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

2018 No. 6

Display Method:
Editorial
Research advances in drug-induced liver injury and existing problems in China
Chen ChengWei
2018, 34(6): 1147-1151. DOI: 10.3969/j.issn.1001-5256.2018.06.001
Abstract:
At present, Drug-induced liver injury (DILI) has become the most common cause of acute liver injury in clinical practice. This article elaborates on the pathogenesis of DILI, new biomarkers, liver tolerance to drug toxicity, adaptability and susceptibility, and testing threshold of alanine aminotransferase. Meanwhile, we should understand the development history of diagnostic scale, develop unified standards and understanding, and attach importance to DILI induced by medicinal herbs and dietary supplements, and in-depth studies on the pathogenesis of DILI should be performed to prevent or reduce DILI. There are several problems in DILI studies in China and obvious gaps between China and foreign countries, with a lack of basic research and blanks in clinical aspects. Therefore, we must strive to keep up with international research so that drugs can better serve the human.
Discussions by experts
Current status of epidemiological studies on drug-induced liver injury in China
Shen Tao, Huang Xin, Wang YuYa, Zhuang Hui
2018, 34(6): 1152-1155. DOI: 10.3969/j.issn.1001-5256.2018.06.002
Abstract:
Drug-induced liver injury (DILI) has been taken more and more seriously by governmental authorities, pharmaceutical companies, clinical physicians, and the general public. An understanding of the incidence, and distribution of DILI and related drugs is helpful for the prevention, clinical diagnosis, and treatment of DILI and may also help the government to perfect related laws and regulations and reduce the incidence of adverse drug reactions. This article reviews the epidemiology of DILI in China.
Differential diagnosis of drug-induced liver injury and autoimmune hepatitis and related therapeutic strategies
Bian ZhaoLian, Shao JianGuo, Ma Xiong
2018, 34(6): 1156-1159. DOI: 10.3969/j.issn.1001-5256.2018.06.003
Abstract:
Drug-induced liver injury (DILI) and autoimmune hepatitis (AIH) have many similar clinical and histological manifestations, which brings difficulties to clinicians in differential diagnosis. This article elaborates on the association between DILI and AIH and their similarities and differences in clinical and histological manifestations, in order to help clinicians with the differential diagnosis of DILI and AIH.This article reviews the selection of therapeutic regimens for DILI and AIH and introduces how to select therapeutic strategies based on patient conditions and make a definite diagnosis when there are difficulties in differential diagnosis.
Diagnosis and treatment of drug-induced liver injury
Yu LeCheng, Fan Ye, Chen ChengWei
2018, 34(6): 1160-1165. DOI: 10.3969/j.issn.1001-5256.2018.06.004
Abstract:
Due to a lack of specific biomarkers, the diagnosis of drug-induced liver injury (DILI) mainly depends on the method of exclusion. The Roussel Uclaf Causality Assessment Method (RUCAM) scale is the most widely used causality assessment scale and is relatively objective, but it is still waiting for further improvement. Another method is global introspection or expert opinion, which is relatively subjective, and the simplified global introspection method is commonly used in clinical practice. The Structured Expert Opinion Procedure (SEOP) created by the US DILI network (DILIN) is very complicated and time-consuming and thus cannot be used in clinical practice. The drug rechallenge test (DRT) with a positive result is considered the gold standard for the diagnosis of DILI, but DILI cannot be excluded based on the negative result of DRT. The value of lymphocyte transformation test (LTT) , modified LTT, monocyte-derived hepatocyte-like cell lactate-dehydrogenase release test, and various predictive models for drug hepatotoxicity in the diagnosis of DILI awaits further assessment.The differential diagnosis of autoimmune-mediated DILI and traditional autoimmune liver diseases usually depends on liver biopsy, the type and titer of autoantibody, and response to glucocorticoids. Reasonable timing of drug withdrawal and application of anti-inflammatory liver-protecting drugs may help most DILI patients recover. Generally, the prophylactic use of anti-inflammatory liver-protecting drugs is not recommended, except in special situations. In-depth studies are needed for the precise diagnosis and prevention/treatment of DILI.
Strengthening the scientific research and supervision of drug-induced liver injury based on big data
Mao YiMin
2018, 34(6): 1166-1168. DOI: 10.3969/j.issn.1001-5256.2018.06.005
Abstract:
Drug-induced liver injury (DILI) is one of the most important drug-induced diseases and has complex clinical phenotypes, which leads to its unpredictability. The involvement of many types of drugs and complex population heterogeneity pose great challenges to the supervision of scientific research on DILI. Most of our knowledge of DILI comes from the international databases of long-term follow-up.However, there are still many unmet clinical needs in the field of DILI. Strengthening the scientific research on drug-induced liver injury based on big data helps us to understand DILI better and it is the premise for scientific supervision.
Drug-induced liver injury caused by Chinese herbal medicine cannot be neglected
Chen Jun
2018, 34(6): 1169-1171. DOI: 10.3969/j.issn.1001-5256.2018.06.006
Abstract:
The hepatotoxicity of Chinese herbal medicine has attracted more and more attention in recent years. The traditional view that Chinese herbs are poisonless and harmless is worth considering. According to related research findings, liver injury due to the abuse of Chinese herbs caused by prescriptions from unqualified physicians is high retention. This paper summarizes the common Chinese medicine causing liver injury, the pathologic types and clinical characteristics of liver injury induced by Chinese medicine, to explore the possible causes of liver injury induced by Chinese herbs. It is recommended to strengthen the management of traditional Chinese medicine prescriptions and prevent the abuse of Chinese materia medica. Liver injury induced by Chinese herbs should be taken seriously.
Significance of liver histopathological examination in diagnosis and treatment of drug-induced liver injury
Yang RuiYuan, Zhao XinYan
2018, 34(6): 1172-1175. DOI: 10.3969/j.issn.1001-5256.2018.06.007
Abstract:
The incidence rate of drug-induced liver injury (DILI) tends to increase in recent years, and early accurate diagnosis and evaluation of the degree of liver injury are great challenges in diagnosis and treatment. The pathomorphological features of DILI are determined by the structure and metabolic features of hepatic lobules. The basis of pathological injury pattern is injury of related targets, i. e., hepatocytes, biliary epithelium, and blood vessel endothelium, which determines the distinct features of DILI. Although DILI has various pathological features, it has major injury patterns of acute hepatitis type, chronic hepatitis type, acute cholestatic type, chronic cholestatic type, and cholestatic hepatitis type. The degree of the pathological injury of DILI is associated with the disease severity and prognosis of patients, and pathology helps to identify small bile duct injury and vascular endothelial injury caused by drugs as early as possible. The liver histological features of DILI overlap with other diseases, and related clinical indices should be used to make an objective, accurate, and timely diagnosis of DILI. This article reviews the pathomorphological features and patterns of DILI and elaborates on the significance of liver histological examination in the diagnosis and treatment of DILI.
Guidelines
Consensus on the management of hepatitis B virus infection in women of childbearing age
Chinese Society of Hepatology, Chinese Medical Association
2018, 34(6): 1176-1180. DOI: 10.3969/j.issn.1001-5256.2018.06.008
Abstract:
An excerpt of diagnosis, staging and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases
Zheng KeXin, Han Bing, Qi XingShun, Guo XiaoZhong
2018, 34(6): 1181-1182. DOI: 10.3969/j.issn.1001-5256.2018.06.009
Abstract:
Recommendations for EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma (2018)
Yu JiongJie, Yan WenTao, Quan Bing, Yang Tian
2018, 34(6): 1183-1186. DOI: 10.3969/j.issn.1001-5256.2018.06.010
Abstract:
Interpretation of EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma (2018)
Ge NingLing, Xue TongChun, Ye ShengLong
2018, 34(6): 1187-1190. DOI: 10.3969/j.issn.1001-5256.2018.06.011
Abstract:
Recommendations for The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines (2018)
Li QianQian, Zhou XinMiao, Qi XingShun, Li HongYu
2018, 34(6): 1191-1192. DOI: 10.3969/j.issn.1001-5256.2018.06.012
Abstract:
An excerpt of European evidence-based guidelines on pancreatic cystic neoplasms (2018)
Guan Fu, Hu JuXiang, Wang FuQun, Wang ShengBing
2018, 34(6): 1193-1197. DOI: 10.3969/j.issn.1001-5256.2018.06.013
Abstract:
Original articles_Viral hepatitis
Influencing factors for low response to hepatitis B vaccination in neonates
Wen SiMin, Wang Chong, Pan YuChen, Zhao Dan, Wang Chuan, Kong Fei, Niu JunQi, Jiang Jing
2018, 34(6): 1198-1203. DOI: 10.3969/j.issn.1001-5256.2018.06.014
Abstract:
Objective To investigate the influencing factors for low response to hepatitis B (Hep B) vaccination in neonates born to HBs Ag-positive mothers. Methods A total of 1152 neonates born to HBs Ag-positive mothers who participated in the project of prevention of mother-to-child transmission of HBV from July 2012 to July 2015 were enrolled. After 96 neonates were excluded, 1056 neonates were included in the final analysis, including 714 neonates born to HBs Ag-positive/HBe Ag-negative mothers and 342 neonates born to HBs Ag-positive/HBe Ag-positive mothers. These two groups of neonates were given immunization at different doses, i. e., 10 μg or 20 μg Hep B derived in Saccharomyces cerevisiae and 100 IU hepatitis B immunoglobulin within 2 hours after birth, followed by the injection of 10 μg or20 μg Hep B at the ages of 1 and 6 months. Venous blood samples were collected at one month after the last immunization to measure the levels of HBs Ag and anti-HBs. The neonates with anti-HBs < 100 m IU/ml were classified as low responders, and those with anti-HBs ≥100 m IU/ml were classified as high responders. The two-independent-samples t test was used for comparison of continuous data between groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. An unconditional logistic regression analysis was used to identify the influencing factors for low response to Hep B in neonates. An analysis of covariance was used for comparison of the level of anti-HBs between groups. Results Compared with the 20 μg group, the 10 μg group had a significantly higher rate of low response (5. 7% vs 2. 0%, χ2= 7. 278, P = 0. 007) , significantly lower maternal HBV DNA load [ (2. 90 ± 1. 50) log10 IU/ml vs (7. 73 ± 1. 07) log10 IU/ml, t =-50. 297, P < 0. 001) ]and proportion of the mothers who received antiviral therapy during pregnancy (0. 7% vs 7. 0%, χ2= 34. 552, P < 0. 001) , and a significantly higher rate of preterm birth (3. 2% vs 1. 2%, χ2= 3. 907, P =0. 048) . The 10 μg group had a significantly lower proportion of neonates with artificial feeding than the 20 μg group (37. 8% vs 66. 4%, χ2= 75. 703, P < 0. 001) . In the 10 μg group, the unconditional logistic regression analysis showed that preterm birth (odds ratio [OR]=3. 31, 95% confidence interval [CI]: 1. 05-10. 40, P < 0. 05) and artificial feeding (OR = 2. 67, 95% CI: 1. 38-5. 07, P < 0. 05) were independent risk factors for low response to Hep B vaccination. The analysis of covariance showed that compared with the full-term infants, the preterm infants had a significantly lower level of anti-HBs (P = 0. 004) ; compared with those given breastfeeding or mixed feeding, the neonates given artificial feeding had a significantly lower level of anti-HBs (P = 0. 001) . In the 20 μg group, no maternal factors or infantile factors were found to be associated with the response to Hep B vaccination (all P > 0. 05) . Conclusion Preterm birth and artificial feeding are risk factors for low response to Hep B vaccination in neonates. Identification of neonates at risk of low response to Hep B vaccination will provide a basis for developing individualized Hep B vaccination schemes.
Original articles_Liver fibrosis and liver cirrhosis
Value of gamma-glutamyl transpeptidase-to-platelet ratio in predicting liver fibrosis stage in chronic hepatitis B patients in Guangdong, China
Huang ChunMing, Yang Zhan, Nie YuQiang, Hu ZhongWei, Zhou YongJian, Zhan YuanJing, Guo JiaWei, Yu WeiHua
2018, 34(6): 1204-1208. DOI: 10.3969/j.issn.1001-5256.2018.06.015
Abstract:
Objective To investigate the value of gamma-glutamyl transpeptidase-to-platelet ratio (GPR) in predicting liver fibrosis stage in chronic hepatitis B (CHB) patients in Guangdong, China. Methods A total of 501 patients who were diagnosed with CHB by liver biopsy in Guangzhou 8 th People's Hospital from January 2010 to December 2016 were enrolled, among whom 335 had HBe Ag-positive CHB and 166 had HBe Ag-negative CHB. The value of GPR, gamma-glutamyl transpeptidase (GGT) , aspartate aminotransferase-to-platelet ratio index (APRI) , and fibrosis-4 (FIB-4) in predicting liver fibrosis stage (F1-F4) was analyzed. The Spearman correlation coefficient was used to analyze the correlation between diagnostic models and liver fibrosis stage, and the area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the value of each model in predicting liver fibrosis stage. Results With liver biopsy as the gold standard, of all patients, 141 had F1 stage, 183 had F2 stage, 139 had F3 stage, and 38 had F4 stage disease. The Spearman correlation analysis showed that in HBe Ag-positive and HBe Ag-negative patients, GGT, GPR, APRI, and FIB-4 were positively correlated with liver fibrosis stage (r = 0. 459, 0. 526, 0. 320, 0. 470, 0. 272, 0. 366, 0. 288, and 0. 388, all P < 0. 001) , and platelet count (PLT) was negatively correlated with liver fibrosis stage (r =-0. 333 and-0. 349, both P < 0. 001) . The ROC curve analysis showed that compared with GGT and APRI, GPR had a significantly better value in predicting marked fibrosis (≥F2) , advanced fibrosis (≥F3) , and early cirrhosis (F4) (all P < 0. 05) in HBe Ag-positive CHB patients, and GPR had a similar predictive value as FIB-4 (P > 0. 05) ; in HBe Ag-negative CHB patients, GPR had a significantly better value in predicting marked fibrosis (≥F2) than GGT and APRI (both P <0. 05) and a significantly better value in predicting advanced fibrosis (≥F3) than GGT (P < 0. 05) , while GPR had a similar value as GGT, APRI, and FIB-4 in predicting early cirrhosis (F4) (all P > 0. 05) . Conclusion GPR can be used as a noninvasive biochemical index for liver fibrosis stage in CHB patients in Guangdong, and in HBe Ag-positive CHB patients, GPR has a comparable predictive value to FIB-4 and APRI.
