Nonalcoholic fatty liver disease( NAFLD) is a multisystem disease involving metabolic disorder and is more common in patients with obesity and type 2 diabetes mellitus( T2 DM),with similar adverse outcomes to these two comorbidities. For a long time,NAFLD has emphasized liver lesions and outcomes of liver diseases,and when treating T2 DM according to the current clinical guidelines for diabetes,endocrinologists often neglect the screening,diagnosis,and treatment of liver lesions. Therefore,in clinical practice,NAFLD renamed as metabolic-associated fatty liver disease has important practical significance. Strategies for T2 DM prevention and treatment aiming at reducing liver lipid content require multidisciplinary cooperation,and prevention and treatment of obesity,fatty liver disease,and diabetes with the same concepts can help to implement the prevention and treatment of the most common chronic diseases.

The terms nonalcoholic steatohepatitis and nonalcoholic fatty liver disease( NAFLD) were first used in the 1980 s to describe a condition of similar liver histological changes to alcoholic liver disease,without excessive drinking nor other factors for liver injury. In-depth research on NAFLD has achieved rapid progress over the past 40 years; however,the unchanged nomenclature of the disease has become an obstacle for routine clinical practice and clinical trials. To overcome the shortcomings of the old term,the international consensus panel proposes to use the term metabolic associated fatty liver disease( MAFLD) to replace NAFLD and further puts forward the comprehensive and simple definition of MAFLD for clinical diagnosis,which makes MAFLD different from other liver diseases. Meanwhile,the panel suggests that MAFLD assessment and severity stratification should be extended beyond the simple dichotomous classification used at present.The new name MAFLD will become an important measure for optimizing clinical practice and improving clinical research and may bring benefits to physicians and patients.

Although nonalcoholic fatty liver disease( NAFLD) is a liver disease,it has attracted more and more attention among endocrinologists. There are complex interactions between the metabolic status of diabetes and the pathology of NAFLD,and they promote the development of each other. In the population with type 2 diabetes mellitus( T2 DM),the incidence rate of NAFLD is as high as 57%-80%,and NAFLD patients with diabetes are more likely to develop progressive liver diseases such as nonalcoholic steatohepatitis( NASH) and liver fibrosis. NAFLD also leads to the deterioration of glucose and lipid metabolism disorder in diabetes patients,as well as the development and progression of chronic macrovascular and microvascular complications in diabetes. The above evidence supports the view that NASH should be considered a complication of T2 DM. Once a definite diagnosis of T2 DM is made in clinical practice,the risk of NASH or progressive fibrosis should be evaluated and intervention should be given as early as possible.

Nonalcoholic fatty liver disease( NAFLD) is associated with a 2-to 3-fold increase in the risk of developing type 2 diabetes( T2 DM) in non-diabetic patients,and therefore,the NAFLD population is considered a large population at a high risk of T2 DM. In the population diagnosed with T2 DM,the prevalence rate of NAFLD reaches as high as 60%-80%. T2 DM is considered a lifelong disease in the traditional view,but recently,more and more evidence supports that T2 DM can be reversed,which brings new light to the prevention and treatment of T2 DM. The remission of T2 DM depends on the appropriate treatment methods and timing. The liver plays a key role in glucose and lipid metabolism,and excessive fat accumulation in the liver may induce insulin resistance,increased production of hepatic glucose,and increased triglyceride export,which further leads to fat deposition in the pancreas and beta-cell injury and eventually causes the onset of T2 DM. Lifestyle intervention can reduce liver fat content and achieve the remission or reversal of diabetes,and NAFLD can be regarded as an“early warning window”for T2 DM. Therefore,the treatment regimen aiming at improving liver fat content may become a good strategy to prevent and reverse diabetes.

Nonalcoholic steatohepatitis( NASH)/nonalcoholic fatty liver disease( NAFLD) has gradually become one of the main causes of hepatocellular carcinoma( HCC) in Western developed countries. Different from the typical evolution process of hepatitis,liver cirrhosis,and liver cancer,nearly 40% NAFLD patients can progress into HCC without experiencing liver cirrhosis,suggesting other mechanisms may play a role in this process. This article elaborates on the latest research advances in the pathogenesis of NAFLD-related HCC.

Nonalcoholic fatty liver disease( NAFLD) is the most common type of liver disease in developed countries,and in recent years,the prevalence rate of NAFLD tends to increase in China,which brings heavy burden to the social health system. The development and progression of NAFLD are affected by the interaction between multiple influencing factors including genetic and epigenetic factors,transcription factors,hormones,nutrition,and environmental factors. This article reviews the research advances in the role of nuclear receptor in the pathogenesis of NAFLD,in order to deepen the understanding of this disease.

The prevention and treatment of COVID-19 nationwide has entered a tackling phase. Effective treatment of severe and critically ill patients is the key to reducing the fatality of the disease. The artificial liver blood purification system can remove inflammatory factors,alleviate the damage of the inflammatory response to the body,and has important value for the treatment of severe COVID-19. Led by academician Li Lanjuan,based on the experience of treating patients across the country,integrating the opinions of experts from all over the country,the center summarized and formulated the consensus including the basic principles,treatment indications,relative contraindications,mode selection,monitoring indicators,and efficacy evaluation of artificial liver,which provides reference for treatment of severe COVID-19 patients.

Distal biliary stricture is a biliary lesion commonly seen in clinical practice and can be caused by benign and malignant diseases.Although endoscopic technique has become a major treatment method for distal biliary stricture,there is still a lack of comprehensive understanding of this condition. Therefore,Asian Group of Interventional Treatment of Pancreaticobiliary Diseases published International consensus statement for endoscopic management of distal biliary stricture in 2019,which elaborates on the consensus statement on the endoscopic management of distal biliary stricture from the aspects of diagnosis,treatment,and follow-up. This article makes an interpretation of some key points in the above consensus statement,in order to provide a reference for clinical practice.

Objective To investigate the pattern of drug resistance mutations of the genes in the reverse transcriptase( RT) region and its association with clinical features in patients with hepatitis B virus( HBV) infection in Xuzhou,Jiangsu,China,as well as the influencing factors for drug resistance. Methods A total of 242 patients with HBV infection who underwent the detection of the HBV RT region in Department of Infectious Diseases,The Affiliated Hospital of Xuzhou Medical University,from May 2014 to April 2019 were enrolled,and the clinical features were compared between the patients with different genotypes and HBeAg statuses. Of all patients,164 had a clear medication history of nucleos( t) ide analogues( NAs),among whom 118 had known mutations at drug resistance loci and 46 did not have such mutations,and the risk factors for drug resistance mutations in the HBV RT region were analyzed for the two groups. The independent samples t-test or the Mann-Whitney U test was used for comparison of 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 risk factors for drug resistance. Results Among the patients with HBV infection in Xuzhou,rtL180 M + rtM204 I/V/S was the most common pattern of drug resistance mutation in the RT region and was observed in 25 patients( 21. 2%),followed by rtA181 T/V in 16 patients( 13. 6%) and rtM204 I/V/S in 15 patients( 12. 7%). Of all 242 patients,13( 5. 4%) had genotype B and 229( 94. 6%) had genotype C,and no other genotypes were found. The patients with genotype B had a significantly higher level of alanine aminotransferase( ALT) than those with genotype C( U =-2. 096,P =0. 036). Compared with the HBeAg-positive group,the HBeAg-negative group had a significantly older age( t = 4. 580,P < 0. 001) and significantly lower HBV DNA load and HBs Ag level( t = 2. 145 and 3. 526,P = 0. 033 and 0. 001). The HBe Ag-negative group had a significantly longer course of disease and a significantly higher level of gamma-glutamyl transpeptidase( GGT) than the HBe Ag-positive group( U =-2. 561 and-2. 016,P = 0. 010 and 0. 044). Compared with the HBe Ag-positive group,the HBe Ag-negative group had a significantly lower proportion of patients with chronic hepatitis B and a significantly higher proportion of patients with liver cirrhosis or hepatocellular carcinoma( χ2= 20. 609,P < 0. 001). The multivariate logistic regression analysis showed that administration of lamivudine + adefovir dipivoxil( OR = 0. 080,95% CI: 0. 008-0. 748,P < 0. 05),administration of adefovir dipivoxil( OR = 5. 493,95% CI: 1. 377-21. 909,P < 0. 05),and improper drug withdrawal( OR = 5. 945,95% CI: 1. 921-18. 403,P < 0. 05) were independent risk factors for drug resistance in patients with HBV infection. Conclusion Most of the patients with HBV infection in Xuzhou are infected with HBV genotype C,with a complex and diverse pattern of drug resistance mutations. HBV DNA replication is active in HBe Ag-positive patients,and therefore,it is recommended to initially select antiviral drugs with high efficiency and low resistance and strengthen the compliance with antiviral therapy.

