Abstract: Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in China and the world. However, heterogeneity exists in the pathogenesis, pathology, and clinical phenotype of NAFLD. Metabolism/obesity and gene polymorphisms are involved in the pathogenesis of NAFLD. As for pathology, NAFLD in adults manifests as atypical fibrosis and sinus fibrosis, while NAFLD in children manifests as fibrosis in the portal area and lobular fibrosis in early stage. As for clinical phenotype, some patients may have diabetes or obesity. Such heterogeneity suggests that there are different strategies and methods for clinical diagnosis, treatment, and outcome evaluation.
Abstract: At present, there are still no effective drugs launched for the treatment of nonalcoholic fatty liver disease (NAFLD) , and many drugs are being evaluated in clinical trials. These drugs have different mechanisms of action in treatment, such as improvement of glycolipid metabolism, anti-inflammation, anti-fibrosis, and improvement of intestinal microbiota. This article elaborates on the research and development of drugs from the following aspects: inflammatory response and immune activation, lipid metabolism and insulin resistance, lipotoxicity, oxidative stress, cell apoptosis and necrosis, collagen formation and degradation, and proliferation of intestinal microbiota.
Abstract: Nonalcoholic fatty liver disease (NAFLD) has become one of the research hotspots in the field of liver disease. However, so far, no drugs have been approved by the U. S. Food and Drug Administration for the treatment of nonalcoholic steatohepatitis, which brings opportunities and challenges to the clinical trials on the treatment of NAFLD. Liver histology is currently considered a reliable surrogate endpoint for tracking the progression of NAFLD, but its invasiveness has limited the development of drugs for the treatment of NAFLD. In recent years, some noninvasive measurement methods have gradually been used as secondary or exploratory endpoints in existing clinical trials.
Abstract: Liver biopsy is the“gold standard”for the diagnosis of nonalcoholic fatty liver disease (NAFLD) /nonalcoholic steatohepatitis (NASH) . Although liver biopsy has several limitations including invasiveness and errors in sampling and evaluation, in clinical trials on NAFLD/NASH follow-up and new drugs, liver histological evaluation is still a main and irreplaceable method for inclusion/exclusion diagnosis and assessment of primary endpoints in cohorts. It often takes 10-20 years for NASH to progress to liver cirrhosis, which is a surrogate endpoint in clinical trials for new drugs, and the NASH Clinical Research Network (NASH-CRN) system is recommended as the histological evaluation system in clinical trials for tracking NAFLD/NASH. The primary endpoint for NASH treatment is usually set as the reversal of NASH without progression of fibrosis; an alternative one is a reduction in NAS score by at least 2 points and a reduction in one or more histological parameters by at least 1 point, without progression of fibrosis, during the full-course treatment. Patients in phase 2 b and 3 clinical trials should be monitored for at least 12 months, and if the improvement of fibrosis is set as the main assessment index, they should be monitored for at least 1-2 years and should be followed up for more than 6 months after drug withdrawal. Histological evaluation is affected by various factors. In order to ensure the quality of such evaluation, the length of tissue for liver biopsy should be larger than 2 cm (containing more than 10 portal areas) . Staining and section preparation should be performed at the same time, and more than two experts specializing in liver pathology should perform single-or double-blinded review of liver biopsies to avoid evaluation bias.
Abstract: The research and development of new drugs for nonalcoholic steatohepatitis (NASH) is a research hotspot in the field of liver diseases. Confirmatory clinical trials are the key clinical trials for new drug registration, while exploratory clinical trials usually provide a basis for confirmatory clinical trials. Due to different objectives of clinical trials in different phases, there are different requirements and strategies for protocol design. Trial design should take into account both ethics and scientificity. Good protocol design needs to consider the methodology of clinical trials, the overall strategy for drug research and development, new drugs under research and their target indications, and clinical epidemiology, diagnosis, and evaluation of NASH.
Abstract: The prevalence rate of nonalcoholic fatty liver disease (NAFLD) is constantly increasing due to the increase in the degree of industrialization in Asian countries and the change in lifestyle and dietary structure. Asia has a large population with uneven distribution and marked regional disparities in economic and education levels and lifestyle, which results in the great difference in the epidemiology of NAFLD across different regions in Asia. An understanding of epidemiological features of NAFLD, including incidence, prevalence, and mortality rates and related risk factors can provide a basis for the research on disease progression and related prevention and control strategies.