Clinical effect of transjugular intrahepatic portosystemic shunt combined with tissue adhesive embolization in treatment of gastroesophageal variceal rebleeding in cirrhotic patients
Chen Min, Zhang Feng, Zhang Ming, Li ZhenLei, He QiBin, Mou ChengCheng, Zhong WenQi, Zhu GeYuZheng
2018, 34(6): 1209-1214. DOI: 10.3969/j.issn.1001-5256.2018.06.016
Abstract:
Objective To investigate the clinical effect of transjugular intrahepatic portosystemic shunt (TIPS) alone versus TIPS combined with stomach and esophageal variceal embolization (SEVE) in the treatment of gastroesophageal variceal rebleeding in cirrhotic patients.Methods A total of 142 cirrhotic patients with gastroesophageal variceal bleeding who underwent TIPS or TIPS + SEVE in Department of Gastroenterology, Drum Tower Hospital, from January 2009 to December 2013 were enrolled and divided into TIPS group with 31 patients and TIPS + SEVE group with 111 patients. The two groups were analyzed in terms of intraoperative conditions, follow-up results, and risk factors for postoperative rebleeding. The independent samples t-test was used for comparison of continuous data between groups, the chi-square test was used for comparison of categorical data between groups, and the Mann-Whitney U test was used for comparison of ranked data between groups. The Kaplan-Meier method was used to plot the curves of rebleeding rate, shunt dysfunction rate, and survival rate, and the Log-rank test was used for the comparison of cumulative rebleeding rate, shunt dysfunction rate, and survival rate. The Cox proportional hazards regression model was used for univariate and multivariate analyses. Results All 142 patients completed the surgery successfully. There were no significant differences between the TIPS group and the TIPS + SEVE group in mean follow-up time (34 ± 23 months vs32 ± 21 months, t = 0. 501, P > 0. 05) and incidence rate of hepatic encephalopathy after surgery (12. 9% vs 18. 9%, χ2= 0. 641, P >0. 05) . There were no significant differences between the TIPS group and the TIPS + SEVE group in 1-, 2-, 3-, and 5-year cumulative rebleeding rates during follow-up (χ2= 1. 511, P > 0. 05) , while there were significant differences between the two groups in 1-, 2-, 3-, and 5-year cumulative shunt dysfunction rates (13%/21%/34%/34% vs 7%/12%/13%/13%, χ2= 4. 087, P < 0. 05) .There were no significant differences between the two groups in 1-, 2-, 3-, and 5-year cumulative survival rates during follow-up (χ2= 0. 471, P > 0. 05) . Preoperative Child-Pugh class (hazard ratio [HR]= 0. 385, 95% confidence interval [CI]: 0. 165-0. 898, P <0. 05) , stent type (HR = 0. 429, 95% CI: 0. 240-0. 766, P < 0. 05) , and postoperative shunt dysfunction (HR = 5. 840, 95% CI: 2. 566-13. 294, P < 0. 05) were influencing factors for postoperative rebleeding in cirrhotic patients with gastroesophageal variceal bleeding. The multivariate analysis showed that bare stent (relative risk [RR]= 0. 527, 95% CI: 0. 290-0. 954, P < 0. 05) and postoperative shunt dysfunction (RR = 4. 436, 95% CI: 1. 899-10. 360, P < 0. 05) were independent risk factors for postoperative rebleeding in cirrhotic patients with gastroesophageal variceal bleeding. Conclusion Compared with TIPS alone, TIPS + SEVE can reduce the incidence rate of postoperative shunt dysfunction in cirrhotic patients with gastroesophageal variceal bleeding, but it cannot reduce postoperative rebleeding rate or increase survival rate. Bare stent and shunt dysfunction are independent risk factors for postoperative rebleeding in cirrhotic patients with gastroesophageal variceal bleeding.
Effect of fibroblast growth factor 21 on hepatic fibrosis in mice and its mechanism
Wang DaXiu, Han JiWu
2018, 34(6): 1215-1219. DOI: 10.3969/j.issn.1001-5256.2018.06.017
Abstract:
Objective To investigate the effect of fibroblast growth factor 21 (FGF21) on hepatic fibrosis in mice and the mechanism of its action. Methods Male ICR mice were randomly divided three groups: control group, model group (treated with CCl4) , and treatment group (treated with CCl4+ 1. 0 mg/kg FGF21) . All mice were sacrificed to collect serum and liver tissues after 36 consecutive days of treatment. Serum levels of alanine transaminase (ALT) , aspartate aminotransferase (AST) , alkaline phosphatase (ALP) , total bilirubin (TBil) , interleukin-6 (IL-6) , interleukin-1β (IL-1β) , and tumor necrosis factor-α (TNF-α) were measured. Liver pathological changes were analyzed by Masson staining. The hepatic 4-hydroxyproline (4-Hyp) level was measured using a hydroxyproline detection kit. The mRNA levels of hepatic collagen I, α-smooth muscle actin (α-SMA) , transforming growth factor-β (TGF-β) , IL-6, IL-1β, and TNF-α were determined by quantitative real-time PCR. Comparison between multiple groups was made by one-way analysis of variance, and comparison between any two groups weas made using the LSD-t test. Results The Masson staining showed that the model group had a significantly higher degree of hepatic fibrosis than the control group, and the treatment group had a significantly lower degree of hepatic fibrosis than the model group. The model group had significantly higher serum levels of ALT, AST, ALP, and TBil (all P < 0. 05) , and the treatment group showed significant reductions in the above parameters compared with the model group (all P < 0. 05) . Enzyme-linked immunosorbent assay indicated that the model group had significantly higher serum levels of IL-1β, IL-6, and TNF-α than the control group (all P < 0. 05) , and the treatment group showed significant reductions in the above parameters compared with the model group (all P < 0. 05) . The hepatic 4-Hyp level and mRNA levels of collagen I and α-SMA were significantly higher in the model group than in the control group (P = 0. 04, < 0. 001, and < 0. 001) , and they were significantly lower in the treatment group than in the model group (P = 0. 005, < 0. 001, and < 0. 001) . The hepatic mRNA levels of TGF-β, IL-6, IL-1β, and TNF-α were significantly higher in the model group than in the control group (all P < 0. 001) , and they were significantly lower in the treatment group than in the control group (all P < 0. 001) . Conclusion FGF21 attenuates hepatic fibrogenesis in mice, possibly by inhibiting the expression of TGF-β, IL-6, IL-1β, and TNF-α in the liver.
Original articles_Liver neoplasms
Clinical efficacy of sorafenib in treatment of primary hepatic carcinoma and its effects on serum VEGFR-2 and PLGF levels
Liao WeiRong, Gu Chao, Zhang DaWei
2018, 34(6): 1220-1224. DOI: 10.3969/j.issn.1001-5256.2018.06.018
Abstract:
Objective To investigate the clinical efficacy of sorafenib in the treatment of primary hepatic carcinoma (PHC) and its effects on serum vascular endothelial growth factor receptor-2 (VEGFR-2) and placental growth factor (PLGF) levels. Methods A total of 110 patients with a confirmed diagnosis of PHC who received treatment in Jinshan Hospital Affiliated to Fudan University from July 2014 to March2016 were randomly and equally divided into observation group and control group. The control group was given routine treatment, while the observation group received sorafenib in addition to the routine treatment. Serum levels of VEGFR-2 and PLGF were measured by ELISA.Liver function parameters, aspartate aminotransferase (AST) , prothrombin time (PT) , total bilirubin (TBil) , albumin (Alb) , and alanine aminotransferase (ALT) , were also recorded. Comparison of continuous data between groups was made by independent samples t-test, and the changes in continuous data after intervention in each group were evaluated by paired samples t-test. Comparison of categorical data between groups was made by chi-square test. Results The observation group showed significant reductions in serum VEGFR-2 and PLGF levels after treatment (VEGFR-2: 7053. 2 ± 1836. 1 ng/L vs 8721. 4 ± 2427. 8 ng/L, t = 4. 089, P < 0. 001; PLGF: 468. 4 ± 136. 5 pg/ml vs 656. 8 ± 191. 4 pg/ml, t = 5. 975, P < 0. 001) . After treatment, the observation group had significantly lower serum VEGFR-2 and PLGF levels than the control group (VEGFR-2: 7053. 2 ± 1836. 1 ng/L vs 8097. 5 ± 2325. 4 ng/L, t = 2. 64, P < 0. 05; PLGF: 468. 4 ±136. 5 pg/ml vs 643. 3 ± 195. 8 pg/ml, t = 2. 48, P < 0. 05) . The observation group showed significant changes in serum AST and ALT levels after treatment (t = 4. 302 and 3. 097, both P < 0. 05) . After treatment, the observation group had significantly lower serum AST and ALT levels than the control group (t = 2. 56 and 2. 39, both P < 0. 05) . Compared with the control group, the observation group had better follow-up results, with a significantly increased disease control rate (27. 3% vs 47. 3%, χ2= 4. 705, P = 0. 030) , and had a significantly higher survival rate at 40 months after treatment (43. 6% vs 69. 1%, χ2= 7. 245, P = 0. 007) . Conclusion Sorafenib is effective in the treatment of PHC patients, as it can significantly reduce the serum levels of VEGFR-2 and PLGF, prolong the survival time of patients, and improve the prognosis of patients.
Original articles_Pancreatic diseases
Evaluation and analysis of the current guidelines for acute pancreatitis using Appraisal of Guidelines for Research and Evaluation Ⅱ
Wang Yu, Rao YouYi, Guo Jun, Yang JianBo, Liu HuaZhu, Zhao XinHua, Pan ShenLiang, Ning Hong
2018, 34(6): 1225-1230. DOI: 10.3969/j.issn.1001-5256.2018.06.019
Abstract:
Objective To investigate the quality of the guidelines for acute pancreatitis in China and foreign countries using Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. Methods According to inclusion and exclusion criteria, Wanfang Data, CNKI, VIP, Pub Med, Cochrane, and Elsevier were searched for the guidelines for the diagnosis and treatment of acute pancreatitis published from 2005 to 2016. As for the guidelines included, the information on the institutions that issued the guidelines, the basis for evidence evaluation, and the year of issuance was collected. The AGREE II instrument was used to evaluate the quality of the guidelines included in this study. The independent-samples nonparametric Mann-Whitney U test was used to compare the scores of guidelines in China and foreign countries. Results A total of 10 guidelines/consensus statements were included, among which 4 were published by China and 6 were published by foreign countries. The AGREE II results of 10 guidelines evaluated by three reviewers had an interclass correlation coefficient of> 0. 75 (all P < 0. 05) , which showed good consistency. The evaluation results showed that these guidelines had high mean scores of“Scope and Purpose”and“Clarity of Presentation” (50. 37% and 53. 15%, respectively) , and the guidelines in foreign countries had significantly higher mean scores than the guidelines in China (64. 51% vs 29. 16%, Z =-2. 558, P = 0. 011; 73. 77% vs 22. 22%, Z =-2. 574, P = 0. 010) . The guidelines had low mean scores of “Stakeholder Involvement”, “Rigour of Development”, and“Applicability” (28. 70%, 30. 49%, and 19. 17%, respectively) , and the guidelines in foreign countries had a significantly higher mean score of“Rigour of Development”than the guidelines in China (48. 96% vs 2. 78%, Z =-2. 557, P = 0. 011) . All guidelines had a mean score of“Editorial Independence”of 41. 39%, and the guidelines in foreign countries had a significantly higher mean score than the guidelines in China (68. 98% vs 0, Z =-2. 648, P = 0. 008) . The recommendation levels of the guidelines in China and foreign countries were C and B, respectively. Conclusion “Stakeholder Involvement”, “Rigour of Development”, and“Applicability”of the guidelines for acute pancreatitis need to be improved. The guidelines for acute pancreatitis in foreign countries are evidence-based guidelines and can be used after appropriate revision. The overall quality of the guidelines in China are inferior to those in foreign countries in the aspects of “Rigour of Development”, “Applicability”, and“Editorial Independence”, and therefore, it is recommended to further regulate the drafting and editing of evidence-based guidelines for acute pancreatitis in China, in order to promote the standard diagnosis and treatment of acute pancreatitis in China.
Clinical effect and safety of nutritional support after pancreaticoduodenectomy: A Meta-analysis
Zhang BaoHua, Yang Ya, Gong JianPing
2018, 34(6): 1231-1236. DOI: 10.3969/j.issn.1001-5256.2018.06.020
Abstract:
Objective To investigate the effect of different nutritional support methods (including total parenteral nutrition, early oral nutrition, early enteral nutrition via nasojejunal tube, early enteral nutrition via gastric fistula, and early enteral nutrition via jejunal fistula) on the prognosis of patients after pancreaticoduodenectomy (PD) . Methods Pub Med, Embase, and The Cochrane Library were searched for articles on nutritional support after PD published from 2007 to 2017. A pooled analysis was performed for related data including sample size, research contents, study population, research roadmap and methods, length of hospital stay, and incidence rates of infection (including postoperative pulmonary infection and incision infection) , pancreatic fistula (grade B/C) , and delayed gastric emptying, and Rev Man 5. 3 software was used for the meta-analysis of total parenteral nutrition and early enteral nutrition via nasojejunal tube after PD. Results A total of 11 articles were included, and 4 were included in the meta-analysis. The horizontal comparison showed no significant difference in the length of hospital stay between the patients undergoing nutritional support via different pathways, while the vertical comparison showed a significant difference. As for complications, the gastric fistula group had a significantly higher incidence rate of pancreatic fistula than the other groups (all P < 0. 01) , and the jejunal fistula group had a significantly higher incidence rate of delayed gastric emptying than the other groups (all P < 0. 01) . The total parenteral nutrition group had an incidence rate of infection of 27. 17%, which was lower than that in the other groups (40. 63% 、46. 58% 、33. 64%) , but there was no statistical significance in the differences (all P > 0. 05) . The meta-analysis showed no significant differences between the total parenteral nutrition group and the nasojejunal tube early enteral nutrition group in length of hospital stay, delayed gastric emptying, and incidence rates of pancreatic fistula and infection. Conclusion Nutritional strategies after PD have similar clinical effects and safety, and a reasonable nutritional support regimen can be developed based on clinical practice and patients' conditions.
Original articles_Others
Clinical features of drug-induced liver injury and related risk factors
Lin YunXia, He XiaoBin
2018, 34(6): 1237-1241. DOI: 10.3969/j.issn.1001-5256.2018.06.021
Abstract:

Objective To investigate the clinical features of drug-induced liver injury (DILI) and related risk factors. Methods A retrospective analysis was performed for the clinical data of 208 patients who were diagnosed with DILI in The Affiliated Hospital of Southwest Medical University from January 2013 to November 2017, including the type of drugs, clinical data, and laboratory examination results, and among these patients, 80 with DILI caused by antitubercular agents, antitumor drugs, and immune agents were enrolled as observation group. A total of 80 patients who used these three types of drugs and did not develop DILI were enrolled as control group. Related risk factors were analyzed. An analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups. The chi-square test was used for unordered variables of categorical data, the Mann-Whitney U test was used for ranked data, and a logistic regression analysis was used to identify risk factors. Results Of all patients with DILI, 30. 8% had DILI caused by traditional Chinese medicine. There were significant differences in sex, alanine aminotransferase, aspartate aminotransferase (AST) , total bilirubin (TBil) , gamma-glutamyl transpeptidase (GGT) , and total bile acid (TBA) between patients with different types of DILI (χ2= 6. 081, H = 54. 349, 45. 993, 78. 902, 49. 940, and 21. 934, all P < 0. 05) . There were significant differences in AST, TBil, GGT, and TBA between the patients with different prognoses (H = 1. 728, 6. 322, 6. 440, and 2. 353, all P < 0. 05) . Smoking (odds ratio [OR]= 2. 856, P = 0. 026) , diabetes (OR = 2. 726, P = 0. 042) , hyperlipidemia (OR = 3. 390, P = 0. 003) , and body mass index (BMI) ≥28 kg/m2 (OR = 3. 142, P =0. 009) were risk factors for DILI. Conclusion Most DILI cases are caused by traditional Chinese medicine, and hepatocellular type is the most common type of liver injury. Smoking, diabetes, hyperlipidemia, and BMI ≥28 kg/m2 are risk factors for DILI.

