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Objective:To analyze the liver pathological characteristics of chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) and negative hepatitis B e antigen (HBeAg), and to evaluate the diagnostic value of different serological models for liver fibrosis.Methods:Retrospective analysis was conducted on the patients with HBeAg-negative CHB who had normal ALT and underwent liver biopsy from August 2016 to December 2019 in the Department of Infectious Diseases, Henan Provincial People′s Hospital. The clinical data, serum indicators of hepatitis B virus (HBV) and HBV DNA were collected. The liver fibrosis stages (S) was assessed by pathological examination. The diagnostic efficacies of gamma-glutamyl transpeptidase to platelet ratio (GPR), fibrosis 4 score (FIB-4), S index, aspartate aminotransferase to platelet ratio index (APRI) and gamma-glutamyl transpeptidase to albumin ratio (γ-GT/ALB) for liver pathological fibrosis were analyzed by the receiver operating characteristic curves. Two variable correlation test was used to explore the relationship between the different models and pathological fibrosis of liver tissue. Chi-square test was used for statistical comparison.Results:The age of 448 patients was (37.98±9.82) years, and the male to female ratio was 1.286 ∶1. The proportions of S≥2 in patients with age>30 years, hepatitis B surface antigen (HBsAg)<2 000 IU/mL and HBV DNA≥2 000 IU/mL were higher than those in patients with age ≤30 years, HBsAg ≥2 000 IU/mL and HBV DNA<2 000 IU/mL, respectively, and the differences were all statistically significant ( χ2=7.68, P=0.006; χ2=11.44, P=0.001; χ2=9.12, P=0.003, respectively). There were 250 cases with pathological fibrosis stage S<2, 162 cases with S=2 and 36 cases with S≥3. FIB-4 (correlation coefficient 0.250), APRI (correlation coefficient 0.218), GPR (correlation coefficient 0.186), S index (correlation coefficient 0.184) and γ-GT/ALB (correlation coefficient 0.127) were positively correlated with the severity of liver fibrosis (all P<0.050). S index had the highest sensitivity (64.1%) in the diagnosis of significant liver fibrosis (S≥2), while γ-GT/ALB had the highest specificity (80.8%). In the diagnosis of severe liver fibrosis (S≥3), γ-GT/ALB had the highest sensitivity (77.8%), while APRI had the highest specificity (78.6%). Conclusions:The incidence of liver fibrosis in CHB patients with normal ALT and negative HBeAg is relatively high. The current serological diagnostic models are not suitable for the evaluation of liver fibrosis in these patients, and timely liver puncture is still necessary.
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Objective:To evaluate the short-term prognostic value of model for end-stage liver disease (MELD) combined with high density lipoprotein-cholesterol (HDL-C) in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF).Methods:From December 2015 to December 2018, 182 patients with HBV-ACLF who were treated in Henan Provincial People′s Hospital were included. Prognosis and clinical data including HDL-C, total bilirubin, international standardized ratio (INR), creatinine of patients within 24 hours after admission were collected and analyzed retrospectively.The values of MELD were calculated. The binary logistic regression analysis was used to analyze the independent risk factors affecting 90-day mortality in HBV-ACLF patients.The receiver operator characteristic curve (ROC) and MedCalc 15.2 software were used to assess the predictive value of MELD, HDL-C and MELD-HDL-C model for prognosis. Kaplan-Meier survival curve was performed to analyze the prognosis of patients in different groups.Results:Sixty patients were divided into the death group and 122 patients were divided into the survival group according to the prognosis during hospitalization and 90 days after discharge. The MELD score of patients in the survival group was 21(19, 24), which was significantly lower than that in the death group (29(25, 34)), and the HDL-C value of patients in the survival group was significantly higher than that in the death group (0.3 (0.1, 0.6) mmol/L vs 0.2(0.1, 0.5) mmol/L). The differences were both statistically significant ( Z=-6.290 and -4.087, respectively, both P<0.01). Multivariate logistic regression analysis showed that MELD score and HDL-C value were the independent risk factors for 90-day mortality in patients with HBV-ACLF(odds ratio ( OR)=1.432, 95% confidence interval ( CI)1.271-1.613; OR=0.584, 95% CI 0.487-0.700, respectively; both P<0.01). Areas under the ROC of MELD, HDL-C and MELD-HDL-C scoring models were 0.775, 0.782 and 0.878, respectively. MELD-HDL-C scoring model was superior to both MELD and HDL-C , and the differences were both statistically significant ( Z=3.944 and 3.104, respectively, both P<0.01). When the MELD-HDL-C Youden′s index was set at 0.72, the optimal threshold was 24.69. Patients with MELD-HDL-C score≥24.69 had lower survival rate than patients with MELD-HDL-C score<24.69, and the difference was statistically significant ( χ2=142.900, P<0.01). Conclusion:MELD, HDL-C and MELD-HDL-C scoring systems could predict the short-term prognosis in patients with HBV-ACLF, and the predictive value of MELD-HDL-C has the superiority.