Abstract: Objective To investigate the clinical features of immune control phase and immune escape phase of chronic hepatitis B virus (HBV) infection. Methods A total of 226 patients with chronic HBV infection (with positive HBsAg, anti-HBe, and anti-HBc) who visited or were hospitalized in Yan'an University Affiliated Hospital from January 2016 to February 2018 were enrolled, and all of them underwent liver biopsy. According to the liver pathological results, the patients were divided into immune control group (121 patients with A <2 and F < 2) and immune escape group (105 patients with A≥2 or F≥2) . The two groups were compared in terms of general data, virology, liver function, and liver stiffness measurement (LSM) . The independent samples t-test or the Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. Results There were no significant differences in sex, age, and family aggregation of hepatitis B between the immune control group and the immune escape group (all P > 0. 05) . There was a significant difference in HBV DNA level between the two groups [1107. 00 (369. 00-3876. 00) IU/ml vs 2171. 00 (596. 00-8887. 00) IU/ml, Z =-2. 425, P = 0. 015], while there were no significant differences in the levels of HBs Ag and anti-HBc (both P > 0. 05) . Compared with group A, group B had significantly higher levels of alanine aminotransferase (ALT) [46. 00 (22. 00-97. 50) U/L vs 30. 00 (19. 00-87. 50) U/L, Z =-2. 261, P = 0. 024], aspartate aminotransferase (AST) (35. 50 ±14. 74 U/L vs 31. 30 ± 12. 17 U/L, t =-2. 351, P = 0. 020) , and LSM (7. 41 ± 1. 51 k Pa vs 4. 76 ± 1. 23 k Pa, t =-9. 021, P <0. 001) . Conclusion Patients with chronic HBV infection (with positive HBsAg, anti-HBe, and anti-HBc) in the immune escape phase have significantly higher viral load, ALT, AST, and LSM than those in the immune control phase. In future, multicenter studies can be performed to clarify the ranges of the references values of the above parameters, in order to provide accurate diagnosis and treatment for patients with chronic HBV infection.
Abstract: Objective To investigate the influence of metabolic syndrome components on significant hepatic fibrosis in patients with chronic hepatitis B (CHB) and related risk factors. Methods The patients with CHB who attended Department of Hepatology in The Fourth Affiliated Hospital of Xinjiang Medical University from January 2016 to May 2017 were enrolled and divided into three groups according to the presence or absence of nonalcoholic fatty liver disease (NAFLD) or abnormal glycolipid. The patients' general information was collected, and transient elastography was performed for all patients. Body height and body weight were measured to calculate body mass index (BMI) . Liver function assessment, routine blood test, and HBsAg quantification were performed, and blood lipids and HBV DNA were measured. Fibrosis-4 (FIB-4) and aspartate aminotransferase-to-platelet ratio index (APRI) were calculated according to equations. 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; the Kruskal-Wallis H rank sum test was used for comparison of non-normally distributed continuous data between groups, and the Wilcoxon rank-sum test was used for further comparison between two groups. The chi-square test was used for comparison of categorical data between groups. Univariate and multivariate logistic regression analyses were used to identify the influencing factors for significant hepatic fibrosis. Results The CHB-NAFLD group had significantly higher controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) than the CHB group and the CHB-abnormal glycolipid group [CAP: 283. 16 ± 38. 43 d B/m vs 230. 61 ± 29. 97 db/m/237. 82 ± 35. 98 dB/m, P < 0. 05; LSM: 9. 40 (7. 50-12. 07) k Pa vs 8. 60 (6. 37-11. 92) k Pa/8. 20 (6. 00-11. 15) kPa, P < 0. 05], and LSM increased with the increase in the severity of NAFLD (H = 7. 76, P = 0. 02) . The CHB patients with abnormal glucose and lipids had a significantly higher LSM than those with abnormal blood lipid levels alone [9. 6 (8. 22-12. 07) vs7. 5 (5. 7-9. 67) , P < 0. 05]. The multivariate logistic regression analysis showed that increasing age (odds ratio [OR]= 1. 134, 95%confidence interval [CI]: 1. 010-1. 273, P < 0. 05) , an increase in body mass index (OR = 1. 297, 95% CI: 1. 084-1. 553, P <0. 05) , a high gamma-glutamyl transpeptidase (GGT) level (OR = 1. 025, 95% CI: 1. 006-1. 045, P < 0. 05) , a low triglyceride (TG) level (OR = 0. 399, 95% CI: 0. 180-0. 882, P < 0. 05) , and a high HBsAg level (OR = 2. 205, 95% CI: 1. 159-4. 194, P < 0. 05) were independent risk factors for significant hepatic fibrosis in CHB patients. Conclusion Besides age and high HBsAg level, overweight, a high GGT level, and a relatively low TG level also increase the risk of significant hepatic fibrosis in CHB patients.