Objective To investigate the expression features of glucocorticoid receptor( GR) and its subtypes α and β in patients with early-or middle-stage hepatitis B virus-related acute/subacute-on-chronic liver failure( HBV-ACLF) treated by glucocorticoid( GC) and their association with sensitivity to glucocorticoid therapy. Methods A prospective non-randomized controlled trial was performed for 33 patients with early-or middle-stage HBV-ACLF who were hospitalized and treated in Beijing YouAn Hospital from September 2015 to June2018,and among these patients,18 received intravenous infusion of methylprednisolone for 7 days in addition to comprehensive medical treatment. Flow cytometry and RT-PCR were used to measure the mRNA expression of GR,GR-α,and GR-β,and the expression of GR,GR-α,and GR-β was observed at baseline and on day 8. According to the response to GC on day 10,the hormone group was further divided into hormone-sensitive group with 13 patients and hormone-insensitive group with 5 patients. The two-independent-samples t test was used for comparison of continuous data between two groups,and the paired t-test was used for comparison within one group before and after treatment; the Fisher's exact test was used for comparison of categorical data between groups. The Kaplan-Meier survival curve was used to analyze 28-day survival,and the log-rank test was used for comparison between groups. Results The hormone group had a significant reduction in the mRNA expression of GR-α on day 8 after hormone administration [( 0. 99 ± 0. 48) × 10-2 vs( 1. 96 ±0. 50) × 10-2,t = 6. 586,P < 0. 001]There was a significant difference in the mRNA expression of GR-α between the hormone group and the non-hormone group on day 8 [0. 99 ± 0. 48) × 10-2 vs( 1. 70 ± 0. 66) × 10-2,t =-3. 518,P = 0. 001]On day 8,the hormone-sensitive group had significantly higher mRNA expression of GR-α than the hormone-insensitive group [1. 21 ± 0. 34) × 10-2 vs( 0. 43 ± 0.31) × 10-2,t = 4. 456,P < 0. 001]and the hormone-sensitive group had a significantly greater reduction in the mRNA expression of GR-α compared with the hormone-insensitive group( t =-2. 904,P = 0. 01). There was no significant difference in the mRNA expression of GR-β on day 8 between the hormone-sensitive group and the hormone-insensitive group [0. 14 ± 0. 08) × 10-2 vs( 0. 10 ±0. 04) × 10-2,t = 1. 092,P = 0. 291]For the hormone group,the mean ratio of reduction in GR-α mRNA expression to baseline value was46% on day 8,and according to this,the patients were divided into ≤46% group with 10 patients and > 46% group with 8 patients. There was a significant difference in the ratio of reduction in GR-α mRNA expression to baseline value between the two groups( 26. 99% ± 25.09% vs 70. 09% ± 16. 08%,t =-4. 203,P = 0. 001). On day 10,there were significant differences between the ≤46% group and the >46% group in the ratio of reduction in total bilirubin( TBil) to baseline value( P = 0. 021) and the ratio of increase in prothrombin time activity( PTA) to baseline value( P = 0. 048). Conclusion In patients with early-or middle-stage HBV-ACLF,there is a significant reduction in the mRNA expression of GR-α after GC treatment. Patients sensitive to hormone have a relatively low degree of reduction in the mRNA expression of GR-α,with better improvements in TBil and PTA on day 28 than those insensitive to hormone. Dynamic change of GR-α mRNA has a certain reference value in predicting the outcome of hormone therapy.

Objective To investigate the value of the COSSH-ACLFs model in predicting the short-term( 90-day) prognosis of patient with hepatitis B virus-related acute-on-chronic liver failure( HBV-ACLF). Methods A total of 573 patients who were diagnosed with HBV-ACLF in The Affiliated Hospital of Southwest Medical University,The First People's Hospital of Neijiang,and The Second People's Hospital of Yibin were enrolled,and their general information and laboratory markers were collected. According to the outcome on day90 after diagnosis,the patients were divided into survival group with 339 patients and death group with 234 patients. The t-test was used for comparison of normally distributed continuous data between two groups,and the Wilcoxon rank sum test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups,and the Wilcoxon rank sum test was used for comparison of ranked data between two groups. The area under the receiver operating characteristic curve( AUC) was used to compare the value of different models in predicting 90-day prognosis. Results Compared with the survival group,the death group had significantly higher age( Z =-0. 304,P = 0. 002),bilirubin( Z =-5. 961,P < 0. 001),peripheral white blood cell count( Z =-6. 027,P < 0. 001),and creatinine( Z =-4. 638,P < 0. 001),significantly lower hemoglobin( Z =-2. 012,P = 0. 044),albumin( Z =-4. 007,P < 0. 001),and Na( Z =-4. 558,P < 0. 001),and significantly higher incidence rates of hepatic encephalopathy( Z =-7. 859,P < 0. 001),peritonitis( Z =-2. 310,P = 0. 021),and upper gastrointestinal bleeding( χ2= 11. 697,P =0. 001). Compared with the death group,the survival group had significantly better coagulation markers,prothrombin time,international normalized ratio,and prothrombin time activity( Z =-7. 737,-7. 672,and-7. 867,all P < 0. 001). MELD,MELD-Na,CLIF-COFs,CLIF-CACLFs,and COSSH-ACLFs had an area under the ROC curve( AUC) of 0. 726,0. 587,0. 712,0. 735,and 0. 750,respectively,and the COSSH-ACLFs model had a significantly larger AUC than the other four models( Z = 7. 89,18. 83,12. 49,and 5. 05,all P < 0. 001). Conclusion The COSSH-ACLFs model has a better value than CLIF-C ACLFs,MELD,CLIF-C OFs,and MELD-Na in predicting the short-term prognosis of patients with HBV-ACLF.

Objective To investigate the real-world viral response of chronic hepatitis C( CHC) patients receiving direct-acting antiviral agent( DAA) treatment and its effect on liver stiffness measurement( LSM) and aspartate aminotransferase-to-platelet ratio index( APRI). Methods The CHC patients who were consecutively admitted to Tianjin Third Central Hospital from April 1,2018 to November30,2018 and received DAA treatment were enrolled,and all patients were treated with DAA( without interferon) for 12-24 weeks. Virologic response was evaluated at week 12 after treatment ended,and the changes of LSM and APRI from baseline to week 12 after treatment were compared. The Wilcoxon rank-sum test was used for comparison of continuous data between two groups. Results A total of 212 CHC patients were enrolled in our study,among whom 35. 4% had liver cirrhosis,and the patients with genotype 1 b,2 a,3 a,or 6 a accounted for75. 0%,18. 4%,4. 2%,and 2. 4%,respectively. Of all patients,174 completed the course of DAA treatment and the 12-week follow-up,and among these patients,98. 3% achieved sustained virologic response( SVR) at the end of DAA treatment and 95. 4% acquired SVR at week 12 after the treatment ended. Among the patients with genotype 1 b,2 a,3 a,or 6 a,96. 3%,93. 1%,80. 0%,and 100%,respectively,achieved SVR at week 12 after the treatment ended. There were significant reductions in LSM [9. 8( 6. 9-16. 3) kPa vs 11. 4( 7. 7-19. 1) kPa,Z =-2. 5,P = 0. 012]and APRI [0. 34( 0. 25-0. 64) vs 0. 76( 0. 56-2. 25),Z =-6. 6,P < 0. 001]from baseline to week 12 after the treatment ended. The patients were divided into groups according to the presence or absence of liver cirrhosis at baseline,and the results showed that from baseline to week 12 after treatment ended,the non-liver cirrhosis group had a significant reduction in LSM[7. 6( 6. 6-10. 7) k Pa vs 8. 8( 7. 2-13. 0) kPa,Z =-2. 7,P = 0. 007],while the liver cirrhosis group had no significant change in LSM [17. 4( 12. 7-22. 1) kPa vs 19. 8( 12. 8-24. 9) kPa,Z =-1. 4,P = 0. 152]. There was a significant reduction in APRI from baseline to week 12 after treatment ended in the liver cirrhosis group [0. 73( 0. 52-1. 34) vs 1. 37( 0. 80-2. 11),Z =-3. 4,P <0. 001] and the non-liver cirrhosis group [0. 29( 0. 21-0. 36) vs 0. 54( 0. 31-0. 95),Z =-6. 8,P < 0. 001]. Conclusion In this real-world study,CHC patients treated with DAA achieve a high overall virological response rate,with significant improvements in LSM and APRI at week 12 after treatment ends.

