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

2019 Vol. 35, No. 8

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Editorial
Myriad faces of genetic liver disorders
Abuduxikuer Kuerbanjiang, Wang JianShe
2019, 35(8): 1657-1662. DOI: 10.3969/j.issn.1001-5256.2019.08.001
Abstract:

With the improvement in quality of life and the level of prevention and treatment of viral hepatitis, as well as the availability of genetic testing, genetic liver disorders have been taken more and more seriously. Genetic liver disorders have various clinical manifestations, such as abnormalities in the liver and intrahepatic or extrahepatic blood vessels/bile ducts, and it can also involve other organs and systems in the human body. These are the myriad faces of genetic liver disorders. This article focuses on different manifestations of genetic liver disorders, in order to help physicians identify the etiology and pathogenic gene of liver disease.

Discussions by experts
Clinical features and diagnosis of inherited metabolic liver disease
Peng ShanShan, Yang YongFeng
2019, 35(8): 1663-1666. DOI: 10.3969/j.issn.1001-5256.2019.08.002
Abstract:
Inherited metabolic liver disease has complex etiologies and various types, and its clinical manifestations lack specificity, which may lead to missed diagnosis and misdiagnosis. A clinical diagnosis should be given based on symptoms, signs, laboratory examination, imaging findings, liver biopsy, and gene detection, in order to provide a basis for early treatment. Therefore, clues from clinical examination play an important role in the diagnosis of this disease. This article summarizes the clinical clues and diagnostic ideas of inherited metabolic liver disease.
Pathogenic mechanism and clinical diagnosis of hereditary abnormal copper metabolism
Chen ShuRu, Chong YuTian, Li XinHua
2019, 35(8): 1667-1672. DOI: 10.3969/j.issn.1001-5256.2019.08.003
Abstract:
Copper is an important trace element in the human body, and copper deficiency or overload can lead to a series of body dysfunctions. This review focuses on hepatolenticular degeneration and related diseases of abnormal copper metabolism. Hepatolenticular degeneration has various clinical phenotypes, and related diseases, such as cholestatic liver disease, hereditary ceruloplasmin deficiency, and congenital abnormal glycosylation, may bring confusion to the clinical diagnosis of hepatolenticular degeneration. With reference to the latest research advances and experience in the diagnosis and treatment of hepatolenticular degeneration, this article discusses the pathogenic mechanism and clinical diagnosis of hereditary abnormal copper metabolism from the perspective of liver diseases.
Genetic diagnosis of hereditary hemochromatosis
Han Yue, Zhang XinXin
2019, 35(8): 1673-1679. DOI: 10.3969/j.issn.1001-5256.2019.08.004
Abstract:
Iron overload is not rarely seen in clinical practice, and hemochromatosis involving the liver is the most common type of iron overload. There is an extremely low incidence rate of the classic form of HFE hereditary hemochromatosis in the Asian population, which is different from the genetic background of the Caucasian population. European and American studies and international guidelines mainly focus on the HFE type, and there is low consistency between guidelines, with a lack of data from the Asian population. Therefore, with reference to the pathogenic genes of hereditary hemochromatosis and related data in China, this article discusses the genetic diagnosis of hereditary hemochromatosis, in order to provide a reference for the diagnosis and studies of hemochromatosis in the Chinese population.
Clinical features and diagnosis of four common types of congenital hyperbilirubinemia
Bai Jie, Zheng SuJun, Duan ZhongPing
2019, 35(8): 1680-1683. DOI: 10.3969/j.issn.1001-5256.2019.08.005
Abstract:
Congenital hyperbilirubinemia is an inherited metabolic liver disease commonly seen in clinical practice, and various atypical manifestations of this disease and a low degree of emphasis may lead to missed diagnosis, misdiagnosis, and delayed diagnosis. This article summarizes the clinical features, common pathogenic genes and their mutation sites, and diagnosis of four common types of congenital hyperbilirubinemia, i. e., Gilbert syndrome, Crigler-Najjar syndrome, Dubin-Johnson syndrome, and Rotor syndrome, in order to provide a reference for clinicians.
Congenital disorders of glycosylation and liver diseases
Abuduxikuer Kuerbanjiang, Wang JianShe
2019, 35(8): 1684-1689. DOI: 10.3969/j.issn.1001-5256.2019.08.006
Abstract:

Congenital disorders of glycosylation (CDGs) is a group of inherited metabolic diseases caused by abnormal glycosylation of protein or lipids, and the number of CDGs are increasing rapidly in recent years. With the advent and popularization of next-generation sequencing, more and more disorders associated with glycosylation-related gene mutations have been discovered. Synthesis of glycoproteins and glycolipids is one of the major roles of the liver, and many CDGs affect hepatobiliary structure or function and may lead to fatty liver disease, liver fibrosis, and ductal plate malformation. This article reports the latest advances in the pathogenesis, diagnosis, and treatment of CDGs and related liver diseases.

Research advances in the pathogenesis, clinical manifestations, and diagnosis/treatment of sodium-taurocholate cotransporting polypeptide deficiency
Song YuanZong
2019, 35(8): 1690-1692. DOI: 10.3969/j.issn.1001-5256.2019.08.007
Abstract:
Sodium-taurocholate cotransporting polypeptide (NTCP) deficiency is a new hereditary bile acid metabolic disease due to biallelic mutations of the SLC10 A1 gene and is not rare in China. Marked and persistent hypercholanemia in childhood is the major clinical feature of NTCP deficiency, and this condition might be involved in the development of neonatal hyperbilirubinemia, cholestasis in early infancy, and cholestasis in pregnancy. At present, there lack specific therapies for NTCP deficiency, but such patients tend to have good prognosis. SLC10 A1 gene detection may facilitate the timely and definite diagnosis of this disease and thus avoid unnecessary examinations and interventions.
Guidelines
The expert consensus on clinical cure (functional cure) of chronic hepatitis B
Chinese Society of Infectious Disease, Chinese Society of Hepatology, Chinese Medical Association
2019, 35(8): 1693-1701. DOI: 10.3969/j.issn.1001-5256.2019.08.008
Abstract(1743) PDF (411KB)(1252)
Abstract:

Chronic hepatitis B virus (HBV) infection remains a major world public health problem. Current guidelines for the prevention and treatment of chronic hepatitis B (CHB) have suggested clinical cure (also known as functional cure) as the ideal therapeutic goal, which is associated with decreased risk of cirrhosis and hepatocellular carcinoma. Clinical cure is defined as sustained, undetectable serum HBsAg, HBeAg and HBV DNA with or without seroconversion to anti-HBs, but with the persistence of residual cccDNA, accompanied by resolution of liver injury after the completion of a finite course of treatment. Accumulating data from a series of randomized controlled trials as well as clinical practice have confirmed certain clinical benefit of optimal sequential/combination strategies of direct acting antiviral drugs (DAA) [such as nucleoside analogues (NA) ]or immunomodulators [such as pegylated interferon alpha (PEG-IFN) ]for appropriately selected CHB patients. This consensus provides an updated and comprehensive analysis of the data supporting the use of combination therapies and summarizes the roadmap towards clinical cure of CHB to guide decision-making in clinical practice.

An excerpt of the 2019 World Gastroenterology Organisation clinical practice guidelines: Diagnosis and treatment of pancreatic cystic lesions
Wang LeJunZi, Zhu RuiZhe, Zhang TaiPing, Zhao YuPei
2019, 35(8): 1702-1705. DOI: 10.3969/j.issn.1001-5256.2019.08.009
Abstract:
An excerpt of hepatitis B management during immunosuppression for haematological and solid organ malignancies: An Australian consensus statement 2019
Sun MengYing, Wang Shuai, Tang ShanHong, Zeng WeiZheng
2019, 35(8): 1706-1707. DOI: 10.3969/j.issn.1001-5256.2019.08.010
Abstract:
An excerpt of Wilson’s disease: Clinical practice guidelines of the Indian National Association for Study of the Liver, the Indian Society of Pediatric Gastroenterology, Hepatology and Nutrition, and the Movement Disorders Society of India (2019)
Wang Le, Deng BaoCheng, Qi XingShun
2019, 35(8): 1708-1709. DOI: 10.3969/j.issn.1001-5256.2019.08.011
Abstract:
Original articles_Viral hepatitis
Screening for hepatitis C virus infection in Peking University People's Hospital in 2015-2018
Kong XiangSha, Yang RuiFeng, Zhang HaiYing, Ji Ying, Zhu Ling, Liu Yan, Wei Lai
2019, 35(8): 1710-1713. DOI: 10.3969/j.issn.1001-5256.2019.08.012
Abstract:
Objective To investigate missed detection in the screening for hepatitis C virus (HCV) infection in a general hospital in 2015-2018. Methods A retrospective analysis was performed for the data of 3659 patients who attended People's Hospital, Peking University, from 2015 to 2018 and underwent the detection of anti-HCV and HCV RNA. Architect I2000 by Abbott and Vitros 3600 by Johnson and Johnson were used to measure anti-HCV, and the Roche Cobas AmpliPrep/Cobas Taqman 96 automatic virus quantification system was used to measure HCV RNA. The specimens were collected from the patients with positive HCV RNA and negative anti-HCV, and Sanger sequencing was used to determine HCV genotype. The patients were followed up to observe the status of HCV infection and clinical conditions. The signal-to-cut-off (S/CO) ratio was used to express the results of anti-HCV detection. GraphPad Prism 5. 0 was used to plot the distribution map of the S/CO ratio of anti-HCV. Results Of all 3659 patients, 6 (0. 16%) had negative anti-HCV based on at least one reagent and positive HCV RNA, with a mean level of (6. 40 ± 1. 86) log10 IU/ml. Among these 6 patients, 5 (83%) had acute leukemia and 1 had respiratory disease; among these patients, 1 had good prognosis, 3 had poor prognosis, and 2 died. Conclusion When antibody is used as the primary screening method for HCV infection, the rate of missed detection reaches 0. 16%, and most of these patients have poor prognosis. HCV RNA detection should be performed for patients with immunodeficiency to avoid missed detection.
Clinical effect and safety of sofosbuvir-based regimens in treatment of hepatitis C virus-associated glomerulonephritis
He CaiNi, Li Yu, Ge Heng, Wei Fu, Ma XiaoTao, Wang WenJun, Gao Ning, Duan ChaoYang, Ji FanPu
2019, 35(8): 1714-1718. DOI: 10.3969/j.issn.1001-5256.2019.08.013
Abstract:

Objective To investigate the clinical effect and safety of sofosbuvir-based regimens in the treatment of hepatitis C virus (HCV) -associated glomerulonephritis (HCV-GN) . Methods A retrospective analysis was performed for the clinical data of 5 patients with HCV-GN who were given sofosbuvir-based antiviral therapy in The Second Affiliated Hospital of Xi'an Jiaotong University from April2015 to October 2018, and their clinical outcome and safety were analyzed. The patients were evaluated in terms of sustained virologic response at 12 weeks after treatment ended (SVR12) , changes in liver/renal function and urinary protein during and after treatment, and safety.Results Five patients were enrolled, with an age of 27-81 years. There were 4 male patients, among whom 2 had liver cirrhosis. Of all patients, 4 had genotype 1 b and 1 had genotype 2 a. Renal biopsy was performed for 2 patients, who were diagnosed with membranoproliferative glomerulonephritis and mesangial proliferative glomerulonephritis, respectively. Of all patients, 2 received sofosbuvir + ribavirin, 2 received ledipasvir/sofosbuvir, and 1 received sofosbuvir/velpatasvir for 12 or 24 weeks. All 5 patients achieved SVR12. There were significant reductions in alanine aminotransferase and 24-hour urinary protein excretion from baseline to the end of treatment and 12 weeks of follow-up, with a slight increase in serum albumin. Blood urea nitrogen and serum creatinine were improved or showed no change. Only 1 patient experienced adverse gastrointestinal events associated with ribavirin. Conclusion Sofosbuvir-based regimens have good clinical effect and tolerability in patients with HCV-GN. Long-term follow-up should be performed to evaluate the long-term prognosis of renal disease after HCV clearance.

Original articles_Liver fibrosis and liver cirrhosis
Safety and efficacy of flow-reducing stent in treatment of recurrent or persistent hepatic encephalopathy after transjugular intrahepatic portosystemic shunt
He ChuangYe, Chen Hui, Lyu Yong, Xia DongDong, Yu TianLei, Yuan XuLong, Li Kai, Wang ZhengYu, Niu Jing, Bai Wei, Guo WenGang, Tie Jun, Yin ZhanXin, Han GuoHong
2019, 35(8): 1719-1722. DOI: 10.3969/j.issn.1001-5256.2019.08.014
Abstract:

Objective To investigate the safety and efficacy of flow-reducing stent in the treatment of recurrent or persistent hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) . Methods A total of 11 patients who were diagnosed with recurrent or persistent HE after TIPS in The First Affiliated Hospital of Air Force Medical University from January 2013 to August 2018 were enrolled. Objective scales were used to evaluate the patients with HE before and after the implantation of flow-reducing stent. Metal covered stents with the same type and an appropriate length were selected as the flow-reducing stents, and conventional portal venography and hepatic venous pressure gradient measurement were performed during and after surgery. The primary endpoint was the change in HE. The paired t-test was used to analyze the changes in related indices after surgery. Results All 11 patients underwent successful implantation of the flow-reducing stent. Within 1 week after implantation, 8 patients had disappearance of HE and 2 had HE reduced to grade 1, among whom 1 had no marked improvement in HE due to severe liver cirrhosis and liver failure. Of all patients, 2 used the 4-mm flow-reducing stent, 8 used the 5-mm flow-reducing stent, and 1 used the 6-mm flow-reducing stent, and there was a significant increase in hepatic venous pressure gradient after surgery [ (6. 09 ± 0. 70) mm Hg vs (15. 36 ± 2. 94) mm Hg, t = 2. 53, P = 0. 003 8]. There was a significant reduction in the time for digital coding test after surgery [ (269 ± 80) s vs (464 ± 90) s, t = 2. 94, P = 0. 001]. The patients had a significant improvement in albumin at 1 month after surgery (t = 1. 75, P = 0. 013) . The 2 patients receiving the 4-mm flow-reducing stent died of gastrointestinal bleeding at 6 and 12 months after surgery, respectively; among the 8 patients receiving the 5-mm flow-reducing stent, 2 experienced rebleeding at 3 months after surgery, 1 experienced massive ascites at 15 months after surgery, and 1 died of jaundice, intrac-table ascites, and liver failure at 2 years after surgery; the 1 patient receiving the 6-mm flow-reducing stent died of acute-on-chronic liver failure on day 25 after surgery. Conclusion Flow-reducing stent can effectively improve recurrent or persistent HE after TIPS and is safe and feasible; however, a small diameter of stent may lead to increased portal hypertension due to stent restenosis.

Original articles_Liver neoplasms
Influence of dual positivity of HBsAg and anti-HBs on the development of hepatocellular carcinoma in patients with chronic hepatitis B: A Meta-analysis
Fan MengJie, Zeng Zheng
2019, 35(8): 1723-1727. DOI: 10.3969/j.issn.1001-5256.2019.08.015
Abstract:

Objective To investigate the influence of dual positivity of HBsAg and anti-HBs on the development of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) infection. Methods PubMed, Embase, Cochrane Library, CNKI, and Wanfang Data were searched for articles on the influence of dual positivity of HBsAg and anti-HBs on the risk of HCC published from July 1, 1975 to March 27, 2019. RevMan5. 3 and Stata11. 2 were used for statistical analysis of data. A heterogeneity analysis was performed for the studies included; a random effects model was used in case of significant heterogeneity, and a fixed effects model was used in case of non-significant heterogeneity. Odds ratio (OR) and corresponding 95% confidence interval (CI) were used to investigate the association of dual positivity of HBsAg and anti-HBs with the development of HCC. Begg funnel plots were used to investigate publication bias. By removing one article each time, the sensitivity analysis was used to assess the quality and reliability of the Meta-analysis. Results A total of 4 articles were included, with 2 studies in the Korean population and 2 in the Chinese population, and there were 3042 patients in total. The meta-analysis showed that there was no significant association between dual positivity of HBsAg and anti-HBs and the development of HCC (OR = 1. 46, 95% CI: 0. 76-2. 80, P = 0. 25) . A country-based subgroup analysis showed significant association between dual positivity of HBsAg and anti-HBs and the development of HCC in the Korean population (OR = 2. 67, 95% CI: 1. 61-4. 43, P = 0. 000 1) , while no significant association was found in the Chinese population (OR = 0. 89, 95% CI: 0. 48-1. 64, P = 0. 70) . Conclusion There is no significant association between dual positivity of HBsAg and anti-HBs and the development of HCC, and further studies are needed in future.