Abstract: Objective To investigate the changes in blood flow indices in patients with nonalcoholic fatty liver disease (NAFLD) and the value of hepatic artery resistance index (HARI) in evaluating progressive liver fibrosis. Methods A total of 148 patients who were diagnosed with NAFLD in The People's Hospital of Gong'an County from January 2016 to December 2017 and 60 healthy volunteers were selected as study subjects. Fasting venous blood samples were collected for liver function evaluation and routine blood test, and then NAFLD fibrosis score (NFS) was calculated for NAFLD patients. According to NFS, the patients with NAFLD were divided into group A (NFS ≤0. 676) and group B (NFS > 0. 676) . The healthy volunteers were enrolled as control group. Color Doppler ultrasound was performed to measure peak portal vein velocity (PPVV) , mean portal vein velocity (MPVV) , and HARI in all subjects. An analysis of variance was used for comparison of continuous data between three groups, and the SNK-q test was used for multiple comparisons; the chi-square test was used for comparison of categorical data between groups. A Spearman' s rank correlation analysis was used to investigate the correlation between assessment indices. Results There were 121 patients in group A and 27 in group B. Group B had the highest HARI (0. 88 ± 0. 05) , followed by the control group (0. 76 ± 0. 09) and group A (0. 64 ± 0. 08) , and there was a significant difference between groups (F =4. 981, P < 0. 01) . The control group had the highest MPVV (22. 84 ± 3. 12 cm/s) and PPVV (19. 02 ± 1. 97 cm/s) , followed by group A (17. 84 ± 2. 87 cm/s and 15. 29 ± 2. 02 cm/s) and group B (15. 31 ± 2. 29 cm/s and 13. 39 ± 1. 92 cm/s) , and there were significant differences between groups (F = 5. 645 and 7. 435, both P < 0. 01) . In the patients with NAFLD, HARI was positively correlated with NFS (r = 0. 763, P < 0. 01) , and MPVV and PPVV were negatively correlated with NFS (r =-0. 463 and-0. 425, both P < 0. 01) . Conclusion There are hemodynamic changes of the liver in NAFLD patients with progressive liver fibrosis. HARI can be used as a noninvasive method to evaluate whether NAFLD patients develop progressive liver fibrosis. The development of progressive liver fibrosis should be considered in case of abnormal increase in HARI.
Abstract: Objective To investigate the clinical significance of fasting C-peptide combined with fibrosis-4 (FIB-4) index in assessing the progression of liver fibrosis in patients with type 2 diabetes mellitus (T2 DM) and nonalcoholic fatty liver disease (NAFLD) . Methods A total of 513 patients who underwent physical examination in Physical Examination Center of China-Japan Union Hospital of Jilin University from May 2016 to July 2017 and were diagnosed with T2 DM and NAFLD were enrolled, and according to liver stiffness measurement (LSM) obtained by FibroScan, they were divided into non-progressive liver fibrosis group with 466 patients and progressive liver fibrosis group with 47 patients. Related data were recorded, including age, abdominal circumference, blood pressure, body mass index, platelet count, fasting blood glucose, fasting C-peptide, liver function, blood lipids, uric acid, and FIB-4 index. The t-test or the Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. Logistic regression was used to establish a joint diagnosis model. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of different indicators. Results Compared with the non-progressive liver fibrosis group, the progressive liver fibrosis group had significantly higher age [51 (49-55) years vs 50 (47-53) years, P = 0. 021], aspartate aminotransferase level [28. 9 (25. 7-35. 1) IU/L vs 27. 1 (22. 2-32. 8) IU/L, P = 0. 017], FIB-4 index [0. 97 (0. 75-1. 34) vs 0. 85 (0. 62-1. 19) , P = 0. 030], and fasting C-peptide level [2. 64 ± 0. 66 ng/ml vs 2. 33 ± 0. 79 ng/ml, P = 0. 004]. Fasting C-peptide (odds ratio [OR]= 1. 77, 95% confidence interval [CI]: 1. 201-2. 633, P = 0. 004) and FIB-4 index (OR = 2. 14, 95% CI: 1. 248-3. 613, P = 0. 004) were independent risk factors for progressive liver fibrosis in patients with T2 DM and NAFLD. Fasting C-peptide combined with FIB-4 index had an area under the ROC curve of 0. 730 (> 0. 70) in evaluating progressive liver fibrosis in patients with T2 DM and NAFLD. Conclusion Fasting C-peptide combined with FIB-4 index has a certain value in the diagnosis of progressive liver fibrosis in patients withT2 DM and NAFLD.