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Objective:To evaluate the efficacy and safety of elbasvir/grazoprevir (EBR/GZR) in patients with genotype 1 chronic hepatitis C in the real-world.Methods:This was an open-label, single-center, retrospective real-world study. A total of 103 genotype 1 chronic hepatitis C patients who were treated with EBR/GZR in Henan Provincial People′s Hospital from May 2018 to October 2019 were enrolled.And the clinical baseline characteristics of patients and the effectiveness and safety of antiviral therapy were respectively evaluated.Results:A total of 103 patients were enrolled in the study with an age of (47.6±13.9) years. Fifty-five (53.4%) patients were male and 48(46.6%) were female. One point nine percent (2/103) patients were genotype 1a hepatitis C and 98.1%(101/103) were genotype 1b hepatitis C. Seventeen genotype 1b hepatitis C patients were previously treated with interferon, and three patients co-infected with hepatitis B virus (HBV). Among the 103 cases, 35 had underlying diseases and 26 had combined medication. Ninty-eight cases completed 12-week treatment and 89 cases completed 12-week follow-up after treatment.Overall, 89 cases achieved sustained virological response. The overall incidence of adverse reactions was 20.4%(21/103), and the main adverse reactions were fatigue, insomnia and anxiety. No serious adverse event occurred. The three patients with HBV co-infection had no hepatitis B activation after treatment.Conclusion:EBR/GZR is effective and safe in the patients with genotype 1 chronic hepatitis C in China.
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Objective To investigate whether there are differences in lymphocyte subsets between chronic hepatitis B (CHB) patients receiving different antiviral treatment regimens, and to determine related predictive factors for HBsAg decline. Methods A retrospective analysis was performed for 68 treatment-experienced CHB patients who attended the outpatient service in Department of Infectious Diseases, Henan Provincial People's Hospital, from October to December 2019, and according to the antiviral treatment regimen, they were divided into PEG-IFNα treatment group with 10 patients, PEG-IFNα+nucleos(t)ide analogues (NAs) treatment group with 21 patients, and NAs treatment group with 37 patients. Related data were recorded, including demographic features, blood routine, albumin, HBsAg, and measurement of lymphocyte subsets. 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 multivariate logistic regression analysis was used to investigate independent influencing factors for HBsAg decline. Results There were significant differences between the three groups in HBsAg decline ( H =8.348, P =0.015), absolute value of lymphocytes ( F =4.643, P =0.013), and T lymphocyte count ( F =7.721, P =0.001). The multivariate logistic regression analysis showed that sex (odds ratio [ OR ]=0.227, 95% confidence interval [ CI ]: 0.059-0.878, P =0.032), age ( OR =0.931, 95% CI : 0.868-0.999, P =0.047), antiviral treatment regimen (PEG-IFN-α treatment group vs NAs treatment group: OR =9.600, 95% CI : 1.982-46.498, P =0.005; PEG-IFN-α+NAs treatment group vs NAs treatment group: OR =4.800, 95% CI : 1.336-17.243, P =0.016), and T lymphocyte count ( OR =0.804, 95% CI : 0.684-0.944, P =0.008) were independent influencing factors for HBsAg decline. Conclusion For CHB patients receiving PEG-IFNα alone or in combination with NAs, monitoring of lymphocyte subsets during the treatment process may help to judge HBsAg decline, and the lower the absolute value of T lymphocytes, the greater the possibility of HBsAg decline.