Effect of cryoablation versus microwave ablation on clinical indices and cytokines in patients with hepatocellular carcinoma
Xiang Jiao, Jia XiaoDong, Lu ShanShan, Wu DaWei, Zhang Ting, Dong JinKe, Huang JiaGan, Li YinYin, Yang Bin, Xu Yong, Dong Zheng, Lu Ying, Zeng Zhen, Lu YinYing
2019, 35(8): 1728-1733. DOI: 10.3969/j.issn.1001-5256.2019.08.016
Abstract:

Objective To investigate the changes in clinical indices and cytokines in peripheral blood after cryoablation or microwave ablation in patients with hepatocellular carcinoma (HCC) and related clinical significance. Methods A total of 62 patients with HCC who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from June to December, 2018, were enrolled, and according to the treatment regimen, these patients were divided into cryoablation group with 30 patients and microwave ablation group with 32 patients. The two groups were compared in terms of routine blood test results [white blood cell count (WBC) , hemoglobin, and platelet count (PLT) ], liver function [alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , total bilirubin (TBil) , and albumin], coagulation function (international normalized ratio) , and peripheral blood cytokines [interleukin-2, tumor necrosis factor-α, interleukin-6 (IL-6) , interleukin-8, hepatocyte growth factor (HGF) , and vascular endothelial growth factor A (VEGFA) ]at 1 week before surgery and on day 2 after surgery. The chi-square test and the Fisher's exact test were used for comparison of categorical data between groups, and the t-test and the Mann-Whitney U test were used for comparison of continuous data between groups. Results Both groups had a significant increase in WBC and a significant reduction in PLT after surgery (cryoablation group: t =-7. 480 and-4. 280, both P < 0. 001; microwave ablation group:t =-5. 735 and-3. 075, both P < 0. 001) , and the cryoablation group had a significantly greater reduction in PLT than the microwave ablation group (Z =-4. 457, P <0. 001) . Both groups had significant increases in ALT, AST, and TBil after surgery (cryoablation group: Z =-4. 457, -4. 445, and-4. 229, all P < 0. 001; microwave ablation group: Z =-3. 617, -4. 703, and-4. 228, all P < 0. 001) , and the cryoab-lation group had significantly greater increases in ALT and AST than the microwave ablation group (Z =-3. 411 and-3. 829, both P <0. 001) . The cryoablation group had significant increases in IL-6, HGF, and VEGFA after surgery (Z =-4. 076, -4. 311, and-3. 123, all P < 0. 05) , with significantly greater increases than the microwave ablation group (Z =-2. 735, -2. 578, and-2. 201, all P <0. 05) . Conclusion Compared with microwave ablation, cryoablation can induce a higher level of acute inflammatory response within the short term after surgery, which may lead to higher rates of postoperative complications and tumor recurrence.

Expression of TM6SF2 in hepatocellular carcinoma tissue and its bioinformatics functions
Xiao JianHan, Liu ShouSheng, Zhao ZhenZhen, Xin YongNing, Xuan ShiYing
2019, 35(8): 1734-1739. DOI: 10.3969/j.issn.1001-5256.2019.08.017
Abstract:

Objective To investigate the expression of TM6 SF2 in hepatocellular carcinoma (HCC) tissue and its biological functions by data mining in tumor databases. Methods The GEPIA database was applied to measure the change in the mRNA expression level of TM6 SF2 in HCC tissue, and OncoLnc was used to analyze the association of TM6 SF2 expression with the survival time of HCC patients. The cBioPortal and LinkedOmics databases were used to analyze the genes associated with the expression of TM6 SF2 in HCC tissue, and the DAVID6. 8 and STRING databases were used to perform a bioinformatics analysis of TM6 SF2 and the genes associated with its expression. The t-test was used to investigate the difference in the mRNA expression of TM6 SF2 between HCC tissue and adjacent tissue. The Spearman correlation coefficient was used to analyze the correlation of gene expression. The Kaplan-Meier method was used to calculate survival percentage, and the log-rank test was used to analyze the difference in survival percentage. Results Compared with the normal liver tissue, the HCC tissue had low mRNA expression of TM6 SF2 (| log2 FC | cut-off = 0. 5, P < 0. 01) . Compared with those with high expression of TM6 SF2, the patients with low expression had a significant reduction in overall survival time (χ2= 9. 897, P < 0. 01) . Data analysis showed that a total of 49 genes were associated with the expression of TM6 SF2 in HCC tissue, and the gene ontology analysis showed that these genes were enriched in the biological processes and functions including fatty acid synthesis, fatty acid ligase activation, and thrombin regulation (P< 0. 05) . The Kyoto Encyclopedia of Genes and Genome pathway analysis showed that these genes were mainly involved in the signaling pathways of alanine metabolism, peroxisome proliferator-activated receptor signaling pathway, and bile secretion (P < 0. 05) . The protein-protein interaction network analysis showed that the genes of SERPINC1, NR1 I2, SERPINA10, and SLC10 A1 had marked or potential interaction with TM6 SF2 (P < 0. 01) . Conclusion Tumor data mining can quickly obtain the information on the expression of TM6 SF2 in HCC tissue and provide a bioinformatics basis for exploring the role of TM6 SF2 in the development and progression of HCC.

Construction and functional enrichment analysis of circRNA-miRNA-mRNA regulatory network for liver cancer based on high-throughput sequencing
Zhao Jing, Yang XingWu, Li JingTao, Wang Qi, Wang Liang, Wang GuoTai
2019, 35(8): 1740-1744. DOI: 10.3969/j.issn.1001-5256.2019.08.018
Abstract:

Objective To construct a protein interaction network based on high-throughput sequencing data of liver cancer-related non-coding RNAs, to perform a functional enrichment analysis, and to screen out circular RNAs (circRNAs) participating in the development and progression of liver cancer via the mechanism of competitive endogenous RNA (ceRNA) . Methods The circRNA-miRNA-mRNA network was constructed using gene expression omnibus (GEO) data based on the ceRNA theory. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analyses were performed to identify circRNAs with potential ceRNA function and explore their functions. Results A total of 9 co-expressed circRNAs, 20 co-expressed miRNAs, and 153 co-expressed mRNAs were screened out from the GEO database, and the liver cancer-related circRNA-miRNA-mRNA network was successfully constructed. The GO analysis revealed 90 biological processes, which mainly involved 12 functional clusters including hepatocyte differentiation, phase-change regulation of cell cycle, and negative regulation of transcription factor activity. The KEGG analysis showed that the co-expressed circRNAs were also involved in the p53 and PI3 K-Akt signaling pathways. Conclusion This study provides new insights for circRNAs mediating the development and progression of liver cancer through the mechanism of ceRNA.