Abstract: Objective To investigate the value of magnetic resonance (MR) morphological imaging in the diagnosis and differentiation of post-hepatitis B cirrhosis. Methods A prospective study was performed for 70 patients with liver cirrhosis who were consecutively admitted to The First Hospital of Lanzhou University from July 2016 to April 2018, among whom 32 had compensated hepatic cirrhosis (CHC) and38 had decompensated hepatic cirrhosis (DHC) . A total of 30 healthy volunteers were enrolled as normal control group. After standardized diagnosis and staging, MR morphological imaging was performed for all subjects to measure the indices including transverse diameter of the right lobe (R1) , sagittal diameter of the right lobe (R2) , transverse diameter of the left lobe (L1) , sagittal diameter of the left lobe (L2) , transverse diameter of the caudate lobe (W1) , sagittal diameter of the caudate lobe (W2) , long diameter of the liver, L1/R1, L2/R2, diameter of the portal vein, and diameter of the splenic vein. The Mann-Whitney U test was used for comparison of continuous data between two groups; the Kruskal-Wallis test was used for comparison between three groups, and the Mann-Whitney U test was used for further comparison between two groups. The chi-square test was used for comparison of categorical data between groups. Spearman rank correlation was used to investigate the correlation between each parameter and the stage of liver cirrhosis. Results There were significant differences between the normal control group and the liver cirrhosis group in R1, R2, L1, long diameter of the liver, L1/R1, L2/R2, diameter of the portal vein, and diameter of the splenic vein (U =-5. 54, -5. 76, 5. 26, -6. 12, 6. 47, 5. 08, 6. 92, and 7. 26, all P < 0. 05) . There were significant differences in R1, L1, L1/R1, diameter of the portal vein, and diameter of the splenic vein between any two groups of the normal control group, the CHC group, and the DHC group (all P < 0. 05) . There were significant differences between the CHC and DHC groups and the normal control group in R2, long diameter of the liver, and L2/R2 (all P < 0. 05) . R1, R2, and long diameter of the liver were negatively correlated with the progression of liver cirrhosis (r =-0. 604, -0. 554, and-0. 48, all P < 0. 001) , and L1, L1/R1, L2/R2, diameter of the portal vein, and diameter of the splenic vein were positively correlated with disease progression (r = 0. 635, 0. 76, 0. 46, 0. 74, and 0. 42, all P < 0. 001) . Conclusion MR morphological changes are closely associated with the progression of liver cirrhosis and can be used as a basis for the diagnosis and staging of liver cirrhosis.
Abstract: Objective To investigate the value of psychometric hepatic encephalopathy score (PHES) in the diagnosis of minimal hepatic encephalopathy (MHE) and related influencing factors, as well as the prevalence rate of MHE among patients with liver cirrhosis and related risk factors. Methods A total of 138 patients with liver cirrhosis aged ≥18 years, who were hospitalized in China-Japan Union Hospital of Jilin University from April 2011 to April 2012, were enrolled as liver cirrhosis group, and 108 individuals who underwent physical examination during the same period of time, patients' family members, and adult volunteers without liver disease were enrolled as normal control group. PHES was determined for all subjects. The influencing factors for the scores on each scale were analyzed, the value of this score in the diagnosis of MHE was evaluated, and the risk factors for MHE were identified. 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.Pearson correlation was used to analyze the correlation between continuous variables, and multivariate linear stepwise regression and logistic regression were used to analyze related factors. Results There were no significant differences in age, education level, drinking, smoking, and occupation between the two groups (all P > 0. 05) . In the normal control group, age and years of education had a linear correlation with PHES, and PHES decreased with the increase in age (r =-0. 259) and the reduction in education level (r = 0. 693) . The formulas of the expected normal reference values of each test associated with age and education level were established as follows: number connection test-A (NCT-A) = 30. 70 + 0. 631 × age-1. 504 × years of education, modified number connection test-BC (NCT-BC) = 54. 93 + 1. 134 ×age-2. 574 × years of education, digit symbol test (DST) = 29. 90-0. 332 × age + 2. 670 × years of education, line-tracing test (LTT) = 48. 82 + 0. 496 × age-1. 120 × years of education, serial dotting test (SDT) = 54. 35 + 0. 402 × age-1. 266 × years of education. For the comparison of test results with corresponding expected normal reference values in the patients with liver cirrhosis, there were significant differences between the patients with stage I overt hepatic encephalopathy (OHE) and those without OHE in PHES (-5. 5 (-2. 0 to-7. 0) vs-10. 0 (-7. 5 to-13. 0) , Z = 3. 65, P < 0. 01) and prevalence rate of MHE (52. 5% vs 80. 0%, χ2= 4. 19, P < 0. 05) . The logistic regression analysis showed that the prevalence rate of MHE was significantly associated with Child-Pugh class (odds ratio = 2. 30, 95%confidence interval: 1. 46-3. 79, P < 0. 01) . Conclusion PHES helps with the early diagnosis of MHE, but it is influenced by age and education level, Child-Pugh class is an important risk factor for the prevalence rate of MHE.
Abstract: Objective To investigate the value of advanced dynamic flow (ADF) versus color Doppler flow imaging (CDFI) in evaluating stent patency after transjugular intrahepatic portosystemic shunt (TIPS) . Methods A total of 60 post-TIPS patients who underwent ADF, CDFI, and contrast-enhanced ultrasound (CEUS) in Shengjing Hospital of China Medical University from September 2016 to May 2018 were enrolled. The grade of the patency of TIPS stent was evaluated according to the results of ADF, CDFI, and CEUS. With the results of CEUS as the gold standard, the Kappa test was used to examine the consistency between ADF and CEUS results, as well as between CDFI and CEUS results, the Z test was used as the hypothesis testing of kappa value. Results There was extremely strong consistency between ADF and CEUS in evaluating stent patency after TIPS (Kappa = 0. 902, P < 0. 05) , while there was moderate consistency between CDFI and CEUS in evaluating stent patency after TIPS (Kappa = 0. 423, P < 0. 05) . The Z test found that the difference was statistically significant (P < 0. 05) .Conclusion Compared with CDFI, ADF has a higher value in evaluating stent patency after TIPS and has certain clinical significance.