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ObjectiveTo investigate the status of abnormal renal function markers and related influencing factors in chronic hepatitis B (CHB) patients receiving oral antiviral drugs for a long time. MethodsA retrospective analysis was performed for the clinical data of 681 CHB patients who attended Henan Provincial People’s Hospital from January to December 2019 and received long-term oral administration of entecavir (ETV)/tenofovir disoproxil fumarate (TDF). All patients received the measurement of blood renal function markers (urea, creatinine, retinol-binding protein ［RBP］, cystatin C ［Cys-C］, and β2-microglobulin ［β2-MG］), urinary renal function markers (α1-microglobulin ［α1-MG］, Cys-C, and N-acetyl-β-D-glucosaminidase ［NAG］), and urine routine parameters. The incidence rate of abnormal renal function markers were analyzed. The McNemar’s test was used for comparison of categorical data between groups, and the multivariate logistic regression analysis was used to investigate independent influencing factors for abnormal renal markers in urine. ResultsThe 681 patients had a mean age of 39.8±11.0 years and received medication for 1.88 (0.80-3.16) years. There were 417 male patients and 264 female patients, and the incidence rate of liver cirrhosis was 27.02% (184/681). Of all 681 patients, 442 received ETV and 239 received TDF. The measurement of blood renal function markers showed that urea, creatinine, retinol-binding protein, Cys-C, and β2-MG had an abnormal rate of 6.9% (47/681), 0.15% (1/681), 0(0/681), 2.21% (15/681), and 5.03% (30/681), respectively, and the abnormal rate of urinary protein was 7.29% (49/672). The measurement of urinary renal function markers showed that α1-MG, NAG, and Cys-C had an abnormal rate of 38.62% (263/681), 37.74% (257/681), and 19.38% (132/681), respectively. The abnormal rate of urine test was higher than that of blood test (P＜0.001). The multivariate logistic regression analysis with urinary α1-MG as the dependent variable showed that sex (odds ratio ［OR］=0.293, 95% confidence interval ［CI］: 0.204-0.419, P＜0.05), age (OR=1298, 95%CI: 1.108-1.521, P＜0.05), and type of nucleoside drug (OR=2.100, 95%CI: 1.431-3.083, P＜0.05) were influencing factors. The multivariate logistic regression analysis with urinary NAG as the dependent variable showed that age (OR=1.177, 95%CI: 1.008-1.375, P=0.040) was an influencing factor. ConclusionCompared with blood renal function markers, urinary renal function markers can identify renal injury earlier in CHB patients, and the elderly patients and the patients receiving TDF are more likely to develop abnormal renal function. However, it is not observed whether the duration of medication and liver cirrhosis can increase the risk of renal injury in CHB patients.
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Objective:To investigate the clinical characteristics of patients with aspergillus spondylitis, and to provide reference for timely diagnosis and treatment.Methods:The clinical manifestations, imaging performance, laboratory examination results, diagnosis and treatment outcomes of six patients with confirmed aspergillus spondylitis in Department of Infectious Diseases, Henan Provincial People′s Hospital during April 30, 2015 and May 1, 2020 were retrospectively analyzed.Results:The main manifestations of six patients were fever and neck pain or low back pain. The time from the onset of clinical manifestations to diagnosis was more than two months to 14 months. Spine magnetic resonance imaging (MRI) showed long T1 and T2 signals on vertebral body, high pressure lipid signal, obvious enhanced scan enhancement, and paravertebral abscess formation might be presented. Among the six patients, C-reactive protein increased in four patients, erythrocyte sedimentation rate increased in five patients, β-D-glucan test (G test) increased in three patients, galactomannan antigen test (GM test) increased in four patients. Six patients with aspergillus spondylitis were all confirmed by biopsy of diseased tissue for fungal smear, tissue culture or metagenomics next generation sequencing. After treatment with voriconazole or itraconazole, five patients recovered and one patient was still under treatment.Conclusions:The clinical manifestations and imaging examination of patients with aspergillus spondylitis are nonspecific. Peripheral blood G test and GM test need to be combined for diagnosis. The diagnosis depends on tissue puncture pathology examination, and the metagenomics next generation sequencing is needed if necessary.
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Objective:To evaluate the efficacy of artificial liver blood purification system in the treatment of severe and critical patients with corona virus disease 2019(COVID-19), and to observe the dynamic changes of lymphocyte subsets and cytokines after treatment.Methods:A total of six patients with COVID-19 admitted to the ward of public health center of Henan Provincial People′s Hospital from January 31 to February 18, 2020 were enrolled, including three severe cases and three critical cases. The protocals of artificial liver treatment were developed according to the patients′ conditions, and the patients′ epidemiological history, clinical characteristics, and laboratory examination data were retrospectively analyzed. At the same time, dynamic changes of lymphocyte subsets and cytokines were detected before and after artificial liver treatment.Results:By February 24, 2020, two severe patients were discharged after cured, and one case was discharged after improved, with an average stay of 19 days. Two critical patients were still hospitalized and one died. Three severe patients were all treated with hemofiltration, while two critical patients were treated with hemofiltration plus plasma exchange, and one was treated with continuous bedside hemofiltration.Among six patients, the ratio of neutrophils to lymphocytes before treatment were 6.42, 2.63, 15.00, 15.09, 12.04 and 30.41, respectively. After treatment, the ratio of neutrophils to lymphocytes became 4.77, 6.05, 4.86, 5.43, 32.77 and 23.46, respectively.The absolute numbers of lymphocytes in six patients before treatment were low, with a median of 382/μL. After treatment of artificial liver, the absolute numbers of lymphocytes increased, with a median of 476/μL. Cytokines were detected in three critical patients, and the interleukin 6 (IL-6) levels in two cases were 26 042.00 ng/L and 282.03 ng/L, respectively before treatment. After treatment, the levels decreased to 226.85 ng/L and 26.15 ng/L, respectively. IL-6 continued increasing from 30.14 ng/L to 709.25 ng/L in one another critical patient, who eventually died.Conclusions:In severe and critical patients with COVID-19, artificial liver treatment can reduce inflammation and increase the absolute numbers of lymphocytes and the subsets. The IL-6 level may be correlated with disease progression and may be a useful prognostic factor for early identification of severe and critical COVID-19.