Original articles_Biliary diseases
Association of serum high-density lipoprotein cholesterol with new-onset cholelithiasis
Sun MiaoMiao, Cao LiYing, Sun WeiDong, Liu XiNing, Cui HaoZhe, Liang MingYang, Wei YaoChen, Wang WanChao, Liu SiQing
2019, 35(8): 1745-1750. DOI: 10.3969/j.issn.1001-5256.2019.08.019
Abstract:
Objective To investigate the influence of serum high-density lipoprotein cholesterol (HDL-C) level on new-onset cholelithiasis. Methods A prospective cohort study was conducted. The physical examination data of 87 891 on-the-job and retired workers in Kailuan Group were collected from July 2006 to December 2015 and were included in the statistical analysis. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, the Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between multiple groups, and the chi-square test was used for comparison of categorical data between groups. The subjects were divided into four groups according to HDL-C quartiles, and the incidence density of cholelithiasis was calculated for each group. The life-table method was used to calculate the cumulative incidence rate of cholelithiasis in each group, the log-rank test was used for comparison between groups, and the Cox regression model was used to analyze the influence of HDL-C level on new-onset cholelithiasis. Results There were significant differences between the four groups in sex, age, body mass index, low-density lipoprotein cholesterol, HDL-C, fasting blood glucose, high-sensitivity C-reactive protein, triglyceride, total cholesterol, hypertension, diabetes, drinking, smoking, and physical exercise (all P < 0. 05) . During the mean follow-up time of 8. 19 ± 0. 85 years, a total of 2881 cases of new-onset cholelithiasis were observed, and the incidence density of cholelithiasis in the four groups was 4. 36 per 1000 person-years, 3. 81 per 1000 person-years, 3. 96 per 1000 person-years, and 3. 90 per 1000 person-years, respectively. The cumulative incidence rates in the four groups were 6. 49%, 6. 01%, 6. 36%, and 6. 16%, respectively, and the log-rank test showed a significant difference between groups (χ2= 25. 34, P < 0. 05) . In the Cox proportional hazards regression model, after the adjustment for possible confounding factors, the results showed that compared with the first quartile group of HDL-C, the second, third, and fourth quartile groups had hazard ratios (95% confidence interval) for gallstone disease of 0. 84 (0. 75-0. 93) , 0. 86 (0. 78-0. 96) , and 0. 78 (0. 70-0. 86) , respectively (P for trend < 0. 05) . Conclusion A high serum level of HDL-C is an independent protective factor against new-onset chole-lithiasis, and the risk of cholelithiasis decreases with the increase in HDL-C.
Role of 99mTc-EHIDA hepatobiliary scintigraphy in the eraluation of gallbladder contraction function before laparoscopic-hard endoscopic gallbladder-preserving cholecystolithotomy
Duan DongFeng, Yang ZhenYu, Du XiLin, Wang Qing, Lu JianGuo
2019, 35(8): 1751-1754. DOI: 10.3969/j.issn.1001-5256.2019.08.020
Abstract:
Objective To investigate the role of radionuclide hepatobiliary scintigraphy in the evaluation of gallbladder contraction function, and to provide a theoretical basis for preoperative evaluation of gallbladder contraction function in patients undergoing laparoscopic-hard endoscopic gallbladder-preserving cholecystolithotomy. Methods A total of 47 patients with gallstones who were admitted to The Second Affiliated Hospital of Air Force Medical University from June to December, 2016, and underwent99 mTc-EHIDA hepatobiliary imaging to evaluate gallbladder contraction function were enrolled. The radioactive count of the gallbladder was measured after fat meal and gallbladder contraction function was evaluated. A comparative analysis was performed based on intraoperative exploration and gallbladder-preserving outcome.Results A total of 26 patients with negative results of the EHIDA gallbladder contraction test underwent a successful gallbladder-preserving surgery, and some of them had no recurrence of stones after 24 months of follow-up. Among the 12 patients with impaired gallbladder contraction function shown by EHIDA, 1 underwent cholecystectomy due to roughness of the gallbladder wall and deposition of a large amount of cholesterol crystal, and 11 underwent gallbladder-preserving cholecystolithotomy. Among the 9 patients without the image of the gallbladder, 1 was found to have stones with a diameter of 2 cm embedded in the neck of the gallbladder by intraoperative exploration and underwent gallbladder-preservation surgery, and no recurrence of gallbladder stones was observed after 24 months of follow-up; the remaining 8 patients underwent cholecystectomy. Conclusion99 mTc-EHIDA hepatobiliary scintigraphy has a certain value in evaluating gallbladder contraction function, but it cannot be used as the only evidence for the selection of surgical approach. Laparoscopic-hard endoscopic intraoperative exploration is a strong evidence for the selection of gallbladder-preserving surgery, and formal industry standards can be developed.
Value of Nutritional Risk Screening 2002 and Mini Nutritional Assessment-Short Form in predicting the survival time of patients with malignant obstructive jaundice after surgery
Han ShanShan, Zhao JunHui, Ye Jun, Liu Rui, Chen WeiWei, Feng ZhiQiang
2019, 35(8): 1755-1759. DOI: 10.3969/j.issn.1001-5256.2019.08.021
Abstract:
Objective To investigate the value of Nutritional Risk Screening 2002 (NRS-2002) and Mini Nutritional Assessment-Short Form (MNA-SF) in assessing the nutritional status of patients with malignant obstructive jaundice (MOJ) and their association with overall survival (OS) after surgery. Methods A total of 78 patients with MOJ who attended Air Force Medical Center from January 2016 to January 2018 and underwent percutaneous transhepatic cholangial drainage and biliary stent implantation were enrolled. Nutritional screening was performed within 24 hours after admission. An 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; the chi-square test was used for comparison of categorical data between groups. The consistency test was used to evaluate the consistency between NRS-2002 and MNA-SF. A multivariate linear regression analysis was used to investigate the independent influencing factors for NRS-2002 and MNA-SF, and univariate and multivariate Cox regression analyses were used to identify the independent risk factors for OS. The log-rank test was used for comparison of OS between patients with different nutritional status. Results According to NRS-2002, there were 10 patients with normal nutrition (12. 8%) , 53 patients with the risk of malnutrition (67. 9%) , and 15 patients with malnutrition (19. 2%) . According to MNA-SF, there were 7 patients with normal nutrition (9. 0%) , 32 patients with the risk of malnutrition (41. 0%) , and 39 patients with malnutrition (50. 0%) . Age and body mass index were independent influencing factors for NRS-2002 and MNA-SF (all P < 0. 05) . There was good consistency between NRS-2002 and MNA-SF (Kappa = 0. 418, P < 0. 001) . Both nutritional scales showed that the patients with malnutrition had significantly shorter OS than those with the risk of malnutrition or normal nutrition (χ2= 42. 081, P < 0. 001) , and the patients with the risk of malnu-trition had significantly shorter OS than those with normal nutrition (χ2= 33. 723, P < 0. 001) . Malnutrition based on NRS-2002 (hazard ratio [HR]= 3. 874, 95% confidence interval [CI]: 1. 065-14. 099) , risk of malnutrition based on MNA-SF (HR = 15. 544, 95% CI:2. 324-103. 968) , and malnutrition (HR = 42. 535, 95% CI: 6. 179-292. 798) were independent influencing factors for OS (P < 0. 05) .Conclusion MNA-SF is superior to NRS-2002 in screening the nutritional status of MOJ patients and can predict OS more accurately.Therefore, it is recommended as a nutritional screening tool for MOJ patients on admission and nutritional intervention can be given based on the results of screening.
Clinical effect of different methods for endoscopic precut sphincterotomy in difficult intubation during endoscopic retrograde cholangiopancreatography: A comparative analysis
Shi BaoPing, Fu Yan, Lu MingLiang, Liu GuoBin, Li XinHua, Wei Li, Hu YiTao, Yang Juan
2019, 35(8): 1760-1765. DOI: 10.3969/j.issn.1001-5256.2019.08.022
Abstract:
Objective To investigate the clinical characteristics of different methods for endoscopic precut sphincterotomy in difficult intubation during endoscopic retrograde cholangiopancreatography (ERCP) . Methods A retrospective analysis was performed for the clinical data of 185 patients who underwent ERCP and precut sphincterotomy in The Second Affiliated Hospital of Kunming Medical University from May2015 to December 2018. According to the method for endoscopic precut sphincterotomy, these patients were divided into needle-knife precut sphincterotomy (NKP) group with 73 patients, needle-knife fenestration (NKF) group with 24 patients, transpancreatic precut sphincterotomy (TPS) group with 30 patients, and arch-knife precut sphincterotomy group (Erlangen group) with 58 patients. These four precut methods were analyzed in terms of advantages and disadvantages, influence on the success rate of intubation, and increase or reduction in complications. 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 comparison within each group; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Nemenyi method was used for further comparison between two groups.The chi-square test was used for comparison of categorical data between multiple groups, and a logistic regression analysis was used to determine risk factors and perform a multivariate analysis. Results The NKF and TPS groups had a significantly higher success rate of intubation than the NKP group (both P < 0. 05) . The TPS group had a significantly lower incidence rate of complications than the NKF group, and the NKF group had a significantly higher incidence rate of complications than the NKP group (both P < 0. 05) . The Erlangen group had asignificantly higher incidence rate of complications than the NKP and TPS groups (both P < 0. 05) . NKF (odds ratio [OR]= 2. 420, 95%confidence interval [CI]: 0. 235-0. 828, P = 0. 036) and TPS (OR = 1. 752, 95% CI: 0. 238-0. 594, P = 0. 029) were influencing factors for successful intubation. Age > 57 years (OR = 0. 094, 95% CI: 0. 028-0. 316, P < 0. 001) and total time of operation (OR =1. 029, 95% CI: 1. 002-1. 057, P = 0. 036) were influencing factors for post-ERCP pancreatitis (PEP) , and further multivariate logistic regression analysis showed that age > 57 years (OR = 0. 065, 95% CI: 0. 017-0. 256, P < 0. 001) was an independent protective factor against the risk of PEP, while total time of operation (OR = 1. 040, 95% CI: 1. 007-1. 074, P = 0. 016) was an independent risk factor for PEP. Conclusion TPS may be safer and more effective than NKP and Erlangen under certain conditions. Age and total time of operation may influence the incidence rate of complications.
Original articles_Pancreatic diseases
Role of CT signs of thoracoabdominal complications, serum calcium, and serum C-reactive protein in evaluating disease severity in patients with acute pancreatitis
Li ManHua, Zhang Wen, Xiang XiaoHui, Xu Wei, Xia ShiHai
2019, 35(8): 1766-1769. DOI: 10.3969/j.issn.1001-5256.2019.08.023
Abstract:
Objective To investigate the role of CT signs of thoracoabdominal complications, serum calcium, and serum C-reactive protein (CRP) in evaluating disease severity in patients with acute pancreatitis (AP) . Methods A retrospective analysis was performed for the results of thoracoabdominal CT and blood examination of 95 patients with AP who were treated in Characteristic Medical Center of Chinese People's Armed Police Force from December 2017 to December 2018. The patients were divided into severe AP (SAP) group with 13 patients and mild AP (MAP) group with 82 patients. The association of CT signs of thoracoabdominal complications, serum calcium, and serum CRP with the severity of AP was analyzed. The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. A logistic regression model was established based on the combination of related indices, and predicted probability was used as a new index for analysis; the receiver operator characteristic (ROC) curve was used to evaluate the effectiveness of each index in predicting disease severity. Results Compared with the MAP group, the SAP group had significantly higher incidence rates of ascites, pneumonia, and pleural effusion (χ2= 8. 561, 8. 120, and 9. 750, all P < 0. 05) , while there was no significant difference in the incidence rate of peritonitis between the two groups (P > 0. 05) . Compared with the MAP group, the SAP group had a significantly higher serum level of CRP (Z = 19. 16, P < 0. 05) , a significantly longer length of hospital stay (t = 3. 97, P < 0. 05) , and a significantly lower level of blood calcium (t = 4. 21, P < 0. 05) . The logistic regression analysis showed that ascites (odds ratio [OR] =4. 992, 95% confidence interval [CI]: 2. 087-6. 543, P = 0. 012) , pneumonia (OR = 1. 273, 95% CI: 1. 013-1. 520, P = 0. 042) , and pleural effusion (OR = 3. 521, 95% CI: 1. 080-4. 691, P = 0. 022) were independent risk factors for SAP, while peritonitis (OR =1. 007, 95% CI: 0. 990-1. 175, P = 0. 156) was not an independent risk factor. The ROC curve analysis showed that in the evaluation of disease severity, peritonitis, ascites, pneumonia, and pleural effusion had an area under the ROC curve (AUC) of 0. 635, 0. 738, 0. 714, and 0. 710, respectively, and the number of these CT signs had an AUC of 0. 807; serum calcium and CRP had an AUC of 0. 789 and0. 835, respectively, and serum calcium and CRP combined with the number of CT signs had an AUC of 0. 901. Conclusion Serum calcium and CRP combined with the number of thoracoabdominal CT signs (peritonitis, ascites, pneumonia, and pleural effusion) have high specificity, sensitivity, and accuracy in predicting disease severity in patients with AP, and therefore, it has a high clinical value and holds promise for clinical application.
Clinical value of the measurement of intra-abdominal pressure, C-reactive protein, and procalcitonin in patients with acute pancreatitis in late pregnancy
Liao WenYan, Yang ChunFen, Qin YongXi, He Jun, Ding ChengMing
2019, 35(8): 1770-1774. DOI: 10.3969/j.issn.1001-5256.2019.08.024
Abstract:

Objective To investigate the clinical value of the measurement of intra-abdominal pressure (IAP) , C-reactive protein (CRP) , and procalcitonin (PCT) in patients with acute pancreatitis in late pregnancy. Methods A total of 80 patients with acute pancreatitis in late pregnancy (≥28 gestational weeks) who were hospitalized in Department of Obstetrics and Gynecology and Department of Hepatobiliary Surgery in The First Affiliated Hospital of Nanhua University from September 2008 to September 2018 were enrolled, and among these patients, 45 with mild or moderately severe acute pancreatitis were enrolled as control group, and 35 with severe acute pancreatitis were enrolled as observation group. Related clinical data were collected, including IAP, CRP, PCT, fetal distress, and neonatal Apgar score. 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. A Pearson correlation analysis was used to investigate the correlation of CRP, PCT, and IAP with the severity of pancreatitis and poor fetal outcomes (fetal distress and neonatal Apgar score at 1 minute after birth) . The receiver operating characteristic (ROC) curve was used to calculate the optimal cut-off values of these indices for accurate diagnosis and corresponding sensitivity and specificity, in order to evaluate their value in predicting acute pancreatitis in late pregnancy. Results Compared with the control group, the observation group had significantly higher levels of CRP (185. 92 ± 23. 59 mg/L vs 120. 92 ± 20. 02 mg/L, t = 13. 318, P < 0. 001) , PCT (12. 93 ± 3. 16 ng/ml vs 5. 67 ± 1. 65 ng/ml, t = 12. 298, P < 0. 001) , and IAP (12. 67 ± 1. 40 mm Hg vs 5. 77 ± 1. 10 mm Hg, t =23. 858, P < 0. 001) . Compared with the observation group, the control group had a significantly lower incidence rate of fetal distress (6/45vs 15/35, χ2= 8. 864, P = 0. 003) and a significantly higher neonatal 1-minute Apgar score (8. 22 ± 0. 67 vs 5. 97 ± 0. 78, t =-13. 817, P < 0. 001) . The correlation analysis showed that IAP was positively correlated with CRP, PCT, and Ranson score for pancreatitis in late pregnancy (r = 0. 814, 0. 712, and 0. 788, all P < 0. 001) and was negatively correlated with neonatal 1-minute Apgar score (r =-0. 820, P < 0. 001) . CRP had an area under the ROC curve (AUC) of 0. 838 at the optimal cut-off value of 158. 32 mg/L, with a sensitivity of77. 1% and a specificity of 93. 3%; PCT had an AUC of 0. 853 at the optimal cut-off value of 10. 23 ng/L, with a sensitivity of 71. 4%and a specificity of 97. 8%; IAP had an AUC of 0. 903 at the optimal cut-off value of 10. 09 mm Hg, with a sensitivity of 82. 9% and a specificity of 95. 6%. Conclusion The measurement of IAP, CRP, and PCT has a good value in the early prediction of severe acute pancreatitis in pregnancy and can help to determine the severity of pancreatitis in late pregnancy and decide the timing of termination of pregnancy.

Original articles_Others
Clinical effect of Silybum marianum preparation in the prophylactic treatment of antitubercular agent-induced liver injury: A Meta-analysis of randomized controlled trials
Tao LiNa, Qu XiaoYu, Zhang Yue, Song YanQing, Zhang SiXi
2019, 35(8): 1775-1781. DOI: 10.3969/j.issn.1001-5256.2019.08.025
Abstract:

Objective To evaluate the clinical effect of Silybum marianum preparation in the prophylactic treatment of antitubercular agent-induced liver injury (ATB-DILI) , since there have always been controversies over the development of Silybum marianum preparation for the prophylactic treatment of ATB-DILI. Methods MEDLINE, PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) on Silybum marianum preparation versus placebo in preventing ATB-DILI published up to November 30, 2018. STATA 12. 0 software was used for statistical analyses. Standardized mean difference (SMD) and risk ratio (RR) with 95% confidence intervals (CI) were used to evaluate the effect of Silybum marianum preparation. The Cochrane handbook was used to assess the quality of RCTs, and funnel plots and Egger's tests were used to evaluate publication bias. A sensitivity analysis was conducted to assess the influence of each RCT on overall effect. Results A total of five RCTs with 1198 patients were included, and among these patients, 585 received Silybum marianum preparation and 613 received placebo. Silybum marianum preparation significantly reduced the risk of the onset of ATB-DILI at week 4 (RR = 0. 33, 95% CI: 0. 15-0. 75, P = 0. 008) . In addition, Silybum marianum preparation had a protective effect on liver function in patients receiving antitubercular agents (alanine aminotransferase: SMD =-0. 15, 95% CI:-0. 24 to-0. 07, P < 0. 001; aspartate aminotransferase: SMD =-0. 14, 95% CI:-0. 23 to-0. 06, P = 0. 001; alkaline phosphatase: SMD =-0. 12, 95% CI:-0. 20 to-0. 03, P = 0. 008) . Silybum marianum preparation had a similar risk of adverse events as placebo (RR = 1. 09, 95%CI: 0. 86-1. 39, P = 0. 47) . Conclusion In patients with tuberculosis, prophylactic treatment with Silybum marianum preparation can significantly reduce the risk of the onset of ATB-DILI after 4 weeks of treatment. In addition, Silybum marianum preparation can also improve the liver function of patients treated with antitubercular agents.

Correlation of severity of infantile cholestatic liver disease with serum vitamin D level
Huang CaiZhi, Nie BoLi, Tang Lian, Mo LiYa
2019, 35(8): 1782-1785. DOI: 10.3969/j.issn.1001-5256.2019.08.026
Abstract:

Objective To investigate the correlation of serum 25-hydroxy vitamin D[25 (OH) D]level with the severity of infantile cholestatic hepatopathy (ICH) . Methods A total of 121 infants with ICH who were admitted or referred to Liver Research Center in our hospital from July 2015 to December 2017 were enrolled, and according to the presence or absence of liver cirrhosis, these infants were divided into liver cirrhosis group with 26 infants and non-liver cirrhosis group with 95 infants. The two groups were compared in terms of age, sex ratio, 25 (OH) D, liver function parameters [total bilirubin (TBil) , direct bilirubin (DBil) , total protein (TP) , albumin (Alb) , alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , gamma-glutamyl transpeptidase (GGT) , alkaline phosphatase (ALP) , total bile acid (TBA) , and prothrombin time (PT) ], serological markers of liver fibrosis [procollagen Ⅲ peptide (PⅢNP) , laminin (LN) , hyaluronic acid (HA) , and type Ⅳ collagen (C-Ⅳ) ], and indices associated with vitamin D metabolism (Ca and P) . The independent samples t-test or the Mann-Whitney U 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. A binary logistic regression analysis was used to investigate the factors associated with the development of liver cirrhosis. Results Of all 121 infants, 107 (88. 43%) had vitamin D deficiency, and all 26 infants with liver cirrhosis had vitamin D deficiency. Compared with the non-liver cirrhosis group, the liver cirrhosis group had significant reductions in the serum levels of 25 (OH) D and Alb (Z = 3. 029, t = 2. 294, P < 0. 05) and significant increases in the levels of DBil, AST, GGT, HA, and C-Ⅳ (Z = 3. 032, 2. 026, 3. 439, 3. 143, and 2. 247, P < 0. 05) , while there were no significant differences in the other indices between the two groups (all P > 0. 05) . The multivariate logistic regression analysis showed that 25 (OH) D (odds ratio [OR]= 0. 865, 95% confidence interval [CI]: 0. 755-0. 922, P = 0. 038) , GGT (OR = 1. 002, 95% CI: 1. 000-1. 004, P = 0. 039) , and HA (OR = 1. 004, 95% CI: 1. 000-1. 008, P = 0. 034) were associated with liver cirrhosis in infants with ICH. Conclusion Serum 25 (OH) D has a certain clinical value in predicting the severity of hepatocyte damage and the development of early liver cirrhosis in infants with ICH.

