypertension based on serological markers is simple, easy, and reproducible, and such serological markers have attracted more and more attention. With in-depth studies on the pathogenesis of cirrhotic portal hypertension, there is an increasing number of studies on serological markers, mainly including pro-inflammatory cytokines, extracellular matrix components, and their cyclic degradation products. This article summarizes and elaborates on the research advances in the role of serological markers in noninvasive assessment of portal hypertension, in order to provide help for early and convenient diagnosis of portal hypertension.
Current status of the diagnose and treatment of spontaneous bacterial peritonitis
Li BeiLing, Zhong GuoTao, Chen JinJun
2019, 35(9): 2079-2081. DOI: 10.3969/j.issn.1001-5256.2019.09.043
Abstract:
Infection is a common complication in patients with liver cirrhosis, and spontaneous bacterial peritonitis ( SBP) is the most common type of infection. This article summarizes the formation process of the diagnostic criteria of SBP based on a number of multinuclear cells of > 250 cells/μl in ascites, limitations of ascites cell counting, and the current status of the treatment of SBP. It is pointed out that novel biomarkers with high sensitivity are needed for the diagnosis of SBP diagnose, in order to guide empirical antimicrobial treatment and optimize the management of patients with SBP in clinical practice.
Regulatory role of microRNA in aerobic glycolysis in hepatocellular carcinoma
Niu YaQian, Chang YuLing, Liu Fang, Zhao Chuan, Chen Che
2019, 35(9): 2082-2084. DOI: 10.3969/j.issn.1001-5256.2019.09.044
Abstract:
Glucose metabolism recombination is an important marker of hepatocellular carcinoma ( HCC) , and cancer cells can quickly adjust their energy sources from mitochondrial oxidative phosphorylation to glycolysis to meet the need of efficient proliferation in the hypoxic environment. In recent years, more and more studies have shown that post-transcriptional regulation of microRNAs ( miRNAs) plays a key role in the fine regulation of metabolic reprogramming, which is closely associated with the clinicopathological features, development, and progression of HCC. There are various influencing factors for glycolysis, and therefore, this article reviews the influence of abnormal expression of miRNAs on the direct and indirect regulation of aerobic glycolysis in HCC, in order to provide a theoretical basis for the early diagnosis, targeted treatment, and prognostic evaluation of HCC.
Epidemiology of nonalcoholic fatty liver disease and related risk factors
Shu YunRan, Li JunQi, Liu Qiong
2019, 35(9): 2085-2090. DOI: 10.3969/j.issn.1001-5256.2019.09.045
Abstract:
The earliest epidemiological studies of nonalcoholic fatty liver disease ( NAFLD) were mainly conducted in Western countries, while more and more studies have shown that NAFLD is very common in the Asia-Pacific region and that there may be great differences in phenotype between the Asia-Pacific and Western countries. Obesity, dyslipidemia, and type 2 diabetes have been shown to be the risk factors for the development of NAFLD. Meanwhile, Western countries have described many other risk factors for NAFLD, such as hypothyroidism, polycystic ovary syndrome, obstructive sleep apnea syndrome, hypopituitarism, and hypogonadism, but these factors have not yet been found to be associated with NAFLD in the Asia-Pacific region.
Association between nonalcoholic fatty liver disease and colorectal tumors
Liu SiFu, Xie ZhengYuan
2019, 35(9): 2091-2094. DOI: 10.3969/j.issn.1001-5256.2019.09.046
Abstract:
Recent studies have shown that nonalcoholic fatty liver disease ( NAFLD) is the manifestation of metabolic syndrome in the liver and is associated with the factors which promote colorectal neoplasia, such as obesity, insulin resistance, hypertension, and hyperlipidemia.This article points out that NAFLD is closely associated with the development and progression of colorectal tumors and summarizes the association between NAFLD and colorectal tumors and possible mechanisms. It is pointed out that NAFLD and colorectal tumors share certain clinical features and pathogenesis, which provides a theoretical basis for future research in this field.