Clinical features and prognosis of drug-induced liver injury: An analysis of 95 cases
Yan Rong, Song ZhengJun
2018, 34(6): 1242-1247. DOI: 10.3969/j.issn.1001-5256.2018.06.022
Abstract:

Objective To analyze and summarize the clinical data of drug-induced liver injury (DILI) , and to investigate the clinical features and prognosis of DILI. Methods A retrospective analysis was performed for the clinical data of 95 patients with DILI who were admitted to The First Affiliated Hospital of Xi'an Medical University from February 2010 to February 2016, including sex, age, medication history, underlying diseases, clinical manifestation, laboratory and imaging findings, treatment, and prognosis. A logistic regression analysis was used to investigate the influencing factors for prognosis. Results Respiratory system diseases ranked first among the underlying diseases treated by drugs that caused DILI and accounted for 25. 26% (24/95) , and of all patients, 23. 16% (22/95) had tuberculosis. Among the drugs that caused DILI, traditional Chinese medicine ranked first and accounted for 44. 21% (42/95) , followed by antitubercular agents which accounted for 22. 11% (21/95) . DILI often occurred within 15-30 days of medication. Poor appetite was the most common symptom of DILI, and jaundice was the most common positive sign. Elevated alanine aminotransferase was the most common laboratory result of DILI.Acute hepatocellular injury type was the most common type of DILI. Most DILI patients had good prognosis, and patients with response to treatment accounted for 95. 79% (91/95) , including those who were improved or cured. Age (odds ratio [OR]= 0. 054, 95% confidence interval (CI) : 0. 002-0. 076, P = 0. 037) , alkaline phosphatase (OR = 0. 004, 95% CI: 0. 001-0. 006, P = 0. 043) , total bilirubin (OR = 0. 028, 95% CI: 0. 001-0. 039, P = 0. 035) , and direct bilirubin (OR = 0. 008, 95% CI: 0. 001-0. 014, P = 0. 036) were independent risk factors for prognosis. Conclusion DILI does not have specific clinical manifestations and can easily be missed or misdiagnosed. Clinicians should use drugs rationally, monitor the presence of hepatotoxicity, and strengthen the public health education on safe medication.

