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Hepatitis B virus （HBV） has the characteristics of wide transmission， a high chronic infection rate， and a low cure rate， and improving the cure rate of HBV may help to improve the long－term prognosis of patients. Heat shock protein 90 （Hsp90） is a chaperone protein widely present in organisms. In recent years， more and more studies have shown that Hsp90 is associated with HBV infection and plays an important role in HBV replication. It can not only interact with specific proteins of the virus to promote its replication， but also interact with the host’s own proteins to perform its function. This article reviews the role of Hsp90 in HBV replication in recent studies， so as to provide new theoretical guidance and directions for the development of new anti－HBV drugs targeting Hsp90 and the prevention and treatment of HBV infection in the future.
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Objective To investigate the independent predictive factors for functional cure after long-term nucleos(t)ide analogue (NUC) antiviral therapy followed by pegylated interferon α-2b therapy in chronic hepatitis B (CHB) patients. Methods A total of 162 CHB patients who were admitted to several hospitals in Qingdao, China, from 2018 to 2021 were enrolled as subjects, and all patients received pegylated interferon α-2b for at least 48 weeks after NUC therapy for one year or longer. According to whether HBsAg clearance was achieved at week 48 of pegylated interferon α-2b treatment, the patients were divided into functional cure group with 79 patients and non-cure group with 83 patients, and related clinical indices were compared between the two groups. The two-independent-samples t test and the Mann-Whitney U rank sum test were used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Spearman correlation analysis was performed, and the univariate and multivariate logistic regression analyses were used to investigate the independent predictive factors for functional cure. The receiver operating characteristic (ROC) curve was plotted for related variables, and the area under the ROC curve (AUC) was used to evaluate the prediction accuracy of the variables. Results Compared with the non-cure group, the functional cure group had a significantly lower HBsAg level at baseline [21.63 (3.33-157.60) IU/mL vs 794.70 (336.10-1 185.34) IU/mL, Z =-8.869, P 1000 IU/mL (0 vs 8.4%, χ 2 =5.073, P =0.024), a significantly lower level of total bilirubin at baseline [12.60 (10.12-15.93) μmol/L vs 15.50 (11.80-24.10) μmol/L, Z =-3.611, P 2×upper limit of normal (16.5% vs 4.8%, χ 2 =5.835, P =0.016). The multivariate logistic regression analysis showed that baseline HBsAg (odds ratio [ OR ]=0.996, 95% confidence interval [ CI ]: 0.995-0.997, P < 0.001), HBsAg at week 12 of pegylated interferon α-2b treatment ( OR =0.990, 95% CI : 0.986-0.994, P < 0.001), HBsAg at week 24 of pegylated interferon α-2b treatment ( OR =0.983, 95% CI : 0.975-0.991, P < 0.001), and baseline total bilirubin ( OR =0.885, 95% CI : 0.826-0.949, P =0.001) were independent predictive factors for functional cure. The ROC curve of baseline HBsAg showed an AUC of 0.904 and the optimal cut-off value of 118.24 IU/mL; the ROC curve of HBsAg at week 12 of pegylated interferon α-2b treatment showed an AUC of 0.948 and the optimal cut-off value of 73.74 IU/mL; the ROC curve of HBsAg at week 24 of pegylated interferon α-2b treatment showed an AUC of 0.975 and the optimal cut-off value of 11.01 IU/mL; the ROC curve of baseline total bilirubin showed an AUC of 0.664 and the optimal cut-off value of 19.9 μmol/L. Conclusion Baseline HBsAg, HBsAg at week 12 of pegylated interferon α-2b treatment, HBsAg at week 24 of pegylated interferon α-2b, and baseline total bilirubin are independent predictive factors for functional cure at week 48 of pegylated interferon α-2b treatment in CHB patients receiving sequential therapy with NUC and pegylated interferon α-2b.