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ObjectiveTo investigate the mechanism of action of miR-196b in regulating the growth and apoptosis of hepatoma cells by targeting nuclear apoptosis-inducing factor 1 (NAIF1). MethodsReal-time PCR was used to measure the expression of miR-196b in hepatoma HuH-7, SNU-449, HepG2, and SMCC7721 cells versus normal human HL7702 hepatocytes. The hepatoma HepG2 cells were collected and divided into Control group (blank control), Anti-NC group (transfected with inhibitor control), Anti-miR-196b group (transfected with miR-196b inhibitor), si-NC group (transfected with siRNA control), si-NAIF1 group (transfected with NAIF1 siRNA), Anti-miR-196b+si-NAIF1 group (co-transfected with miR-196b inhibitor and NAIF1 siRNA), and Anti-miR-196b+si-NC group (co-transfected with miR-196b inhibitor and siRNA control). MTT assay was used to measure the change in proliferation, plate colony formation assay was used to measure colony formation ability, flow cytometry was used to measure cell apoptosis, and Western blot was used to measure the protein expression of Bax and C-caspase-3. Target gene prediction software predicted that NAIF1 might be a target gene of miR-196b, and the luciferase reporting system was used to identify the targeting relationship. 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 the SNK-q test was used for further comparison between two groups. ResultsThere was a significant difference in the expression level of miR-196b between hepatoma HuH-7, SNU-449, HepG2, and SMCC7721 cells and normal human HL7702 hepatocytes (1.85±0.16/1.63±012/2.36±0.25/1.92±0.13 vs 1.00±0.09, F=29.05, P＜0.001). Compared with the Anti-NC group, the Anti-miR-196b group had significant reductions in the expression level of miR-196b (0.42±0.03 vs 1.02±0.10, P＜0.05), cell proliferation (0.20±0.02 vs 0.30±0.05, P＜0.05), and colony formation ability (64.35±6.97 vs 119.54±11.82, P＜0.05) and significant increases in apoptosis rate (22.30%±2.09% vs 4.26%±0.35%, P＜0.05) and relative protein expression of Bax (0.69±0.08 vs 0.30±0.05, P＜0.05) and C-caspase-3 (0.63±0.05 vs 0.21±0.04, P＜0.05). Compared with the si-NC group, the si-NAIF1 group had significant increases in proliferation ability (0.46±0.05 vs 0.31±0.04, P＜0.05) and colony formation ability (138.92±9.66 vs 118.47±838, P＜0.05) and significant reductions in apoptosis rate (4.12%±0.40% vs 1.23%±0.12%, P＜0.05), NAIF1 (0.10±0.01 vs 0.17±0.02, P＜0.05), and protein expression of Bax (0.18±0.02 vs 0.29±0.03, P＜0.05) and C-caspase-3 (0.12±0.01 vs 020±0.03, P＜0.05). Compared with the Anti-miR-196b+si-NC group, the Anti-miR-196b+si-NAIF1 group had significant increases in proliferation ability (0.28±0.02 vs 0.21±0.03, P＜0.05) and colony formation ability (97.12±8.23 vs 66.35±5.20, P＜0.05) and significant reductions in apoptosis rate (9.60%±1.11% vs 21.14%±1.32%, P＜0.05), NAIF1 (0.30±0.04 vs 0.52±0.06, P＜0.05), and protein expression of Bax (0.28±0.03 vs 0.67±0.06, P＜0.05) and C-caspase-3 (0.22±0.05 vs 0.60±004, P＜0.05). ConclusionDownregulation of miR-196b can inhibit the growth and induce the apoptosis of hepatoma cells via negative regulation of NAIF1.