Expression of programmed death-ligand 1 on peripheral blood T cells and its correlation with liver inflammation grade in patients with type 1 autoimmune hepatitis
Xiong KeGong, Ke KunYu, Kong JinFeng, Liu LiJuan, Chen LiFang, Lin XiaoQin
2018, 34(6): 1248-1252. DOI: 10.3969/j.issn.1001-5256.2018.06.023
Abstract:

Objective To investigate the expression of programmed death-ligand 1 (PD-L1) on the surface of peripheral blood CD4+and CD8+T cells and its correlation with liver inflammation grade in patients with type 1 autoimmune hepatitis (AIH) . Methods A total of 62 patients with type 1 AIH (43 in the active stage and 19 in the remission stage) who were admitted to Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2014 to August 2017 were enrolled, and 20 healthy persons were enrolled as control group. Flow cytometry was used to measure the expression of PD-L1 on the surface of eripheral blood CD4+and CD8+T cells. The t-test or the Mann-Whitney U test was used for the comparison of continuous data between two groups, and a one-way analysis of variance and the least significant difference t-test or the Kruskal-Wallis H test were used for the comparison between multiple groups; the chi-square test was used for comparison of categorical data between groups; Pearson correlation and Spearman rank analysis was performed to investigate correlation.Results Compared with the control group, the type 1 AIH group had significantly higher expression rates of PD-L1 on the surface of peripheral blood CD4+and CD8+T cells (10. 94% ± 4. 52%/9. 93% ± 3. 32% vs 5. 42% ± 2. 64%/4. 86% ± 2. 16%, t = 7. 12 and 6. 41, both P < 0. 05) ; compared with the remission stage group and the control group, the active stage group had significantly higher expression rates of PD-L1 on the surface of peripheral blood CD4+and CD8+T cells (12. 45% ± 5. 61%/11. 13% ± 4. 63% vs 7. 88% ± 3. 85%/7.36% ± 3. 12% and 5. 42% ± 2. 64%/4. 86% ± 2. 16%, F = 15. 76 and 13. 54, both P < 0. 05) , and the remission stage group also had significantly higher expression rates than the control group (both P < 0. 05) . There were gradual increases in the expression rates of PD-L1 on the surface of peripheral blood CD4+and CD8+T cells in the patients with type 1 AIH in G0 group (7. 88% ± 3. 85% and 5. 36% ±3. 12%) , G1-2 group (10. 13% ± 4. 74% and 10. 45% ± 4. 34%) , and G3-4 group (15. 63% ± 5. 98% and 14. 73% ± 5. 12%) (χ2=12. 14 and 10. 32, P < 0. 05) . In the patients in the active stage of type I AIH, the expression rates of PD-L1 on the surface of peripheral blood CD4+and CD8+T cells were positively correlated with total bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, and immunoglobulin G (CD4+T cells: r = 0. 687, 0. 736, 0. 702, 0. 647, and 0. 824, all P < 0. 01; CD8+T cells: r = 0. 673, 0. 719, 0. 680, 0. 631, and 0. 817, all P < 0. 01) ; the expression rates of PD-L1 on the surface of peripheral blood CD4+and CD8+T cells were also positively correlated with liver inflammation grade (rs= 0. 768 and 0. 721, both P < 0. 05) . Conclusion In patients with type I AIH, high expression of PD-L1 on peripheral blood T cells is closely associated with liver inflammation grade, suggesting that PD-L1 may be involved in the development and progression of type 1 AIH.

Clinical features of IgG4-associated sclerosing cholangitis: An analysis of 12 cases
Wang Yan, Pan Jing, Huo Na, Zhang ZhenZhen, Cheng Hao, Wang GuiQiang
2018, 34(6): 1253-1258. DOI: 10.3969/j.issn.1001-5256.2018.06.024
Abstract:

Objective To investigate the clinical features, steroid response, and recurrence of Ig G4-associated sclerosing cholangitis (Ig G4-SC) , and to shorten the time for clinical diagnosis and reduce recurrence rate. Methods A total of 12 patients with Ig G4-SC who were admitted to Peking University First Hospital from December 2011 to March 2017 were enrolled, and they all met the clinical diagnostic criteria for Ig G4-SC in 2012. A retrospective analysis was performed for their clinical data, clinical features, and follow-up data. Results Of all 12 patients, the male/female ratio was 11∶ 1. The mean age of onset was 61. 7 ± 8. 6 years, and the mean time to a confirmed diagnosis was 24. 2 months. Of all 12 patients, 11 (92%) had jaundice, with a mean serum total bilirubin level of 198. 7 ± 57. 7 μmol/L. There were varying degrees of increase in serum alanine aminotransferase level (range 55-453 U/L) . Of all patients, 5 (41. 7%) had acute abdominal pain, with a mean CA19-9 level of 60. 8 ± 12. 5 U/ml. Serum Ig G4 was increased by 1. 5-18. 9 times, with a mean level of 7. 7 ± 2. 0 g/L. Magnetic resonance cholangiopancreatography (MRCP) performed for all patients showed typical manifestations including bile duct wall thickening, lumen stenosis, and intrahepatic and extrahepatic bile duct dilatation; 11 patients (92%) were found to have autoimmune pancreatitis, and 2 (16. 7%) had involvement of more than 3 visceral organs. In two patients who underwent biliary stent implantation before treatment, the biliary stent was removed after 4-6 weeks of steroid treatment. The mean duration of steroid response was 5. 4 months. Among the 8 patients who underwent steroid treatment, 4 (50%, 4/8) experienced recurrence during the reduction of the dose of steroid, among whom 2 experienced recurrence within 8-12 weeks after drug withdrawal. Conclusion Ig G4-SC needs a long time for prognosis, with frequent misdiagnosis and missed diagnosis. Serum Ig G4 level should be measured for elderly male patients with an acute onset of jaundice and bile duct stenosis, bile duct wall thickening, and involvement of the pancreas on MRCP. Steroid treatment should be given as early as possible after diagnosis. Patients may need at least 5-6 months to achieve steroid response. The dose of steroid should be reduced slowly and recurrence and tumorigenesis should be closely monitored.

A clinical analysis of Uygur patients with acute ischemic cerebral infarction complicated by nonalcoholic fatty liver disease in Urumqi, China
Chen QinQin, Liang CanCan, Yang LiJun, Meng Qing, Ding YongNian
2018, 34(6): 1259-1263. DOI: 10.3969/j.issn.1001-5256.2018.06.025
Abstract:

Objective To investigate the association between acute ischemic cerebral infarction (AICI) and nonalcoholic fatty liver disease (NAFLD) in Uygur patients in Urumqi, China and possible risk factors. Methods A retrospective analysis was performed for the clinical data of 294 Uygur patients with AICI who were admitted to The Second Affiliated Hospital of Xinjiang Medical University from September2011 to July 2017, and according to the diagnosis based on abdominal ultrasound, these patients were divided into case group with 110 patients (AICI complicated by NAFLD) and control group with 184 patients (without NAFLD) . The two groups were observed in terms of general information, biochemical parameters, and intima-media thickness (IMT) of the common carotid artery. The AICI patients were divided into ≤30 years group, 31-45 years group, 46-60 years group, 61-75 years group, and ≥60 years group according to age, and the incidence rate of NAFLD was compared between these groups. The t-test was used for comparison of continuous data between groups, the chi-square test was used for comparison of categorical data between groups, and a multivariate logistic regression analysis was performed.Results Compared with the control group, the case group had significantly higher age, body mass index, waist-hip ratio, Hb A1 c, fasting blood glucose, uric acid, alanine aminotransferase (ALT) , gamma-glutamyl transpeptidase, triglyceride (TG) , total cholesterol, and low-density lipoprotein cholesterol (LDL-C) and a significantly lower aspartate aminotransferase level (t = 9. 814, 5. 569, 8. 139, 3. 592, 3. 514, 15. 703, 15. 113, 8. 092, 10. 834, 7. 719, 11. 481, and 7. 561, all P < 0. 05) . The case group had a significantly higher proportion of the patients with a smoking history than the control group (χ2= 14. 060, P < 0. 05) . The logistic regression analysis showed that the increases in age (odds ratio [OR]= 1. 301, 95% confidence interval [CI]: 1. 065-1. 589, P < 0. 05) and serum levels of ALT (OR =1. 383, 95% CI: 1. 059-1. 805, P < 0. 05) , TG (OR = 1. 335, 95% CI: 1. 091-1. 634, P < 0. 05) , and LDL-C (OR = 1. 358, 95%CI: 1. 125-1. 639, P < 0. 05) and a smoking history (OR = 1. 423, 95% CI: 1. 105-1. 833, P < 0. 05) were closely associated with NAFLD in AICI patients. The incidence rate of NAFLD in AICI patients increased with age, and there was a significant difference between different age groups (χ2= 13. 558, P = 0. 009) ; the 61-75 years group and the > 76 years group had an incidence rate of NAFLD of44. 09% and 51. 35%, respectively, which were significantly higher than that in the other three groups (P < 0. 05) . Conclusion Increases in age and serum levels of ALT, TG, and LDL-C and a smoking history are independent risk factors for NAFLD in patients with AICI, and AICI patients aged over 60 years have a high incidence rate of NAFLD.