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Objective To investigate the application value of tenofovir alafenamide fumarate (TAF) in elderly patients with chronic hepatitis B (CHB) and its influence on bones and kidneys. Methods A total of 36 CHB patients, aged ≥60 years, who received TAF antiviral therapy in Qingdao Municipal Hospital, The Affiliated Hospital of Qingdao University, Qingdao Sixth People's Hospital, Chengyang People's Hospital, and Jimo People's Hospital from June 2021 to October 2022 were enrolled in this study, and all patients received TAF (25 mg/d) antiviral therapy. Related data were collected at baseline and weeks 24 and 48 of treatment, including virological indicators, biochemical parameters, urinary protein electrophoresis indices, transient elastography (FibroScan), and bone mineral density. Virological indicators included high-sensitivity HBV DNA quantification; biochemical parameters included total bilirubin, direct bilirubin (DBil), indirect bilirubin (IBil), alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, total bile acid (TBA), glucose, blood urea nitrogen, creatinine, estimated glomerular filtration rate, and cystatin C (Cys C); urinary protein electrophoresis indices included urinary β2 microglobulin (β2-MG), urinary retinol (URBP), and urinary α1 microspherin (α1-MG). The paired t -test was used for comparison of normally distributed continuous data before and after treatment, and the Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment; the chi-square test or the Fisher's exact test was used for comparison of categorical data. Results A total of 36 CHB patients completed 24 weeks of follow-up. The complete virological response rate after 24 weeks of treatment was higher than that at baseline [83.3% (30/36) vs 77.8% (28/36), χ 2 =0.36, P =0.55], and there were significant reductions in DBil ( t =-2.42, P =0.02) and Cys C ( t =-4.34, P 0.05). Conclusion TAF has a good antiviral effect in CHB patients aged ≥60 years and can help more CHB patients achieve complete virological response, without causing damage to the kidney, and it can also improve bone mineral density and liver fibrosis degree.
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There are a large number of individuals with HBV infection in China, which seriously endangers public health safety. As a first-line drug used in clinical practice, tenofovir alafenamide fumarate (TAF) has the characteristics of strong efficacy, low drug resistance, and bone and kidney safety. This article summarizes the role of TAF in patients with special types of chronic hepatitis B, such as low-level viremia, multidrug resistance, pregnancy, liver failure, and liver transplantation, and the analysis shows that TAF can reduce viral load in patients with low-level viremia to achieve virologic response, provide new regimens for patients with drug resistance, block mother-to-child transmission, reduce the mortality rate of patients with end-stage liver disease, and improve renal function in patients with chronic kidney disease.
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Objective To construct a Pnpla3 148M/M Tm6sf2 167K/K double mutant mouse model by crossbreeding Pnpla3 148M/M homozygous mice and Tm6sf2 167K/K homozygous mice. Methods Pnpla3 148I/M Tm6sf2 167E/K heterozygous mice were bred by hybridization of Pnpla3 148M/M Tm6sf2 167E/E and Pnpla3 148I/I Tm6sf2 167K/K homozygous mice, and the Pnpla3 148M/M Tm6sf2 167K/K mice were obtained by the self-crossbreeding of Pnpla3 148I/M Tm6sf2 167E/K mice. Male mice of Pnpla3 148M/M Tm6sf2 167K/K ( n =6), Pnpla3 148M/M Tm6sf2 167E/E ( n =6), and Pnpla3 148I/I Tm6sf2 167K/K ( n =6) genotypes and Wt mice ( n =6) were fed with normal diet for 8 weeks, and then the glucose and lipid metabolism indices were measured. 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 bewteen two groups. Results Agarose gel electrophoresis and nucleic acid sequencing results showed that the Pnpla3 148M/M Tm6sf2 167K/K double mutant mouse model was successfully constructed. There were no significant difference in body weight between the Pnpla3 148M/M Tm6sf2 167K/K mice and the Pnpla3 148M/M Tm6sf2 167E/E , Pnpla3 148I/I Tm6sf2 167K/K , and Wt mice (all P > 0.05). The Pnpla3 148M/M Tm6sf2 167K/K mice had a significantly higher liver wet weight than the Wt mice ( P 0.05). Also, there were no significant differences in the serum levels of biochemical indices between the Pnpla3 148M/M Tm6sf2 167K/K mice and the Pnpla3 148M/M Tm6sf2 167E/E , Pnpla3 148I/I Tm6sf2 167K/K , and Wt mice (all P > 0.05). Oil red O staining of the liver showed that more lipid accumulation was observed in the Pnpla3 148M/M Tm6sf2 167K/K mice than in the Pnpla3 148M/M Tm6sf2 167E/E and Wt mice. Conclusion The Pnpla3 148M/M Tm6sf2 167K/K double mutant mouse model was successfully constructed. Pnpla3 Ⅰ 148M and Tm6sf2 E 167K double mutations can cause abnormal glucose metabolism in mice.