Value of second harmonic generation/two-photon excitation fluorescence in quantitative evaluation of liver fibrosis in mice with nonalcoholic fatty liver disease
Wang XiaoXiao, Zhao Jie, Li XiaoHe, Rao HuiYing, Wei Lai, Liu Feng
2019, 35(8): 1786-1790. DOI: 10.3969/j.issn.1001-5256.2019.08.027
Abstract:

Objective To investigate the dynamic changes in collagen parameters in mice with nonalcoholic fatty liver disease (NAFLD) by second harmonic generation (SHG) /two-photon excitation fluorescence (TPEF) , to establish the parameters for automatic quantitative evaluation of mice with NAFLD induced by methionine-and choline-deficient diet (MCD) , and to provide an experimental basis for the application of SHG/TPEF in clinical practice. Methods Liver tissue specimens of MCD mice were collected at weeks 0, 4, 8, 12, 16, 20, and 24, and HE staining, Masson staining, and sirius red (SR) staining were performed. Collagen proportionate area (CPA) and hydroxyproline (HYP) were calculated. SHG/TPEF was used to analyze 100 collagen parameters. With time points and fibrosis stage (S0-S4) as criteria, the SVM model was used to analyze the collagen parameters. A receiver operating characteristic (ROC) curve analysis was performed for the collagen parameters, and these parameters were compared with CPA and HYP in terms of the area under the ROC curve (AUC) . Results In the MCD mice, HE and SR staining showed that over the time of modeling, hepatic steatosis was observed in hepatic lobules, with gradual aggravation of fibrosis. A total of 26 parameters were screened out based on their correlation with time point, and 27 parameters were screened out based on their correlation with liver fibrosis stage. The analysis based on the SVM model identified 7 shared parameters (#StrCV, #ShortStrCV, #ThickStrCV, #StrPTAgg, #StrPSAgg, #LongStrPSAgg, and StrLengthPSAgg) . These 7 parameters had anAUC of 0. 857-0. 923 (P < 0. 05) in predicting different stages of liver fibrosis and an AUC of 0. 823-0. 976 (P < 0. 05) in predicting liver fibrosis at different time points. These 7 parameters were compared with CPA and HYP in terms of their value in predicting liver fibrosis, and it was found that the 7 parameters had a similar AUC as CPA and HYP in predicting S0 fibrosis, while the 7 parameters had a significantly higher AUC than CPA and HYP in predicting S1-S4 fibrosis. The 7 parameters had a similar AUC as CPA and HYP at week 0 of modeling, while at week 4 of modeling, the 7 parameters had a significantly higher AUC than CPA and HYP. Conclusion Seven parameters associated with fibrosis stage and time point can accurately reflect the changes in liver fibrosis in different stages and at different time points in a model of MCD-induced NAFLD, and therefore, they can be used for specific and accurate monitoring of liver fibrosis in a quantitative manner in this model.

Role of the specific inhibitor of 5-lipoxygenase-activating protein MK886 in inhibiting alcoholic liver disease in mice
Yang ShuJuan, Guo YaLing, Fu Shan, He YingLi, Zhao YingRen, Tian Zhen
2019, 35(8): 1791-1796. DOI: 10.3969/j.issn.1001-5256.2019.08.028
Abstract:

Objective To investigate the effect of MK886, a specific inhibitor of 5-lipoxygenase-activating protein (FLAP) , on alcoholic liver disease (ALD) in mice. Methods A total of 48 male Kunming mice were randomly divided into ALD group, ALD/MK886 group, control group, and normal group. The mice in the ALD group and the ALD/MK886 group were fed with Tipoe-Nanji alcohol liquid diet and were given alcohol by gavage 6 weeks later to establish a model of acute ALD. The mice in the control group were given control diet without alcohol, and those in the normal group were given normal diet. After 2 days of alcohol intake, the mice in the ALD/MK886 group were given intraperitoneally injected MK886 (0. 01 mg/10 g) once a day. The mice were sacrificed at 9 hours after the administration of alcohol by gavage. Serum levels of aspartate aminotransferase (AST) , alanine aminotransferase (ALT) , lactate dehydrogenase (LDH) , and triglyceride (TG) and the levels of TG and malondialdehyde (MDA) in liver tissue were measured. HE staining was performed for liver tissue and pathological score was determined. Western blot was used to measure the expression of FLAP and 5-lipoxygenase (5-LO) in liver tissue and Thp-1 cells, and flow cytometry was used to measure the apoptosis of Thp-1 cells. One-way ANOVA was used for comparison between groups; the least significant difference t-test was used for comparison of data with homogeneity of variance, and the Tamhane's T2 test was used for comparison of data with heterogeneity of variance. Results The ALD group and the ALD/MK886 group had a reduction in body weight within the first week of modeling, followed by a gradual increase; at the end of modeling, the ALD group had significantly lower bodyweight and liver index than the normal group and the control group (all P < 0. 05) , and the ALD/MK886 group had significantly higher body weight and liver index than the ALD group (both P < 0. 05) . Compared with the normal group and the control group, the ALD group had significant increases in the levels of AST, ALT, LDH, and TG in serum and the levels of TG and MDA in liver tissue (all P < 0. 05) , and compared with the ALD group, the ALD/MK886 group had significant reductions in the above indices (all P < 0. 05) . The ALD group had a significantly higher score of hepatic steatosis than the normal group and the control group (both P < 0. 05) , and compared with the ALD group, the ALD/MK886 group had a significant reduction in this score (P < 0. 05) . Compared with the normal group and the control group, the ALD group had significant increases in the expression of 5-LO and FLAP in the liver (all P < 0. 05) , and the ALD/MK886 group had significant reductions compared with the ALD group (P < 0. 05) . Lipopolysaccharide (LPS) upregulated the expression of FLAP and 5-LO in Thp-1 cells, and MK886 alleviated such effect of LPS (all P < 0. 05) ; MK886 promoted the apoptosis of Thp-1 cells, and LPS alleviated the effect of MK886 in promoting cell apoptosis (all P < 0. 01) . Conclusion MK886 can inhibit the expression of 5-LO, induce the apoptosis of Kupffer cells, and thus exert a therapeutic effect on ALD in mice.