Establishment of a noninvasive diagnosis equation for nonalcoholic fatty liver disease
Feng Gong, Han HaiJing, Qi Xue, Mi Man, Tian QiuMei, Niu ChunYan
2018, 34(6): 1264-1267. DOI: 10.3969/j.issn.1001-5256.2018.06.026
Abstract:

Objective To establish a noninvasive diagnosis equation for nonalcoholic fatty liver disease (NAFLD) using related clinical and laboratory markers, and to investigate the value of this equation in the prediction and diagnosis of NAFLD. Methods A total of 127 patients who were diagnosed with NAFLD in The First Affiliated Hospital of Xi' an Medical University from November 2016 to November 2017 were enrolled, and 30 healthy individuals were enrolled as healthy controls. Related data were recorded, including sex, age, body mass index (BMI) , medical history, alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , gamma-glutamyl transpeptidase (GGT) , blood urea nitrogen (BUN) , uric acid (UA) , serum creatinine (SCr) , total cholesterol (TC) , triglyceride (TG) , high-density lipoprotein (HDL) , low-density lipoprotein (LDL) , Hb Alc, free fatty acid (FFA) , fasting blood glucose (FPG) , fasting insulin (FINS) , platelet count (PLT) , and results of ultrasound examination and Fibro Scan examination. The t-test was used for comparison of continuous data between groups; the Pearson correlation analysis was performed to investigate correlation; the multiple linear regression equation model was used to establish the regression equation; the receiver operating characteristic (ROC) curve was plotted to calculate the sensitivity and specificity of this regression equation. Results The indices related to fatty liver included BMI (r = 0. 308, P = 0. 005) , ALT (r = 0. 379, P < 0. 001) , AST (r = 0. 318, P = 0. 004) , GGT (r = 0. 293, P = 0. 009) , UA (r = 0. 244, P = 0. 033) , and FFA (r = 0. 249, P =0. 030) . A multiple regression analysis was performed for controlled attenuation parameter (CAP) on Fibro Scan; the regression model of CAP had statistical significance (F = 11. 113, P < 0. 001) , and its adjusted determination coefficient R2 was 0. 274, suggesting that the variation caused by regression accounted for 27. 4% of all variations; ALT had the greatest influence on CAP (β = 0. 358, P = 0. 001) , followed by BMI (β = 0. 258, P = 0. 012) . The regression equation established was CAP = 113. 163 + 0. 252 × ALT + 6. 316 × BMI. This diagnostic equation had an area under the ROC curve of 0. 927, a sensitivity of 87. 68%, and a specificity of 90. 00%, at the cut-off value of277. 67 (P < 0. 001) , suggesting that it had high diagnostic efficiency. Conclusion Compared with current diagnosis equations, the equation established in this study has a larger area under the ROC curve and higher specificity and sensitivity. It also has a simple calculation method and strong practicability and operability and helps to screen out early NAFLD and improve the awareness of self-intervention, which can further reduce the harm and delay the progression of NAFLD in the world.

Influence of bisphenol A on intestinal mucosal barrier in rats with nonalcoholic fatty liver disease
Ding WenJin, Yuan Tao, Shen Feng, Zhou Da, Sun Chao, Fan JianGao, Chen YuanWen
2018, 34(6): 1268-1272. DOI: 10.3969/j.issn.1001-5256.2018.06.027
Abstract:

Objective To investigate the influence of bisphenol A (BPA) , an environmental endocrine disruptor, on inflammatory response in rats with nonalcoholic fatty liver disease (NAFLD) , as well as its adverse effect on intestinal mucosal barrier. Methods A total of 18 mature male rats were randomly divided into normal group, NAFLD group, and NAFLD + BPA group, with 6 rats in each group. liver pathological changes were observed under a light microscope; ELISA was used to measure the serum levels of tumor necrosis factor-α (TNF-α) , interleukin-1β (IL-1β) , interleukin-6 (IL-6) , and interleukin-8 (IL-8) ; the terminal colorimetric analysis with Limulus amebocyte lysate was used to measure the level of endotoxin; an immunofluorescence assay was used to measure the expression of occluding protein in the intestinal mucosa; real-time PCR was used to measure the mRNA expression of ZO-1 in the intestinal mucosa. 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 Liver pathological examination showed that the rat model of NAFLD was established successfully. After the 8-week treatment with 100 nmol/L BPA, compared with the normal group and the NAFLD group, the NAFLD + BPA group had significant increases in the expression of TNF-α (127. 65 ± 22. 4 pg/ml vs 64. 87 ± 10. 83 pg/ml and 92. 34 ± 10. 68 pg/ml, P < 0. 05) , IL-6 (199. 34 ± 17. 46 pg/ml vs 91. 27 ± 9. 82 pg/ml and 181. 93 ± 20. 11 pg/ml, P < 0. 05) , and IL-8 (258. 79 ± 12. 82 pg/ml vs 123. 76 ±19. 68 pg/ml and 201. 64 ± 22. 34 pg/ml, P < 0. 05) and the level of endotoxin (0. 88 ± 0. 26 EU/ml vs 0. 27 ± 0. 09 EU/ml and 0. 63 ±0. 15 EU/ml, P < 0. 05) . The NAFLD group and the NAFLD + BPA group had a significantly higher level of IL-1β than the normal group (186. 31 ± 20. 06 pg/ml and 208. 78 ± 13. 77 pg/ml vs 112. 84 ± 23. 12 pg/ml, both P < 0. 05) , but there was no significant difference between these two groups. Compared with the normal group, the NAFLD group and the NAFLD + BPA group had significant reductions in the expression of occluding protein and the mRNA expression of ZO-1 in the intestinal mucosa, and the NAFLD + BPA group had a significantly greater reduction in the mRNA expression of ZO-1 than the control group and the NAFLD group (33. 25 ± 11. 04 vs 68. 03 ± 11. 73/45. 24 ±6. 98, P < 0. 05) . Conclusion In the background of NAFLD, long-time exposure to low-dose BPA can increase the release of some inflammatory factors, promote endotoxemia, and thus damage intestinal mucosal barrier.

Antioxidant effect of berberine in a rat model of nonalcoholic steatohepatitis
Jiang Yu, Hu JuLong, Ma JiaLi, Li Ping, Zhou YuLing, Liang XiuXia, Ai ZhengLin, Yao ShuKun
2018, 34(6): 1273-1276. DOI: 10.3969/j.issn.1001-5256.2018.06.028
Abstract:

Objective To investigate the antioxidant effect of berberine in a rat model of nonalcoholic steatohepatitis (NASH) and an in vitro model of oxidative stress induced by H2 O2. Methods High-fat diet was used to establish a rat model of NASH. After three weeks of treatment with berberine 18 mg/kg/d by gavage, HE staining was used to observe liver pathological changes, and the activities of glutathione (GSH) and superoxide dismutase (SOD) and the level of malondialdehyde (MDA) in liver tissue were measured. An in vitro model of oxidative stress induced by reactive oxygen species (ROS) due to H2 O2 was established; flow cytometry was used to measure the level of ROS, and the activities of SOD, GSH, lactate dehydrogenase (LDH) , and chloramphenicol acetyltransferase (CAT) in hepatocytes were measured. A one-way analysis of variance was used for comparison of continuous data between groups, and the Bonferroni test was used for further comparison between two groups; the t-test was used for comparison of continuous data between two groups. Results NASH rats had significant improvements in the extent of infiltration of inflammatory cells, focal necrosis, and ballooning degeneration of hepatocytes after berberine treatment. Compared with the NASH model group, the berberine group had significant increases in the activities of GSH (29. 8 ±2. 4 U/mg vs 19. 9 ± 1. 3 U/mg, P < 0. 001) and SOD (26. 6 ± 1. 9 μg/mg vs 19. 7 ± 1. 4 μg/mg, P < 0. 001) and a significant reduction in the level of MDA (19. 8 ± 1. 5 nmol/mg vs 24. 0 ± 2. 0 nmol/mg, P < 0. 001) . In the in vitro model of oxidative stress induced by H2 O2, the H2 O2 group had a significant increase in the level of ROS compared with the berberine + H2 O2 group (69. 8% ± 1. 9% vs 50. 4% ±6. 5%, t = 24. 42, P = 0. 008) . Compared with the H2 O2 group, the berberine + H2 O2 group had significant increases in the activities of SOD (25. 5 ± 1. 3 μg/mg vs 18. 8 ± 1. 0 μg/mg, P < 0. 001) and GSH (27. 1 ± 0. 6 U/mg vs 16. 79 ± 3. 8 U/mg, P < 0. 001) in hepatocytes; there was no significant difference in the level of LDH between the berberine + H2 O2 group and the H2 O2 group (P = 0. 103) , and there was no significant difference in the activity of CAT across all groups (F = 3. 76, P = 0. 060) . Conclusion Both in vivo and in vitro models show that berberine has a good antioxidant effect, possibly by increasing the activities of antioxidant enzymes.