Objective To investigate the value of transient elastography( FibroScan) in the diagnosis of liver fibrosis in chronic hepatitis B( CHB) children of different ages. Methods A total of 280 CHB children,aged < 18 years,who were hospitalized in The Fifth Medical Center of Chinese PLA General Hospital from June 2015 to December 2019 and planned to receive antiviral therapy were enrolled,among whom there were 157 preschool children( aged ≤6 years),74 school-aged children( aged 6-12 years),and 49 adolescents( aged 12 ～18 years). Liver biopsy was performed for all children to evaluate the degree of liver fibrosis,and according to the Matevia score,the children were divided into mild group( 0≤F < 2),moderate group( 2≤F < 3),and severe group( F≥3); FibroScan was used to determine liver stiffness measurement( LSM). LSM was compared between the children with the same degree of liver fibrosis and different ages to analyze the influence of age on LSM in judging the degree of liver fibrosis. The receiver operating characteristic( ROC) curve was used to analyze the cut-off values of LSM in the diagnosis of significant liver fibrosis( F≥2) and advanced liver fibrosis( F≥3) in children of different ages. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups,and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups; the Wilcoxon test was used for further comparison between two groups. The chi-square test was used for comparison of categorical data between multiple groups.The Spearman rank correlation analysis was used to evaluate correlation. Results Mild liver fibrosis was found in 186 children,and LSM was 4. 9( 4. 3-5. 6) k Pa in the preschool group,5. 5( 4. 5-6. 3) kPa in the school-aged group,and 6. 0( 5. 4-7. 0) k Pa in the adolescent group,with a significant difference between the preschool group and the adolescent group( Z = 10. 929,P = 0. 003). Moderate liver fibrosis was observed in 60 children,and LSM was 5. 6( 4. 5-6. 5) k Pa in the preschool group,6. 4( 5. 4-7. 7) k Pa in the school-aged group,and 7. 1( 6. 3-8. 0) k Pa in the adolescent group,with a significant difference between the preschool group and the adolescent group( Z = 8. 517,P = 0. 011). Severe liver fibrosis was found in 34 children,and LSM was 8. 3( 7. 1-9. 2) k Pa in the preschool group,9. 1( 8. 5-13. 1) k Pa in the school-aged group,and 11. 1( 8. 5-12. 0) k Pa in the adolescent group,with no significant difference between the three groups( χ2= 4. 553,P = 0. 103). LSM was significantly correlated with the degree of liver fibrosis in the children aged ≤12 years( r = 0. 447,P < 0. 001). LSM had a cut-off value of 5. 8 k Pa and an area under the ROC curve( AUC) of 0. 74( 0. 68-0. 80) in the diagnosis of significant liver fibrosis and a cut-off value of 7. 0 k Pa and an AUC of 0. 94( 0. 90-0. 97) in the diagnosis of advanced liver fibrosis. LSM was significantly correlated with the degree of liver fibrosis in the children aged > 12 years( r = 0. 722,P < 0. 001),with a cut-off value of 6. 6 k Pa and an AUC of 0. 82( 0. 69-0. 92) in the diagnosis of significant liver fibrosis and a cut-off value of 8. 0 k Pa and an AUC of 0. 95( 0. 85-0. 99) in the diagnosis of advanced liver fibrosis. Conclusion LSM is positively correlated with the degree of liver fibrosis in CHB children,and therefore,it can be used as a noninvasive indicator for the diagnosis of advanced liver fibrosis. LSM increases with age,and the children aged > 12 years have a higher diagnostic threshold than those aged ≤12 years.

Objective To investigate the clinical effect of terlipressin combined with somatostatin in the treatment of esophagogastric variceal bleeding( EVB) in patients with liver cirrhosis. Methods A retrospective analysis was performed for the clinical data of 73 patients with liver cirrhosis and EVB who were treated in Department of Gastronenterology and Hepatology,Beijing YouAn Hospital,Capital Medical University,from September 2017 to February 2019. In addition to anti-acid therapy,43 patients were treated with somatostatin,8 patients were treated with terlipressin,and 22 patients were treated with terlipressin combined with somatostatin. The three groups were compared in terms of 24-hour success rate of hemostasis,hemostatic time,early rebleeding rate,delayed rebleeding rate,improvement rate of acute kidney injury( AKI),and half-year cumulative survival rate. A one-way analysis of variance was used for comparison of normally distributed continuous data between the three groups,and the Kruskal-Wallis H rank sum test was used for comparison of non-normally distributed continuous data between the three groups; the chi-square test was used for comparison of categorical data between groups. The cumulative incidence function was used to describe mortality rate,and a competing risk model( Gray's Test) was used for comparison of survival rates between the three groups. Results There were no significant differences between the combination group,the somatostatin group,and the terlipressin group in 24-hour success rate of hemostasis( 54. 5%,41. 9%,and 37. 5%,respectively),hemostatic time [1. 00( 1. 00-3. 00) d,2. 00( 1. 00-3. 00) d,and 2. 00( 1. 00-3. 00) d,respectively],early rebleeding rate( 25%,27. 5%,and 16. 7%,respectively),and delayed rebleeding rate( 16. 7%,27. 3%,and 40%,respectively)( all P > 0. 05). There was no significant difference in the improvement rate of AKI patients after treatment between the combination group and the somatostatin group( 100% vs 50%,P = 0. 429).There was no significant difference in the half-year cumulative survival rate between the three groups( SHR = 1. 40,95% confidence interval:0. 60-3. 27,P = 0. 436). Conclusion Terlipressin combined with somatostatin,somatostatin alone,and terlipressin alone can effectively control EVB in liver cirrhosis and have similar clinical effects. Compared with somatostatin alone,somatostatin combined with terlipressin has a potential advantage in improving AKI.

Objective To investigate the value of Child-Pugh score,Model for End-Stage Liver Disease( MELD) score,MELD combined with serum sodium concentration( MELD-Na score),APASAL score,and R-score in predicting rebleeding and death in cirrhotic patients with esophagogastric variceal bleeding. Methods The patients with liver cirrhosis and gastroesophageal variceal bleeding who underwent endoscopic therapy for bleeding for the first time in Beijing Ditan Hospital,Capital Medical University,from January 2013 to January 2016 and were followed up for more than 3 years were enrolled. Observation indices included age,sex,body weight,blood pressure,routine blood test results,hepatic and renal function,coagulation,radiological examination( including abdominal ultrasound),and complications( including hepatic encephalopathy,ascites,and infection). Variceal rebleeding was the primary endpoint,and death was the secondary endpoint. The t-test or the Wilcoxon rank-sum 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 Spearman correlation analysis was performed,and the receiver operating characteristic( ROC) curve was used to investigate the value of these five risk scoring systems in the diagnosis of rebleeding and death. Results A total of 305 patients were enrolled,among whom 53( 17. 38%) experienced variceal rebleeding during follow-up. There were significant differences between the rebleeding group and the non-rebleeding group in age,alanine aminotransferase,direct bilirubin,international normalized ratio,diameter of the portal vein,MELD score,MELD-Na score,and R-score( all P < 0. 05). The correlation analysis showed a significant correlation between any two scores except between APASAL score and MELD score/R-score and between MELD-Na score and R-score( all P < 0. 05). The ROC curve analysis showed that MELD score,MELD-Na score,and R-score had a certain value in predicting rebleeding,with an area under the ROC curve( AUC) of 0. 645( 95% confidence interval [CI]: 0. 563-0. 727,P = 0. 001),0. 637( 95% CI: 0. 552-0. 723,P = 0. 002),and 0. 647( 95% CI: 0. 565-0. 729,P = 0. 001),respectively,and Child-Pugh score had a certain diagnostic value for death,with an AUC of 0. 610( 95% CI: 0. 541-0. 680,P = 0. 002). Conclusion Child-Pugh score,MELD score,MELD-Na score,APASAL score,and R-score have a limited value in predicting variceal rebleeding,and only Child-Pugh score has a certain diagnostic value for death.

Objective To investigate the expression of the N-myc downstream regulated gene( NDRG) family in hepatocellular carcinoma( HCC) and its association with pathological features and prognosis based on bioinformatics mining. Methods The expression of the NDRG family and the survival data of patients with HCC were obtained using ONCOMINE,GEPIA,and Kaplan-Meier Plotter. The gene expression data of the NDRG family were obtained from 419 HCC tissue samples,which were divided into liver cancer group with 369 samples and normal liver tissue group with 50 samples. Survival data were collected from 364 HCC tissue samples,which were divided into low expression groups( NDRG1 group with 212 samples,NDRG2 group with 185 samples,NDRG3 group with 182 samples,and NDRG4 group with 184 samples) and high expression groups( NDRG1 group with 152 samples,NDRG2 group with 179 samples,NDRG3 group with 182 samples,and NDRG4 group with 180 samples). The t-test was used for comparison of continuous data between two groups,a one-way analysis of variance was used for comparison between multiple groups,and then the Dunnett-t test was performed; the log-rank test were used for survival analysis. Results The expression of NDRG1 and NDRG3 in HCC tissue was higher than that in normal liver tissue,while the expression of NDRG2 in cancer tissue was lower than that in normal liver tissue( all P < 0. 05). There were significant differences in the expression of NDRG1,NDRG2,NDRG3,and NDRG4 between the patients with different pathological stages( F = 3. 67,2. 97,5. 51,and 3. 56,all P<0. 05). The survival analysis showed that compared with the group with low transcription of NDRG1 and NDRG3,the group with high transcription of NDRG1 and NDRG3 had significantly shortened overall survival( OS)( NDRG1: hazard ratio [HR]= 1. 75,95% confidence interval [CI]: 1. 24-2. 47,P < 0. 05; NDRG3: HR = 1. 83,95% CI: 1. 28-2. 60,P < 0. 05) and progression-free survival( PFS)( NDRG1: HR = 1. 39,95% CI: 1. 03-1. 87,P < 0. 05; NDRG3: HR = 1. 71,95% CI: 1. 27-2. 30,P < 0. 05). Compared with the group with low transcription of NDRG2,the group with high transcription of NDRG2 had significantly shortened OS( HR = 0. 43,95% CI:0. 30-0. 62,P < 0. 05) and PFS( HR = 0. 59,95% CI: 0. 44-0. 80,P < 0. 05). There was no significant difference in OS between the group with high transcription of NDRG4 and the group with low transcription of NDRG4( HR = 1. 4,95% CI: 0. 99-1. 98,P >0. 05),and compared with the group with low transcription of NDRG4,the group with high transcription of NDRG4 had significantly prolonged PFS( HR = 0. 53,95% CI: 0. 39-0. 72,P < 0. 05). Conclusion The high expression of NDRG1 and NDRG3 and the low expression of NDRG2 may be associated the progression of HCC and suggest the poor prognosis of HCC patients.