Abstract: Objective To investigate the influence of time schedule of radiofrequency ablation (RFA) on the safety and prognosis of patients with colorectal cancer liver metastasis treated with RFA combined with XELOX regimen. Methods A retrospective analysis was performed for the clinical data of 48 patients with colorectal cancer liver metastasis who received RFA combined with XELOX regimen in Beijing Ditan Hospital from January 2011 to August 2017, and according to the time schedule of RFA, these patients were divided into group A (25 patients treated with RFA and sequential systemic chemotherapy ± targeted therapy) and group B (23 patients treated with chemotherapy ±targeted therapy and then RFA) . The patients with a stable disease or partial remission continued to take Xeloda orally until disease progression or intolerable side effects. The primary endpoint was objective response rate (ORR) of tumor, and the secondary endpoints included time to progression (TTP) , overall survival (OS) , and safety. Results There was no significant difference in ORR between group A and group B [68. 0% (8 patients with complete response and 9 with partial response) vs 43. 5% (2 patients with complete response and 9 with partial response) , χ2= 2. 927, P = 0. 087]. There were no significant differences between group A and group B in median TTP (9. 0 months vs 8. 0 months, χ2= 2. 660, P > 0. 05) and median OS (33 months vs 30 months, χ2= 0. 562, P > 0. 05) . For the patients with liver metastasis alone, there was a significant difference in median TTP between group A and group B (15. 0 months vs 8. 0 months, χ2= 4. 331, P = 0. 037) . Both groups had similar incidence and degree of common adverse events (AEs) (all P > 0. 05) . Most treatment-related AEs were mild or moderate; the most common mild AE (grade I/II) was leucopenia (93. 8%) , followed by nausea (91. 7%) and abdominal pain (81. 3%) . There were no fatal AEs, and the most common grade III/IV treatment-related AE was hematological toxicity observed in14 patients (29. 2%) . All AEs were resolved without sequelae. Conclusion RFA combined with XELOX-Xeloda maintenance chemotherapy is well tolerated and has a good clinical effect in patients with colorectal cancer liver metastasis. For patients with liver metastasis alone, RFA followed by chemotherapy can improve ORR of tumor.
Abstract: Objective To investigate the effect of tumor-stroma crosstalk on amino acid metabolism in hepatic stellate cells (HSCs) .Methods Human hepatoma cell lines HepG2, Hep3 B, and Huh7 and the HSC LX-2 were cultured separately. HSCs were cultured in HSC LX-2 conditioned medium (LX2-CM) and HepG2/Hep3 B/Huh7 mixed conditioned medium (Hep-CM) , respectively. The supernatants were collected and an amino acid analyzer was used to measure the change in aminogram. The t-test was used for comparison of continuous data between groups. Results There was a significant change in amino acid metabolism in HSCs. Compared with the LX2-CM control group, the Hep-CM experimental group had significant reductions in the levels of citrulline (t = 3. 426, P = 0. 027) , valine (t = 2.892, P = 0. 045) , isoleucine (t = 4. 224, P = 0. 013) , leucine (t = 4. 150, P = 0. 014) , tyrosine (t = 3. 556, P = 0. 024) , phenylalanine (t = 4. 023, P = 0. 016) , and lysine (t = 3. 369, P = 0. 028) in cell supernatant. Conclusion Tumor-stroma crosstalk can influence amino acid metabolism in HSCs in tumor microenvironment, and such change in turn makes hepatoma cells better adapted to hypoxic microenvironment.
Abstract: Objective To investigate the antitumor effect of cyclooxygenase-2 (COX-2) antisense RNA combined with celecoxib on hepatoma CBRH7919 cells. Methods The effect of celecoxib on in vitro proliferative activity, cell cycle, and apoptosis of hepatoma cell lines CBRH7919, CBRH7919-E, and CBRH7919-A (transfected with COX-2 antisense gene segment) were observed. MTT assay, cell cycle analysis, and RT-PCR were used to evaluate the change in in vitro proliferation of hepatoma cell lines. A multivariate analysis of variance was used for comparison of continuous data between groups, and the SNK-q test was used for further comparison between two groups.Results After the treatment with celecoxib, CBRH7919-A cells had a significant reduction in growth rate compared with CBRH7919 and CBRH7919-E cells (F = 38. 303, P < 0. 01) , in a time-and dose-dependent manner (F = 162. 638 and 22. 666, both P < 0. 01) .Celecoxib significantly increased the proportion of cells in G0/G1 phase and had a marked inhibitory effect on cells in S phase in a dose-dependent manner (F = 32. 515, P < 0. 01) , while there was no significant change in the proportion of cells in G2/M phase. Compared with CBRH7919 and CBRH7919-E cells, CBRH7919-A cells were more sensitive to celecoxib (F = 1219. 506, P < 0. 01) . After the treatment with celecoxib at different concentrations (40 and 80 μmol/L) , all three groups had a significant increase in cell apoptosis (all P <0. 01) , and there was no significant difference in apoptosis between the three groups (P > 0. 05) . Conclusion COX-2 antisense RNA combined with celecoxib can inhibit the in vitro growth and proliferation and cell cycle of hepatoma CBRH7919 cells, promote apoptosis, and thus exert a potential therapeutic effect on hepatoma cells.
