Inflammatory bowel disease(IBD) not only involves the intestinal tract,but also has several comorbidities outside the intestinal tract,among which there are various types of special comorbidities,including hematological system diseases,immune system diseases,and nervous system diseases. IBD with special comorbidities brings difficulties to the diagnosis and treatment of IBD,increases the disability rate and mortality rate of IBD patients,and greatly affects patients' quality of life. This article elaborates on the definition,prevalence trend,pathogenesis,and diagnosis and treatment strategies for IBD with special comorbidities,in order to improve the understanding of the importance of multidisciplinary cooperation in the diagnosis and treatment of IBD among clinicians.

Inflammatory bowel disease(IBD) is often accompanied by chronic liver diseases in a variety of situations. Due to the overlapping factors in the pathogenesis of IBD and autoimmune liver diseases including primary sclerosing cholangitis( PSC),primary biliary cholangitis,and autoimmune hepatitis,the co-existence of these diseases is not uncommon,among which PSC with IBD has the highest probability of more than 80%. The probability of IBD with chronic hepatitis B virus(HBV)/hepatitis C virus(HCV) infection is associated with local infection rate,and if the screening for HBV/HCV infection is ignored before the application of immunosuppressive agents,there may be a risk of aggravated HBV/HCV infection or HBV reactivation. Long-term treatment with antibiotics,steroids,and immunosuppressants may cause drug-induced liver injury in patients with IBD. Although IBD patients often have weight loss due to the factors including diarrhea and absorption disorders,these patients may have a higher probability of nonalcoholic fatty liver disease than the general population.

Inflammatory bowel disease( IBD) is a series of non-specific chronic inflammatory diseases,including ulcerative colitis and Crohn's disease. Besides gastrointestinal symptoms,IBD patients often have extraintestinal symptoms which may involve various systems such as the skeleton and muscle,skin,eyes,liver and gallbladder,pancreas,nerves,urogenital system,lungs,heart,and blood. Biliary diseases are extraintestinal manifestations of IBD and mainly include primary sclerosing cholangitis,IgG4-associated sclerosing cholangitis,primary biliary cirrhosis,and cholelithiasis. Biliary diseases may manifest as transient abnormal liver function in asymptomatic patients and even life-threatening liver failure,and different biliary diseases may have different treatment methods and prognoses and thus require careful differential diagnosis. This article reviews biliary diseases in IBD patients,in order to help clinicians get familiar with the clinical manifestations and diagnosis and treatment strategies for biliary diseases in IBD patients.

Inflammatory bowel disease( IBD) is a multisystem disease,and pancreatic diseases in patients with IBD should be taken seriously in clinical practice. This article systematically elaborates on the research status of acute pancreatitis,chronic pancreatitis,autoimmune pancreatitis,pancreatic exocrine dysfunction,pancreatic cancer,and asymptomatic laboratory examination and imaging abnormalities in IBD patients and analyzes the diagnosis and treatment strategies for these diseases,so as to provide an important reference for clinical identification and treatment of such diseases.

Hepatobiliary and pancreatic diseases are common comorbidities of inflammatory bowel disease( IBD),and the presence of such diseases may affect the diagnosis,treatment,and prognosis of IBD and has certain value in identifying the cause of IBD. This article elaborates on the epidemiology of IBD with hepatobiliary and pancreatic diseases,so as to provide new insights for understanding the pathogenesis of IBD and formulating effective clinical treatment regimens.

Inflammatory bowel disease( IBD) is a non-specific chronic intestinal inflammatory disease with unknown etiology and pathogenesis and is often accompanied by extraintestinal manifestations involving multiple organs including the liver,the gallbladder,and the pancreas,with an important impact on the prognosis of IBD. Hepatobiliary and pancreatic complications mainly include primary sclerosing cholangitis,primary biliary cholangitis,autoimmune hepatitis,IgG4-associated sclerosing cholangitis,acute pancreatitis,chronic pancreatitis,autoimmune pancreatitis,and nonspecific increase in pancreatic enzyme. IBD-related hepatobiliary and pancreatic complications are caused by the combination of environmental and immune-mediated factors in individuals with genetic susceptibility,and this article summarizes the current research advances in the pathogenesis of such hepatobiliary inflammatory bowel disease; liver diseases; biliary tract diseases;pancreatic diseases; and pancreatic complications.

Mother-to-child transmission( MTCT) of hepatitis B virus( HBV) is the main cause of chronic hepatitis B( CHB) in China,and the prevention of MTCT plays a critical role in controlling CHB. Based on Clinical guidelines for the prevention of mother-to-child transmission of hepatitis B virus( First Edition) issued in 2013,the current clinical guidelines have updated the recommendations,mainly including:( 1) all pregnant women should undergo the prenatal screening for hepatitis B serological markers;( 2) neonates whose mothers have negative HBsAg should receive hepatitis B vaccination according to the regimen of “0,1,and 6 months”,and there is generally no need for hepatitis B immunoglobulin( HBIG);( 3) neonates whose mothers have positive HBsAg need intramuscular injection of HBIG at one dose and the first dose of hepatitis B vaccine within 12 hours after birth( the sooner the better),followed by injection of the second and third doses of hepatitis B vaccine at the age of 1 and 6 months,respectively;( 4) to further reduce MTCT of HBV,pregnant women with HBV DNA > 2 × 105 IU/ml or with positive HBe Ag may start to take oral antivirals at the 28-32 weeks of gestation until the day of delivery;( 5) cesarean section,with the purpose to reduce MTCT of HBV,is not recommended.