Objective To investigate the effect of extracellular ubiquitin on the proliferation,invasion,and migration of hepatoma cells by in vitro cell experiments. Methods The hepatoma cells( HepG2) were treated with extracellular ubiquitin at different concentrations( 200,400,and 800 ng/ml); CCK-8 assay was used to observe cell proliferation,Transwell assay was used to observe the effect of extracellular ubiquitin at different concentrations on the invasion ability of hepatoma cells,and wound healing assay and Western blotting were used to observe the effect of extracellular ubiquitin on the migration ability of hepatoma cells. 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 CCK-8 assay showed that extracellular ubiquitin significantly promoted the proliferation of hepatoma cells in a concentration-dependent manner,with the most significant effect at the concentration of 400 ng/ml,and the intervention group had a significantly higher relative absorbance value than the control group at 48,72,and 96 hours( all P < 0. 05). The Transwell assay showed that different concentrations of extracellular ubiquitin significantly promoted the invasion of hepatoma cells,with the most significant effect in the group treated by400 ng/ml extracellular ubiquitin( 134. 00 ± 8. 18 vs 347. 33 ± 18. 90,t = 17. 94,P < 0. 001). The Wound healing assay and Western blotting showed that 400 ng/ml extracellular ubiquitin significantly increased the migration ability of HepG2 cells. Conclusion Extracellular ubiquitin can significantly promote the proliferation,invasion,and migration of HepG2 cells in vitro in a concentration-dependent manner.

Objective To investigate the association of the clinical features of liver cancer patients,including albumin-bilirubin( ALBI)and neutrophil-lymphocyte ratio( NLR),with the traditional Chinese medicine( TCM) syndrome types of primary liver cancer,and to establish a clinical judgment model for TCM syndrome differentiation of primary liver cancer. Methods A total of 289 previously untreated patients who were admitted to The Affiliated Tumor Hospital of Guangxi Medical University from November 1,2016 to October 31,2018 and were diagnosed with primary liver cancer based on pathology or clinical examination were enrolled,and TCM syndrome differentiation was performed for all patients. 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. The data with significant difference in the univariate analysis were included in the logistic regression analysis,and the receiver operating characteristic( ROC) curve was used to evaluate the efficiency of these clinical features in the TCM syndrome differentiation of liver cancer. Results There were significant differences between the patients with different TCM syndrome types of liver cancer in ALBI( F = 5. 487,P < 0. 001),NLR( χ2= 30. 146,P < 0. 001),BCLC stage( χ2= 71. 973,P <0. 001),albumin( Alb)( χ2= 18. 887,P < 0. 001),total bilirubin( TBil)( χ2= 12. 138,P = 0. 007),alanine aminotransferase( ALT)( χ2= 18. 001,P < 0. 001),aspartate aminotransferase( χ2= 12. 067,P = 0. 007),absolute neutrophil count( F = 6. 262,P < 0. 001),absolute lymphocyte count( F = 2. 934,P = 0. 034),diameter of intrahepatic primary tumor( F = 4. 905,P = 0. 002),ascites( χ2=9. 034,P = 0. 021),portal vein tumor thrombus( χ2= 13. 434,P = 0. 004),and number of extrahepatic metastatic lesions( χ2= 2. 529,P= 0. 002). The logistic regression analysis showed that ALT( odds ratio [OR]= 1. 002,95% confidence interval [CI]: 1. 003-1. 021,P< 0. 05) and BCLC stage( OR = 0. 591,95% CI: 0. 413-0. 845,P < 0. 05) were independent factors for judging damp-heat accumulation; ALT( OR = 0. 985,95% CI: 0. 974-0. 997,P < 0. 05) and BCLC stage( OR = 3. 191,95% CI: 2. 042-4. 986,P < 0. 05) were also independent factors for judging liver depression and spleen deficiency; TBil( OR = 0. 966,95% CI: 0. 937-0. 995,P < 0. 05),Alb( OR = 1. 259,95% CI: 1. 064-1. 490,P < 0. 05),and ALBI( OR = 0. 088,95% CI: 0. 013-0. 607,P < 0. 05) were independent factors for judging Qi stagnation and blood stasis. The ROC curve analysis showed that ALT and BCLC stage had an area under the ROC curve( AUC) of 0. 662( 95% CI: 0. 605-0. 717),a sensitivity of 69. 4%,and a specificity of 58% in judging damp-heat accumulation,at the cut-off values of 36 U/L for ALT and stage C for BCLC stage; ALT and BCLC stage had an AUC of 0. 753( 95% CI: 0. 699-0. 801),a sensitivity of 72. 7%,and a specificity of 68. 2% in judging liver depression and spleen deficiency,at the cut-off values of 64 U/L for ALT and stage B for BCLC stage; TBil,Alb,and ALBI had an AUC of 0. 634( 95% CI: 0. 576-0. 690),a sensitivity of 56. 7%,and a specificity of 65. 3% in judging Qi stagnation and blood stasis,at the cut-off values of 28. 4 μmol/L for TBil,37. 8 g/L for Alb,and 1. 95 for ALBI. Conclusion The clinical judgment model based on ALT,BCLC stage,TBil,Alb,and ALBI can differentiate between the TCM syndrome types of damp-heat accumulation,liver depression and spleen deficiency,and Qi stagnation and blood stasis for liver cancer,and this model is simple,convenient,and objective and thus holds promise for clinical application.

Objective To investigate the association between nonalcoholic fatty liver disease( NAFLD) and colorectal adenomatous polyps and the correlation of NAFLD severity with the risk of colorectal adenomatous polyps. Methods A total of 67 patients with colorectal adenomatous polyps who were hospitalized in Department of Gastroenterology,The Second Affiliated Hospital of Kunming Medical University,from March to August 2019 were enrolled as adenoma group,and 45 patients who attended our hospital during the same period of time and had normal results of colonoscopy or were diagnosed with inflammatory and proliferative polyps based on pathology were enrolled as control group.The two groups were compared in terms of baseline data and controlled attenuation parameter( CAP) of the liver. All subjects were divided into non-fatty liver group and mild,moderate,and severe NAFLD groups according to FibroTouch,and the correlation of the severity of NAFLD with the risk of colorectal adenomatous polyps was analyzed. The t-test was used for comparison of normally distributed continuous data between two groups; 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. For non-normally distributed continuous data,the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the Kruskal-Wallis H test was used for comparison 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 groups. A logistic regression analysis was used to investigate the risk factors for colorectal adenoma. Results Compared with the control group,the adenoma group had significantly higher proportion of male patients [49( 73. 13%) vs23( 51. 11%),χ2= 5. 687,P = 0. 017],age( 56. 24 ± 12. 44 years vs 50. 84 ± 11. 49 years,t =-2. 319,P = 0. 022),body mass index( BMI)( 24. 69 ± 3. 36 kg/m2 vs 22. 54 ± 3. 31 kg/m2,t =-3. 346,P = 0. 001),waist circumference( 89. 45 ± 10. 51 cm vs 83. 44 ±10. 30 cm,t =-2. 753,P = 0. 007),systolic pressure( 128. 78 ± 16. 92 mm Hg vs 117. 00 ± 15. 91 mm Hg,t =-3. 698,P < 0. 001),alanine aminotransferase( ALT) [24. 00( 18. 00 ～ 40. 00) U/L vs 22. 00( 16. 00 ～ 29. 00) U/L,Z =-1. 957,P = 0. 022 ],total cholesterol( TC)( 4. 73 ± 0. 96 mmol/L vs 4. 27 ± 0. 90 mmol/L,t =-2. 537,P = 0. 013),low-density lipoprotein( LDL)( 2. 92 ± 0. 78 mmol/L vs 2. 59 ± 0. 68 mmol/L,t =-2. 295,P = 0. 024),and CAP( 257. 51 ± 34. 22 d B/m vs 238. 67 ± 33. 44 d B/m,t =-2. 789,P= 0. 006). The logistic regression analysis showed that age( odds ratio [OR]= 1. 054,95% confidence interval [CI]: 1. 009-1. 102,P= 0. 019),BMI( OR = 1. 191,95% CI: 1. 026-1. 382,P = 0. 021),LDL( OR = 2. 058,95% CI: 1. 034-4. 097,P = 0. 040),ALT( OR = 1. 038,95% CI: 1. 008-1. 070,P = 0. 013),and CAP( OR = 1. 320,95% CI: 1. 163-1. 481,P = 0. 001) were independent risk factors for colorectal adenomatous polyps. The severe,moderate,and mild NAFLD groups had a significantly higher proportion of patients with colorectal adenomatous polyps than the non-fatty liver group [73. 08%( 19 patients)/73. 08%( 19 patients)/53. 85%( 14 patients) vs 40. 74%( 11 patients),χ2= 8. 088,P = 0. 040]. The logistic regression analysis showed that in the models 1 and 2,moderate NAFLD( model 1: OR = 1. 044,95% CI: 1. 007-1. 083,P = 0. 019; model 2: OR = 1. 011,95% CI: 1. 001-1. 022,P = 0. 033) and severe NAFLD( model 1: OR = 1. 183,95% CI: 1. 034-1. 354,P = 0. 015; model 2: OR = 1. 129,95% CI: 1. 030-1. 236,P = 0. 009)were risk factors for colorectal adenomatous polyps. In model 3,after adjustment for age,sex,BMI,smoking history,hypertension,diabetes mellitus,uric acid,triglyceride,LDL,and ALT,severe NAFLD( OR = 1. 078,95% CI: 1. 023-1. 136,P = 0. 005) was still a risk factor for colorectal adenomatous polyps. Conclusion NAFLD is an independent risk factor for colorectal adenomatous polyps,and patients with higher severity of NAFLD tend to have a higher risk of colorectal adenomatous polyps. Therefore,NAFLD patients,especially those with severe NAFLD,should undergo regular colonoscopy for early identification and treatment of colorectal adenomatous polyps,so as to eventually reduce the incidence rate and mortality rate of colorectal tumor in China.

