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Analyses Of Clinical Characteristics,Prognostic Factors And Brain-Derived Neurotrophic Factor Gene Polymorphisms In Cirrhosis

Posted on:2020-06-17Degree:DoctorType:Dissertation
Country:ChinaCandidate:H C ShuFull Text:PDF
GTID:1364330575499207Subject:Internal Medicine
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Background and objectives:Cirrhosis is the common outcome of various chronic liver diseases,with high morbidity and mortality.Hospitalized patients with liver cirrhosis generally progress to decompensation and have a poor prognosis.Exploring the clinical characteristics and prognostic factors of hospitalized patients with liver cirrhosis for guiding clinical practice is important way to improve the prognosis of patients.The present study provides a basis for improving patient prognosis and improving survival rate through clinical case analysis and prognosis analysis of large sample hospitalized patients with cirrhosis.At the same time,the serum brain-derived neurotrophic factor(BDNF)levels and BDNF gene polymorphisms in patients with liver cirrhosis were analyzed,which provided a genetic basis for the prevention and treatment of liver cirrhosis.Methods:1.Collecting cases of cirrhosis and its clinical data: The medical records of patients with liver cirrhosis who were hospitalized from January 2014 to January 2017 in the First Affiliated Hospital of Nanchang University were retrospectively collected,and the survival status of the patients was followed up.There were 1708 cases with complete data.Patients were included in the study.2.To analyze the clinical features of patients with cirrhosis: statistical analysis of the collected clinical data,including demographic data,etiology,main symptoms,laboratory tests,auxiliary examination,liver function grading,etc.,to analyze the clinical characteristics of patients with cirrhosis.3.To analyze the prognosis and related factors of patients with cirrhosis: statistical analysis of 1,3,and 5 years survival rate of patients with cirrhosis,and analyze the relationship between the above data and survival rate;single factor COX regression analysis of the data on the prognosis of patients with cirrhosis Impact;multivariate COX regression analysis of independent prognostic factors in the above prognostic factors;calculation of raw data derived indicators,including Child-Pugh score,MELD score and ALBI score,and their relationship with cirrhosis prognosis.4.Analysis of serum levels and genetic polymorphisms of BDNF: 182 patients with hepatitis B(HBV)-related cirrhosis(case group)and 186 healthy subjects(control group)were enrolled.Peripheral blood of the study subjects were collected,serum and blood cells were separated,and clinical data of the subjects were collected simultaneously.Serum BDNF levels were determined by enzyme-linked immunosorbent assay(ELISA).The genomic DNA of blood cells was extracted,and the genotypes of BDNF gene rs6265(A/G)and rs10835210 were detected by PCR-RFLP.The serum levels of BDNF and their genetic polymorphisms were correlated with liver function status and cirrhosis risk.Results1.Demographic characteristics and clinical features of patients with cirrhosis:In this group,there were significantly more males than females(73.5% vs.26.5%),and the average age of onset of males was lower than that of females(50.9 ±11.6 years vs.55.8±11.9 years).The proportion of hospitalization for upper gastrointestinal bleeding was the highest(52.5%),and the other from high to low were chest and ascites(23.8%),liver function abnormalities(9.9%),infection(4.1%),and gastrointestinal symptoms(3.1%),hepatic encephalopathy(2.0%).88.6% of patients with cirrhosis have intrahepatic nodules.The proportion of cirrhosis clinical stage 1-4 was 10.2%,9.9%,26.9% and 53.0%,respectively.Child-Pugh grades of liver function,A,B,and C grades accounted for 41.9%,45.7%,and 12.4%,respectively.2.the characteristics of cirrhosis etiology: a total of 1059 cases(62.0%)of patients with hepatitis B cirrhosis,including 792 males(74.8%)and 267 females(25.2%)(P < 0.001).There were 155 cases of alcoholic cirrhosis,accounting for 9.1%,including 150 males(96.4%)and 