In hepatobiliary carcinoma,serologic and histologic biomarkers including proteins and genes have been recommended and categorized for cancer diagnosis,targeted therapy and immunotherapy regimen selection,as well as prognostic prediction at different levels. To standardize the application of molecular biomarkers in clinical diagnosis,therapeutic evaluation,and prognosis prediction of primary hepatobiliary carcinoma,the specialist committee has summarized the current well studies biomarkers with clinical significance in both serum and tumor tissue as well as provided professional agreements on their potential utilization in this consensus. Moreover,we have made recommendations on standards for laboratory detection,technical operation,data analysis,result interpretation,clinical report,and the whole-process quality management in serological,histopathological detection and next-generation sequencing. According to these,the committee aims to offer clinical staffs with scientific and practical references and guidance to achieve better personalized treatment decisions from these up-to-date knowledges of molecular diagnosis on hepatobiliary carcinoma.

Objective To investigate the changes in the senescence-and function-related parameters of CD8+T cells after direct-acting antiviral( DAA) treatment and their clinical significance in patients with hepatitis C virus( HCV) infection. Methods A total of 26 patients with HCV infection who attended the Second Affiliated Hospital of Air Force Medical University from January 2017 to December 2018 were enrolled,and all patients were given sofosbuvir and daclatasvir tablets. A total of 22 patients who were cured and 20 healthy controls were enrolled. Flow cytometry was used to measure the expression of silent information regulator 1( SIRT1),CD57,programmed death-1( PD-1),and Tim-3 on CD8+T cells; RT-PCR was used to measure the expression of p21 and p53; Luminex liquid suspension chip was used to observe senescence-associated secretory phenotype in peripheral blood. A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups. Results There were significant differences in the expression of SIRT1,PD-1,and Tim-3 between the three groups( F = 6. 712,4. 202,and 4. 575,all P < 0. 05). Compared with the healthy control group,the HCV group had significant increases in the expression of SIRT1,PD-1,and Tim-3 on CD8+T cells( all P < 0. 05),and the HCV cured group had a significant increase in the expression of Tim-3( P< 0. 05),with no significant changes in SIRT1 and PD-1( both P > 0. 05). There were significant differences in the expression of p53 and p21 between the three groups( F = 11. 144 and 6. 594,both P < 0. 05). Compared with the healthy control group,the HCV cured group and the HCV group had significant reductions in the expression of p53( both P < 0. 001) and p21( both P < 0. 05),and there were no significant differences between the HCV group and the HCV cured group( both P > 0. 05). There were significant differences in interleukin-6 ( IL-6) and tumor necrosis factor α( TNFα) between the three groups( F = 3. 920 and 6. 337,both P < 0. 05),and compared with the healthy control group,the HCV group had significant increases in the levels of IL-6 and TNFα in peripheral blood( both P < 0. 05). There were no significant changes in IL-6 and TNFα in the HCV cured group( both P > 0. 05),and compared with the HCV group,the HCV cured group had a significant reduction in the level of TNFα( P = 0. 007). Conclusion Senescence of CD8+T cells is observed in patients with HCV infection and is alleviated after DAA treatment,with partial recovery of the function of CD8+T cells.

Objective To investigate the molecular mechanism of the anti-liver fibrosis effect of curcumol by observing the effect of curcumol on the TLR4/NF-κB signaling pathway in liver sinusoidal endothelial cells. Methods A total of 50 mice were randomly divided into blank group,model group,and curcumol group,and cells were divided into blank control group,LPS positive control group,curcumol intervention group,and PDTC group. HE staining and Masson staining were used to observe the change in liver structure; Western blot and quantitative real-time PCR( RT-PCR) were used to measure the protein and mRNA expression of the key molecules TLR4 and NF-κB in the TLR4/NF-κB signaling pathway; immunofluorescence assay was used to observe the expression and nuclear import of NF-κB in cells. A one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups. Results RT-PCR showed that compared with the positive control group,the curcumol intervention group had significant reductions in the mRNA expression of TLR4 and NF-κB( both P < 0. 05). Western blot showed that compared with the positive control group,the curcumol intervention group had significant reductions in the expression of TLR4 and NF-κB( both P <0. 05). Immunofluorescence assay showed that compared with the positive control group,the curcumol intervention group had significant improvement in NF-κB nuclear import. Conclusion Curcumol can exert an anti-liver fibrosis effect possibly by inhibiting the activity of the TLR4/NF-κB signaling pathway.

Objective To investigate the expression of elastin in a mouse model of carbon tetrachloride( CCl4)-induced liver fibrosis and the molecular mechanism of elastin deposition. Methods A mouse model of CCl4-induced liver fibrosis was established. Western blot,soluble protein,and Victoria blue staining were used to measure the change in elastin in the early stage of liver fibrosis( after 4 weeks of CCl4 injection) and the progressive stage of liver fibrosis( after 8 weeks of CCl4 injection). The mice treated with olive oil were enrolled as healthy control group. A model of spontaneous reversal of fibrosis was established; liquid chromatography-tandem mass spectrometry( LC-MS/MS) was used to measure the change in serum proteomics at different time points of reversal( at weeks 0,4,8,and 12 of reversal) and identify the potential molecules associated with elastin deposition,and qPCR was used for validation. A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least signficant difference Tukey test was used for further comparison between two groups. Results The relative expression of elastin was 0. 82 ± 0. 05 in the early fibrosis group and 1. 59 ± 0. 58 in the progressive fibrosis group,and compared with the healthy control group,the progressive fibrosis group had a significant increase in the expression of elastin( 1. 59 ± 0. 58 vs 1. 00 ± 0. 11,P < 0. 05). The measurement of insoluble elastin showed that compared with the healthy control group( 207. 9 ± 34. 7 μg/10 mg),the early fibrosis group had no significant change in insoluble elastin( 213. 5 ± 26. 7 μg/10 mg,P >0. 05),and the progressive fibrosis group had a significant increase in insoluble elastin( 352. 0 ± 57. 0 μg/10 mg,P < 0. 05). Elastin staining of liver tissue showed that compared with the healthy control group,the early fibrosis group and the progressive fibrosis group had a significant increase in the area of liver tissue with positive elastin expression( 2. 08 ± 0. 16/4. 39 ± 0. 51 vs 1. 03 ± 0. 14,both P < 0. 05). The mRNA expression of elastase 12 was measured,and the results showed that compared with the healthy control group,the early fibrosis group and the progressive fibrosis group had a significant increase in the mRNA expression of elastase 12( 15. 50 ± 2. 90/22. 70 ± 4. 10 vs 1. 30 ±0. 10,both P < 0. 05),suggesting that the mRNA expression of elastase 12 increased with the progression of liver fibrosis. During the reversal of liver fibrosis,45 proteins associated with the progression and reversal of liver fibrosis were isolated and identified by LC-MS/MS,among which lysyl oxidase-like protein-1( LOXL-1) and fibulin-1( FBLN-1) were associated with elastin deposition. Validation of LOXL-1 and FBLN-1 by q PCR showed that the mRNA expression of LOXL-1 and FBLN-1 reached the peak after 8 weeks of CCl4 injection( week 0 of reversal) and then gradually decreased over the time of reversal. Conclusion Elastin deposition is one of the important features in a mouse model of progressive liver fibrosis,and elastin deposition mediated by LOXL-1 and FBLN-1 may become a treatment target for liver fibrosis,liver cirrhosis,and end-stage liver disease.

