Association of liver enzyme and long-term weight growth in adults.
Chinese Journal of Hepatology.2015;23(9):694-696. doi:10.3760/cma.j.issn.1007-3418.2015.09.012
Chinese Journal of Hepatology
2002 (v1, n1) to Present ISSN: 1671-8925
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Effects of fenofibrate on hepatocyte apoptosis in nonalcoholic fatty liver.
Chinese Journal of Hepatology.2015;23(9):688-693. doi:10.3760/cma.j.issn.1007-3418.2015.09.011
OBJECTIVETo use a rat model of nonalcoholic liver disease (NAFLD) to observe effects of the peroxisome proliferator-activated receptor-a (PPAR-a) agonist fenofibrate on hepatic steatosis in nonalcoholic fatty liver and to investigate the underlying mechanism.
METHODSSixty-six Sprague-Dawley rats were given adaptive feeding for 1 week and then randomly allocated into the following three groups: unmodeled control (group C,n =18), untreated NAFLD model (group M, n =24), and fenofibrate-treated NAFLD model (group F, n =24).Group C rats were given a normal diet, while group M and group F rats were given a high-fat diet. After model establishment, the group F rats were treated with fenofibrate (10 mg/kg/d, intraperitoneal) and the group C and group M rats were given sham-treatment with cosolvent (5 mL/kg/d, intraperitoneal). At the end of treatment weeks 4, 6 and 8, one-third of rats in each group were euthanized.Liver tissues were assessed by hematoxylin-eosin (HE) staining to determine level of steatosis and inflammaion activity, and by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling to measure changes in hepatocyte apoptosis index. Changes in expression levels of the PPAR-a receptor and apoptosis factors (bcl-2, bax and caspase-3) were assessed by reverse transcription-PCR and immunohistochemistry.
RESULTSThe NAFLD modeled rats showed appropriate induction of hepatic steatosis, hepatic inflammation, and hepatocyte apoptosis. Compared to the group M rats, the group F rats showed lower expression of PPAR-and bcl-2 and higher expression of bax and caspase-3 at both the mRNA and protein level.
CONCLUSIONFenofibrate can ameliorate hepatic steatosis in an experimental rat model of NAFLD, and the mechanism may be associated with inhibition of hepatocyte apoptosis.
Animals ; Apoptosis ; Caspase 3 ; metabolism ; Diet, High-Fat ; Fenofibrate ; pharmacology ; Hepatocytes ; drug effects ; Non-alcoholic Fatty Liver Disease ; pathology ; Peroxisome Proliferator-Activated Receptors ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein ; metabolism
Chinese Journal of Hepatology.2015;23(9):684-687. doi:10.3760/cma.j.issn.1007-3418.2015.09.010
OBJECTIVETo compare the acute kidney injury classification systems of RIFLE,AKIN,KDIGO and conventional criteria for determining prognosis of acute-on-chronic liver failure (ACLF) patients.
METHODSPatients with ACLF admitted to our hospital between July 2008 and March 2014 were enrolled in the study. The incidence, stages, and outcomes of acute kidney injury were determined according to the RIFLE, AKIN,KDIGO and conventional criteria.ROC curves were generated to compare the predictive ability for 30-day mortality of the four systems.Chi-square test and Fisher's exact test were used for statistical analyses, as well.
RESULTSAll four classification systems detected acute kidney injury among the patients in the study population (n =358), but the detection rates were not consistent (expressed as % of total): KDIGO criteria: 45.0%, AKIN: 38.8%, rIFLE: 35.5%, conventional criterion: 20.4%. The KDIGO and AKIN criteria showed higher sensitivity (72%), especially to early kidney injury, but the conventional criterion showed higher specificity (92%). The AUC for 30-day mortality was highest for the conventional criteria (0.75), followed by AKIN (0.72), rIFLE (0.70) and KDIGO (0.69) (all, P less than 0.05). In-hospital mortality increased with severity of AKI in a stepwise manner.
CONCLUSIONAmong the four common evaluation systems for acute kidney injury, the conventional criteria has the highest specificity for predicting short-term prognosis of patients with ACLF, while the AKIN and KDIGO criteria have the highest sensitivity for the presence of acute kidney injury, especially at the early stage.