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ObjectiveTo investigate the association of KCNJ11 rs5210 single nucleotide polymorphism with nonalcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) in the Chinese Han population in Qingdao, China. MethodsA total of 246 patients with NAFLD who attended Qingdao Municipal Hospital from December 2018 to September 2019 were enrolled as NAFLD group, 201 patients with CAD were enrolled as CAD group, and 116 patients with NAFLD and CAD were enrolled as NAFLD+CAD group; 342 healthy individuals were enrolled as control group. Fasting venous blood samples were collected for biochemical analysis. Whole blood genomic DNA was extracted, and PCR was used to determine KCNJ11 rs5210 genotype. The chi-square test was used to analyze whether the distribution of KCNJ11 rs5210 gene frequencies met the Hardy-Weinberg equilibrium, in order to determine whether the tested samples could represent the population. The chi-square test was used to analyze the differences in sex and genotype/allele frequency between groups. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Bonferroni method was used for further comparison between two groups. The unconditional logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval. ResultsThree genotypes (AA, GA, and GG) of KCNJ11 rs5210 were found by gene sequencing. There were no significant differences in rs5210 allele frequency and genotype distribution between the control group, the NAFLD group, the CAD group, and the NAFLD+CAD group (all P＞0.05), and there were still no significant differences after adjustment for sex, age, and body mass index (BMI) (all P＞0.05). For all subjects, the subjects with AA genotype had a higher level of alkaline phosphatase than those with GA genotype (P=0.048); in the NAFLD group, the patients with GA genotype had significantly higher BMI and total bilirubin than those with AA genotype (P=0.042 and 0.002). The unconditional logistic regression analysis showed that elevated BMI was associated with the risk of NAFLD (OR=1.35, P＜0.01), while decreased high-density lipoprotein (HDL) might indicate an increase in the risk of NAFLD (OR=0.33, P＜0.01); elevated fasting plasma glucose and decreased HDL might indicate an increase in the risk of CAD (OR=1.51 and 0.11, both P＜0.01) and NAFLD with CAD (OR=1.46 and 0.06, both P＜0.01). ConclusionThere is no significant association between KCNJ11 rs5210 polymorphism and the risk of NAFLD and CAD in the Chinese Han population in Qingdao.
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Objective To establish a mouse model of hepatocyte-specific TM6SF2 knockout, and to investigate the role of TM6SF2 in the development of nonalcoholic fatty liver disease (NAFLD). Methods The CRISPR/Cas9 technique and the Cre/LoxP strategy were used to establish a stable mouse model of hepatocyte-specific TM6SF2 knockout. The mice with hepatocyte-specific TM6SF2 knockout and the control mice were given a normal diet or a high-fat diet (HFD) for 16 weeks, and related indices were measured, including general status (body weight and liver weight), glucose metabolic indices (fasting blood glucose and insulin), and lipid metabolism (plasma triglyceride, cholesterol, and liver triglyceride). The t -test was used for comparison of normally distributed continuous data between two groups. Results Under the condition of HFD, compared with the control mice, the mice with hepatocyte-specific TM6SF2 knockout had significantly higher liver weight (2.235±0.175 g vs 1.258±0.106 g, t =4.789, P 0.05). Under the condition of HFD, there were no significant differences in the levels of plasma triglyceride and cholesterol between the mice with hepatocyte-specific TM6SF2 knockout and the control group ( P > 0.05), while the mice with hepatocyte-specific TM6SF2 knockout had a significant increase in the level of liver triglyceride compared with the control mice (23.969±0.978 mg/g vs 18.229±1.633 mg/g, t =3.015, P =0.024). Conclusion Hepatocyte-specific knockout of TM6SF2 can aggravate liver lipid accumulation and liver injury in mice with NAFLD.