Objective To investigate the distribution characteristics of intestinal flora in patients with liver cirrhosis,the driving factors for intestinal flora variation,and their association with the severity of liver cirrhosis. Methods Blood and stool specimens were collected from10 healthy volunteers and 70 patients with liver cirrhosis who were recruited by Shanxi Provincial Hospital of Traditional Chinese Medicine from August 2017 to August 2019. High-throughput sequencing of bacterial 16 S rDNA was performed to identify differentially expressed bacterial genera in intestinal flora of patients with liver cirrhosis. A one-way analysis of variance was used for comparison of normally distributed continuous data between groups,and the Kruskal-Wallis H 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 Spearman correlation analysis was performed,and CANOCO5. 0 software was used to perform RDA analysis to investigate the association of clinical indices with intestinal flora variation. Results Specific changes were observed in the species of intestinal flora in patients with liver cirrhosis,and compared with the healthy control group,the patients with liver cirrhosis had 81 unique operational taxonomic units( OTUs) in the metagenome of intestinal flora,among which there were 39 albumin-bilirubin( ALBI) grade 1 OTUs,34 ALBI grade 2 OTUs,and 8 ALBI grade 3 OTUs. With the progression of liver cirrhosis,there were significant reductions in Chao1 index and ACE index( H = 8. 111 and 9. 112,P = 0. 044 and0. 028),which were significantly negatively correlated with ALBI grade( r =-0. 287 and-0. 297,P = 0. 016 and 0. 012). Compared with the healthy control group,the patients with liver cirrhosis had significant increases in four genera of pathogenic bacteria( Roseburia,Veillonella,Streptococcus,and Haemophilus) and significant reductions in two genera of probiotic bacteria( Coprococcus and Clostridium)as the main features of intestinal flora imbalance( H = 15. 96,13. 01,8. 94,11. 09,13. 07,and 16. 27,all P < 0. 05). There was a positive correlation between the two genera of probiotic bacteria( P < 0. 05) and the four genera of pathogenic bacteria( P < 0. 001),while Coprococcus of probiotic bacteria was negatively correlated with the four genera of pathogenic bacteria( P < 0. 001). The correlation analysis of the differentially expressed genera and clinical indices showed that Coprococcus of probiotic bacteria was positively correlated with albumin( Alb)( r = 0. 273,P = 0. 022) and negatively correlated with prothrombin time( PT) and ALBI score( r =-0. 300 and-0. 263,both P < 0. 05); the pathogenic bacteria Rossella,Veillonella,Streptococcus,and Haemophilus were negatively correlated with Alb and positively correlated with PT,total bilirubin( TBil),ALBI score( all P < 0. 05). The RDA analysis showed that PT,TBil,and aspartate aminotransferase were highly correlated with the distribution of intestinal flora,among which PT had the most significant effect on intestinal flora variation( P = 0. 002). In the healthy control group,ALBI grade 1/2/3 OTUs had a cirrhosis dysbiosis index of genus( CDIG) of 2. 58,0. 76,0. 24,and 0. 04,respectively( H = 16. 750,P < 0. 001),and CDIG was negatively correlated with TBil,PT,and ALBI( r =-0. 313,-0. 323,and-0. 366,P = 0. 008,0. 006,and 0. 002). Conclusion Excessive growth of pathogenic bacteria,a lack of probiotic bacteria,and the ratio imbalance between various bacterial genera are the main characteristics of intestinal flora imbalance in patients with liver cirrhosis,and PT is the main driving factor for intestinal flora variation. CDIG can reflect the degree of intestinal flora imbalance in patients with liver cirrhosis,and the severity of liver cirrhosis increases with the reduction in CDIG.