Acute Kidney Injury ; classification ; diagnosis ; Acute-On-Chronic Liver Failure ; diagnosis ; Hospital Mortality ; Humans ; Incidence ; Prognosis ; ROC Curve ; Retrospective Studies ; Sensitivity and Specificity
Clinical characteristics of 4132 patients with alcoholic liver disease.
Chinese Journal of Hepatology.2015;23(9):680-683. doi:10.3760/cma.j.issn.1007-3418.2015.09.009
OBJECTIVETo study the clinical characteristics of patients with alcoholic liver disease (ALD).
METHODSThe records of the 302 Hospital of People's Liberation Army (Beijing, China) were searched to identify patients diagnosed with liver disease for retrospective analysis of ALD. Measurement data was summarized as mean +/- standard deviation and intergroup comparisons were made using ANOVA; count data was assessed using the chi-square test.
RESULTSAmong the total 4132 ALD cases, 97.68% were male and 2.32% were female; ages ranged from 18 to 95 years-old,with the average age being 48.11+/-10.58 years and the range of 40 to 60 years-old being the most frequently represented.Considering all patients with liver disease from 2003 to 2012,ALD cases increased over time (from 2.00% in 2003 to 5.05% in 2012). The overall ALD cases were represented by alcoholic cirrhosis (70.35%), alcoholic hepatitis (19.26%), alcoholic fatty liver (6.29%), and alcoholic liver failure (4.09%). Among the ALD patients between 40 and 60 years of age, 73.81% had cirrhosis,compared to 50.42% of ALD patients less than 40 years-old (P less than 0.001). Comparison of ALD cases in 5-year increments showed increasing trends in rates of alcoholic cirrhosis and alcoholic hepatic failure;moreover, there was an increasing annual trend in the percentage of alcoholic liver failure cases among the total cases of liver failure in our hospital.
CONCLUSIONFrom 2003 to 2012,our hospital admissions increased for patients with alcoholic liver disease, and the patients were primarily in the age range of 40-60 years-old. In general, incidences of alcoholic liver failure and cirrhosis increased in recent years, and cirrhosis has been common among the elderly patients with ALD.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Beijing ; Fatty Liver, Alcoholic ; epidemiology ; Female ; Hepatitis, Alcoholic ; epidemiology ; Humans ; Incidence ; Liver Cirrhosis ; epidemiology ; Liver Diseases, Alcoholic ; epidemiology ; Liver Failure ; epidemiology ; Male ; Middle Aged ; Retrospective Studies ; Young Adult
Chinese Journal of Hepatology.2015;23(9):675-679. doi:10.3760/cma.j.issn.1007-3418.2015.09.008
OBJECTIVETo explore the relationship between nonalcoholic fatty liver disease (NAFLD) and the incidence of type 2 diabetes mellitus (T2DM) in Chinese adults.
METHODSA total of 4847 Chinese adults were enrolled in this prospective study. All participants underwent physical examination at one of three hospitals in Nanjing during 2008. According to results from B ultrasound, the participants were grouped according to NAFLD diagnosis, with 1468 in the NAFLD group and 3379 in the control group.Participants were followed up until diagnosis of T2DM or for 4 years. The cumulative incidence rates of T2DM were calculated for and compared between the NAFLD group and the control group. The relationship between NAFLD and risk of T2DM was examined by Cox proportional hazards modeling.
RESULTSDuring the 4-year follow-up,387 (8.0%) of the patients were diagnosed with T2DM. The cumulative incidence rates of T2DM in the NAFLD group and the control group were 17.2% and 4.0%, respectively. After adjusting for age,sex,body mass index,blood pressure,triglyceride level and alanine aminotransferase level, NAFLD was found to be closely related to the incidence of T2DM (relative risk:3.465,95% confidence interval:2.755-4.358).
CONCLUSIONNAFLD is associated with elevated risk of T2DM in adult patients in Nanjing,China. The general population of this region may benefit from focused public health intervention and treatment strategies targeting to prevent development of T2DM in conjunction with NAFLD.