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Objective@#To recognize the efficacy and safety of paritaprevir/ritonavir-ombitasvir combined with dasabuvir (OBV/PTV/RTV+DSV) in the treatment of genotype 1b chronic hepatitis C.@*Methods@#Patients with genotype 1b chronic hepatitis C who were admitted to the People's Hospital of Henan Province, Huashan Hospital of Shanghai and the Fifth Medical Center of the General Hospital of the People's Liberation Army of China between November 2017 to August 2018 were enlisted. All patients received OBV/PTV/RTV+DSV antiviral therapy. HCV RNA levels were measured at baseline, weeks 1, 2, 3, 4, 8, 12, and 24, then 12 weeks, and 24 weeks after completion of treatment; patients’ comorbidity, concomitant medications, and clinical adverse events were recorded.@*Results@#108 patients were enrolled in the study, with an average age of 49.1 years, 44 patients were male (40.8%), 96.3% (104/108) were newly diagnosed, and four patients had previous treatment history, of whom three were treated with IFN and one with IFN + DAA. Ninety-eight cases completed 12 weeks treatment and 89 cases were in follow up for 12 weeks, after discontinuation of the drug. Overall, 89 cases (100%) achieved SVR12.One patient treated with PR and DAA had HCV RNA level of 869175 IU/mL at 4 weeks of treatment, which was significantly higher than the baseline HCV RNA level (301776IU/ML), and was judged as failure of treatment; and follow-up was discontinued. Of all enrolled patients, 19 (17.6%) had underlying diseases and 15 (13.9%) had combined medications. During treatment, adverse events (AE) occurred in 11 patients (10.1%). The main adverse events were pruritus and elevated bilirubin.@*Conclusion@#Combined antiviral therapy (OBV/PTV/RTV+DSV) of 12 weeks are highly effective with good safety profile in the treatment of Chinese patients with genotype 1b chronic hepatitis C.
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Since 2014, the United States and Europe has approved all oral, interferon free- regimens that combine with direct-acting antiviral agents. Hence, the sustained virological response rate of patients with chronic HCV genotype 1 infection has improved over 90%, and the treatment modalities has introduced a new era. These drugs, ombitasvir and dasabuvir, received customary authorization of Food and Drug Administration in 2015 and are the first combined direct-acting antiviral agents for treating HCV genotype 1 infection. It has superior application prospects in China because of its high-sustained virological response rate and safety profile. This article reviews the pharmacokinetics, drug interactions, efficacy and safety of this therapeutic regimen.
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Chronic Hepatitis C is a global epidemic,and people with different sexes,ages,races,and nationalities are susceptible to hepatitis C virus (HCV) infection.This article elaborates on the management method and individualized treatment regimens for special populations,including children with hepatitis C,patients with renal injury,patients undergoing liver transplantation,patients with liver cirrhosis,patients with HIV infection,and patients with acute hepatitis C.
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Many factors can cause liver fibrosis and cirrhosis in clinical practice, and liver cirrhosis caused by liver vascular lesions often has insidious progression. Due to a lack of knowledge in clinicians and limited diagnostic and treatment techniques, patients often have poor prognosis. The liver vascular system has a unique structure, and patients with different locations and extents of lesion have different clinical manifestations and outcomes. Correct diagnosis and differentiation of liver cirrhosis caused by different types of liver vascular lesions is an important and difficult issue and needs careful attention in clinical practice. This article summarizes the association of portal vein lesion, hepatic vein lesion, hepatic sinusoid lesion, and hepatic artery lesion with liver cirrhosis. A deep understanding of the clinical manifestations, pathological features, and key points in differential diagnosis of these lesions helps with correct diagnosis and treatment of such disease.
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Objective To explore the efficacy and safety of daclatasvir (DCV ) combined with asunprevir (ASV) for chronic genotype 1b (GT1b) hepatitis C .Methods Twenty-nine GT1b hepatitis C patients who were treated with DCV combined ASV in Henan Provincial People′s Hospital from September 2017 to November 2017 were included .Hepatitis C virus (HCV ) RNA levels were tested before treatment ,1 week ,2 weeks ,3 weeks ,4 weeks ,8 weeks ,12 weeks and 24 weeks after treatment , and 12 weeks after the end of the treatment .The comorbidities ,combined use of drugs and adverse clinical events were registered .T test was used to compare the measurement data with normal distribution and M (P25,P75) was used for measurement data with non-normal distribution .Results A total of 29 patients with GT1b were included ,with 4 cirrhosis cases and 25 non cirrhotic cases .Seven patients had history of previous interferon and ribavirin combination treatment .There were 9 patients with comorbidity and 7 patients with combined medication . Finally , 25 patients completed a 24-week course of antiviral treatment ;3 patients were lost to follow-up ,and 1 patient withdrew after 16weeks of antiviral treatment because of a virus rebound .Of the 26 followed up patients ,25 achieved sustained virological response at 12-week (SVR12 ) , and one patient failed .And the HCV RNA NS5A resistance-associated variants (RAV) were detected in the patients with treatment failure .No severe adverse clinical events occurred in 26 patients .Conclusions DCV combined with ASV is effective and safe in the treatment of GT 1b chronic hepatitis C .However , the effect of RAV on therapeutic efficacy should be concerned during the treatment .