Objective To investigate the association of platelet and its endogenous 5-hydroxytryptamine( 5-HT) with the prognosis of patients with hepatocellular carcinoma( HCC). Methods A retrospective analysis was performed for the clinical data of 210 patients with HCC who were treated in The First Affiliated Hospital of Xi'an Jiaotong University from January 2004 to December 2012,and according to platelet count,the patients were divided into low platelet group and high platelet group. Related factors and prognosis were compared between two groups. Peripheral blood samples were collected from 20 patients with recurrent/metastatic liver cancer and 32 patients with non-recurrent/metastatic liver cancer; ELISA was used to measure the serum level of 5-HT,and the platelet aggregation instrument was used to measure platelet aggregation rate. The chi-square test was used to investigate the association between platelet count and the clinicopathological characteristics of liver cancer,and the Mann-Whitney U test was used to compare platelet count,platelet aggregation rate,and 5-HT level in peripheral blood between groups. A univariate linear regression analysis was used to investigate the association between platelet count and survival time,as well as the association of 5-HT level with platelet count and platelet aggregation rate. The Kaplan-Meier method was used to analyze survival rate and recurrence rate,the log-rank test was used for comparison between groups,and a Cox regression analysis was used to investigate the influencing factors for the prognosis of HCC patients. Results There were significant differences between the patients with different platelet counts in age( χ2= 32. 304,P = 0. 044),tumor size( χ2= 35. 201,P = 0. 001),number of tumors( χ2=31. 304,P = 0. 032),Child class( χ2= 31. 250,P = 0. 036),and TNM stage( χ2= 35. 201,P = 0. 001). The multivariate Cox regression analysis showed that age,alpha-fetoprotein( AFP) level on admission,platelet count on admission,and treatment modality were independent risk factors associated with overall survival( all P < 0. 05),while age,AFP level on admission,tumor size,platelet count on admission,and treatment modality were risk factors associated with recurrence-free survival( all P < 0. 05). The survival analysis showed that compared with the low platelet group,the high platelet group had a significantly lower overall survival rate( χ2= 34. 060,P < 0. 001) and a significantly higher recurrence rate( χ2= 31. 030,P < 0. 001). With the increase in platelet count,overall survival and recurrence-free survival tended to decrease( R2 OS= 0. 034,POS= 0. 007; R2 DFS= 0. 045,PDFS= 0. 002). Compared with the non-recurrent/metastatic liver cancer group,the recurrent/metastatic liver cancer group had significantly higher platelet count( U = 2. 950,P = 0. 041),platelet aggregation rate( U = 2. 363,P = 0. 043),and serum free 5-HT level( U = 3. 082,P = 0. 048). The correlation analysis showed that serum 5-HT level was positively correlated with platelet count and maximum platelet aggregation rate in peripheral blood( both P < 0. 05). Conclusion Platelet count is an independent risk factor for overall survival and recurrence/metastasis in patients with HCC. Peripheral 5-HT level is positively correlated with platelet count and platelet aggregation rate and may be one of the potential indices for predicting the prognosis of HCC patients.

Objective To investigate the association of TLR4 gene polymorphism with the susceptibility to hepatitis B virus( HBV)-related primary liver cancer and its influence on the prognosis of patients. Methods A total of 106 patients with HBV-related liver cancer who were admitted to Beijing YouAn Hospital which cooperated with Dongzhimen Hospital of Beijing University of Chinese Medicine from June2015 to July 2017 were enrolled as liver cancer group; 120 patients with chronic hepatitis B who were admitted during the same period of time in Dongzhimen Hospital of Beijing University of Chinese Medicine were enrolled as hepatitis B group,and 100 healthy control subjects were enrolled as control group. Blood samples were collected from each group to detect TLR4 D299 G,T399 I,and A896 G polymorphisms,and postoperative recurrence was analyzed for liver cancer patients with different genotypes. An analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups;the chi-square test was used for comparison of categorical data between two groups,and the Kruskal-Wallis H test was used for comparison between multiple groups. An unconditional logistic regression model and odds ratio( OR) used to estimate relative risk were used to investigate the association of each factor with the onset risk of HBV-related primary liver cancer; the Kaplan-Meier curves were plotted for survival analysis,and the log-rank test was used for comparison of survival curves between groups. Results There were no significant differences in the genotype and allele distributions of TLR4 D299 G and TLR4 A896 G between the three groups( χ2= 1. 436,1. 949,1. 851,and2. 599,all P > 0. 05),while there were significant differences in the genotype and allele distributions of TLR4 T399 I between the three groups( χ2= 11. 654 and 14. 995,both P < 0. 05),and the liver cancer group had a significantly higher frequency of T allele than the hepatitis B group and the control group( P < 0. 05). The unconditional logistic regression model showed that CC genotype of TLR4 T399 I had an OR of 1. 682( 95% confidence interval[CI]: 1. 109-2. 243,P = 0. 027),TT genotype of TLR4 T399 I had an OR of 2. 103( 95% CI:1. 347-2. 896,P < 0. 001),and T allele of TLR4 T399 I had an OR of 1. 872( 95% CI: 1. 192-2. 374,P = 0. 002). There was no significant difference in recurrence-free survival after surgery between the liver cancer patients with different genotypes of TLR4 D299 G and TLR4 A896 G( χ2= 0. 022 and 0. 471,both P > 0. 05). The liver cancer patients with CC genotype of TLR4 T399 I had significantly better recurrence-free survival after surgery than those with CT or TT genotype( χ2= 6. 781,P < 0. 05). Conclusion TLR4 T399 I gene polymorphism is closely associated with the susceptibility to HBV-related primary liver cancer,and T gene of TLR4 T399 I may be an important factor for tumorigenesis and poor prognosis.