Research advances in the role of the TNF-α/NF-κB signaling pathway in the regulation of nonalcoholic fatty liver disease
Sun TingTing, Li JingTao, Wei HaiLiang, Yan ShuGuang, Li Qian, Guo YingJun, Chang ZhanJie
2019, 35(9): 2095-2098. DOI: 10.3969/j.issn.1001-5256.2019.09.047
Abstract:
Tumor necrosis factor-α ( TNF-α) can induce liver inflammation and promote hepatocyte degeneration and necrosis, and as an important transcription regulator, nuclear factor-κB ( NF-κB) can promote hepatic steatosis in nonalcoholic fatty liver disease ( NAFLD) .The TNF-α/NF-κB signaling pathway promotes the development of NAFLD under the stimulation of various signals. This article discusses the mechanism of action of the TNF-α/NF-κB signaling pathway in NAFLD, so as to provide new therapeutic targets for patients with NAFLD.
Research advances in vitamin K1 in treatment of coagulopathy of liver failure
Xiong Zhuang, Liu YangYang, Huo ShaoKai, Gong JiaLian, Jin TianYi, Wang Qiang, Wang HuiLin, Liu TieJun, Leng Yan
2019, 35(9): 2099-2103. DOI: 10.3969/j.issn.1001-5256.2019.09.048
Abstract:
Liver failure is a type of liver injury caused by a variety of factors, and there are still controversies over the clinical effect of vitamin K1 in the treatment of coagulopathy of liver failure. This article reviews the guidelines for the diagnosis and treatment of liver failure in various countries and the articles on vitamin K1 in the treatment of coagulopathy of liver diseases. It is concluded that blind application of vitamin K1 cannot improve the coagulation function of patients with liver disease; however, vitamin K1 is necessary for patients with vitamin K deficiency and coagulopathy during liver failure. In addition, the state of cholestasis may be considered an independent factor, but further studies are needed for verification.
Research advances in mesenchymal stem cells in treatment of end-stage liver disease and their application prospect
Zhang YiTong, Xin Lei, Li ZhaoShen
2019, 35(9): 2104-2107. DOI: 10.3969/j.issn.1001-5256.2019.09.049
Abstract:
End-stage liver disease is the end point of various progressive liver diseases and has high mortality, which greatly threatens human health. Recent studies in China and foreign countries have shown that mesenchymal stem cell ( MSC) transplantation is a safe and effective treatment method for end-stage liver disease. This article summarizes the animal experiments, clinical trials, and basic research in this field and discusses the feasible strategies to enhance the clinical effect of MSCs and the application prospect of MSCs.
Research advances in the mechanism of drug-induced liver injury due to paracetamol
Yu PengFei, Wu Qiao, Duan ZhongPing, Chen Yu
2019, 35(9): 2108-2112. DOI: 10.3969/j.issn.1001-5256.2019.09.050
Abstract:
Drug-induced liver disease, also known as drug-induced liver injury ( DILI) , is the second largest cause of non-infectious liver disease in China and the leading cause of liver failure or liver transplantation in the United States. DILI is classified into idiosyncratic and dose-dependent DILI. Idiosyncratic DILI is currently not predictable in preclinical safety studies, while dose-dependent hepatotoxicity due to most drugs can be identified in preclinical safety studies, and thus these drugs are not used in clinical practice. One notable exception is paracetamol ( APAP) , which is safe within therapeutic dose, but an overdose of this drug may cause severe liver injury and even acute liver failure. APAP overdose is the major cause of acute liver failure in developed countries in Europe and America. Therefore, further clarification of cellular and molecular mechanisms of DILI due to APAP, especially the mechanism of hepatocyte death, may help with the early identification of risk factors for acute liver failure and poor prognosis and the development of treatment targets and regimens to block the progression of liver injury.