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Objective To analyze hepatitis C virus genotype(HCV GT)1b NS5A resistance-associated variants(RAV)and its related factors,and to provide references for direct-acting antivirals (DAA)agent selection and application.Methods From January 2017 to July 2017,53 hepatitis C patients were selected from the Department of Infectious Diseases of Henan Province People's Hospital. The mutations of L31M and Y93H in NS5A RAV were analyzed in 43 HCV GT1b patients,and their correlations with hepatitis C virus,liver function,platelet and liver fibrosis diagnostic model[APRI, gamma-glutamyl transpeptidase to platelet ratio(GPR),FIb-4]were analyzed.The quantitative data were compared by two independent samples t test,and the qualitative data were compared by chi square test. Results Fifty-three subjects were enrolled,including 43 GT1b(9 males and 34 females)and 10 GT2a(2 males and 8 females).No other genotype was detected.The incidence of NS5A RAV in 43 HCV GT1b patients was 13.9%(6/43),of which L31M and Y93H were 1/43(2.3%)and 5/43(11.6%)with no significant difference(χ2= 1.500,P= 0.219).There were no significant differences in HCV RNA, ALT,AST,albumin,platelets and age between patients with or without mutation(all P> 0.05). Conclusions The incidence of NS5A RAV in HCV GT1b patients is high,but not affected by virus, biochemical factors and liver fibrosis.The detection of NS5A RAV before HCV treatment is helpful for rational selection of DAA,which could reduce the drug resistance.
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Objective To explore the molecular mechanisms of hepatic stimulator substance (HSS) gene knockout in promoting the development and progression of nonalcoholic steatohepatitis (NASH).Methods NASH model mice (n=20) with HSS wild-type (HSS+/+) or HSS gene knockout (HSS-/-) were constructed using modified choline-deficient diet (CD-diet),untreated C57BL6-HSS-/-and C57BL6-HSS+/+ mice (n=20) were considered as control.Ten mice of each group were killed at month 1 and 2,respectively.The levels of triglyceride (TG) and total cholesterol (TC) in liver were measured using ELISA method.Histopathology and collagen deposition in liver tissue were observed using HE staining and Masson staining,respectively.Lipid content in liver tissue was observed and calculated using oil red O staining.The levels of mRNA and proteins of peroxisome proliferators activated receptor gama coactivator 1 alpha (PGC-1α),mitochondrial transcription factor A (TFAM),transcription factor-E2 related factor α (Nrf2),[-loop,dynamin-related protein 1 (Drp1),mitochondrial fission 1 protein (Fis1),mitofusins 1 (Mfn1),autophagy related gene 3 (Atg3) in liver tissue were detected using Real-time PCR and Western blot,respectively.Content of malonaldehyde (MDA),cyclooxygenase Ⅳ (COX Ⅳ) and adenosine tirphosphate (ATP) were measured using kits,and the activity of respiratory chain complex Ⅴ and cytochrome C oxidase in liver tissue were measured using spectrophotometry.the comparison between groups was done by t test.Results The levels of HSS mRNA and protein in mice-HSS-/-were 0.154± 0.04 and 0.08± 0.01,respectively,which were both significantly lower than those in mice-HSS+/+ (0.952 ± 0.08 and 1.362±-0.130,respectively),and t he differences had statistical significance (t =10.244 and 10.375,respectively,both P＜0.05).One month and 2 months after NASH modeled,TC contents in mice-HSS-/ were (248.6±21.5) μmol/g and (217.4±18.0) μmol/g,respectively,which were both remarkably higher than those in mice-HSS+/+ [(153.5 ± 11.2) μmol/g and (140.8 ±7.5) μmol/g,respectively],and the differences had statistical significance (t=15.270 and 10.524,respectively,both P＜0.05).The results form HE staining,oil red O staining and Masson staining indicated that fat deposition,collage deposition and inflammation in liver tissues of mice-HSS-/-were severer than those in mice-HSS+/+.One month after NASH modeled,protein levels of Drp1,Fis1,Mfn1 and Atg3 in liver tissues of mice-HSS-/ were all significantly decreased compared with those in mice-HSS+/+,and the differences had statistical significance (t=10.705,24.072,9.892 and 17.540,respectively,all P＜ 0.05).Two months after NASH modeled,protein levels of Drp1,Fis1,Mfn1and Atg3 in liver tissues of mice-HSS-/ were all significantly decreased compared with those in mice-HSS+/+,and the differences had statistical significance (t=125.378,15.926,34.330 and 13.437,respectively,all P＜0.05).One month after NASH modeled,mRNA