Objective To investigate whether fatty liver disease is a risk factor for lacunar infarction. Methods A retrospective analysis was performed for the clinical data of 457 patients with lacunar infarction (lacunar infarction group) and 120 control patients, who were hospitalized in our hospital from 2007 to 2017, to analyze whether fatty liver disease is a risk factor for lacunar infarction. The chi-square test was used for comparison of categorical data between groups, and the t-test was used for comparison of continuous data between groups. Univariate and multivariate regression analyses were used to screen out the risk factors for lacunar infarction. Results The lacunar infarction group had a significantly higher incidence rate of fatty liver disease than the control group (60. 39% vs 39. 17%, χ2= 17. 379, P < 0. 001) .The multivariate regression analysis showed that after adjustment for age, sex, smoking, drinking, hypertension, and diabetes, fatty liver disease was an independent risk factor for lacunar infarction (odds ratio [OR]= 1. 96, 95% confidence interval [CI]: 1. 21-3. 02, P =0. 003) . There was a significant interaction between obesity and fatty liver disease (P = 0. 001) . Non-obese fatty liver disease was an independent risk factor for lacunar infarction (OR = 3. 29, 95% CI: 1. 55-7. 23, P < 0. 001) ; however, in the obese subgroup, obese fatty liver disease was not an independent risk factor for lacunar infarction (P = 0. 532) , Age (OR = 6. 67, 95% CI: 1. 98 ～ 121. 56, P < 0. 001) , hypertension (OR = 6. 38, 95% CI: 5. 12 ～ 12. 06, P < 0. 001) were independent risk factors for lacunar infarction. Conclusion Non-obese fatty liver disease is an independent risk factor for lacunar infarction.
Objective To systematically analyze the value of probiotics in the treatment of nonalcoholic fatty liver disease (NAFLD) .Methods PubMed, The Cochrane Library, Embase, Medline, CNKI, VIP, and Wanfang Data were searched for randomized controlled trials (RCTs) on probiotics in the treatment on NAFLD published before December 2017. Secondary screening was performed for retrieval results, the risk of bias of the studies included was evaluated, and related data were extracted. Rev Man 5. 3 was used for the meta-analysis.Results A total of 11 RCTs with 599 NAFLD patients were included. The results showed that probiotics significantly improved the levels of alanine aminotransferase (mean difference [MD]=-15. 23, 95% confidence interval [CI]:-19. 63 to-10. 82, P < 0. 000 01) , aspartate aminotransferase (MD =-17. 08, 95% CI:-24. 23 to-9. 92, P < 0. 000 01) , gamma-glutamyl transpeptidase (MD =-20. 49, 95%CI:-26. 23 to-14. 74, P < 0. 000 01) , triglyceride (MD =-0. 12, 95% CI:-0. 24 to-0. 01, P = 0. 04) , total cholesterol (MD =-0. 33, 95% CI:-0. 56 to-0. 11, P = 0. 003) , high-density lipoprotein (MD =-0. 07, 95% CI:-0. 14 to-0. 01, P = 0. 03) , tumor necrosis factor-α (MD =-0. 38, 95% CI:-0. 52 to-0. 24, P < 0. 000 01) , and homeostasis model assessment of insulin resistance (MD =-0. 39, 95% CI:-0. 53 to-0. 24, P < 0. 000 01) . However, probiotics had no significant effect on body mass index (MD =-0. 73, 95% CI:-1. 91 to 0. 46, P = 0. 23) and low-density lipoprotein (MD =-0. 30, 95% CI:-0. 60 to 0. 01, P = 0. 06) .Conclusion Probiotics can significantly reduce the levels of liver aminotransferases, blood lipids, inflammatory factors, and insulin resistance in patients with NAFLD and thus exerts a certain therapeutic effect on NAFLD.