Objective To investigate the clinical effect of vitamin E in the treatment of nonalcoholic fatty liver disease( NAFLD) in children. Methods PubMed,Web of Science,The Cochran Library,Embase,OVID/NEJM,CNKI,and Wanfang Data were searched for the articles on vitamin E in the treatment of NAFLD in children published up to December 2019. The data of 8 parameters were analyzed,i. e.,body mass index( BMI),liver enzymes [alanine aminotransferase( ALT) and aspartate aminotransferase( AST) ],blood lipid levels [triglyceride( TG),total cholesterol( TC),low-density lipoprotein( LDL),and high-density lipoprotein( HDL) ],and remission rate of hepatic steatosis. RevMan 5. 3 was used to perform a Meta-analysis. Continuous variables were analyzed by standardized mean difference( SMD) and 95% confidence interval( CI),and the changes after intervention were analyzed; categorical variables were analyzed by risk difference( RD) and 95% CI. A fixed effects model was used for homogeneous data,and a random effects model was used for heterogeneous data. Funnel plots were used to evaluate publication bias. Results A total of 599 articles were retrieved,among which 9 were included in the Meta-analysis,with 607 subjects in total. Vitamin E significantly improved the level of ALT( SMD =-0. 27,95% CI:-0. 48 to-0. 06,P = 0. 01),but it did not improve the levels of BMI( SMD =-0. 09,95% CI:-0. 28 to 0. 10,P = 0. 34),AST( SMD =-0. 20,95% CI:-0. 42 to 0. 02,P = 0. 07),TG( SMD =-0. 19,95% CI:-0. 51 to 0. 12,P = 0. 22),TCHO( SMD =-0. 11,95% CI:-0. 31 to 0. 08,P = 0. 24),HDL( SMD =-0. 02,95% CI:-0. 27 to 0. 23,P = 0. 88),LDL( SMD =-0. 04,95% CI:-0. 27 to0. 19,P = 0. 72),and the remission rate of hepatic steatosis( RD = 0. 06,95% CI:-0. 05 to 0. 17,P = 0. 29). Conclusion Vitamin E can significantly improve the level of ALT in children with NAFLD and can be considered as an adjuvant drug for clinical treatment.

Objective To investigate the similarities and differences in the clinical features of acute versus chronic drug-induced liver injury( DILI). Methods Clinical data were collected from 183 patients who were hospitalized and diagnosed with DILI in Department of Infectious Diseases,Peking University First Hospital,from January 2015 to December 2018,and the patients were divided into acute group with 138 patients and chronic group with 45 patients. Related data were collected,including general information,underlying diseases,history of suspected drugs,history of allergy,drinking history,symptoms and signs,laboratory examination,radiological examination,liver biopsy,treatment,and prognosis. Roussel Uclaf Causality Assessment Method( RUCAM) score was determined for all patients diagnosed with DILI,and the type and severity of liver injury were determined. 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 analysis was used to investigate the influencing factors for chronicity of DILI. Results Among the 138 patients in the acute group,105( 76. 1%) had DILI caused by Chinese herbal medicine and 15( 10. 9%) had DILI caused by antibiotics,while among the 45 patients in the chronic group,33( 73. 3%) had DILI caused by Chinese herbal medicine and 5( 11. 1%) had DILI caused by antibiotics. There were significant differences between the two groups in sex( χ2= 4. 774,P = 0. 029),type of liver injury( χ2= 9. 848,P = 0. 02),and severity of DILI( χ2= 8. 012,P = 0. 046);77. 8% of the patients in the chronic group had a RUCAM score of ≤6,while 79. 7% of the patients in the acute group had a RUCAM score of ≥6,and there was a significant difference between the two groups( χ2= 21. 471,P = 0. 002). There were significant differences between the two groups in platelet count( PLT),alanine aminotransferase( ALT),aspartate aminotransferase,direct bilirubin,creatinine,detection rate of ANA,and detection rate of SMA( all P < 0. 05). Compared with the acute group,the chronic group had a significantly longer incubation period and a significantly higher proportion of patients with liver cirrhosis or no response to treatment( all P < 0. 05); there was a significant difference between the two groups in the proportion of patients treated with glucocorticoids( χ2= 27. 109,P < 0. 05) or glucocorticoids combined with azathioprine( χ2= 27. 408,P < 0. 05). A total of 16 patients( 11. 6%) in the acute group and 7( 15. 6%) in the chronic group had autoimmune hepatitis-like DILI; 29 patients in the acute group underwent liver pathological examination,among whom2( 6. 9%) had an unknown cause, while 27 patients in the chronic group underwent liver pathological examination, among whom6( 22. 2%) had an unknown cause. ALT( odds ratio [OR]= 0. 997,95% confidence interval [CI]: 0. 985-0. 999,P = 0. 003) and PLT( OR = 0. 997,95% CI: 0. 986-0. 998,P = 0. 013) were independent predictive factors for chronicity of DILI. Conclusion Compared with acute DILI,chronic DILI is more common in female patients and is difficult to diagnose,with a long incubation period,a higher proportion of patients with cholestasis type,and a higher detection rate of autoantibody,and it requires glucocorticoid and immunosuppressive therapy more and tends to have poorer prognosis. ALT and PLT may be independent predictive factors for the chronicity of DILI.

Objective To investigate the expression characteristics and significance of ABCB11( bile salt export pump,BSEP),ABCC2( multidrug resistant protein 2,MRP2),and ABCB4( multidrug resistance associated protein 3,MDR3) in the liver tissue in bile duct injury type of drug-induced liver injury( DILI). Methods Clinical data were collected from 112 patients who had a definite history of medication and were diagnosed with bile duct injury type of DILI based on liver biopsy in The Fifth Hospital of Shijiazhuang from January 2010 to June 2017. The patients were divided into mixed hepatitis group with 40 patients,cholestatic hepatitis group with 40 patients,and simple cholestasis group with 32 patients,and 20 hepatitis B virus carriers without cholestasis were enrolled as control group. Liver biopsy was performed for all subjects to perform immunohistochemical staining of BSEP,MDR3,and MRP2,and the expression characteristics of the three proteins and their association with pathomorphological changes were observed. The expression of these three transport proteins was compared between the three subtypes and its correlation with total bilirubin( TBil),direct bilirubin( DBil),alkaline phosphatase,gamma-glutamyl transpeptidase,and total bile acid( TBA) was analyzed. A one-way analysis of variance was used for comparison of continuous data between groups,and the least significant difference t-test was used for further comparison between two groups; a Pearson correlation analysis was performed to investigate correlation. Results Compared with the control group,the mixed hepatitis group,the cholestatic hepatitis group,and the simple cholestasis group had significant reductions in the expression of BSEP,MDR3,and MRP2 in liver tissue( F =48. 765,45. 424,and 77. 434,all P < 0. 05),and the comparison between any two groups showed that the cholestatic hepatitis group had significantly greater reductions than the mixed hepatitis group and the simple cholestasis group( all P < 0. 05). The degree of hepatocyte swelling and feather-like degeneration due to cholestasis increased with the reduction in the expression of BSEP,MRP2 and MDR3 in the area of cholestasis. In the cholestatic hepatitis group,BSEP was moderately negatively correlated with TBA( r =-0. 640,P = 0. 008),and in the simple cholestasis group,MRP2 was moderately negatively correlated with TBil( r =-0. 597,P = 0. 019) and DBil( r =-0. 643,P = 0. 011). Conclusion There are reductions in the positive expression of BSEP,MDR3,and MRP2 in each subtype of bile duct injury type of DILI,which is one of the important mechanisms of cholestasis in DILI.