Objective To investigate the association between nonalcoholic fatty liver disease( NAFLD) and epicardial adipose tissue( EAT). Methods Databases including PubMed,Embase,Web of Science,Wanfang Data,and CNKI were searched for the articles on the association of thickness and volume of EAT with NAFLD published up to January 1,2019. Stata12. 0 was used to calculate standardized mean difference( SMD) and 95% confidence interval( CI); the I2 test was used to evaluate heterogeneity between studies,and sensitivity analysis and subgroup analysis were used to explore the source of heterogeneity. Results A total of 13 articles were included,with 4672 subjects in total( 2586 subjects in the normal control group and 2086 subjects in the NAFLD group). The NAFLD group had a significant increase in EAT compared with the normal control group( SMD = 0. 58,95% CI: 0. 39-0. 77,P < 0. 001). There were significant differences between the NAFLD group and the normal control group in the thickness and volume of EAT( thickness: SMD = 0. 61,95% CI:0. 40-0. 83,P < 0. 001; volume: SMD = 0. 47,95% CI: 0. 17-0. 76,P = 0. 002). As for the Asian population,compared with the normal control group,the NAFLD group had a significant increase in EAT( SMD = 0. 37,95% CI: 0. 06-0. 68,P = 0. 018); as for the European/American population,compared with the normal control group,the NAFLD group had a significant increase in EAT( SMD = 0. 66,95% CI: 0. 40-0. 92,P < 0. 001). Compared with the normal control group,the NAFLD patients aged ≥50 years had a significant increase in EAT( SMD = 0. 46,95% CI: 0. 31-0. 62,P < 0. 001); there was a significant difference in EAT between the NAFLD patients aged < 50 years and the normal control group( SMD = 0. 72,95% CI: 0. 37-1. 06,P < 0. 001). The NAFLD patients with a body mass index( BMI) of ≥30 kg/m2 had significantly thicker EAT than the normal control group( SMD = 0. 79,95% CI: 0. 43-1. 15,P < 0. 001); the NAFLD patients with a BMI of < 30 kg/m2 also had significantly thicker EAT than the normal control group( SMD = 0. 42,95% CI: 0. 21-0. 62,P < 0. 001). Compared with the normal control group,the NAFLD patients undergoing radiological examination had a significant increase in EAT( SMD = 0. 44,95% CI: 0. 26-0. 63,P < 0. 001); compared with the normal control group,the NAFLD patients undergoing liver biopsy also had a significant increase in EAT( SMD = 1. 05,95% CI: 0. 82-1. 29,P < 0. 001). Publication bias was assessed by funnel plots( symmetric),Begg's test( P = 0. 583),and the Egger's test( P = 0. 126),and the results showed high reliability. Conclusion NAFLD is significantly associated with EAT cardiovascular risk factors,which will help NAFLD patients to establish effective strategies for the prevention and control of cardiovascular events.

Objective To investigate the metabolic characteristics of nonalcoholic fatty liver disease( NAFLD) and related risk factors in non-obese population. Methods A retrospective analysis were performed for 12 125 individuals who underwent physical examination in Physical Examination Center of PLA Rocket Force Characteristic Medical Center from July 2013 to April 2019. According to body mass index( BMI) < 25 kg/m2,these individuals were divided into non-obese group with 8528 individuals and obese group with 3597 individuals; according to the results of abdominal ultrasound,the non-obese group was further divided into NAFLD group with 1025 individuals and non-NAFLD group with 7503 individuals. According to BMI < 25 kg/m2,3281 individuals with NAFLD were divided into non-obese NAFLD subgroup with 1025 individuals and obese NAFLD group with 2256 individuals. Related clinical data were collected,including sex,age,BMI,fasting blood glucose,uric acid,total cholesterol,triglyceride,high-density lipoprotein,low-density lipoprotein,and hemoglobin.Non-normally distributed continuous data were expressed as M( P25-P75),and the Mann-Whitney U test was used for comparison between groups; the chi-square test was used for comparison of categorical data between groups. A multivariate logistic regression analysis was performed to investigate risk factors. Results Among the 12 125 individuals who underwent the physical examination,the detection rate of NAFLD was 27. 06%,and the detection rate of non-obese NAFLD was 8. 45%,accounting for 12. 02% of the non-obese population.The multivariate logistic regression analysis,based on the univariate analysis,had a diagnostic accordance rate of 89%,and the results showed that the increase in age,BMI,fasting blood glucose,uric acid,triglyceride,low-density lipoprotein,and hemoglobin were independent risk factors for non-obese NAFLD( odds ratio [OR]= 1. 043,1. 716,1. 161,1. 004,1. 791,2. 587,and 1. 011,P < 0. 001,< 0. 001, = 0. 001,< 0. 001, < 0. 001, < 0. 001,and = 0. 011),suggesting that non-obese NAFLD had the strongest association with low-density lipoprotein and had no association with age,uric acid,and hemoglobin. Total cholesterol and high-density lipoprotein were non-susceptible factors for non-obese NAFLD( OR = 0. 521 and 0. 523,P = 0. 007 and 0. 024). Conclusion Non-obese NAFLD is closely associated with metabolic disorders,and further studies are needed to explore the association between serum cholesterol and non-obese NAFLD.

Objective To investigate whether abdominal obesity and hypertriglyceridemia have a synergistic effect on the development of nonalcoholic fatty liver disease( NAFLD). Methods A prospective cohort study was conducted. Physical examination data were collected from 70 776 on-the-job or retired employees of Kailuan Group who underwent physical examination from July 2006 to June 2007,and the development of NAFLD was observed during the follow-up every two years. The subjects were divided into four groups according to the waist-to-height ratio and triglyceride( TG) level,and the person-year incidence rate was calculated. 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.The life-table method was used to calculate the cumulative incidence rate of NAFLD in each group,and the log-rank test was used for comparison between groups. With the non-abdominal obesity and non-hypertriglyceridemia group as the control group,the Cox proportional hazards model was used to analyze the risk of NAFLD and related 95% confidence interval( CI) for each group,and the influence of the interaction between abdominal obesity and hypertriglyceridemia on the development of NAFLD was further analyzed. Results During the mean follow-up time of 5. 03 ± 1. 67 years in this study,a total of 15 684 cases of NAFLD were observed,with a 6-year cumulative incidence rate of 25. 44% and a person-time incidence rate of 44. 03/1000 person-years. The log-rank test showed a significant difference in cumulative incidence rate between groups( χ2= 2479. 40,P < 0. 001). With the non-abdominal obesity and non-hypertriglyceridemia group as the control group,after adjustment for related confounding factors,the abdominal obesity-hypertriglyceridemia group had a hazard ratio( HR) of 2. 50( 95% CI: 2. 38-2. 62) for the development of NAFLD,which was significantly higher than the HR of 1. 99( 95%CI: 1. 92-2. 07) in the abdominal obesity and non-hypertriglyceridemia group and the HR of 1. 71( 95% CI: 1. 59-1. 84) in the non-abdominal obesity and hypertriglyceridemia group. After adjustment for the same confounding factors,the interaction analysis showed multiplicative interaction between abdominal obesity and hypertriglyceridemia( P < 0. 001),and co-existence of abdominal obesity and hypertriglyceridemia had a relative excess risk of 0. 77( 95% CI: 0. 68-0. 86),an attributable proportion of 30. 83%,and an interaction index of 2. 06( 95% CI: 1. 90-2. 24). Conclusion Abdominal obesity and hypertriglyceridemia have a synergistic effect on the development of NAFLD.

