| Section one The concentration of peripheral blood cortisol inhepatitis B virus-related acute-on-chronic liver failure patientsObjective：Hepatitis B virus (HBV)-related acute-on-chronic liver failure(ACLF) has been described as a life-threatening syndrome that is progressedin chronic liver disease and characterized by variant complications such asprogressive jaundice, hepatic encephalopathy, ascites and so on. Themechanisms of HBV-related ACLF remain extremely unclear and it is veryimportant to judge the prognosis of disease. In the present study, weinvestigated the profile of peripheral blood cortisol concentration in patientswith hepatitis B virus (HBV)-related acute-on-chronic liver failure and toexplore the relationship with the disease severity and it is evaluation on theprognosis of HBV-related ACLF patients, and provide theoretical basis fortreatment HBV-related ACLF patients with cortisol.Methods：45hepatitis B virus (HBV)-related ACLF patients (including15early-stage,15medium-stage and15end-stage patients),15severe chronichepatitis B patients were involved in our research. The patients were recruitedconsecutively at the Third Hospital of Hebei Medical University and The FifthHospital of Shijiazhuang from September2010to December2011. And thestudy protocol was approved by the Ethics Committee of the Third AffiliatedHospital of Hebei Medical University and written informed consent wasobtained by all participants. Serum biochemical parameters, coagulationfunction, HBV serological markers and HBV DNA load were determined.Peripheral blood cortisol concentration was tested using chemiluminesenceimmunoassay. The MELD score was calculated using the following formula: 3.78×[Ln TB(mg/dl)]+11.2×[Ln INR]+9.57×[Ln Scr(mg/dl)]+6.43×etiology (constant for etiology:0=if cholestatic or alcoholic,1=otherwise). Peripheral blood cortisol concentrations were compared indifferent groups using SPSS l8statistical software, and we also explored thecorrelations between cortisol concentration and laboratory markers assessedby Spearman correlation analysis and the prognosis of liver disease.Furthermore, finding the independent risk factors which influence theprognosis of HBV-related ACLF patients by using Logistic regressionanalysis.Results：1Decreased peripheral blood cortisol concentrations in patients withACLFPatients with HBV related-ACLF had a significantly lower concentrationof peripheral cortisol(11.78±5.54μg/dl)than severe CHB patients(vs.21.58±4.13μg/dl), and there was statistical significance (P<0.001). Moreover,early-stage ACLF patients had a significantly higher concentration ofperipheral cortisol (17.97±3.16μg/dl) than medium-stage ACLF patients (vs.11.01±2.94μg/dl) and end-stage ACLF patients (vs.6.66±2.60μg/dl)(P<0.001or P<0.05). Similarly, there is a significant difference inconcentration of peripheral cortisol between medium-stage ACLF patients andend-stage ACLF patients (P<0.001).2The correlation between peripheral blood cortisol concentrations andlaboratory markers and MELD scoreIn ACLF patients, the peripheral blood cortisol concentrations werepositively correlated with PTA (r=0.83, P<0.01), and were negativelycorrelated with TBIL (r=-0.34, P<0.05), MELD score (r=-0.60, P<0.001),AST/ALT (r=-0.35, P<0.05) and INR (r=-0.59, P<0.001). However, theconcentration of peripheral blood cortisol were no significantly correlated withthe serum ALT, AST, ALB and HBV DNA load.3The concentrations of peripheral blood cortisol in ACLF patients withdifferent MELD score groups HBV related ACLF patients were divided into three groups (less than30points group,30to40points group and more than40points group). less than30points group patients with HBV related-ACLF had a significantly higherconcentrations of peripheral blood cortisol (14.91±4.50μg/dl) than30to40points group patients (vs.11.38±5.62μg/dl) and more than40points grouppatients (vs.6.81±2.52μg/dl)(all P <0.01). Similarly, there is a significantdifference in concentrations