Objective To investigate the features of liver injury in patients with coronavirus disease 2019( COVID-19),and to provide a reference for clinical diagnosis and treatment. Methods Medical records were collected from 201 patients with COVID-19 who were admitted to Xiangyang Central Hospital from January 19 to March 5,2020,and these patients were divided into non-critical( mild/common type) group with 173 patients and critical( severe/critical type) group with 28 patients. The data on alanine aminotransferase( ALT),aspartate aminotransferase( AST),total bilirubin( TBil),direct bilirubin( DBil),and albumin( Alb) were collected. The t-test was used for comparison of normally distributed continuous data between groups,the chi-square test was used for comparison of categorical data between groups,and the Wilcoxon rank-sum test was used for comparison of ranked data between groups. Results Among the 201 patients,37( 18. 4%) had liver injury,with 19 in the critical group and 18 in the non-critical group,and there was a significant difference in the incidence rate of liver injury between the two groups( 67. 9% vs 10. 4%,χ2= 52. 963,P < 0. 05). There were significant differences between the 19 patients with liver injury in the critical group and the 18 patients with liver injury in the non-critical group in the duration of abnormal ALT and/or AST( on admission and during hospitalization)( χ2= 11. 906,P < 0. 05) and the increase in ALT and/or AST( Z =-2. 869,P < 0. 05),and most patients had mild or moderate liver injury. Among the 201 patients,only one patient had elevated bilirubin( TBil < 2 × upper limit of normal,mainly indirect bilirubin) and had non-critical liver injury. The critical group had a significantly lower level of Alb than the non-critical group( t =-8. 002,P < 0. 05). Among the 201 patients,75 had a reduction in Alb,among whom 50( 50/201,24. 9%) had a reduction on admission and 25( 25/201,12. 4%) had a reduction during hospitalization,and there were significant differences in Alb( t =-4. 967,P < 0. 05) and hypoalbuminemia( χ2= 26. 645,P < 0. 05) between the two periods of time. Conclusion Liver injury is relatively common in patients with COVID-19,mainly mild or moderate liver injury. There is a low incidence rate of abnormal bilirubin and a high incidence rate of the reduction in Alb. There are significant differences in the incidence rate and severity of liver injury between the crucial and non-critical patients. Alb level can be used as one of the indicators to evaluate and predict the severity of COVID-19 patients.

Objective To investigate the effect of magnesium isoglycyrrhizinate(MgIG) on concanavalin A(ConA)-induced acute liver failure in mice and its mechanism. Methods A total of 60 healthy BALB/C mice were randomly divided into control group with 10 mice,MgIG control group with 10 mice,ConA model group with 20 mice,and MgIG-ConA pretreatment group with 20 mice. The liver and peripheral blood were collected to evaluate survival rate,serum levels of aminotransferases,and degree of liver injury by HE staining of liver tissue; TUNEL fluorescence staining and activity of caspase-3 protein were used to evaluate the apoptosis of hepatocytes; the liquid chip method was used to measure the serum levels of the inflammatory cytokines interleukin-1β(IL-1β) and tumor necrosis factor α(TNFα).A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups. Results The overall survival rate of mice was 40% in the ConA model group and80% in the MgIG-ConA pretreatment group. The ConA model group had significantly increased serum levels of alanine aminotransferase( ALT) and aspartate aminotransferase( AST) compared with the control group( both P < 0. 01),while the MgIG + ConA pretreatment group had significantly reduced serum levels of ALT and AST compared with the ConA model group( both P < 0. 01). The control group,the MgIG control group,the ConA model group,and the MgIG-ConA pretreatment group had a pathological score of 1. 0 ± 0. 2,1. 2 ± 0. 3,3. 7 ±0. 6,and 2. 3 ± 0. 5,respectively,and there was a significant difference between groups( F = 2. 7,P < 0. 05); the apoptotic cells/100 cells ratio was 0. 2 ± 0. 1,0. 1 ± 0. 1,7. 8 ± 1. 3,and 2. 2 ± 0. 4,respectively,in these four groups,and there was a significant difference between groups( F = 27. 6,P < 0. 001); the activity of caspase-3 protein was 0. 813 ± 0. 022,0. 930 ± 0. 033,1. 347 ± 0. 042,and1. 060 ± 0. 053,respectively,in these four groups,and there was a significant difference between groups( F = 51. 072,P < 0. 001).Compared with the control group,the Con A model group had significant increases in serum levels of IL-1β and TNFα( both P < 0. 05);compared with the Con A model group,the Mg IG + Con A pretreatment group had significant reductions in serum levels of IL-1β and TNFα( both P < 0. 05). Conclusion Mg IG exerts a marked protective effect against Con A-induced acute liver failure in mice and can alleviate liver injury possibly by reducing hepatocyte apoptosis and alleviating liver inflammatory response caused by IL-1β and TNFα.