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Objective To investigate whether there was a correlation between serum liver enzyme levels and blood pressure in the Chinese Han population with nonalcoholic fatty liver disease (NAFLD) in Shandong coastal regions in China. Methods A total of 269 NAFLD patients who lived in Shandong coastal regions and attended or underwent physical examination in Qingdao Municipal Hospital from December 2019 to June 2020 were enrolled, among whom 105 had hypertension and 164 did not have hypertension. Morning blood pressure was measured to calculate mean arterial pressure (MAP), and laboratory tests were performed to measure the serum levels of liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP)] and fasting blood glucose (FBG). The independent samples t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U 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. A Pearson correlation analysis was used to investigate the correlation of four liver enzymes with the indices including MAP, and a binary logistic regression model was used to analyze the impact of serum liver enzymes on hypertension. Results Compared with the non-hypertension group, the hypertension group had significantly higher body mass index (BMI), MAP, and GGT (all P < 0.05). For all NAFLD patients and the NAFLD patients without hypertension, male patients had significantly higher BMI, MAP, ALT, AST, and GGT than female patients (all P < 0.05), and for the NAFLD patients with hypertension, male patients had a significantly higher level of GGT than female patients ( P < 0.05). There was a significant difference in the distribution of GGT between the hypertension group and the non-hypertension group, and compared with the non-hypertension group, the hypertension group had a significantly higher proportion of patients with GGT exceeding the normal range ( χ 2 =4.781, P =0.029). Serum GGT level was correlated with MAP within the normal range (70-105 mm Hg) ( r =0.178, P =0.011), while there was no significant correlation when MAP exceeded the normal range ( P =0.415). After adjustment for age and sex, the binary logistic regression model showed that AST level was positively associated with hypertension in the population with NAFLD (odds ratio [ OR ]=1.011, 95% confidence interval [ CI ]: 1.000-1.022, P =0.040), and after further adjustment for BMI and FBG, the results showed that AST level was still positively associated with hypertension ( OR =1.011, 95% CI : 1.000-1.022, P =0.044). Conclusion In Chinese Han population with NAFLD in Shandong coastal regions, higher levels of AST may predict an increased risk of hypertension.
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ObjectiveTo investigate the association of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) rs8192678 single nucleotide polymorphism (SNP) with the risk of nonalcoholic fatty liver disease (NAFLD) and the influence of PPARGC1A rs8192678 SNP on NAFLD-related biochemical parameters. MethodsA total of 119 NAFLD patients who attended Qingdao Municipal Hospital Affiliated to Qingdao University from December 2017 to December 2018 were enrolled as NAFLD group, and 213 individuals who underwent physical examination during the same period of time were enrolled as control group. Clinical data and blood samples were collected from all subjects to measure related biochemical parameters and detect PPARGC1A rs8192678 SNP. The chi-square test was used to determine whether the genotype distribution of samples was in accordance with the Hardy-Weinberg equilibrium. 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 binary logistic regression analysis was used to investigate the risk factors for NAFLD. ResultsThere were no significant differences in the genotype and allele frequencies of PPARGC1A rs8192678 between the NAFLD group and the control group (χ2=0.011 and 0.015, P=0.918 and 0.904). The binary logistic regression analysis showed that CT genotype of PPARGC1A rs8192678 was not a risk factor for NAFLD (odds ratio=0.951, 95% confidence interval: 0.368-2.457, P=0.918). In the NAFLD group, the patients carrying CT genotype had a significantly higher level of gamma-glutamyl transpeptidase (GGT) than those carrying CC genotype (Z=-2.331, P=0.020). ConclusionPPARGC1A rs8192678 SNP does not increase the risk of NAFLD, while NAFLD patients carrying CT genotype tend to have a higher serum level of GGT.