Clinical features of sinusoidal obstruction syndrome induced by pyrrolidine alkaloids in China
Guo Yan, Zhang ShiRong, Wen LiangZhi, Liu KaiJun, Hu Lu, Sun WenJing, Wang Bin, Wei YanLing, Chen DongFeng
2018, 34(6): 1277-1281. DOI: 10.3969/j.issn.1001-5256.2018.06.029
Abstract:

Objective To investigate the clinical manifestations, treatment, and prognosis of sinusoidal obstruction syndrome induced by pyrrolidine alkaloids in China. Methods Related databases were searched, and 107 articles on sinusoidal obstruction syndrome published from January 1980 to April 2017 in China were included, with 407 patients in total. Related data of this disease were analyzed, including sex, age, regional distribution, clinical manifestations, imaging and pathological findings, and prognosis. Results The male/female ratio of 407 patients was 1: 1. 22, and the age of onset ranged from 13 months to 81 years. Major clinical manifestations included abdominal distension, abdominal pain, ascites, and hepatomegaly. The most typical abdominal CT findings were hepatomegaly and a map-like or patchy change after enhancement. Pathological examination showed sinusoidal expansion and congestion and varying degrees of stenosis of small hepatic veins. Of all 407 patients, 302 had response and 90 died, resulting in a mortality rate of 22. 1%. Conclusion In China, the male population has a higher incidence rate of sinusoidal obstruction syndrome than the female population, and sinusoidal obstruction syndrome can occur at any age. Major clinical manifestations include abdominal distension, abdominal pain, ascites, and hepatomegaly, which can be used to make a definite diagnosis in combination with typical liver CT manifestations. Pathological findings by liver biopsy are the gold standard for diagnosis. Symptomatic treatment is the major treatment modality, and some patients may have poor prognosis.

An analysis of risk factors for early complications after liver transplantation
Jie EnBo, Xuan FengHui, Sun XiaoDong, Sun DaWei, Lu: GuoYue
2018, 34(6): 1282-1288. DOI: 10.3969/j.issn.1001-5256.2018.06.030
Abstract:

Objective To investigate the risk factors for early complications after liver transplantation and to improve the prognosis. Methods The clinical data of 147 patients who underwent orthotopic liver transplantation in the Hepatic Transplantation Center of The First Hospital of Jilin University from September 2011 to April 2017 were retrospectively analyzed. According to the presence or absence of early complications after surgery, these patients were divided into non-complication group (n = 11) and complication group (n = 136) . The possible factors associated with early complications after surgery were collected, including donor factors (age and whether the blood type of the donor matches that of the recipient) , recipient factors (sex, age, primary disease, Model for End-Stage Liver Disease [MELD]score, aspartate aminotransferase [AST], alanine aminotransferase[ALT], albumin [Alb], platelet [PLT], hemoglobin [Hb], fibrinogen, total bilirubin, creatinine, PLT/Alb ratio [PAR], and neutrophil/lymphocyte ratio [NLR]) , intraoperative factors (cold ischemia time, warm ischemia time, intraoperative blood loss, and duration of anhepatic phase) , and postoperative factors (AST and ALT immediately and 12, 24, 48, and 72 hours after operation) . The clinical data were analyzed to investigate the association between these factors and early complications.The t test was used for comparison of normally distributed continuous data; 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. Backward logistic regression was used for multivariate analysis. Results MELD score (t =-3. 86, P = 0. 002) , Alb (t = 2. 19, P = 0. 049) , PLT (Z = 467. 00, P = 0. 039) , PAR (Z = 500. 00, P = 0. 068) , fibrinogen (t = 1. 80, P = 0. 096) , TBil (Z =-1. 98, P = 0. 047) , preoperative AST (Z = 417. 00, P =0. 015) , and preoperative ALT (Z = 501. 50, P = 0. 070) were associated with postoperative complications. PAR and preoperative AST were independent risk factors for early complications (odds ratio [OR]= 3. 84, 95% confidence interval [CI]: 1. 03-14. 34, P < 0. 05; OR =0. 25, 95% CI: 0. 07-0. 94, P < 0. 05) . The 147 patients were divided into high-PAR group (PAR ≥3 × 109/g; n = 55) and low-PAR group (PAR < 3 × 109/g; n = 92) ; PAR was associated with postoperative vascular and biliary complications (χ2= 2. 87, P = 0. 090;χ2= 3. 54, P = 0. 060) . The 147 patients were divided into normal preoperative AST group (AST < 40 U/L; n = 93) and abnormal preoperative AST group (AST ≥40 U/L; n = 54) ; preoperative AST level was associated with postoperative pleural effusion (χ2= 3. 03, P =0. 082) . Conclusion Fibrinogen, PLT, Alb, TBil, PAR, MELD score, and preoperative AST and ALT are associated with the development of early complications after liver transplantation, and PAR and preoperative AST are independent risk factors for early complications.To improve the prognosis and postoperative survival, these factors, particularly PAR, should be fully assessed for the liver transplantation recipient before operation, and specific interventions should be provided accordingly.