Adult ; Asian Continental Ancestry Group ; China ; epidemiology ; Diabetes Mellitus, Type 2 ; epidemiology ; Humans ; Incidence ; Non-alcoholic Fatty Liver Disease ; epidemiology ; Prospective Studies ; Risk Factors
Chinese Journal of Hepatology.2015;23(9):669-674. doi:10.3760/cma.j.issn.1007-3418.2015.09.007
OBJECTIVETo investigate the effect and molecular mechanism of cisplatin (DDP) combined with Matrine (Ma;plant alkaloid) against hepatocellular carcinoma using a nude mouse model with xenografted human tumors.
METHODSTwenty-four 6-week old male BALB/c nude mice were subcutaneously injected with HepG2 cells into the axilla, and randomly divided into four groups:control (NS) group,Ma treatment group,DDP treatment group and DDP+Ma combination treatment group. All treatments were delivered via intraperitoneal injection.Changes in whole body weights and tumor volume were assessed by before and after treatment measurements and plotting of growth curves. After 14 days of drug intervention, the mice were sacrificed for collection of tumor tissue and assessment of the tumor inhibition rates for each treatment. Affects on expression of survivin and caspase-3 were assessed by immunohistochemistry. ANOVA test and t-test were performed for the statistical analyses.
RESULTSThe tumor inhibition rates for the various treatments were:37.5%,Ma alone;75.0% DDP alone;83.3%,DDP+Ma group DDP combined. The DDP+Ma-induced inhibition was significantly greater than that achieved wit Ma or DDP alone (both P less than 0.05). The average weight of the DDP+Ma group (21.5 g) was lower than that of the NS group (28.5 g) and the Ma group (26.67 g),but higher than that of the DDP group (17.33 g).In addition, the DDP+Ma group also showed more robust general health,as indicated by activity,participation in life routines and appetite,than the DDP group. The rate of positive staining for survivin expression in tumor tissues was significantly lower in the DDP+Ma group (19.58%+/-4.52%) than in the NS group (83.26%+/-15.56%), the Ma group (62.50%+/-8.09%), and the DDP group (38.67%+/-8.26%) (all P less than 0.05).In contrast, the rate of positive staining for Bax expression was significantly higher in the DDP+Ma group (78.26%+/-6.09%) than in the NS group (21.15%+/-3.68%), the Ma group (35.13%+/-10.57%), and the DDP group (65.88%+/-4.81%) (all P less than 0.05).
CONCLUSIONTreatment with Ma alone or DDP alone is sufficient to inhibit the growth ofxenografted human hepatocellular carcinoma cells in nude mice. The DDP+Ma combination treatment,however,shows greater inhibitory effect,suggesting that Ma may enhance DDP's anticancer properties. The improved health status of mice treated with DDP+Ma suggests that Ma may reduce DDP toxicity. The mechanism underlying these beneficial treatment effects may involve modulation of survivin/caspase-3 expression and subsequent apoptosis.
Alkaloids ; pharmacology ; Animals ; Apoptosis ; Carcinoma, Hepatocellular ; drug therapy ; metabolism ; Caspase 3 ; metabolism ; Cisplatin ; pharmacology ; Hep G2 Cells ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Liver Neoplasms ; drug therapy ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Quinolizines ; pharmacology ; Tumor Burden
Chinese Journal of Hepatology.2015;23(9):663-668. doi:10.3760/cma.j.issn.1007-3418.2015.09.006
OBJECTIVETo investigate the mortality rates of hepatocellular carcinoma (HCC) in Nantong,China from 1999 to 2011, in order to uncover dynamic trends and provide reasoned advice on intervention strategies to decrease HCC incidence and mortality in Nantong in the future.
METHODSVersions 10 and 9 of the WHO International Classification of Diseases (ICD-10 and ICD-9) were used to determine the number of HCC deaths in Nantong,China for the study's range of years. Thex2 test was applied to compare the HCC mortality rates according to sex and age. The Grey system GM(1,1) model was used to predict the next-5-year HCC mortality for Nantong.
RESULTSAnalysis of the standardized mortality in Nantong showed a slight decreasing trend from 1999 to 2011 (x2=57 545.98, P less than 0.001),with males showing a steeper decrease than females. The total mortality of HCC during these years was 53.41 per 100,000 people,with mortality among males being significantly higher than that among females (80.81 per 100,000 people vs. 26.94 per 100,000 people; x2=13 625.42, P less than 0.001). In general, HCC mortality increased with increase in age (general trend:x2=57 545.98, P less than 0.001; male trend: x2=39 878.8, P less than 0.001; female trend: x2=20 105.3, P less than 0.001). However,HCC mortality increased significantly in women after the age of 40 and in men after the age of 35. The GM(1,1) equation was: Yt=-1265.28e(-0.0375t)+1315.5, which predicted that the HCC mortality will decrease to 25.56 per 100,000 people in 2016.