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<p><b>OBJECTIVE</b>To investigate the role and mechanism of action of fibroblast growth factor-21 (FGF-21) in reducing triglyceride (TG) in the in vitro and in vivo models of nonalcoholic fatty liver disease (NAFLD).</p><p><b>METHODS</b>(1) A mixture of free fatty acids was used to establish a model of steatosis in L02 cells, and the cells were treated with various concentrations of FGF-21 or fenofibrate. Twenty-four hours later, oil red O staining was performed to observe the degree of steatosis, and intracellular TG content was determined. RT-PCR and Western blot were applied to measure the mRNA and protein expression of sterol regulatory element-binding protein-1c (SREBP-1c). (2) High-fat diet was used to establish a mouse model of steatosis, and these mice were intraperitoneally injected with FGF-21 or fenofibrate. Eight weeks later, whole blood and liver samples were collected, and HE staining was performed to observe steatosis. Meanwhile, the serum levels of TG, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured, and TG content in the liver was also measured. One-way analysis of variance was used for comparison of data between multiple groups, and the least significant difference t-test was used for comparison between any two groups.</p><p><b>RESULTS</b>(1) Compared with the control group, the model group showed significant steatosis, with significant increases in intracellular lipid droplets and TG content (t = -20.57, P < 0.01), while FGF-21 reduced the number of intracellular lipid droplets and TG content (F = 98.16, P < 0.01) in a dose-dependent manner. In addition, the model group had significantly increased mRNA and protein expression of SREBP-1c compared with the control group (t = -10.73 and -0.1006, both P < 0.01), while FGF-21 down-regulated the mRNA and protein expression of SREBP-1c (F = 161.35 and 36.72, both P < 0.01). (2) Compared with the mice in the control group, those in the model group showed significant steatosis and had significant increases in serum TG level and TG content in the liver (t = -18.84 and 15.71, both P < 0.01). FGF-21 relieved hepatic steatosis and reduced the serum TG level and TG content in the liver (t = 18.11 and 9.46, both P < 0.01). Moreover, FGF-21 reduced the serum levels of ALT and AST in NAFLD mice (t = 25.93 and 12.50, both P < 0.01).</p><p><b>CONCLUSION</b>FGF-21 can inhibit the synthesis of TG through suppressing the expression of SREBP-1c, which further confirms the potential therapeutic effect of FGF-21 in the treatment of NAFLD. This may provide new ideas for the treatment of NAFLD.</p>
Subject(s)
Animals , Mice , Alanine Transaminase , Blood , Aspartate Aminotransferases , Blood , Cell Line , Diet, High-Fat , Disease Models, Animal , Fenofibrate , Pharmacology , Fibroblast Growth Factors , Pharmacology , Non-alcoholic Fatty Liver Disease , Blood , Drug Therapy , Sterol Regulatory Element Binding Protein 1 , Metabolism , Triglycerides , BloodABSTRACT
ObjectiveTo investigate the mechanism of action of PNPLA3 I148M mutation in the development and progression of non-alcoholic fatty liver fibrosis. MethodsThe lentiviral vectors carrying the mutant or wild-type PNPLA3 I148M gene were constructed and transfected into rat hepatic stellate (HSC-T6) cells. Quantitative real-time PCR was applied to measure the mRNA expression of transforming growth factor β1 (TGF β1). The t-test was applied for statistical analysis. ResultsThe lentiviral vectors carrying the mutant or wild-type PNPLA3 I148M gene were successfully constructed and transfected into HSC-T6 cells, and a HSC-T6 cell line with stable expression of the mutant or wild-type PNPLA3 gene was established. Compared with the cell line carrying the wild-type gene, the cell line carrying the mutant gene showed significantly higher mRNA expression of TGF β1 (1.25±0.15 vs 0.48±0.07; t=11.826, P＜0001). ConclusionPNPLA3 I148M mutation can increase the expression of TGF β1 in HSC-T6 cells, which provides a new cell model and new research ideas for investigating the role of PNPLA3 I148M mutation in non-alcoholic fatty liver fibrosis.