Objective To investigate the association between liver fibrosis and serum uric acid in patients with type 2 diabetes mellitus( T2 DM) and nonalcoholic fatty liver disease( NAFLD). Methods A total of 328 patients with T2 DM and NAFLD who attended Cangzhou People's Hospital from January 2018 to August 2019 were enrolled,and according to NAFLD fibrosis score( NFS) and fibrosis-4( FIB-4)index,they were divided into low-risk fibrosis group with 136 patients,intermediate-risk fibrosis group with 145 patients,and high-risk fibrosis group with 47 patients. A total of 141 patients with T2 DM,matched for age and sex,were enrolled as T2 DM group. Serum uric acid was compared between groups. A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between multiple groups,and the chi-square test was used for comparison of categorical data between groups. A logistic regression analysis was used to determine the influencing factors for liver fibrosis,and the receiver operating characteristic( ROC) curve was used to evaluate the predictive efficiencies of risk factors. Results Compared with the T2 DM group,the T2 DM + NAFLD group had a significant increase in serum uric acid( 313. 04 ± 100. 90 vs 265. 00 ± 77. 01,t =-5. 619,P < 0. 001). The high-risk fibrosis group had a significant increase in serum uric acid compared with the low-risk fibrosis group( 392. 77 ± 108. 37 vs 290. 70 ± 95. 46,P < 0. 05) and the intermediate-risk fibrosis group( 392. 77 ± 108. 37 vs 328. 15 ± 90. 85,P < 0. 05),and the high-risk fibrosis group had a significantly higher prevalence rate of hyperuricemia than the low-risk fibrosis group and the intermediate-risk fibrosis group( 47. 00% vs 11. 72% vs 11. 76%,P < 0.01). The logistic regression analysis showed that serum uric acid( odds ratio = 1. 133,95% confidence interval: 1. 064-1. 312) was an independent risk factor for liver fibrosis in patients with T2 DM and NAFLD. The ROC curve showed that serum uric acid had a certain value in predicting liver fibrosis,with an area under the ROC curve of 0. 745. Conclusion The high level of serum uric acid is an independent risk factor for the development and progression of liver fibrosis in patients with T2 DM and NAFLD.

Objective To investigate the association between microRNA-155( miR-155)/SH2-containing inositol phosphatase-1( SHIP-1) and cardiovascular events in patients with nonalcoholic fatty liver disease( NAFLD). Methods A total of 104 patients with NAFLD who were admitted to our hospital from March 2018 to July 2019 were enrolled as NAFLD group,and 110 healthy volunteers who underwent physical examination in our hospital during the same period of time were enrolled as control group. Related indices were measured,including body mass index( BMI),blood pressure,fasting plasma glucose( FPG),total cholesterol( TC),triglyceride( TG),low-density lipoprotein cholesterol( LDL-C),high-density lipoprotein cholesterol( HDL-C),alanine aminotransferase( ALT),aspartate aminotransferase( AST),gamma-glutamyl transpeptidase( GGT),and total bilirubin( TBil),and quantitative real-time PCR was used to measure the mRNA expression of miR-155 and SHIP-1 in peripheral blood. The t-test was used for comparison of continuous data between two groups,the chi-square test was used for comparison of categorical data between two groups,and the Kruskal-Wallis H test was used for comparison of ranked data between groups. A Pearson correlation analysis was performed,and the receiver operating characteristic( ROC) curve was used to investigate the value of miR-155/SHIP-1 ratio in predicting cardiovascular events. Results Compared with the control group,the NAFLD group had significantly higher levels of BMI,FPG,TC,TG,LDL-C,ALT,AST,GGT,and TBil and a significantly lower level of HDL-C,as well as significantly higher relative mRNA expression of miR-155,significantly lower relative mRNA expression of SHIP-1,and a significantly higher incidence rate of cardiovascular events( t = 6. 617,9. 323,6. 668,8. 633,4. 285,22. 099,24. 093,20. 438,12. 366,6. 515,18. 893,18. 411,and 29. 967,χ2= 10. 476,all P < 0. 01). The patients were divided into three groups according to miR-155/SHIP-1 ratio,there were significant differences between the three groups in BMI,FPG,TC,TG,LDL-C,HDL-C,ALT,AST,GGT,TBil,and incidence rate of cardiovascular events( H = 20. 923,7. 936,6. 256,16. 181,21. 572,8. 435,18. 912,22. 869,7. 665,18. 657,and 9. 701,all P < 0. 05). The miR-155/SHIP-1 ratio was significantly correlated with BMI,FPG,TC,TG,LDL-C,HDL-C,ALT,AST,GGT,and TBil( r = 0. 297,0. 317,0. 332,0. 327,0. 286,-0. 279,0. 334,0. 352,0. 342,and 0. 350,all P < 0. 001). The patients with cardiovascular events had a significantly higher miR-155/SHIP-1 ratio than those without cardiovascular events( 3. 642 ± 1. 082 vs 2. 237 ± 0. 703,t = 11. 104,P < 0. 05),and the miR-155/SHIP-1 ratio had an area under the ROC curve of 0. 902 in predicting cardiovascular events in patients with NAFLD. Conclusion Abnormal glycolipid metabolism and liver function in patients with NAFLD are closely associated with the expression of miR-155/SHIP-1,and miR-155/SHIP-1 ratio has a certain value in predicting cardiovascular events in patients with NAFLD.

Objective To investigate the clinical effect and safety of magnesium isoglycyrrhizinate in the treatment of autoimmune-like drug-induced liver injury. Methods A total of 53 patients with autoimmune-like drug-induced liver injury who were hospitalized in Beijing YouAn Hospital,Capital Medical University,from July 2016 to January 2019 was enrolled as observation group,and 50 patients with drug-induced liver injury who had no autoimmune symptoms were enrolled as control group. All patients were given magnesium isoglycyrrhizinate( 200 mg/d) for 4 weeks. Liver function and immunological indices were observed before and after treatment,and adverse reactions were recorded for all patients. Liver function was followed up every month for 6 months after treatment. 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 or the Fisher's exact test was used for comparison of categorical data between groups.Results After treatment,the observation group had significant reductions in alanine aminotransferase( ALT) [35. 4( 29. 2-42. 0) U/L vs 289. 0( 226. 6-460. 3) U/L,Z =-8.661,P<0. 001],aspartate aminotransferase( AST) [46. 3( 15.6-183.5) U/L vs 306. 3( 32. 2-589. 8) U/L,Z =-5. 271,P < 0. 001],gamma-glutamyl transpeptidase( GGT) [77. 0( 53. 2-183. 2) U/L vs 129. 0( 77. 8-232. 5) U/L,Z =-3. 437,P =0. 001],alkaline phosphatase( ALP) [83. 1( 64. 9-83. 1) U/L vs 119. 4( 104. 9-146. 9) U/L,Z =-3. 485,P < 0. 001],and total bilirubin( TBil)( 27. 5 ±10. 3 μmol/L vs 59. 7 ±18.6 μmol/L,t =6. 673,P <0. 001),and the control group also had significant reductions in ALT[33. 1( 14. 9-106. 4) U/L vs 300. 6( 206. 8-679. 5) U/L,Z =-8. 232,P < 0. 001],AST [44. 1( 20. 8-151. 6) U/L vs 321. 7( 36. 2-553. 2) U/L,Z =-3. 549,P < 0. 001],GGT [82. 7( 50. 6-168. 5) U/L vs 133. 5( 72. 2-254. 2) U/L,Z =-2. 364,P = 0. 018],ALP [87. 6( 74. 3-139. 4) U/L vs 128. 0( 106. 3-201. 4) U/L,Z =-4. 303,P < 0. 001],and TBil( 23. 8 ± 10. 9 μmol/L vs 58. 3 ±19. 8 μmol/L,t =-8. 450,P < 0. 001); however,there were no significant differences between the two groups after treatment( P >0. 05). For the observation group,the level of Ig G decreased from 15. 8 ± 3. 2 g/L before treatment to 14. 2 ± 2. 0 g/L after treatment,and among the 22 patients with elevated Ig G( > 16 g/L) before treatment,18( 81. 8%) had an Ig G level back to normal. Among the 36 patients with positive anti-nuclear antibody,19( 52. 7%) achieved negative conversion. No serious adverse reaction was observed in the two groups. In terms of the patients who underwent liver biopsy,the observation group had a significantly higher proportion of patients with neutrophil and/or eosinophil infiltration than the control group [53. 1%( 17/32) vs 17. 5%( 3/17),χ2= 5. 785,P = 0. 016]. Conclusion Magnesium glycyrrhizinate is safe and effective in the treatment of autoimmune-like drug-induced liver injury and can thus be selected as an alternative treatment method in clinical practice.