CONCLUSIONAlthough HCC mortality generally decreased from 1999 to 2011, the rate remained high. Public health intervention strategies may be more effective if they focus on males over the age of 35 and females over the age of 40.
Carcinoma, Hepatocellular ; mortality ; China ; epidemiology ; Female ; Humans ; Incidence ; Liver Neoplasms ; mortality ; Male
Chinese Journal of Hepatology.2015;23(9):658-662. doi:10.3760/cma.j.issn.1007-3418.2015.09.005
OBJECTIVETo investigate the mechanisms underlying the ability ofheparin-treated dendritic cells (DCs) to promote Th0 to Th1 differentiation in chronic hepatitis B (CHB).
METHODSPeripheral blood mononuclear cells (PBMCs) were isolated from CHB patients and cultured in RPMI-1640 with recombinant GM-CSF and IL-4 with or without heparin to obtain DCs for study. The levels of Toll-like receptors (TLRs) on the DCs were measured using FACS and qPCR techniques.DC subsets with high expression of TLRs were selected for analysis of functional changes by treatment with the corresponding TLR-siRNA. The CD4+ T cell subpopulation was purified from peripheral blood by Dynal immunomagnetic beads, and then the production of IL-12 by DCs in the presence of poly(I:C) or R848 and ofIFN and IL-4 by Th cells co-cultured with DCs was evaluated by ELISA. The t-test was used for statistical analysis.
RESULTSTLR3 expression, and not expression of TLR 7 or TLR8,was significantly increased in heparin-treated DCs as compared to levels detected in the DCs without heparin treatment (t =2.849,P less than 0.05;t =3.027,P less than 0.05). The level of IL-12 produced by heparin-treated DCs stimulated with poly(I:C) was obviously higher than that produced by DCs without heparin treatment and stimulated with poly(I: C) (t =8.68,P less than 0.01) or with R848 (t =19.01,P less than 0.01). However, the IL-12 production by TLR3-siRNA transfected-DCs was significantly reduced (t =31.49, P less than 0.01).When Th cells from allogenic patients with CHB were co-cultured with the TLR3-siRNA transfectedDCs, the frequency ofCD4+ IFN+ cells was significantly reduced (1.64+/-0.57% vs.6.31+/-0.88%,P less than 0.01),as was the capability of Thl to generate IFNg (t =20.83,Pless than 0.01).
CONCLUSIONHeparin may have up-regulated the TLR3 expression level of DCs, and sequentially promoted Th0 to Th1 differentiation.
CD4-Positive T-Lymphocytes ; cytology ; Cell Differentiation ; Coculture Techniques ; Dendritic Cells ; cytology ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Heparin ; pharmacology ; Hepatitis B, Chronic ; immunology ; Humans ; Interferon-gamma ; metabolism ; Interleukin-12 ; metabolism ; Interleukin-4 ; pharmacology ; Monocytes ; cytology ; Recombinant Proteins ; pharmacology ; Toll-Like Receptor 3 ; metabolism
Chinese Journal of Hepatology.2015;23(9):653-657. doi:10.3760/cma.j.issn.1007-3418.2015.09.004
OBJECTIVETo determine the prevalence of mutations in the non-structural protein 5B (NS5B) of the hepatitis C virus (HCV),which are associated with natural resistance to non-nucleoside and nucleoside polymerase inhibitors (PIs),in treatment-naive hepatitis C patients in south China.
METHODSA nested PCR protocol that amplified three different regions of NS5B was used to detect the naturally occurring drag-resistant substitutions.Direct PCR sequencing was performed to analyze the sequences.