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<p><b>OBJECTIVE</b>To investigate the relationship between SREBP-1c and the risk of liver disease associated with the triacylglyceride lipase PNPLA3 I148M variant using a human hepatoma cell line model transfected with recombinant lentiviruses.</p><p><b>METHODS</b>Huh7 cells were transfected with control lentivirus or lentivirus containing the PNPLA3 I148M variant (variant). The two cell groups were compared to assess differences in triglyceride content (using oil red O staining), levels of triglyceride and cholesterol (using automated biochemical analyzer), expression of SREBP-lc mRNA (using fluorescence quantitative PCR), and expression of SREBP-1c protein (using western blot.</p><p><b>RESULTS</b>Cells expressing the PNPLA3 I148M variant showed higher triglyceride content (0.54+/-0.03 mmol/L vs. control cells: 0.23+/-0.02 mmol/L; t=22.58, P<0.001), cholesterol level (0.28+/-0.03 mmol/L vs. control cells: 0.13+/-0.02 mmol/L; t =11.83, P<0.001), SREBP-1cmRNA expression (13.59+/-0.60 vs. 11.81+/-0.82; [The abstract and text in the paper say variant increases, but the data shown says the higher value is in the control cells. Please correct to properly express the data.] P=0.001), and SREBP-1c protein expression. The level of SREBP-1c was positively correlated with serum triglyceride in the cells expressing the PNPLA3 I148M variant (r=0.912, P<0.01).</p><p><b>CONCLUSION</b>The risk of liver disease associated with the PNPLA3 I148M variant, which increases lipogenesis, may involve SREBP-1c and a pathway that increases triglycerides.</p>
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Humans , Cell Line, Tumor , Lipase , Liver Diseases , Membrane Proteins , Risk Factors , Sterol Regulatory Element Binding Protein 1 , TriglyceridesABSTRACT
<p><b>OBJECTIVE</b>To investigate the cell cycle of Huh-7 cells affected by I148M polymorphism of PNPLA3 gene and the possible mechanisms.</p><p><b>METHODS</b>Huh-7 cells which could respectively overexpress PNPLA3 wild type and I148M variant were cultured and Huh-7 cells with zero load plasmids were used as matched control, Flow cytometry was conducted to detect the cell cycles of these 3 type of Huh-7 cells and western blot and realtime fluorescence quantitative PCR were applied to investigate the expression of regulatory factors (Cyclin D1 and p53) of cell cycle. t-test was used in statistical analysis.</p><p><b>RESULTS</b>Cell cycle phase distribution was presented by the proportion of cells in each phases (%), compared with the control group, the cell cycle phase distribution (G1 phase 59.27 ± 0.15, G2/M phase 24.23 ± 0.31, S phases 16.50 ± 0.26) had no differences in wild type group (G1 phase 58.53 ± 0.35, G2/M phase 24.87 ± 0.60, S phases 16.60 ± 0.26; Probability value less than 0.05). While between variant type group and wild type group, G1 phase was significantly decreased (variant type group G phase 38.37 ± 0.21, Probability value less than 0.05), S phase and G2/M phase were increased (variant type group S phase 27.47 ± 0.35, P less than 0.05; G2/M phase 34.17 ± 0.15, P less than 0.05), respectively. compared with control group, the relative expression of P53 mRNA in variant type group was significantly upregulated (control group 1.06 ± 0.41, variant type group 6.54 ± 0.34; Probability value less than 0.05) and there was no statistical significance in wild type group (1.66 ± 0.30, P more than 0.05); Cyclin D1 expression showed no statistical significance in any of these three groups, control group 1.00 ± 0.10, wild type group 1.06 ± 0.03, variant type group, 1.11 ± 0.04; P > 0.05).</p><p><b>CONCLUSION</b>I148M polymorphism of PNPLA3 gene affects cell cycles of Huh-7 cells via up-regulatating P53.</p>
Subject(s)
Humans , Carcinoma, Hepatocellular , Cell Cycle , Cell Line, Tumor , Cyclin D1 , Flow Cytometry , Lipase , Liver Neoplasms , Membrane Proteins , Polymorphism, GeneticABSTRACT