levels of Drp1,Fis1,Mfn1 and Atg3 in liver tissues of mice-HSS-/-were all significantly decreased compared with those in mice-HSS+/+,the differences had statistical significance (t=36.337,40.825,33.508 and 28.104,respectively,all P＜0.05).Two months after NASH modeled,mRNA levels of Drp1,Fis1,Mfn1 and Atg3 in liver tissues of mice-HSS-/-were all significantly decreased compared with those in mice-HSS+/+,and the differences had statistical significance (t=35.210,42.375,27.753 and 20.560,respectively,all P＜0.05).The protein levels of PGC-1α,TFAM,Nrf2 and D-loop in liver of C57BL6-HSS-/-group were lower than those in liver of C57BL6-HSS+/+ group,and the differences had statistical significance (one month:t=20.548,31.036,19.445 and 10.974,respectively;two months:t=9.887,13.330,22.375 and 18.903,respectively,all P＜0.05).The mRNA levels of PGC-1α,TFAM,Nrf2 and D-loop in liver of C57BL6-HSS-/-group were all lower than those in C57BL6-HSS+/+ group,and the differences had statistical significance (one month:t=9.087,12.582,21.451 and 7.774,respectively;two months:t=23.758,17.924,9.924 and 15.209,respectively,all P＜0.05).One month and 2 months after NASH modeled,the levels of ATP mRNA in liver of C57BL6-HSS / group were both significantly lower than those in C57BL6-HSS+/+,and the differences had statistical significance 0=43.775 and 28.375,respectively,both P＜0.05);the levels of COXⅣ mRNA in liver of C57BL6-HSS / group were 0.142 ± 0.06 and 0.068± 0.001,respectively,which were both significantly lower than those in C57BL6-HSS+/+ group (0.255± 0.08 and 0.172 ±0.06,respectively),and the differences had statistical significance (t=28.337 and 19.782,respectively,both P＜0.05);the levels of MDA mRNA in liver of C57BL6-HSS-/-group were 0.973 ±0.112 and 1.253±0.054,respectively,which were both significantly lower than those in C57BL6-HSS+/+ group (0.366±0.02 and 0.872±0.05,respectively),and the differences had statistical significance (t=8.357 and 6.582,respectively,both P＜0.05).Conclusion Deletion of HSS accelerates NASH progression via inhibiting mitochondrial fusion,which leads to dysfunction of mitochondrial respiratory chain and inhibition of fatty acid oxidation.
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Hepatitis C and its complications are one of the highlights in liver disease prevention and control in China,and from the clinical practice 20 years ago to a cure rate of nearly 100％ at present,standardized diagnosis and treatment of hepatitis C,a large number of scientific studies,and drug research and development are the basis for the clearance of HCV.Direct-acting antiviral agents play an important role in the clearance of HCV,and the clearance of HCV does not equal to the cure of chronic hepatitis C.For patients with hepatitis C who have achieved a high sustained virologic response rate after using direct-acting antiviral agents,their long-term prognosis should be taken seriously.Correct and reasonable application of hepatitis C treatment is still a hot issue that needs to be discussed at present.
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Objective@#To investigate the influence of hepatitis B virus X gene (HBx) on apoptosis of hepatic cells mediated by Fas in HePG2 cells.@*Methods@#HBx eukaryotic vector pcDNA3.1(+)-X was transfected into HEPG2 cells with lipofectamine, and the null vector pcDNA3.1(+) and untransfected HEPG2 were used as normal controls. The cells were collected 72 h after transfection, and the expression of HBx mRNA and protein was determined using RT-PCR and Western blot, respectively. The mRNA expression of apoptosis-related genes Bcl-2 and Bax mRNA was also determined using RT-PCR. Cytotoxicity and apoptosis were evaluated using CCK-8 and flow cytometry, respectively, after HepG2-HBx and HepG2-3.1 cells were treated with stimulatory monoclonal antibody anti-Fas CH11. The t test was used for pairwise comparison.@*Results@#The cell line HepG2-HBx was successfully established, as confirmed by RT-PCR and Western blot, and RT-PCR results showed that HepG2-HBx cells had significantly higher expression of Bcl-2 mRNA than HepG2-3.1 and HepG2 cells (P < 0.05), but had significantly lower expression of Bax mRNA than HepG2-3.1 and HepG2 cells (P < 0.05); CCK-8 and flow cytometry showed that anti-Fas CH11 had a lower cytotoxicity to HepG2-HBx cells and allowed for a lower apoptosis rate of HepG2-HBx cells compared with HepG2-3.1 and HepG2 cells.@*Conclusions@#HBx can inhibit apoptosis of hepatic cells mediated by the Fas pathway.