RESULTSNS5B mutations known to confer resistance to nucleoside PIs,such as A15G,S96T and S282T,were mainly detected in HCV genotype 6a (20/88,22.73%).Of the NS5B mutations known to confer resistance to non-nucleoside PIs,C316N and S365A were detected in HCV genotype lb (60/60,100% and 2/60,3.33%, respectively) and I482L and V499A were mainly detected in HCV genotype 2a (9/9,100% and 4/4,100%, respectively) and HCV genotype 6a (9/9,100% and 4/4,100%, respectively).Other NS5B mutations found in the study population included A1 5S,S365F,S365P,S368A and S368L;although none of these has been previously shown to confer resistance to PIs.
CONCLUSIONNaturally occurring dominant PI resistance mutations in NS5B exist in treatment-na(i)ve hepatitis C patients in south China and may be related to the virus genotype.
Antiviral Agents ; pharmacology ; China ; Drug Resistance, Viral ; Genotype ; Hepacivirus ; drug effects ; genetics ; Hepatitis C ; drug therapy ; virology ; Humans ; Mutation ; Viral Nonstructural Proteins ; genetics
Chinese Journal of Hepatology.2015;23(9):647-652. doi:10.3760/cma.j.issn.1007-3418.2015.09.003
OBJECTIVETo investigate the efficacy and safety of antiviral treatment in patients with hepatitis C virus (HCV) infection and decompensated cirrhosis and determine the effects of virological response on long-term prognosis.
METHODSSixty-six consecutive,interferon (IFN)-na(i)ve patients with HCV infection and decompensated cirrhosis were enrolled in this prospective study. All patients were given a 48-to 72-week course of IFN plus ribavirin (RBV) combined therapy,with a low accelerating dosage regimen using either:pegylated (PEG)-IFNa-2b at 1.0-1.5 mug/kg/week,PEG-IFNa-2a at 90-180 mug,or standard IFN-a-2b at 3MU,every other day.RBV was given at 800 to 1000 mg/day. All patients were routinely monitored for adverse drug reactions and virological response.Effects of treatments on patient survival were assessed by Kaplan-Meier analysis.
RESULTSAt the end of treatment,74.2% of patients were HCV RNA-negative,with 45.5% having achieved sustained virological response and 28.8% having relapsed;the remaining 25.7% of patients showed non-virological response (NVR). Among the patients with HCV genotype 1, 65.9% achieved end-of-treatment virological response (ETVR) and 34.1% achieved SVR;among the patients with HCV genotype 2,90.9% achieved ETVR and 68.2% achieved SVR. The positive and negative predictive values of early virological response (EVR) for ETVR were 95.7% and 75.0% respectively, and for SVR were 65.2% and 100% respectively. Compared with baseline,patients who achieved ETVR had better liver function,as evidenced by changes in levels of total bilirubin,alanine aminotransferase and albumin,as well as prothrombin activity and Child-Pugh score (t =4.564,11.486,2.303,2.699,3.694 respectively, all P less than 0.05).Compared with the NVR patients, the ETVR patients had lower risk of hepatic decompensation and hepatocellular carcinoma, and had improved survival (x2=18.756,6.992,7.580, respectively, all P less than 0.05).Twelve (18.2%) patients experienced serious adverse events,with 10 requiring premature treatment withdrawal and 2 dying.
CONCLUSIONAntiviral treatment for patients with HCV infection and decompensated cirrhosis using interferon in a low accelerating dosage regimen in combination with ribavirin is feasible.Patients who achieved ETVR had significantly improved long-term prognosis.
Alanine Transaminase ; Antiviral Agents ; therapeutic use ; Carcinoma, Hepatocellular ; Drug Therapy, Combination ; Genotype ; Hepacivirus ; genetics ; Hepatitis C ; diagnosis ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Kaplan-Meier Estimate ; Liver Cirrhosis ; drug therapy ; virology ; Liver Neoplasms ; Polyethylene Glycols ; therapeutic use ; Prospective Studies ; Recombinant Proteins ; therapeutic use ; Ribavirin ; therapeutic use ; Treatment Outcome
Country
China
Publisher
Editorial Department of Journal of Clinical Hepatology
ElectronicLinks
https://zhgzbzz.yiigle.com/Editor-in-chief
zhgz@vip.163.com
Abbreviation
Chinese Journal of Hepatology
Vernacular Journal Title
中华肝脏病杂志
ISSN
1007-3418
EISSN
Year Approved
2008
Current Indexing Status
Currently Indexed
Start Year
1993
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