<p><b>OBJECTIVE</b>To investigate the efficacy and safety of telbivudine for blocking mother-to-child transmission of hepatitis B virus (HBV) in pregnant women with high viremia.</p><p><b>METHODS</b>A total of 128 pregnant women with high HBV load (HBV DNA ≥ 1.0*10⁷ copies/ml and positive for hepatitis B surface antigen (HBsAg)) were enrolled in the study from January 2009 to January 2013 and divided into the following three groups:group A (n=42) treated with telbivudine at 12 weeks of gestation until postpartum 12 weeks; group B (n=41) treated with telbivudine at 20 to 28 weeks of gestation until postpartum 12 weeks; group C (n=45; control group) with no telbivudine treatment.All study participants were given compound giyeyrrhizin for liver protection. All infants born to the women from the three groups were vaccinated with hepatitis B immunoglobulin (200 IU) and the HBV vaccine (20 tg) ager birth. The mother-to-infant transmission of HBV was indicated by the presence of HBsAg in infants at 7 months after birth.The maternal HBV DNA levels of the women in the three groups were statistically compared with the HBsAg positive rates in their neonates.</p><p><b>RESULTS</b>There were no significant differences in the HBV DNA levels between the three groups before treatment (P more than 0.05). The pre-delivery level of HBV DNA in group A (0.553 ± 1.588 log10 copies/ml) and in group B (0.486 ± 1.429 log10 copies/ml) was significantly decreased compared to that in group C (7.698 ± 0.255 log10 copies/ml) (both P < 0.01).The post-delivery (12 weeks) level of HBV DNA in group A (0.381 ± 1.116 log10 copies/ml) and in group B (0.335 ± 1.073 log10 copies/ml) was significantly decreased compared to that in group C (7.728 ± 0.277 log10 copies/ml) (both P < 0.01).There were no significant differences in the HBV DNA levels between group A and group B (P > 0.05). No infants in group A or group B were HBsAg-positive,while the HBsAg-positive rote was 17.4% in group C (P=0.012; P=0.015).</p><p><b>CONCLUSIONS</b>Telbivudine treatment starting from the 12th week of gestation or from the 20-28th week of gestation can significantly decrease the serum HBV DNA level in peripheral blood of pregnant women with high viremia and reduce the infection rate of HBV in their neonates.</p>
Subject(s)
Female , Humans , Infant, Newborn , Pregnancy , Hepatitis B Surface Antigens , Hepatitis B Vaccines , Hepatitis B virus , Immunoglobulins , Infectious Disease Transmission, Vertical , Mothers , Pregnancy Complications, Infectious , Thymidine , ViremiaABSTRACT
Objective To investigate the association between (beta-parvin) PARVB gene rs5764455 polymorphism and susceptibility to non-alcoholic fatty liver disease (NAFLD). Methods A total of 230 patients with NAFLD (NAFLD, n = 230) and 230 control subjects (control, n = 330) were genotyped by PCR and direct sequencing. Clinical information was detected and compared in different groups. Genotypic frequency and gene frequency distribution in the two groups and relative risks to NAFLD susceptibility were assessed statistically , respectively. Results No statistical differences were observed between PARVB gene rs5764455 genotypic frequency with gene frequency distribution and the two groups, respectively (Genotypic frequency χ2 = 0.182, P = 0.913; gene frequency χ2 = 0.180, P = 0.672). Comparing C/T + T/T genotype carrier with C/C genotype carrier, there were no differences concerning the relative risks to NAFLD susceptibility (OR = 1.266, P =0.178;adjusted OR =1.631, P =0.096) before and after adjusting body mass, BMI and so on. In the latter group, there are significant differences in the increases of body mass, BMI, TG, ALT and AST (P < 0.05). Conclusion Non-relationship was observed between PARVB gene rs5764455 polymorphism and the risk of NAFLD in Qingdao Han Chinese.