Objective To investigate the effect of aerobic exercise combined with silybin in improving intestinal mucosal barrier injury in mice with obstructive jaundice by activating the microRNA-21/TLR4/NF-κB pathway axis in intestinal tissue. Methods Healthy male Kunming mice were selected,and a model of obstructive jaundice was established by the method of hanging the common bile duct using an operating suture line at a right angle. The mice were randomly divided into model group( M group),exercise group( E group),silybin group( S group),and exercise + silybin group( ES group),and a sham-operation group was also established,with 10 mice in each group.After the intervention of aerobic exercise combined with intragastric administration of silybin for 7 weeks,general behavioral observation,ELISA,HE staining of ileal tissue,immunohistochemical staining,measurement of the protein and mRNA expression of intestinal tissue-related factors,and a sequencing analysis of mRNA expression profiles in liver tissue were performed to observe intervention effect. A one-way analysis of variance was used for continuous data,and the least significant difference t-test was used for comparison between groups. A multivariate analysis of variance was used to investigate the interaction effect between aerobic exercise and silybin,and a simple effect analysis was performed. Results The mice in the M group had severe jaundice on the skin of the abdomen and tail,yellow urine,and light gray feces,and laparotomy showed cystic dilatation at the bile duct suspension. Compared with the M group,the E,S,and ES groups had signif-icant reductions in the liver function parameters alanine aminotransferase,aspartate aminotransferase,and total bilirubin( F = 567. 56,1376. 09,and 512. 81,all P < 0. 001),as well as significant reductions in the plasma levels of diamine oxidase( DAO),D-lactic acid,and endotoxin( F = 650. 29,1130. 05,and 396. 04,all P < 0. 001),and there was a synergistic effect between aerobic exercise and silybin in all the above indices except DAO( all P < 0. 05). Microscopic observation showed that the M group had severe damage of the structure of the intestinal mucosa,sparse villi with different heights,a reduction in the depth of intestinal crypts,atrophy and detachment of some glands,and local infiltration of inflammatory cells and muscular atrophy. Compared with the M group,the E and S groups had significant improvements in the above pathological symptoms,and the ES group had the best intervention effect. Compared with the M group,the E,S,and ES groups had significant reductions in the mRNA and protein expression of TLR4,NF-κB,and TNFα( mRNA: F = 104. 69,153. 55,and 262. 38,all P < 0. 01; protein: F = 2683. 83,419. 73,and 572. 41,all P < 0. 01),as well as a significant increase in the expression of microRNA-21( F = 194. 58,P < 0. 01),and there was a synergistic effect between aerobic exercise and silybin in all the above indices except the expression of microRNA-21( all P < 0. 05). According to Illumina high-throughput sequencing for the screening of liver inflammation-related factors and correlation analysis,the differentially expressed factors were mainly enriched in the inflammatory pathways such as NF-κB,TGFβ,TNF,and TLR,which involved tissue cell signal transduction,apoptosis inhibition,immune response,and toxicity,and aerobic exercise and silybin significantly reduced the enrichment of inflammation and immune-related signaling pathways.Conclusion In mice with obstructive jaundice,aerobic exercise or intragastric administration of silybin for 7 weeks can exert a protective effect on intestinal mucosal barrier by upregulating the expression of microRNA-21 in intestinal tissue and inhibiting the TLR4/NF-κB signaling pathway and the release of its downstream inflammatory factors,and aerobic exercise combined with silybin has the optimal effect.

On January 20,2020,WHO defined the epidemic of novel coronavirus pneumonia as a public health emergency of international concern,and the epidemic attracted worldwide attention. While effectively controlling source of infection,cutting off the route of transmission,and protecting the susceptible population,it is of great importance to reduce the delay in the diagnosis and treatment of patients with acute abdominal disease and ensure normal clinical work. Therefore,with reference to the current diagnosis and treatment protocols and guidelines and the actual situation in Baoding Second Hospital,this article summarizes the experience in outpatient triage,treatment process,operation classification,prevention and control,and ward management for patients with acute biliary tract infection. The analysis shows that the formulation of emergency plans for patients with acute biliary tract infection during the epidemic of novel coronavirus pneumonia can help to differentiate such patients from the patients with novel coronavirus pneumonia and avoid transmission and cross-infection of novel coronavirus during standardized diagnosis and treatment of acute biliary tract infection.

Chronic hepatitis B( CHB) is one of the most common chronic infectious diseases in China,and the prevalence rate of HBeAg-negative CHB has been increasing year by year,causing serious harm to the security of public health in China. With reference to the pathogenesis,diagnosis,and treatment of HBeAg-negative CHB,this article reviews the clinical research advances in recent years and summarizes the new advances in the diagnosis and treatment of HBeAg-negative CHB.

With the improvement in clinical treatment and the increase in life expectancy,the incidence rate of osteoporosis is gradually increasing in patients with hepatitis B. However,the specific mechanism of different stages of hepatitis B on osteoporosis is still complex and remains unclear,and there are few studies on the prevention and treatment of osteoporosis in patients with hepatitis B. This article reviews the pathogenesis and clinical prevention and treatment of osteoporosis in patients with hepatitis B,in order to provide better guidance for clinical management and treatment.

Coronavirus disease 2019( COVID-19) has spread to many countries in the world,and some patients show liver injury during the epidemic of COVID-19. In order to improve the awareness of COVID-19 among patients with viral hepatitis cirrhosis and strengthen patients' self-protection and disease management,this article discusses the pathogenic mechanism of liver injury caused by COVID-19 and reasonable epidemic prevention,standardized medical treatment,and scientific medication for such patients and gives related recommendations,so as to ensure the routine management of viral hepatitis and reduce the risk of infection in such population.