Case reports
Hepatitis-associated aplastic anemia in children: A case report
Mu Jing, Chen Fang, He Qiang
2019, 35(8): 1797-1799. DOI: 10.3969/j.issn.1001-5256.2019.08.029
Abstract:
Senile intestinal lymphangiectasia with drug-induced liver injury: A case report
Kong XiaoLu, Shao Xue, Li DongFu
2019, 35(8): 1800-1802. DOI: 10.3969/j.issn.1001-5256.2019.08.030
Abstract:
A case of chronic drug-induced liver injury caused by psoralen decoction
Meng CunYing, Liu Jia, Cao Dan, Chen WenJing, Yuan BeiBei, Dong Bing, Ji Dong, Chen YanPing
2019, 35(8): 1803-1805. DOI: 10.3969/j.issn.1001-5256.2019.08.031
Abstract:
Autoantibody-negative autoimmune hepatitis overlapping with primary biliary cholangitis and primary sclerosing cholangitis: A case report
Meng Miao, Hu Zhen, Gong Lei, Lu ZhongHua, Peng XiaoBin, Tang XueJun, Wang XiaoYun
2019, 35(8): 1806-1808. DOI: 10.3969/j.issn.1001-5256.2019.08.032
Abstract:
Polymyositis misdiagnosed as autoimmune liver disease: A case report
Zhang LiJuan, Gao YinJie, Zhou Xia, He Xi, Feng DanNi, Zhang DaLi, Liu HongLing
2019, 35(8): 1809-1810. DOI: 10.3969/j.issn.1001-5256.2019.08.033
Abstract:
X-linked lymphoproliferative disease type 2 with cholestatic liver disease as initial manifestation: A case report
Zhou Fang, Li XiaoQin, Wang RuiFeng, Sun Bo
2019, 35(8): 1811-1814. DOI: 10.3969/j.issn.1001-5256.2019.08.034
Abstract:
A case of retroperitoneal Castleman's disease
Ren XueKang, Wang ShuPeng, Wang ShouQian, Liu YaHui
2019, 35(8): 1815-1816. DOI: 10.3969/j.issn.1001-5256.2019.08.035
Abstract:
Hepatic space-occupying lesions caused by Trichinella: A case report
Tian Bing, Liu MeiLi, Deng BaoCheng
2019, 35(8): 1817-1818. DOI: 10.3969/j.issn.1001-5256.2019.08.036
Abstract:
Neuroendocrine carcinoma of the extrahepatic bile duct: A report of 2 cases
Wang ShuPeng, Su JingHan, Wang ShouQian, Xu HongJi, Liu YaHui
2019, 35(8): 1819-1820. DOI: 10.3969/j.issn.1001-5256.2019.08.037
Abstract:
Reviews
Value of HBsAg quantification in individualized anti-HBV treatment with nucleos (t) ide analogues
Zhou YouQian, Li Cui
2019, 35(8): 1821-1823. DOI: 10.3969/j.issn.1001-5256.2019.08.038
Abstract:
Nucleos (t) ide analogues can effectively prevent or delay disease progression in patients with chronic hepatitis B virus (HBV) infection, but the course of treatment is long and long-term medication may bring the risk of adverse drug reactions and drug resistance. Recent studies have found that HBsAg quantification has an important value in individualized antiviral treatment for patients with chronic hepatitis B. This article reviews the research advances in the value of HBsAg quantification in judgment of indication for antiviral treatment with nucleos (t) ide analogues, prediction of therapeutic outcome, and timing of drug withdrawal, and it is pointed out that HBsAg quantification can help to determine the timing of antiviral treatment and predict the treatment outcome of patients at the beginning of antiviral treatment, during the treatment process, and when drug withdrawal is considered. Further studies are needed to determine the optimal predictive thresholds for different stages of HBeAg-positive or HBeAg-negative patients, as well as the optimal time point and thresholds for predicting treatment outcome during antiviral treatment with different nucleos (t) ide analogues.
Research advances in the diagnosis and treatment of patients in the immune tolerance stage of chronic hepatitis B virus infection
Zhou LuLu, Liu Na, Li ChunXia, Dong Bing, Bai XiaoXiao, Zhang Nan, Xu GuangHua
2019, 35(8): 1824-1827. DOI: 10.3969/j.issn.1001-5256.2019.08.039
Abstract:
Patients in the immune tolerance stage of chronic hepatitis B virus (HBV) infection are in a state of high viral replication and low inflammation in the liver, and they often have no disease progression. Therefore, antiviral therapy is not recommended in related guidelines.Recent studies have found that the patients in the immune tolerance stage have immune response and liver injury, which is a risk factor for liver cancer, and therefore, antiviral therapy should be actively initiated to prevent disease progression. This article summarizes the research advances in the diagnosis and treatment of patients in the immune tolerance stage of chronic HBV infection and points out that there are still controversies over the application of antiviral therapy in such patients. Appropriate timing of antiviral therapy has a great significance in improving patients' prognosis and reducing their economic burden.
Research advances in the clinical effect of tenofovir alafenamide in treatment of chronic hepatitis B
Wang SuNa, Lian JianQi, Jia ZhanSheng, Zhang Ying
2019, 35(8): 1828-1833. DOI: 10.3969/j.issn.1001-5256.2019.08.040
Abstract:
Tenofovir alafenamide (TAF) is a novel nucleoside reverse transcriptase inhibitor used in the treatment of human immunodeficiency virus (HIV) infection and chronic hepatitis B virus (HBV) infection. Compared with tenofovir disoproxil fumarate, TAF has better plasma stability and stronger liver-targeting ability and can significantly reduce the adverse events of renal injury and reduced bone mineral density. This article summarizes the research advances in the pharmacological characteristics, metabolic pathways, drug interactions, drug resistance, and renal safety of TAF and its role in patients with chronic HBV infection.
Association of biological characteristics of hepatitis B virus with the progression of liver fibrosis
Chang XiuJuan, Li YinYin, Yang Bin, Ceng Zhen, Huang JiaGan, Yang YongPing
2019, 35(8): 1834-1837. DOI: 10.3969/j.issn.1001-5256.2019.08.041
Abstract:
Hepatitis B virus (HBV) causes liver injury by stimulating host immune response and may lead to liver fibrosis, liver cirrhosis, and liver cancer. Progression of liver fibrosis is a key factor in liver disease-related death. This article summarizes the association of HBV genotype, HBV gene mutation in basic core promoter region/pre-C region, pre-S region, and X region, HBV gene splicing, HBV RNA, HBcAg, and HBsAg with the progression of liver fibrosis. It is pointed out that the above biological characteristics of HBV are closely associated with the progression of liver fibrosis.
Current status of the imaging diagnosis of liver fibrosis
Zheng You, Xu YongSheng, Zhang XuXia, Liu HaiFeng, Liu Zhao, Lei JunQiang
2019, 35(8): 1838-1841. DOI: 10.3969/j.issn.1001-5256.2019.08.042
Abstract:

Liver fibrosis is the result of the progressive development of various chronic liver diseases and can develop into liver cirrhosis and liver cancer with high mortality rates. Early diagnosis of liver fibrosis is of great significance for disease reversal. At present, liver biopsy is considered the gold standard for the diagnosis of liver fibrosis, but it cannot be used as a routine screening method due to its shortcomings.In recent years, progress has been made in various noninvasive imaging methods, and this article reviews the current status of the research on computed tomography, magnetic resonance imaging, nuclear medicine, and ultrasound in the diagnosis of liver fibrosis.

Role of FOXO1/3 in the pathogenesis of hepatic fibrosis
Li Tian, Wu Yan, Ji Ting, Jin ZhenXiao
2019, 35(8): 1842-1846. DOI: 10.3969/j.issn.1001-5256.2019.08.043
Abstract:
Hepatic fibrosis refers to the pathological process of abnormal proliferation of connective tissue in the liver caused by various pathogenic factors. Hepatic fibrosis is observed in the whole process of liver injury repair and healing, and long-term chronic injury factors may induce the progression of hepatic fibrosis into liver cirrhosis. Epidemiological data show that there are 1. 1805 million new cases of hepatitis B and 243 thousand cases of hepatitis C reported in 2017. Chronic viral hepatitis has brought heavy social and economic burden. Forkhead transcription factor (FOXO) belongs to the forkhead family and plays an important role in various cell life activities. Studies have shown that FOXO1/3 can regulate hepatic stellate cell activity through the TGFβ pathway and thus play an important role in hepatic fibrosis. This article reviews the research advances in the pathogenesis of hepatic fibrosis, the mechanism of action of FOXO1/3 in the regulation of hepatic fibrosis, and targeted therapy for FOXO1/3 (one of the sites for hepatic fibrosis) .
Role of the Numb gene in the progression of liver fibrosis
Xu Wen, Xu YanNan, Liu Ping, Mu YongPing
2019, 35(8): 1847-1850. DOI: 10.3969/j.issn.1001-5256.2019.08.044
Abstract:
Liver fibrosis is the response of the body to wound repair, and it is the only way for various chronic liver diseases to develop into liver cirrhosis. At present, there is still no chemical or biological drugs for blocking or reversing liver fibrosis. Liver fibrosis has a complex pathogenesis, which involves the TGF-β/Smad, Notch, Wnt, and Hedgehog signaling pathways. However, how to use simple methods to solve this complex issue remains a key scientific problem in the treatment field. As a critical determinant for cell fate, Numb is involved in the regulation of various signaling pathways such as Notch, Wnt, and Hedgehog, but its role in anti-fibrosis has not been taken seriously.This article reviews the potential value of Numb in anti-fibrosis.
Early diagnosis of spontaneous bacterial peritonitis in liver cirrhosis
Zhang YaNan, Jiang Chang, Xu Ying, Gao YanHang
2019, 35(8): 1851-1853. DOI: 10.3969/j.issn.1001-5256.2019.08.045
Abstract:
Spontaneous bacterial peritonitis is a common complication of liver cirrhosis, and once it occurs, the disease might progress quickly to liver failure and multiple organ failure, which has a high mortality rate. It has been documented that delayed diagnosis of peritonitis is an important factor for high mortality rate, but there is still no sensitive, rapid, and accurate method for early diagnosis of this disease in clinical practice. Therefore, how to make an early diagnosis of spontaneous bacterial peritonitis remains a research hotspot at present. This article introduces the pathogenesis, risk factors, and methods for early diagnosis of spontaneous bacterial peritonitis in patients with liver cirrhosis, so as to improve the awareness of this disease in clinical practice.
Association between intestinal barrier and bacterial translocation in patients with liver cirrhosis
Li PeiBo, Qin FanBo, Gong JianPing
2019, 35(8): 1854-1857. DOI: 10.3969/j.issn.1001-5256.2019.08.046
Abstract:
Decompensated liver cirrhosis has various life-threatening complications such as spontaneous bacterial peritonitis, hepatic encephalopathy, and sepsis, and the development of such complications is closely associated with bacterial translocation. Pathological bacterial translocation in patients with liver cirrhosis is caused by the impairment of intestinal barrier function, and thus bacteria can cross the intestinal barrier and enter the mesenteric lymph nodes or other sites. Therefore, a better understanding of the association between intestinal barrier and bacterial translocation in liver cirrhosis can provide new theoretical support for the treatment of liver cirrhosis. This article discusses the four major components of the intestinal barrier, namely the mechanical barrier, the immune barrier, the chemical barrier, and the biological barrier, as well as their changes during bacterial translocation.
Current status and perspectives of multimodality therapy for hepatocellular carcinoma
Tan YunHua, Shang YangYang, Zhang Tao, Li JianBo, Zheng MingYou
2019, 35(8): 1858-1860. DOI: 10.3969/j.issn.1001-5256.2019.08.047
Abstract:
Hepatocellular carcinoma (HCC) has high morbidity and mortality rates worldwide, and due to the complexity of the development of HCC, the management strategy for HCC has not been completely unified. During the past decade, the treatment of HCC has developed into a multidisciplinary and multimodality therapy centered on surgical operation. Besides hepatectomy and liver transplantation, ablation therapy is another radical treatment, and at present, it can be used as the first-line treatment regimen for HCC patients who have a tumor diameter of < 3 cm and cannot undergo liver transplantation. Transarterial chemoembolization is the preferred treatment for advanced HCC not suitable for radical treatment. Molecular targeted therapy is mainly used in patients who are diagnosed with advanced HCC or progress to advanced HCC after treatment failures. Cellular immunotherapy is a new treatment for HCC and can help patients with progressive HCC to achieve good remission rate and survival benefit. A deep understanding of the features of each treatment method for HCC, development of individualized treatment regimens, and rational multimodality therapy for HCC can help to improve the overall therapeutic outcome of HCC.
Current status of the research on psychosocial factors in patients with nonalcoholic fatty liver disease
He ShiHua, Hu GuoXin
2019, 35(8): 1861-1864. DOI: 10.3969/j.issn.1001-5256.2019.08.048
Abstract:
Unhealthy dietary habits and a sedentary lifestyle have led to a significant increase in the prevalence rate of non-alcoholic fatty liver disease (NAFLD) in children, adolescents, and adults. In recent years, the biological-psychological-social medical pattern has attracted more and more attention, and internal psychosocial factors have become an important influencing factor for disease progression, treatment, and prognosis. Studies have shown that patients with NAFLD may experience psychosocial disorders, and this article summarizes the common psychosocial problems of these patients.
Current status of research on mouse models of nonalcoholic fatty liver fibrosis
Wang Xin, Hu YiYang, Feng Qin
2019, 35(8): 1865-1869. DOI: 10.3969/j.issn.1001-5256.2019.08.049
Abstract:

At present, nonalcoholic fatty liver fibrosis is one of the highlights of the research on nonalcoholic fatty liver disease (NAFLD) , and there is an urgent need for exploring its pathogenesis and treatment drugs in clinical practice. Animal model is an important tool for basic research, and the mouse model becomes the most widely used animal model of nonalcoholic fatty liver fibrosis because of susceptibility, low costs, and genomes highly homologous to those of the human being. This article reviews the methods for establishing a mouse model of nonalcoholic fatty liver fibrosis, including nutritional factor, gene knockout or mutation, and induction with various factors, as well as the features of these models, in order to provide a reference for the selection of model tools in the basic research on this disease.

Influencing factors for the prognosis of primary biliary cholangitis
Xu Li, Zheng YueQi, Shi Zhen, Chen YiYun, Shao HuiJiang, Chen JianJie
2019, 35(8): 1870-1873. DOI: 10.3969/j.issn.1001-5256.2019.08.050
Abstract:
Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune disease and may progress to liver fibrosis, liver cirrhosis, and even end-stage liver disease without timely and effective treatment. The main purpose of PBC treatment is to prevent the development of end-stage liver disease and improve related clinical symptoms and quality of life. Timely and accurate risk stratification may bring benefits to patients with refractory PBC, and an accurate evaluation of the prognosis of PBC patients is of vial importance for clinical treatment. This article reviews the research advances in the prognostic factors for PBC from the aspects of host factors, laboratory examination, and pharmacotherapy.
Immunological mechanism of Treg/Th17 and Th1/Th2 balance in autoimmune hepatitis and new targets for diagnosis and treatment
Wang WeiZhao, Xiang XiaoXing
2019, 35(8): 1874-1877. DOI: 10.3969/j.issn.1001-5256.2019.08.051
Abstract:
Autoimmune hepatitis (AIH) is a chronic autoimmune disease in the liver, with major clinical manifestations of positive autoantibody, abnormal elevation of aminotransferases, and hypergammaglobulinemia. Current studies have shown that regulatory T (Treg) /T helper17 (Th17) and T helper 1 (Th1) /T helper 2 (Th2) imbalance is one of the mechanisms of the development and progression of AIH. OX40 (also known as CD134, TNFRSF4, or ACT35) and its ligand OX40 L are members of the tumor necrosis factor family, and they participate in immune response as co-stimulators of T cell activation and can regulate Treg/Th17 and Th1/Th2 balance, thus affecting the progression of various autoimmune diseases. However, there are few reports on the role of OX40 and OX40 L in AIH. With reference to related articles, this article reviews the role of Treg/Th17 and Th1/Th2 balance in AIH and the potential association between OX40/OX40 L (new targets for immunological diagnosis and treatment) and AIH.
Value of indocyanine green clearance test in assessing liver reserve function
Zhang MingMing, Zhang LingYi
2019, 35(8): 1878-1881. DOI: 10.3969/j.issn.1001-5256.2019.08.052
Abstract:
Basic liver functions can guarantee substance metabolism necessary for the body, and the liver itself has the ability of self-healing and self-regeneration. Routine liver function tests cannot fully reflect the potential of liver parenchyma, i. e., the actual status of liver reserve function. Indocyanine green clearance test is considered an ideal index for liver reserve function. This article reviews the value of indocyanine green clearance test in clinical practice, in order to improve the awareness of the importance of liver reserve function assessment among clinicians.
Research advances in the role of protective autophagy in regulating vasculogenic mimicry formation in malignancies such as cholangiocarcinoma
Wu YanBin, Wang XueWen, Niu HongKai, Cheng Yu
2019, 35(8): 1882-1884. DOI: 10.3969/j.issn.1001-5256.2019.08.053
Abstract:
Cholangiocarcinoma is a primary malignant tumor derived from the epithelium of the intrahepatic and extrahepatic bile ducts, and vasculogenic mimicry induced by hypoxia and lack of nutrition is a key factor for malignant proliferation, recurrence, and metastasis of cholangiocarcinoma. Previous studies have shown that autophagy maintains cell nutrition metabolism under the condition of a lack of nutrition, and preliminary experiments have confirmed that autophagy was associated with VM in cholangiocarcinoma and there was high expression of PAT4 in cholangiocarcinoma cells; on the basis of these studies, it is pointed out that in cholangiocarcinoma, protective autophagy regulates VM formation by maintaining intracellular metabolic balance and cellular homeostasis. As a nutrient sensor in tumor microenvironment, PAT4 mediates protective autophagy via the PI3 K-Akt-m TORC1 signaling pathway to regulate VM formation. Histological, cellular molecular, and in vivo experiments have confirmed that autophagy regulates VM formation by maintaining cell metabolism, stem cell features, and extracellular matrix remodeling, which helps to investigate the signal mechanism for PAT4 mediating autophagy to regulate VM. It is suggested that autophagy is the source of energy and nutrition in cholangiocarcinoma cells under the condition of a lack of nutrition, and PAT4 is the trigger point for autophagy in regulating VM formation. These findings provide new thoughts for the metabolism of cholangiocarcinoma cells and lay a theoretical foundation for antiangiogenic drugs combined with autophagy inhibitors in the treatment of highly aggressive tumors.
Role of long non-coding RNA in the development and progression of cholangiocarcinoma
Zhang ShiLong, Gao WeiDong, Feng ZanJie, Duan YuLing, Fan GuoXin, Peng CiJun
2019, 35(8): 1885-1888. DOI: 10.3969/j.issn.1001-5256.2019.08.054
Abstract:
Cholangiocarcinoma is a malignant tumor originating from the epithelial cells of the bile duct, and its incidence and mortality rates keep increasing year by year. Unknown pathogenesis of this disease has led to the difficulties in early diagnosis and treatment. With the development of genetic engineering and bioinformatics, more and more studies have found that long non-coding RNA (lncRNA) is closely associated with the pathophysiological process of cholangiocarcinoma. This article summarizes the research advances in the role of lncRNA in mediating the biological behaviors of cell proliferation, apoptosis, metastasis, invasion, epithelial-mesenchymal transition, and drug resistance in cholangiocarcinoma, as well as the association of lncRNA with clinical features and prognosis.