of peripheral blood cortisol between30to40points group patients and more than40points group patients (P <0.01).4Dynamic changes of the concentrations of peripheral blood cortisol inACLF patients with different outcomesAccording to the prognosis at the30-days observation, the45HBV-related ACLF patients were divided into survival group and non-survivalgroup. The survival group had a initially higher concentration of peripheralblood cortisol compared with the non-survival group (16.58±4.40μg/dl vs.9.53±3.93μg/dl, P<0.01), and showed an increasing trend with meanconcentration of peripheral blood cortisol of (15.38±4.27μg/dl,15.74±4.91μg/dl,18.10±4.32μg/dl, and23.43±4.06μg/dl) on day7,14,21, and28,respectively. In contrast, the non-survival group exhibited a decreasing trendwith values of (8.72±2.94μg/dl,8.11±2.45μg/dl,6.55±1.80μg/dl, and5.30±1.06μg/dl) at above mentioned time points.5Results of the logistic regression analysisAccording to the prognosis of30-days observation, the45HBV-relatedACLF patients were divided into survival group and non-survival group.Furthermore, finding the independent risk factors which influence theprognosis of HBV-related ACLF patients by using Logistic regression analysis.The20included variables were: sex, age, family history, anti-virus treatment,HBeAg, HBV DNA, cortisol, white blood count (WBC), ALB, AST/ALT, TB,total cholesterol (TC), triglycerides (TG), serum sodium, serum potassium, Cr,PTA, MELD score, AFP, complications. Univariate analysis showed: thesignificant differences in cortisol, HBeAg, ALB, AST/ALT, TB, TC, Cr, PTA,MELD score and complications (P<0.05). Multiple Logistic regression analysis showed: MELD score, cortisol, albumin and total cholesterol were theindependent risk factors of prognosis of HBV-related ACLF patients. TheLogistic regression equation was: logitP=-21.378+2.213ALB+2.705MELD+2.3TC+1.979cortisol.Conclusions：1The peripheral blood cortisol concentration of HBV-related ACLFpatients exhibited decreased than severe CHB patients, and graduallydecreased as the disease progresses.2The peripheral blood cortisol concentration of HBV-related ACLFpatients have been associated with the severity of the liver damage and moresevere degrees of liver disease.3The baseline level of peripheral blood cortisol concentration and theirdynamic change trends during treatment may serve as markers for theshort-term prognosis of HBV-related ACLF.4Multiple Logistic regression analysis showed: MELD score, cortisol,albumin and total cholesterol were the independent risk factors of prognosis ofHBV-related ACLF patients. The Logistic regression equation was:logitP=-21.378+2.213ALB+2.705MELD+2.3TC+1.979cortisol. Section two Clinical efficacy and safety of glucocorticoids on treatmentof patients with severe viral hepatitis: A Meta-analysisObjective: To evaluate the clinical efficiency and safety ofglucocorticoids on treatment of patients with severe viral hepatitis.Methods: Search for literature in PubMed, EMCC, Springer, CNKI,CBM and so on, which published in Chinese and English, as well as thereferences in the relevant literature. We screened the retrieved studies according to the predefined inclusion and exclusion criteria. Use RevMan5.0statistical software for Meta-analysis. Then the statistic test, sensitivity andpublication bias about the data were measured by forest plot, funnel plot andfail-safe number.Results: Twenty-four trials (involving a total of1,525patients) wereenrolled in the study. The indicators of therapeutic efficacy: MortalityRR=0.39,95%CI (0.32,0.47), Z=9.75(P<0.00001); TB WMD=-88.03,95%CI (-112.80,-63.26), Z=6.97(P<0.00001); ALT WMD=-25.04,95%CI(-42.23,-7.84), Z=2.85(P<0.05); PTA WMD=21.56,95%CI (6.52,36.60),Z=2.81(P<0.05).Conclusion: The mortality of the severe viral hepatitis patients could bereduced by glucocorticoids treatment, which could reduce the levels of the TB,ALT, improve the levels of the PTA. |
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