Childhood nonalcoholic fatty liver disease( NAFLD) is one of the most common cause of chronic liver diseases in children and adolescents; its unique histopathological and clinical features may lead to its progression to liver fibrosis,liver cirrhosis,and liver cancer,and compared with adult NAFLD,it is more likely to cause other diseases and increase mortality rate. Therefore,early identification of risk factors for childhood NAFLD,effective screening of high-risk population,active prevention,and early diagnosis and treatment are key to effective clinical management of this disease. This article elaborates on the risk factors,screening methods,and preventive healthcare measures for childhood NAFLD,in order to standardize the comprehensive management of NAFLD,reduce the prevalence rate of NAFLD,delay its progression,and alleviate the economic and public health burden brought by the disease.

Nonalcoholic fatty liver disease( NAFLD) has become the most important chronic liver disease and is recognized as the hepatic manifestation of metabolic syndrome,which may progress to liver fibrosis,liver cirrhosis,and even hepatocellular carcinoma in the advanced stage. Gut microbiota,as important symbiotic organisms in the human body,affects metabolic function and may be closely associated with NAFLD,and the theory of gut-liver axis provides a theoretical basis for understanding that intestinal dysbacteriosis may cause liver pathological changes. This article explores the association between NAFLD and gut microbiota,so as to lay a theoretical foundation for the future research on the therapy for NAFLD targeting gut microbiota.

Nonalcoholic fatty liver disease( NAFLD) has now become the most common liver disease around the world,and there is an urgent need for better diagnosis and treatment of NAFLD. The osteoprotegerin( OPG)/receptor activator of nuclear factor-kappa B ligand( RANKL)/receptor activator of nuclear factor-kappa B( RANK) signaling pathway is an important signaling pathway involved in the balance of bone metabolism. This article introduces the OPG,RANKL,RANK,and OPG/RANKL/RANK systems and elaborates on the current research on the role of the OPG/RANKL/RANK signaling pathway in regulating the production of inflammatory factors and promoting the progression of NAFLD by activating NF-κB. It is pointed out that the OPG/RANKL/RANK system may be used as a potential target for the treatment of NAFLD.

At present,hepatitis B virus( HBV) infection is recognized as an important risk factor for hepatocellular carcinoma( HCC) in the world; however,during the development and progression of hepatitis B,liver cirrhosis,and liver cancer,other factors may promote the development of HCC independently or synergistically with HBV,such as sex,age,family history,alanine aminotransferase/aspartate aminotransferase,smoking and drinking history,metabolic syndrome,and HCV or HIV infection. This article reviews the research advances in the risk factors associated with HCC.

Hepatocellular carcinoma( HCC) is a common malignant tumor and patients with HCC often have liver cirrhosis,with an extremely high 5-year recurrence rate and poor prognosis even after curative treatment. In recent years,sarcopenia has attracted more and more attention as a poor prognostic factor for various malignant tumors; however,there is still a lack of studies on the association between skeletal muscle index and prognosis of HCC in China. Evidence in foreign countries has shown that sarcopenia may be an a negative prognostic factor for HCC patients. This article reviews the etiology and possible pathogenesis of HCC-related sarcopenia and related intervention measures including nutritional supplementation,appropriate physical exercise,and medication,in order to provide a reference for related studies in China.

Chronic inflammation of the liver is a risk factor that promotes the progression of hepatocellular carcinoma,and in the presence of viral infection,enhanced Fc receptor signal will further aggravate inflammatory response and participate in the process of canceration. Polymeric immunoglobulin receptor( pIgR) not only plays a critical role in first-line anti-infection immunity,but also promotes the metastasis and growth of early-stage hepatocellular carcinoma. Identifying pIgR as a predictive index for metastatic potential in patients with early-stage liver cancer can help to promote the stratification and treatment decisions for such patients,which has a positive significance in improving patient prognosis. Targeted inhibition of the pIgR/Yes signal cascade as a potential treatment option may provide more treatment options for controlling tumor size to allow resection or transplantation.

The development and progression of liver cancer have the stages of hepatitis,liver cirrhosis,precancerous lesion,and liver cancer,among which the malignant transformation of precancerous lesions of liver cancer is closely associated with the activation of hepatic stellate cells( HSC). By describing the activation of HSC,the generation of precancerous cells of liver cancer,the formation of inflammatory fibrotic microenvironment,and the association between HSC activation and precancerous lesion,this article points out that microRNAs can affect the malignant transformation of precancerous lesion of liver cancer by regulating the expression of related target genes and HSC activation,and the research in this field is expected to provide new ideas and targets for the prevention and treatment of liver cancer.

Mitophagy is the process of selective clearance of damaged mitochondria by autophagy. There are several regulatory mechanisms for mitophagy,and the PINK1/Parkin pathway is considered the main pathway for mitophagy. Recent studies have shown that PINK1/Parkin-mediated mitophagy plays an important role in the pathogenesis of various diseases including Parkinson's disease. This article introduces the mechanism of PINK1/Parkin-mediated mitophagy and its role in various liver diseases including nonalcoholic fatty liver disease,liver fibrosis,and hepatocellular carcinoma,in order to provide new clues and ideas for the treatment of diseases.

microRNAs( miRNAs) are low-molecular-weight non-coding RNAs that regulate various physiological and pathological functions through the regulation of gene expression at the post-transcriptional level. More and more evidence has shown that microRNA-27 a( miRNA-27 a) plays a role in the development and pathogenesis of liver diseases. By reviewing and updating related studies,this article introduces the research advances in the role of miRNA-27 a in various liver diseases including fatty liver disease,hepatitis,hepatic fibrosis,and liver cancer and analyzes the role of miRNA-27 a in liver regeneration and its potential as a biomarker,so as to provide a reference for future studies and more possibilities for new treatment ideas for chronic hepatic diseases.