Research advances in liver injury induced by programmed death protein-1 inhibitors
Yan Qi, Song LiSha, Xin GuiJie
2019, 35(9): 2113-2115. DOI: 10.3969/j.issn.1001-5256.2019.09.051
Abstract:
With the application of programmed cell death-1 ( PD-1) inhibitors in tumor treatment, related side effects and immune-related adverse events ( irAEs) are observed in the whole body; however, there are few studies on liver injury in irAEs. This article elaborates on the features of liver injury induced by PD-1 inhibitors from the aspects of molecular mechanism, disease grade, incidence rate, onset time, serology, histology, imaging, and biomarkers and related treatment methods, so as to provide a comprehensive understanding of liver injury in irAEs. It is believed that although there is a low incidence rate of liver injury caused by PD-1 inhibitors, high-grade liver injury has a high level of risk. Such liver injury should be taken seriously by the medical staff, and early identification and proper treatment should be performed.
Research advances in the genotype-phenotype correlation, diagnosis, treatment, and screening of Wilson's disease
Liang Chen, Bai Li, Zheng SuJun
2019, 35(9): 2116-2119. DOI: 10.3969/j.issn.1001-5256.2019.09.052
Abstract:
Wilson's disease ( WD) is a treatable hereditary disease, and its pathological basis is the deposition of a large amount of copper in the liver, the brain, and other organs due to copper metabolic disorder caused by ATP7 B gene mutation. The clinical manifestation of WD varies greatly among patients, and common features of this disease include progressive liver disease and neurological symptoms. Different mutation sites of the ATP7 B gene are observed in different regions. Correlation between ATP7 B genotype and clinical manifestation of WD can help to predict the onset, type, and severity of WD, but there are still controversies over the current research findings. At present, Leipzig score is widely accepted as the diagnostic criteria for WD, and a patient can be diagnosed with WD when Leipzig score is greater than or equal to 4. The treatment of WD aims to reduce copper overload by different mechanisms, and effective treatment methods include drug therapy, liver transplantation, and plasma exchange. Patients with early diagnosis and treatment tend to have good prognosis, and therefore, it is of great significance to carry out WD screening among the direct relatives of WD proband.
Research advances in the role of gut microbiota in liver diseases
Wang DanDan, Song Jia, Zhang XiaoLan
2019, 35(9): 2120-2123. DOI: 10.3969/j.issn.1001-5256.2019.09.053
Abstract:
Intestinal dysbacteriosis is an important pathogenic factor for liver diseases. There exists a gut-liver axis between the gut and the liver, which helps with the interactions between these two organs. The liver is an important immune organ, and after being exposed to intestinal bacteria and their metabolites via the portal vein, the liver may activate innate immunity and adaptive immunity, which may lead to liver injury. As an important component of the gut-liver axis, gut microbiota is not only a triggering factor but also a potential therapeutic target for liver diseases. This article elaborates on the association between gut microbiota and liver diseases and points out that in-depth studies should be performed to explore the mechanism of action of gut microbiota and their metabolites in liver disease and further clarify the physiopathological role of gut-liver axis, in order to provide a basis for the prevention and treatment of liver diseases.
Role of type 2 innate lymphoid cells in immunoregulation of liver diseases
Han Jing, Guo JinBo, Zhang XiaoLan
2019, 35(9): 2124-2128. DOI: 10.3969/j.issn.1001-5256.2019.09.054
Abstract:
Innate lymphoid cells ( ILCs) are a new type of innate immune cells discovered in recent years, and type 2 ILCs ( ILC2 s) are a subset of ILCs and can produce type 2 T-helper cytokines after being activated by interleukin-25 and interleukin-33, which helps to start and maintain type 2 immune response. ILC2 s belong to innate immune cells and can regulate adaptive immunity and participate in various pathophysiological processes such as inflammation, tissue repair, cell proliferation, metabolism, and immunoregulation. The liver is recognized as an important metabolic and immune organ in the human body and contains several types of immune cells. ILC2 s can regulate immune response, inflammation, and tissue repair in liver diseases. This article summarizes the physiological function of ILC2 s and the immunomodulatory mechanism of ILC2 s in liver disease.