Objective To investigate the value of betatrophin in predicting nonalcoholic fatty liver disease (NAFLD) . Methods A total of160 patients with NAFLD who were diagnosed and treated in our hospital from January 2017 to January 2018 were enrolled in this study and were divided into low fat content (LFC) group with 65 patients and high fat content (HFC) group with 95 patients. A total of 72 healthy individuals were enrolled as control group. Related indices were measured, including fasting plasma glucose (FPG) , HbA1 c, total cholesterol (TC) , triglyceride (TG) , high-density lipoprotein cholesterol (HDL-C) , low-density lipoprotein cholesterol (LDL-C) , alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , creatinine (Cr) , blood urea nitrogen (BUN) , uric acid (UA) , and betatrophin.Comparison between multiple groups was made by one-way analysis of variance, and comparison between any two groups was made using the LSD-t test, comparison of categorical data between multiple groups was made by chi-square test. Pearson analysis was performed to investigate the correlation of serum betatrophin with other biochemical parameters, and multivariate linear stepwise regression analysis was used to analyze the independent risk factors for fat content. Results The LFC group and the HFC group had a significantly higher serum level of betatrophin than the control group (269. 3 ± 15. 4 pg/ml and 290. 2 ± 30. 5 pg/ml vs 250. 2 ± 20. 1 pg/ml, F = 16. 134, P <0. 001) , and the HFC group had a higher level than the LFC group (P < 0. 05) . The serum level of betatrophin was correlated with fat content and TC (r = 0. 301 and 0. 128, P = 0. 012 and 0. 027) . The multiple linear stepwise regression analysis showed that fat content was positively correlated with betatrophin (t = 3. 361, P = 0. 005) , TG (t = 2. 610, P = 0. 010) , and AST (t = 2. 015, P = 0. 012) and was negatively correlated with HDL-C (t =-1. 847, P = 0. 048) . Conclusion Liver fat content increases with the increase in the serum level of betatrophin. Serum betatrophin may be used as a predictive factor for NAFLD, which needs further research in the future.
Objective To investigate the preventive and therapeutic effects of Babaodan on hepatic encephalopathy in rats with acute liver failure and possible mechanisms. Methods A total of 50 Wistar rats were randomly divided into normal group, model group, low-dose Babaodan group, high-dose Babaodan group, and lactulose group. The rats in the low-dose Babaodan group, the high-dose Babaodan group, and the lactulose group were given the corresponding drugs by gavage once a day, and those in the normal group and the model group were given an equal volume of 0. 3% sodium carboxymethyl cellulose. On day 4 of gavage, intraperitoneal injection of thioacetamide (350 mg/kg) was performed to induce hepatic encephalopathy, and the rats in the normal group were injected with an equal volume of normal saline, once every 24 hours for 3 times. The rats were sacrificed at 12 hours after the last injection. HE staining was used to observe pathological changes of the liver and the brain; related kits were used to measure blood ammonia and liver function parameters; RT-PCR was used to measure the changes in related genes in liver and brain tissues. The 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 Compared with the model group, the low-and high-dose Babaodan groups had significant reductions in the levels of blood ammonia, total bilirubin, total bile acid, alanine aminotransferase, and aspartate aminotransferase (all P < 0. 05) and a significant increase in total protein level (P < 0. 05) , and the high-dose Babaodan group had a significant increase in albumin (P < 0. 05) . Both the low-and high-dose Babaodan groups had significant improvements in liver necrosis and inflammation and brain necrosis and karyopyknosis. Compared with the model group, the low-and high-dose Babaodan groups had significant reductions in the mRNA expression of tumor necrosis factor-α (TNF-α) , interleukin-1 (IL-1) , interleukin-6, nuclear factor-kappa B, Bax, caspase-3, and caspase-8 in liver tissue (all P < 0. 05) , and the high-dose Babaodan group had a significant increase in the mRNA expression of Bcl-2 (P < 0. 05) ; the low-and high-dose Babaodan groups also had significant reductions in the mRNA expression of IL-1, TNF-α, inducible nitric oxide synthase, and glutamine synthetase in brain tissue (all P < 0. 05) . Conclusion Babaodan can effectively regulate the expression of inflammatory factors, inhibit the apoptosis and necrosis of hepatocytes, and reduce the production of blood ammonia and inflammatory infiltration, thus alleviating brain injury and exerting therapeutic effect on hepatic encephalopathy in rats with acute liver failure.
Objective To investigate the effect of the warming and heat-clearing method on the percentage of regulatory T (Treg) /T helper 17 (Th17) cells in rats with acute-on-chronic liver failure (ACLF) and the mechanism of its anti-liver failure activity. Methods A total of 140 Sprague-Dawley rats were randomly divided into normal group, model group, heat-clearing group, warming group, and warming + heat-clearing group. A rat model of immune liver fibrosis was established by sensitization with bovine serum albumin, and then an ACLF model was established by D-galactosamine + lipopolysaccharide attack. Serum liver function parameters [alanine aminotransferase (ALT) and total bilirubin (TBil) ], liver pathological changes, and number of peripheral Treg and Th17 cells were observed within 24 hours, and Treg/Th17 ratio was calculated. One-way ANOVA 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 Compared with the normal group, the model group had significant increases in ALT and TBil at each time point (all P < 0. 01) , with the damage of lobular structure, bridging and piecemeal necrosis in hepatocytes, and inflammatory cell infiltration in the portal area. Compared with the normal group, the model group also had significant increases in the percentage of peripheral Treg and Th17 cells (P < 0. 01) , and the percentage of Th17 cells was higher than that of Treg cells; there was a significant reduction in Treg/Th17 ratio in the model group (P < 0. 01) . Compared with the model group, the heat-clearing group, the warming group, and the warming + heat-clearing group had significant reductions in ALT and TBil (P< 0. 05) , with a more complete lobular structure, patchy and spotted necrosis in hepatocytes, and mild fibrous tissue hyperplasia at the portal area; these three groups also had significant reductions in the percentage of peripheral Treg and Th17 cells (P < 0. 05) , and Th17 cells had a greater reduction than Treg cells; the warming + heat-clearing group had significantly greater reductions than the heat-clearing group and the warming group (P < 0. 05) . Conclusion〗 The warming and heat-clearing method can regulate Treg/Th17 imbalance in rats with ACLF and is one of the mechanisms of its anti-liver failure activity.