Case reports
A case of pituitary stalk interruption syndrome with liver cirrhosis
Tian Hua, Xu TianJiao, Zhu Bing, You ShaoLi, Lu: Sa
2018, 34(6): 1289-1291. DOI: 10.3969/j.issn.1001-5256.2018.06.031
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A case of intrahepatic biliary cystadenoma
Cheng PengRui, Su Yang
2018, 34(6): 1292-1293. DOI: 10.3969/j.issn.1001-5256.2018.06.032
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A case of acute drug-induced liver injury caused by norethindrone
Huang DeLiang, Dai Wei
2018, 34(6): 1294-1295. DOI: 10.3969/j.issn.1001-5256.2018.06.033
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An asymptomatic case of Caroli disease
Cao Dan, Xin JieJing, Chen YanPing
2018, 34(6): 1296-1297. DOI: 10.3969/j.issn.1001-5256.2018.06.034
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Conservative treatment of cholecystoduodenal fistula complicated by gallstone ileus: A case report
Wang KeShen, Zhang XiangXiang, Ren YanXian, Ding YongQiang, Wang ShiYao, Jiao ZuoYi
2018, 34(6): 1298-1299. DOI: 10.3969/j.issn.1001-5256.2018.06.035
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Portal hypertension caused by pancreatic tuberculosis: A case report
Mao MiaoMiao, Zhang Duan, Gao Hui, Yang QianQian, Wen XiaoYu, Jin QingLong
2018, 34(6): 1300-1301. DOI: 10.3969/j.issn.1001-5256.2018.06.036
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Reviews
Value of highly sensitive serum virological markers in hepatitis B patients with a low viral load
Gu JiuLian, Liu ShouSheng, Li ChangFei, Xiao JianHan, Xin YongNing, Xuan ShiYing
2018, 34(6): 1302-1307. DOI: 10.3969/j.issn.1001-5256.2018.06.037
Abstract:
HBV detection plays an important role in the prevention and treatment of hepatitis B. Clinical studies have shown that some patients with undetectable HBV DNA or negative HBs Ag could still progress to liver cirrhosis and hepatocellular carcinoma. Therefore, it is urgent to improve the sensitivity of HBV detection and develop new technologies and biomarkers for HBV detection. In recent years, we gradually realize the important value of serological and serum virological markers in hepatitis B patients with a low viral load. This article summarizes the value of some highly sensitive serum markers (HBV DNA, HBs Ag, and HBV RNA) and serum HBcr Ag in hepatitis B patients with a low viral load. It is pointed out that clinicians should guide the clinical management of such patients with reference to their conditions and the changes in above markers, in order to realize the cure of hepatitis B.
Changes in diagnostic criteria for hepatorenal syndrome and the application of new renal injury indices in cirrhotic patients
Liu QinYu, Li Hai
2018, 34(6): 1308-1312. DOI: 10.3969/j.issn.1001-5256.2018.06.038
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Hepatorenal syndrome is a serious complication of decompensated cirrhosis and has high short-term mortality. There still lacks effective medical treatment at present. Although some drugs are effective, but their effects reported in the literature were different due to a lack of uniform diagnostic criteria. This article introduces the changes in the diagnostic criteria for hepatorenal syndrome and points out that uniform diagnostic criteria will become the basis for clinical research on hepatorenal syndrome and may also help clinicians to understand this serious complication of liver cirrhosis.
Current status of treatment of primary hepatocellular carcinoma in the elderly population
Huang YongJie, Wu DeQuan, Yuan JunHui
2018, 34(6): 1313-1317. DOI: 10.3969/j.issn.1001-5256.2018.06.039
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With the global aging, the incidence rate of HCC in the elderly population is gradually increasing, and thus it has become a global health issue. With reference to relevant literature, this article analyzes the clinical features of elderly HCC patients and reviews the current status of therapies and clinical outcomes. The review of clinical outcomes is mainly based on the comparison of therapeutic outcome between elderly and non-elderly HCC patients in many countries and regions in the world. This article points out that elderly HCC patients have their own clinical features, and since elderly HCC patients often have other diseases, such as diabetes, renal failure, and lung and cardiovascular diseases, there is an increase in the risk of treatment, but they often have positive treatment outcomes. With the deepening of research and the improvement of various treatment methods, the therapeutic outcome of elderly HCC patients will also be improved. Therefore, positive attitude and strategies should be adopted in the clinical treatment of elderly HCC patients.
Research advances in metabolic markers for hepatocellular carcinoma
Sun WenBo, Liu XiangLiang, Li Wei
2018, 34(6): 1318-1324. DOI: 10.3969/j.issn.1001-5256.2018.06.040
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Hepatocellular carcinoma (HCC) has high incidence and mortality rates and poor prognosis and greatly threatens human health.Early identification and diagnosis is an important method for reducing the incidence and mortality rates of HCC. The sensitivities and specificities of commonly used serum tumor markers cannot meet the need in clinical practice. Metabolomics focuses on the changes in metabolites produced by organisms, such as lipids, bile acid, and amino acids, which are located at the downstream of systems biology and can directly reflect the biochemical status of tissues. With the help of the techniques including chromatography, mass spectrometry, and magnetic resonance, metabolomics can identify the differences in metabolites in serum, urine, and tissue samples, evaluate their diagnostic values, and help to find potential markers for HCC. In the early screening of tumors, metabolomics has the advantages of easily available specimens, simple operation, and processing a large number of specimens simultaneously. This article reviews the recent research advances in metabolic markers for HCC with the application of metabolomics.
The association between the intestinal microbiota-lipopolysaccharide-Toll-like receptor 4 axis and hepatocellular carcinoma
Huang Rong, Ni JiaJia, Gao Yi
2018, 34(6): 1325-1328. DOI: 10.3969/j.issn.1001-5256.2018.06.041
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Hepatocellular carcinoma is the major complication of various end-stage chronic liver diseases. Studies have shown that intestinal barrier injury and intestinal flora disturbance are commonly seen in patients with liver diseases, which may cause intestinal bacterial translocation and endotoxemia. Toll-like receptor 4 (TLR4) is a pattern recognition receptor in the liver and can bind to lipopolysaccharide (LPS) , the active ingredient of endotoxin, result in immune inflammatory response via various signal transduction pathways, and finally promote hepatic fibrosis and tumorigenesis. This article reviews the intestinal microbiota-LPS-TLR4 axis and the pathogenesis of hepatocellular carcinoma.
Research advances in the role of CCL20/CCR6 in liver cancer and other tumors
Wu Jing, Meng QingHua
2018, 34(6): 1329-1332. DOI: 10.3969/j.issn.1001-5256.2018.06.042
Abstract:
The role of chemokines/receptors in the pathophysiological activities such as inflammation and tissue injury has been clarified. In recent years, there have been increasing studies on their effect on tumors in the tumor microenvironment. This article reviews research advances in C-C motif chemokine ligand 20 (CCL20) and its receptor CCR6 in liver cancer and other tumors in recent years and analyzes the possible mechanism by which CCL20 and CCR6 promote tumor progression and their effect on tumor prognosis. Blocking CCL20/CCR6 interaction may provide a new direction for the targeted therapy for liver cancer.
Research advances in Epstein-Barr viral hepatitis
Huang JiangWei, Han FangZheng
2018, 34(6): 1333-1337. DOI: 10.3969/j.issn.1001-5256.2018.06.043
Abstract:
Epstein-Barr virus hepatitis is liver inflammation caused by Epstein-Barr virus infection, mainly self-limited hepatitis or mild or moderate liver injury. It often has good prognosis, but it may progress to chronic liver disease, severe hepatitis, and even intrahepatic cholangiocarcinoma. The clinical manifestations and histopathological features of this disease lack specificity, which may lead to missed diagnosis or misdiagnosis, and thus it should be taken seriously by clinicians. This article introduces the mechanism of Epstein-Barr virus infection and reviews the research advances in Epstein-Barr viral hepatitis.
Latest clinical advances in autoimmune hepatitis in special populations and special types of autoimmune hepatitis
Li YanQing, Dong HongJing, Liu XiaoWen, Gao YanHang
2018, 34(6): 1338-1342. DOI: 10.3969/j.issn.1001-5256.2018.06.044
Abstract:
In recent years, the incidence rate of autoimmune hepatitis (AIH) is gradually increasing, which has attracted more and more attention from clinicians. However, there still lacks standardization in the diagnosis and treatment of special types of AIH and AIH in special populations. This article summarizes the latest advances in the clinical diagnosis and treatment of special types of AIH (including asymptomatic AIH, fulminant AIH, treatment-experienced AIH, overlap syndrome, drug-induced AIH, post-liver transplantation AIH, and autoantibody-negative AIH) and AIH in special populations (including children, pregnant women, male patients, and elderly patients) , in order to provide help to the management of the special conditions of this disease in clinical practice. With the increase in the incidence rate of AIH, clinicians should deepen the understanding of AIH in special populations and special types of AIH in order to facilitate clinical work. At present, many serious issues in the management of AIH need to be resolved. Large-scale prospective clinical trials and in-depth basic research on AIH will be conducted in future.
The role of gut microbiota in the development and progression of nonalcoholic steatohepatitis
Chang Yue, Li Hai
2018, 34(6): 1343-1346. DOI: 10.3969/j.issn.1001-5256.2018.06.045
Abstract:
Currently, the pathogenesis of nonalcoholic steatohepatitis (NASH) remains unclear, while the theory of " two hits" is insufficient to explain the pathogenesis of NASH in all cases. More and more attention has been paid to the relationship between the change in gut microbiota and the development and progression of NASH in recent years. The energy metabolism disorder, lipopolysaccharide endotoxemia, increased endogenous ethanol production, bile acid metabolism disorder, altered choline metabolism, and immune dysfunction caused by gut microbiota are related to NASH. This article reviews the role of gut microbiota in the development and progression of nonalcoholic steatohepatitis.
Association of Th17 cells, regulatory T cells, and their imbalance with nonalcoholic fatty liver disease
Gao WeiHua, Ge KuanXue, Xiang XiaoXing
2018, 34(6): 1347-1350. DOI: 10.3969/j.issn.1001-5256.2018.06.046
Abstract:
Nonalcoholic fatty liver disease (NAFLD) is closely associated with insulin resistance and genetic susceptibility and is one of the chronic liver diseases that threaten human health. Under certain conditions, Th17 cells and regulatory T (Treg) cells can be transformed to each other to maintain immune homeostasis. In recent years, more and more studies have been performed on the involvement of Th17 and Treg cells in the development and progression of liver diseases. Th17 cells, Treg cells, and their balance may become the new targets for the treatment of NAFLD. This article reviews the latest research advances in the association of Th17 and Treg cells with NAFLD and the role of Th17/Treg balance in the development and progression of NAFLD.
Research progress in prognostic models of acute-on-chronic liver failure
Zhang DongJing, Zhou Bin, Hou JinLin
2018, 34(6): 1351-1356. DOI: 10.3969/j.issn.1001-5256.2018.06.047
Abstract:
Acute-on-chronic liver failure (ACLF) is characterized by the rapid deterioration of liver function resulting from acute insults in patients with pre-existing liver disease, which is usually correlated with multisystem organ failure. There is still no ideal therapy available for ACLF untill now. An early and accurate evaluation of the prognosis of patients with ACLF is helpful for physicians to optimize treatment strategies and improve the outcome of these patients. This article highlights the characteristics and predictive power of diffrent scoring systems in an attempt to guide the therapeutic strategy and prognostic assessment by reviewing the prognostic models for ACLF in recent years.
Diagnosis and treatment of vascular complications of acute pancreatitis
Zhu Chang, Zhu YiZhou, Wang Ying, Xu XiaoRong
2018, 34(6): 1357-1360. DOI: 10.3969/j.issn.1001-5256.2018.06.048
Abstract:
Severe acute pancreatitis is a disease involving multiple organs and systems and can lead to a series of complications. It is reported that a quarter of patients with severe pancreatitis may develop vascular complications, which is the major cause of death. Vascular complications can be divided into intravenous and arterial complications. Diagnosis and treatment should be given according to clinical manifestations, laboratory results, and imaging findings, and at present, individualized treatment is emphasized in clinical diagnosis and treatment.This article reviews the advances in the diagnosis and treatment of vascular complications of acute pancreatitis.