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Objective To investigate the association between the Adiponectin rs266729 and rs2241766 gene polymorphisms and nonalcoholic fatty liver disease in the Han Chinese population residing in Qingdao. Methods Adiponectin rs266729 and rs2241766 gene polymorphisms were genotyped in patients with NAFLD (n = 336) and healthy controls (n = 280) using polymerase chain reaction (PCR). Serum lipid profiles and adiponectin levels were determined using biochemical methods. Statistical analyses were performed using Pearson Chi square test, logistic regression analysis, t test, linear regression analysis. Results We found a significant association between the Adiponectin rs266729 genotype frequencies and allele frequencies between NAFLD pa-tients and controls (χ2= 9.929, P = 0.007; χ2= 9.809, P = 0.002). After adjustment of confounding factor, the rs266729 G allele was associated with an increased risk of NAFLD compared to the C allele (OR = 1.410, 95%CI: 1.082-1.831, P = 0.008) No significant differences were found in the rs2241766 genotype frequencies and allele frequencies between NAFLD population and the controls (OR = 1.410, 95%CI: 1.082-1.831, P = 0.008). Conclusion The Han Chinese in Qingdao carrying the rs266729 G allele are at increased risk of NAFLD.
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<p><b>OBJECTIVE</b>To investigate the association between the PNPLA3 rs738409 polymorphism and chronic hepatitis B (CH[B) in a Han Chinese population residing in Qingdao.</p><p><b>METHODS</b>Peripheral blood samples were collected from 185 CHB patients and 164 healthy controls and subjected to polymerase chain reaction (PCR) and DNA sequencing to determine the PNPLA3 genotypes. The relative risk of the rs738409 polymorphism for CHB was estimated by calculating the odds ratio (OR) and 95% confidence interval.</p><p><b>RESULTS</b>The rs738409 G allele frequency was significantly different between the CHB and control groups (31.9% vs.21.9% respectively, P less than 0.05). Compared to he rs738409 C allele, the G allele was associated with an increased risk of developing CHB (OR =1.67, 95% CI:1.18-2.34, P =0.003). Logistic regression model analysis, with adjustment for confounding factors, indicated that carriers of the PNPLA3 rs738409 GG + GC genotype had increased risk of CHB than carriers of the CC genotype (OR =1.76 ,95% CI:1.14-2.71, P =0.011).</p><p><b>CONCLUSION</b>Qingdao Han Chinese who are carriers of the rs738409 G allele are at increased risk of CHB.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Asian People , Genetics , Case-Control Studies , China , Epidemiology , Gene Frequency , Genetic Predisposition to Disease , Genotype , Hepatitis B, Chronic , Epidemiology , Genetics , Lipase , Genetics , Membrane Proteins , Genetics , Polymorphism, Single Nucleotide , Risk FactorsABSTRACT
<p><b>OBJECTIVE</b>To investigate the association between two polymorphisms of the APOC3 gene (T-455C and C-482T) and hereditary risk of non-alcoholic fatty liver disease (NAFLD).</p><p><b>METHODS</b>A total of 287 patients with NAFLD and 310 control subjects were genotyped by PCR and direct sequencing. Serum lipid profiles were also detected by standard biochemical</p><p><b>METHODS</b>One-hundred-and-eighty of the study participants were used to measure the APOC3 content by enzyme-linked immunosorbent assay. Inter-group differences and associations were assessed statistically using Chi square and t tests and logistic and linear regression analyses.</p><p><b>RESULTS</b>The frequencies of neither the genotypes or alleles were significantly different between the NAFLD cases and the controls. Compared with the most common genotypes-455TT or-482CC, none of the variants showed a significant increase in risk of NAFLD or for the clinical and biochemical parameters. The adjusted odds ratios (with 95% confidence intervals) of NAFLD were 1.25 (0.79-1.96) and 1.20 (0.76-1.89) for carriers of the APOC3-455C and-482 T variants respectively (P more than 0.05).</p><p><b>CONCLUSION</b>The T-455C and C-482T polymorphisms of the APOC3 gene are not associated with risk of NAFLD, pathogenic changes in lipid profiles, or insulin resistance in Han Chinese.</p>