Objective To investigate the changes in the expression of semaphorin 3 A( Sema3 A) and receptor neuropilins-1( NRP-1) in the prefrontal cortex and the hippocampal CA1,CA3,and DG regions in rats with hepatic encephalopathy( HE) and their possible significance. Methods A total of 40 Sprague-Dawley rats were randomly divided into control group and 1-,15-,and 30-day HE groups,with 10 rats in each group. Bile duct ligation and ammonium acetate by gavage were used to establish a rat model of chronic HE( type C).The behavioral and neurological changes were observed; ELISA was used to measure blood ammonia and related biochemical parameters; HE staining was used to observe morphological changes of the liver and brain tissue; real-time PCR was used to measure the mRNA expression of Sema3 A and NRP-1 in each brain region; immunohistochemistry and Western blot were used to measure the protein expression of Sema3 A and NRP-1 in the cerebral cortex and the hippocampal CA1,CA3,and DG regions. 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 between the four groups in nerve reflex level,blood ammonia,and HE grade( F =76. 39,417. 07,and 71. 56,all P < 0. 001),and compared with the control group,the 1-,15-,and 30-day HE groups had significant increases in nerve reflex score,blood ammonia,and HE grade( all P < 0. 05). There were significant differences between the four groups in total bile acid,albumin,total bilirubin,aspartate aminotransferase,alanine aminotransferase,and alkaline phosphatase( F = 1022. 61,171. 56,685. 18,421. 01,675. 98,and 2405. 04,all P < 0. 001),and compared with the control group,the 1-,15-,and 30-day HE groups had a significant reduction in albumin( P < 0. 05) and significant increases in the other indices( all P < 0. 05). The pathological results showed that compared with the control group,the HE groups had varying degrees of degeneration,necrosis,and inflammatory cell infiltration in the liver,with the pathological signs of swelling,tortuous,and ruptured nerve axons in the prefrontal cortex and the hippocampal CA1,CA3,and DG regions. There were significant differences between the four groups in the mRNA expression of Sema3 A and NRP-1( Sema3 A: F = 273. 83,158. 84,103. 59,and 128. 90,all P < 0. 001; NRP-1: F = 88. 78,173. 02,156. 44,and 289. 09,all P<0. 001),and compared with the control group,the 1-,15-,and 30-day HE groups had significantly higher relative mRNA expression of Sema3 A and NRP-1 in the prefrontal cortex and the hippocampal CA1,CA3,and DG regions( all P < 0. 05). There were increases in the protein expression of Sema3 A and NRP-1 after modeling,and immunohistochemistry showed that the HE groups had positive staining of Sema3 A and NRP-1 in the prefrontal cortex and the hippocampal CA1,CA3,and DG regions. Western blot showed that there were significant differences between the four groups in the protein expression of Sema3 A and NRP-1 in the prefrontal cortex and the hippocampal CA1,CA3,and DG regions( Sema3 A: F = 835. 14,774. 16,282. 60,and 856. 29,all P < 0. 001; NRP-1 : F = 876. 59,472. 48,402. 36,and 207. 47,all P < 0. 001),and compared with the control group,the 1-,15-,and 30-day HE groups had significant increases in the protein expression of Sema3 A and NRP-1 in the prefrontal cortex and the hippocampal CA1,CA3,and DG regions( all P < 0. 05). Conclusion Sema3 A/NRP-1 is upregulated in the brain tissue of chronic HE rats and is involved in the pathophysiological process of nerve injury in HE.

Objective To screen out the scoring system with the highest predictive value by analyzing the comprehensive scoring systems which can assess the severity and prognosis of acute pancreatitis in the early stage( within 24 hours) after admission. Methods A retrospective analysis was performed for the clinical data of 254 patients with acute pancreatitis who were admitted to Department of Gastroenterology,The Second Affiliated Hospital of Kunming Medical University,from September 2016 to September 2019,and they were divided into mild acute pancreatitis( MAP) group,moderate-severe acute pancreatitis( MSAP) group,and severe acute pancreatitis( SAP) group.The three groups were compared in terms of general data,comorbidities,and scores of early admission scoring systems,including BISAP score,SIRS score,MEWS score,PANC3 score,HAPS score,CTSI score,and SPS score,and these scoring systems were compared in terms of their value in predicting the severity and prognosis of acute pancreatitis. An analysis of variance was used for comparison of normally distributed continuous data between groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups. The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. The receiver operating characteristic( ROC) curve was plotted and the area under the ROC curve( AUC) was compared. Results The SAP group had a significantly longer length of hospital stay and significantly higher hospital costs than the other two groups( H = 48. 82 and 76. 93,both P<0. 05). As for comorbidities,there were significant differences in the presence or absence of pulmonary infection,pancreatic necrosis,multiple organ dysfunction syndrome( MODS),and death between the three groups( H = 64. 84,98. 19,53. 09,and 8. 09,all P < 0. 05). As for the early scoring systems,there were significant differences between the three groups in BISAP score,SIRS score,MEWS score,HAPS score,CTSI score,and SPS score( H = 93. 19,21. 24,23. 99,16. 57,67. 09,and 33. 95,all P < 0. 05). The early scoring systems were further compared in terms of the severity of pancreatitis and complications based on the ROC curve,and it was found that BISAP score had the highest value in predicting SAP and pulmonary infection within 24 hours after admission,with sensitivities of 86. 10% and 51. 20%,respectively,and specificities of 81. 70% and 83. 50%,respectively,at the cut-off value of >2. CTSI score had the highest value in predicting pancreatic necrosis,with a sensitivity of 82. 70% and a specificity of 89. 10% at the cut-off value of > 3. In terms of MODS,both HAPS and BISAP scores had good predictive value,with sensitivities of 63. 70% and 75. 00%,respectively,and specificities of 90. 00%and 76. 10%,respectively. Conclusion Different scoring systems have their own advantages in predicting the severity and complications of pancreatitis in the early stage,among which BISAP score has a high value in predicting SAP,pancreatitis with pulmonary infection,and MODS,CTSI score has a high value in predicting pancreatic necrosis,and HAPS score has a high value in excluding MODS in the early stage.

Nucleos( t) ide analogues( NAs) are effective inhibitors for HBV replication and have become the preferred antiviral regimen for most patients with chronic hepatitis B( CHB). HBeAg seroconversion is an important index used to evaluate the durability and efficacy of antiviral therapy in HBeAg-positive CHB patients. The search for biomarkers that can predict HBeAg clearance or seroconversion after NAs treatment plays an important role in the selection of antiviral drugs,the adjustment of treatment regimens,and the achievement of individualized treatment. This article reviews the value of related markers,including HBV DNA,HBV RNA,anti-HBc,and HBcrAg,in predicting HBeAg clearance or seroconversion in CHB patients treated with NAs.

Liver cirrhosis is a pathological stage in which most chronic liver diseases progress to the advanced stages,and the main complications of liver cirrhosis include portal hypertension,gastroesophageal variceal bleeding,and liver cancer. Transient elastography( TE) uses acoustic waves to obtain liver stiffness measurement( LSM) noninvasively and is currently widely used in clinical practice. At present,various studies on LSM and liver cirrhosis and its complications suggest that TE has the ability to identify liver cirrhosis and its complications and can thus reduce unnecessary invasive procedures to a certain degree. This article summarizes and elaborates on the advances in the clinical application of TE in liver cirrhosis and its complications.

Hepatic fat content is an important index for the early diagnosis,disease grading,and outcome evaluation of nonalcoholic fatty liver disease( NAFLD). Various magnetic resonance imaging( MRI) methods have been used to determine hepatic fat content in NAFLD,among which proton density fat fraction obtained by magnetic resonance spectroscopy and chemical-shift-encoded MRI can achieve precise quantification of hepatic fat and therefore,it is considered the imaging gold standard for the diagnosis of fatty liver disease and has been applied in clinical research. This article reviews the research advances in the MRI techniques for quantification of hepatic fat content,in order to provide a reference for clinical application and experiment.

Nonalcoholic fatty liver disease( NAFLD) has replaced viral hepatitis and become the most important chronic liver disease in the world. Abdominal ultrasound remains the main method for the diagnosis of NAFLD in China. The studies in China showed that in the last two decades,the prevalence rate of NAFLD was 13%-43% and tended to increase year by year,and the new cases accounted for about 4%each year,with a certain proportion of patients with non-obese NAFLD. There is a significant difference in prevalence rate between the populations from different regions,with a higher prevalence rate of NAFLD in the well-developed southeast coastal regions where people have a similar lifestyle to those in Western countries. Metabolic disorders,such as type 2 diabetes,obesity,hyperlipidemia,hyperuricemia,and hypertension,are risk factors for NAFLD. National-wide large-sample epidemiological investigation is still needed in China to help support the diagnosis,treatment,and prevention of NAFLD.

Enterohepatic circulation plays an important role in the pathogenesis of nonalcoholic fatty liver disease( NAFLD). Bile acid is the basic substance of enterohepatic circulation and plays an important role in lipid metabolism,intestinal flora regulation,and host immunity. This article summarizes the research advances in bile acid which acts as a signal molecule to activate bile acid receptors in the liver and intestine,such as farnesoid X receptor,G protein-coupled receptor 5,pregnane X receptor,and vitamin D receptor,and is thus involved in the pathogenesis of NAFLD. It is expected to develop effective drugs for the treatment of NALFD based on the above targets,but there is still a need for further exploration.