Abstract: Tuberculosis patients with positive antibody to hepatitis C virus (TB-HCV patients) are often seen in clinical practice, and these TB-HCV patients include those with HCV infection. That makes the clinical management and diagnosis/treatment of TB-HCV difficult. This article introduces the prevalence of TB-HCV around the world, and analyzes the potential issues in the diagnosis and treatment of TB-HCV patients, such as drug-drug interactions, drug-induced liver injury, HCV reactivation, and TB reactivation. Through this review, it is recommended that the management should be strengthened and the appropriate therapeutic regimen should be selected in the diagnosis and treatment of TB-HCV patients.
Abstract: Traditional Chinese medicine (TCM) therapy has the advantage of regulating cytokines associated with liver fibrosis and is a candidate for the treatment of liver fibrosis in the future. This article summarizes the research advances in the role of TCM in regulating cytokines associated with liver fibrosis and points out that TCM has certain significance in blocking and reversing liver fibrosis by regulating related cytokines.
Abstract: Microvascular invasion, as a predictive factor for postoperative recurrence of hepatocellular carcinoma (HCC) , can only be diagnosed by the gold standard of pathological histology at present. Conventional imaging examination and serological markers have low sensitivity and specificity in evaluating microvascular invasion. Preoperative prediction and evaluation of microvascular invasion has an important value in selecting clinical treatment and assessing patient diagnosis. In recent years, magnetic resonance (MR) functional imaging and new contrast agents have been developing rapidly and have become the research hotspots in early diagnosis of HCC, postoperative follow-up of treatment outcome, and recurrence evaluation. This article elaborates on the significance of apparent diffusion coefficient of diffusion-weighted magnetic resonance imaging in evaluating microvascular invasion, as well as the potential value of intravoxel incoherent motion-magnetic resonance imaging and a new diffusion model of diffusion kurtosis imaging. This article also analyzes the application of dynamic contrast-enhanced magnetic resonance imaging and Gd-EOB-DTPA-specific MR in evaluating microvascular invasion and predicting postoperative recurrence. The analysis shows that the development of MR functional imaging and the application of several new techniques play an important role in the assessment of microvascular invasion of HCC and can determine the risk of postoperative recurrence and metastasis and provide reliable quantitative assessment indices for early diagnosis and reasonable application of surgery and other treatment methods.
Abstract: Posthepatectomy liver failure (PHLF) is a major cause of perioperative death after hepatectomy. This article summarizes the current status of research on risk factors contributing to PHLF, prediction methods, preventive measures, and related expert consensus, and it is pointed out that an objective evaluation of liver function before surgery, a reasonable design of the method of liver resection, and accurate operation are the key measures to reduce the incidence rate of PHLF.
Abstract: With the increase in the incidence rates of obesity and other metabolic syndromes, nonalcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases. More and more studies have shown that NAFLD is one of the risk factors for hepatocellular carcinoma (HCC) , but the mechanism of NAFLD in HCC remains unclear. Recent studies have found that intestinal microflora imbalance, inflammatory response, adipokines, insulin resistance, hyperinsulinemia, adipose progenitor cells, and genetic mutation are involved in the development of NAFLD-related HCC. Major treatment methods for NAFLD include exercise and diet intervention, insulin sensitizer, antioxidants, probiotics, and lipid-lowering drugs. However, it is still unknown whether these methods can effectively prevent NAFLD-related HCC. This article reviews recent advances in the prevalence, pathogenesis, prevention, monitoring, and screening of NAFLD-related HCC.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is a chronic disease with complex lesions, and it is difficult to determine the clinical stage. Liver biopsy is still the gold standard for the diagnosis of NAFLD; however, its clinical application is limited by various factors.Therefore, noninvasive methods for the accurate diagnosis of NAFLD are research hotspots at present. Imaging examinations help to achieve qualitative and quantitative evaluations of hepatic steatosis and fibrosis and thus has a promising future in clinical practice. This article summarizes the research advances in the imaging diagnosis of nonalcoholic fatty liver disease in recent years.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is a disease affecting about a quarter of the general population and has become the most important chronic liver disease in China and Western countries, causing huge medical and economic burdens. The prevalence rate of NAFLD is estimated to be as high as 40% in patients with inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease. This article mainly introduces the current status, economic burden, and risk factors for NAFLD in IBD patients and summarizes the current status and prospects of such diseases, in order to lay a foundation for further research in this field.