5 females(3.2%)(P<0.001).72 cases of cirrhosis caused by schistosomiasis,accounting for 4.2%.Hepatitis C cirrhosis in 25 cases(1.5%).There were 137 cases(8.0%)with mixed cirrhosis and 221 cases(12.9%)with cryptogenic cirrhosis.39 cases(2.3%)of cases of cirrhosis caused by other causes(cholestasis,autoimmune liver disease,etc.)3.Prognosis and related factors of cirrhosis: The survival time of patients with cirrhosis of this group was 0-72 months,and the average survival time was 34.4 ±18.1 months.Univariate analysis of the classification data showed that 13 risk factors including pleural and ascites,portal thrombosis,collateral circulation,infection,Child-Pugh classification,and MELD classification were associated with the prognosis of cirrhosis.Multivariate analysis showed that MELD score,portal vein thrombosis,collateral circulation,infection,PT,Fbg,and HBcAb positive were independent prognostic factors for cirrhosis.HBcAb positivity was a protective factor,and other factors were risk factors.4.serum BDNF levels and gene polymorphism analysis: serum BDNF levels in patients with hepatitis B cirrhosis were significantly lower than the normal control group(P <0.05).With the Child-pugh classification from A to C,serum BDNF levels gradually decreased(P < 0.05),and were associated with multiple liver function indicators.The GG,GA,AA genotypes and G and A allele frequencies of BDNF gene rs6265 polymorphisms were significantly different(P<0.01),and correlated with liver function grading and serum BDNF levels(P<0.05).The A allele(OR=1.652,95 CI 1.234-2.211)and the genotype GA(OR=1.939,95% CI 1.176-3.198,AA(OR=2.532,95% CI 1.431-4.480)are risk factors for cirrhosis.The genotype of BDNF gene rs10835210 polymorphism was not statistically different between cirrhosis and normal controls(P=0.129-0.944),and was not related to liver function grading and serum BDNF levels.The GC haplotype at the two sites was Protective factors for cirrhosis(OR=0.605,95% CI 0.452-0.810).Conclusions:1.Analysis of clinical cases of 1708 hospitalized patients with liver cirrhosis found that males are the main cause;hepatitis B is still the main cause of cirrhosis,and the proportion of alcoholic cirrhosis is also high.Many patients have mixed cirrhosis and cryptogenicity.Liver cirrhosis;the highest proportion of upper gastrointestinal bleeding in hospitalization,followed by chest and ascites,liver dysfunction,infection,etc.;clinical stage is mostly stage 3,4;liver function Child-Pugh classification is mostly grade A,B It may be related to more patients receiving endoscopic treatment.It is suggested that active treatment of hepatitis B,alcohol withdrawal,and prevention of variceal hemorrhage in male patients with liver disease is still of great significance in the prevention and treatment of liver cirrhosis.2.Analysis of prognostic factors in 1708 hospitalized patients with liver cirrhosis found that the survival time of patients with cirrhosis was 0-72 months,with an average of 34.4 months.There was no difference between men and women.Multivariate analysis showed that MELD score was high.Pulse thrombosis,collateral circulation,infection,PT prolongation,and elevated Fbg are independent risk factors for cirrhosis prognosis.HBcAb positivity is a protective factor.It is suggested that protection and improvement of liver function and reduction of complications are important for improving the prognosis of patients with cirrhosis.3.Through analysis of BDNF gene polymorphism and serum levels in cirrhosis and normal controls,serum BDNF levels decreased with liver function,and were associated with multiple liver function indicators;A allele of BDNF gene rs6265 locus The gene is a risk factor for cirrhosis,and the rs10835210 locus gene polymorphism is not associated with cirrhosis risk;the GC haplotype at two sites is a protective factor for cirrhosis.It suggests that there are genetic susceptibility factors in cirrhosis,and screening related susceptibility genes will help to prevent and treat cirrhosis.
Keywords/Search Tags:liver cirrhosis, clinical features, etiology, prognostic factors, brain-derived neurotrophic factor
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