Recent studies have shown that intestinal flora can play a role in the treatment of nonalcoholic fatty liver disease( NAFLD),and intestinal flora regulation can provide new thoughts for the treatment of NAFLD. This article reviews the research advances in the role of intestinal flora regulation in traditional Chinese and Western medicine therapy for NAFLD and explores the current situation of probiotics,fecal flora transplantation,antibiotics,and traditional Chinese medicine therapy in regulating intestinal flora and improving NAFLD,so as to provide a basis for clinical practice.

Recent studies have found that visfatin is involved in lipid metabolism in patients with nonalcoholic fatty liver disease( NAFLD),and about 25% of NAFLD patients have thyroid dysfunction. It has also been found that visfatin is involved in autoimmune regulation through the autocrine or paracrine pathways,which is associated with the involvement of the thyroid gland in autoimmune regulation of the body. This article preliminarily explores the association of visfatin with thyroid dysfunction in NAFLD patients and points out that the measurement of visfatin may help with the early identification of thyroid dysfunction in NAFLD patients.

In recent years,immune checkpoint inhibitor( ICI) in the treatment of unresectable liver cancer has attracted great attention in China and foreign countries and great progress has been achieved,but ICI monotherapy cannot bring benefits to most patients with liver cancer. Therefore,it is a new trend to explore the combination of ICI with other treatment methods. This article summarizes the advances in ICI combination therapy for unresectable liver cancer in China and foreign countries,including ICI combined with molecular targeted therapy,PD-1/PD-L1 inhibitor combined with CTLA-4 inhibitor,and ICI combined with local therapy. The results show that for patients with unresectable liver cancer,ICI combined with other treatment methods has a significantly better effect than ICI monotherapy; however,further studies are needed to explore which treatment method combined with ICI can bring the greatest benefits to patients.

At present,there is still a lack of uniform treatment strategies for hepatocellular carcinoma( HCC). Immunotherapy,especially PD-1/PD-L1 checkpoint inhibitors,is a novel therapy for HCC and can bring survival benefits to patients with advanced HCC. However,research data show that only a small number of HCC patients can benefit from this treatment regimen. To date,few biomarkers have been reported to predict the clinical effect of PD-1/PD-L1 checkpoint inhibitors in HCC patients. This article reviews the biomarkers studied for HCC and other tumors and explores the possible predictive factors for the clinical effect of PD-1/PD-L1 checkpoint inhibitors in HCC,in order to optimize the selection of treatment population and improve the clinical effect of PD-1/PD-L1 checkpoint inhibitors in the treatment of HCC.

Hepatic macrophages are an important cell component in the natural immune system. In the physiological environment,they can recognize and eliminate necrotic or apoptotic cell fragments,pathogens,and presenting antigens and participate in adaptive immunity and immune surveillance,while in the pathological state,activated macrophages can produce and release a large number of inflammatory factors and cytokines and recruit other immune cells to participate in local anti-infection or tissue repair,and therefore,they are the key factor in the pathogenesis and progression of fatty liver disease. As an important component of hepatic immune cells,hepatic macrophages have attracted great attention due to its role in the pathogenesis of the disease and the hepatic macrophage-targeted therapy. This article reviews the challenges and opportunities in hepatic macrophage-targeted therapy for fatty liver disease.

Primary biliary cholangitis( PBC) is a chronic autoimmune liver disease characterized by progressive destruction of the small intrahepatic bile ducts. Patients with PBC often have extrahepatic autoimmune diseases,which can involve multiple organs and systems including the gastrointestinal tract,lung,rheumatoid immune system,and endocrine system. This article summarizes the research advances in the disease spectrum,pathogenesis,treatment,and prognosis of PBC with extrahepatic autoimmune disease.

The outbreak of viral pneumonia caused by severe acute respiratory syndrome coronavirus 2( SARS-CoV-2) in Wuhan,China poses a major threat to public health. SARS-CoV-2 is highly homologous to severe acute respiratory syndrome-associated coronavirus and Middle East respiratory syndrome-associated coronavirus,all of which may cause severe respiratory symptoms. In addition to respiratory symptoms,a considerable proportion of patients with SARS and SARS-CoV-2 infection have varying degrees of liver injury,but their epidemiological features and pathogenesis remains unclear. This article summarizes the epidemiology of SARS-CoV-2 and elaborates on the current status of the research on SARS-CoV-2,possible mechanism of liver injury caused by SARS-CoV-2,and effective treatment regimens,so as to provide a reference and new research ideas for the prevention and treatment of liver injury in patients with SARS-CoV-2 infection.

Severe liver disease during pregnancy is uncommon in clinical practice. The most common cause of liver disease during pregnancy is liver dysfunction,with an overall prevalence rate of approximately 3%. Liver disease during pregnancy is classified into the liver diseases directly caused by pregnancy and those co-existing with pregnancy,i. e.,pre-existing liver disease or occasional liver disease during pregnancy. A differential diagnosis of pre-existing and co-existing liver diseases may help to improve maternal and fetal outcome. During clinical diagnosis and selection of treatment and intervention measures,priority should be given to the potential impact on mother and fetus.This article introduces the latest research advances in the general information,pathogenesis,treatment,and pregnancy outcome of major liver diseases during pregnancy and elaborates on the risk of pregnancy and related coping measures for patients with pre-existing liver disease,so as to guide clinical diagnosis and treatment and patient management.

Sarcopenia is a component of malnutrition in patients with liver cirrhosis. Studies have shown that both sarcopenia and hepatic encephalopathy can reduce quality of life and increase the risk of adverse events,including death,in patients with liver cirrhosis. This article reviews the association between sarcopenia and hepatic encephalopathy and the advances in treatment,so as to provide a reliable basis for the treatment of patients with sarcopenia and liver cirrhosis,prevent the development of hepatic encephalopathy,and thereby improve the quality of life and prolong the survival time of patients with liver disease.

Liver failure is a syndrome of severe liver diseases commonly seen in clinical practice,and it has a high mortality rate and thus becomes one of the critical diseases in internal medicine. Massive hepatocyte death and the extent of hepatocyte death exceeding the liver's regenerative capacity are considered the core events in the development and progression of liver failure,and direct injury and immune-mediated inflammatory injury are the two main factors in this process. An increasing number of evidence has shown that host immune response and inflammatory cascade play an important role in the pathogenesis of liver failure. This article reviews the mechanism of action of immunoregulation( congenital and adaptive) and inflammatory injury( inflammation inducers,receptor cells,and inflammatory mediators) in the process of hepatic failure,as well as the interactions between immune response and immune cells and between inflammatory response and inflammatory factors,in order to help understand the pathogenesis of liver failure and provide new ideas for the diagnosis and treatment of liver failure and drug research and development.

At present,the epidemic of coronavirus disease 2019 is still serious,and the prevention and control of this epidemic is taken seriously throughout the country. As one of the most common acute abdominal diseases in hepatobiliary surgery,gallstones with acute cholecystitis has sudden onset and rapid progression and thus requires early diagnosis and timely and effective treatment. During the prevention and control of the epidemic,patients should be admitted properly to reduce nosocomial infection. Gallstones with acute cholecystitis is often accompanied by pyrexia,and therefore,the presence or absence of severe acute respiratory syndrome coronavirus 2 infection should be clarified. Treatment regimen should be selected appropriately and individualized treatment measures should be developed. While ensuring that patients receive timely and effective diagnosis and treatment,hospitals should adopt prevention and control measures for patients and their caregivers to reduce nosocomial infection. The personal protection of medical personnel should also be taken seriously,and scientific measures should be implemented to guarantee their safety.

Hemolytic jaundice has various etiologies and clinical manifestations. Although some patients have hemolysis,they may have jaundice as the initial manifestation due to unobvious or mild anemia,and the disease may last for a long time with difficulties in treatment and can be misdiagnosed as unexplained chronic hepatitis and jaundice with unknown cause. In addition,it may be easily confused with congenital indirect bilirubinemia including Gilbert's syndrome,which may lead to missed diagnosis and delays in diagnosis and treatment. Physicians in hepatology should master the knowledge of hemolytic jaundice and chronic hemolytic diseases. This article summarizes the clinical features of hemolytic jaundice and thoughts in differential diagnosis and briefly introduces the clinical features of common chronic hemolytic diseases,so as to provide a reference for clinical physicians.

Severe acute pancreatitis( SAP) is a disease with dangerous course and poor prognosis,and although medical technology keeps improving over the years,the mortality rate of SAP remains high. As the latest achievement in the field of blood purification over the past 30 years,continuous blood purification has made great achievements in the treatment of SAP; however,there are still many controversies,and further studies are needed to explore therapeutic effect and mechanism. This article reviews the studies on continuous blood purification in the treatment of SAP in recent years and elaborates on its therapeutic mechanism,treatment mode,and treatment effect.