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Objective To investigate the diagnostic value and biological features of protein induced by vitamin K absence or antagonist Ⅱ (PIVKA-Ⅱ) and alpha-fetoprotein (AFP) in hepatocellular carcinoma (HCC).Methods Serum samples of 72 patients with HCC (HCC group), 54 patients with hepatitis B cirrhosis (cirrhosis group) and 30 patients with chronic hepatitis B (CHB) without cirrhosis (CHB group) were tested with the PIVKA-Ⅱ and AFP detection kits.Diagnostic efficacies of PIVKA-Ⅱ and AFP were evaluated by receiver-operating characteristic curve (ROC).The cut-off value of PIVKA-Ⅱ for diagnose HCC was also determined.Sensitivities and specificities of PIVKA-Ⅱ and AFP were compared.Results The medians of PIVKA-Ⅱ levels in HCC group, cirrhosis group and CHB group were 14.36, 11.21, and 329.88 mAU/mL, respectively.The serum PIVKA-Ⅱ level in the HCC group was significantly higher than that in cirrhosis group (U=342.50, P0.05).The serum PIVKA-Ⅱ levels in patients with BCLC stage A, B, C in HCC group were 22.13, 345.46, and 13 057.72 mAU/mL, respectively.After comparison of stage A and C with stage B, the differences were both statistically significant (stage A to B: U=119.0, P<0.01;stage B to C: U=158.0, P<0.01).The sensitivity and specificity of PIVKA-Ⅱ with a cut-off value of 30.01 mAU/mL by means of Youden index were 0.750 and 1.000, respectively.When combined PIVKA-Ⅱ with AFP, the sensitivity and specificity were 0.800 and 0.964, respectively.The area under the curve (AUC) was highest (AUC=0.930, 95%CI: 0.852-0.974), and significantly higher than that using PIVKA-Ⅱ alone (AUC=0.892, 95%CI: 0.834-0.950,x2=21.43,P<0.01).Conclusions The diagnostic value of serum PIVKA-Ⅱ is superior to AFP.Combined with AFP, serum PIVKA-Ⅱ can improve the detection rate of HCC, and has advantages during the development of HCC and can be used to monitor the condition of HCC patients.
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ObjectiveTo investigate the clinical features and risk factors for patients with liver failure complicated by invasive pulmonary aspergillosis (IPA), and to provide a reference for clinical diagnosis and treatment. MethodsThe clinical data of 477 patients with liver failure who were diagnosed and treated in Henan Provincial People′s Hospital from January 2010 to December 2014 were collected, and the clinical features, laboratory markers, and results of imaging examinations of patients with IPA were retrospectively analyzed. Another 49 patients with liver failure who were hospitalized within the same period, had similar ages, and were not complicated by pulmonary infection were randomly selected as controls. The independent samples t-test was used for comparison of continuous data between groups, the chi-square test or Fisher′s exact test were used for comparison of categorical data between groups, and multivariate logistic regression analysis was performed to analyze the risk factors for liver failure complicated by IPA. ResultsAmong the 447 patients with liver failure, 43(96%) were complicated by IPA. Age (P=0.023), hepatic encephalopathy (P=0.021), long-term use of broad-spectrum antibiotics (P=0.007), use of hormone (P=0.016), and deep venous catheterization (P＜0.001) were independent risk factors for the development of IPA. Clinical manifestations of liver failure patients with IPA lacked specificity. Lung CT scan showed multiple nodules, masses, and wedge-shaped consolidation near the pleura in both lungs, but typical halo sign and air crescent sign were rarely seen. Among the 35 patients who received antifungal therapy, 30 were improved or cured, 3 died of digestive tract bleeding, 2 clied of plumonary infection, and all the other patients who did not receive therapy also died. ConclusionPatients with liver failure have various risk factors for the development of IPA, and the clinical manifestations are not typical, with high incidence and fatality rates. Early detection and treatment is the key to improving survival rates.
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Liver cirrhosis is a necessary stage of various types of liver diseases progressing into end-stage liver diseases. The changes in coagulation function are still a hot topic in research. The tendency to bleeding and thrombosis is a difficult issue in clinical diagnosis and treatment. This article reviews the mechanism of coagulation in liver cirrhosis, investigates the characteristics of bleeding and thrombosis, and points out that the evaluation of coagulation status in patients with liver cirrhosis is still a difficult issue in clinical diagnosis and treatment. An early evaluation of coagulation status in such patients may help to improve their long-term survival rate.