Prognostic Significance Of Liver Function Markers In Secondary Hemophagocytic Lymphohistiocytosis

Part oneThe prognosis role of AST/ALT Ratio in Patients with adult secondary haemophagocytic lymphohistiocytosisObjectiveSecondary haemophagocytic lymphohistiocytosis(s HLH)accompanied by liver involvement,can present with wide range of hepatic dysfunction ranging from mild elevation of transaminases to liver failure,characterized by hepatomegaly and increased liver enzymes,are usually associated with elevated mortality.However,the magnitude of these associations remains unknown.Our objective was to assess the associations of the aspartate transaminase/alanine transaminase(AST/ALT,De Ritis)ratio with overall survival among adult patients with s HLH.Material and methodsA retrospective analysis was performed on 257 patients aged 18–86 years with detailed clinical features,laboratory examination results at diagnosis of s HLH.Correlation analysis was used to calculate the degree of correlation between De Ritis ratio and clinical indicators.After fully adjusting for confounding factors,multivariate Cox regression analyses and restricted cubic splines were conducted to address the association between the De Ritis ratio and the risk of mortality.ResultsThe median De Ritis ratio for the entire study population was 1.34(IQR:0.84-2.29).After a median follow-up time of 60(range 17-227.5)days,205 deaths occurred.De Ritis ratio was divided into three groups according to the distribution range of the study population(T1:?1.0,T2:1.0-1.79,T3:>1.79).After fully adjusting for hepatomegaly,albumin,fibrinogen,EBV,ferritin,etiologies and treatment strategies,the adjusted hazard ratios(HRs)with corresponding confidence intervals(CIs)of mortality for the 2 st tertile and 3 st tertile were 1.2(0.8-1.7)and1.6(1.1-2.2),respectively(P<0.01 for trends).Restricted cubic spline confirmed a linear association between the log₂-transformed De Ritis ratio and the risk of mortality.Moreover,this trend persisted in subgroups with MHLH,hyperferrinaemia,s CD25?20,000 ng/L,patients without EBV infection and those received treatment.ConclusionThrough the survival analysis of s HLH patients,it was found that the De Ritis ratio had a good prognostic value for the patients'OS,and a high ratio of De Ritis suggested that the patients had a short OS and a poor prognosis.In future work,we need further multicenter to further verify the prognostic guiding value of De Ritis.Part twoPrognostic and predictive value of the pretreatment albumin-bilirubin score for short-and long-term survival in patients with non-Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis with hepatic injuriesObjectiveThis study aimed to assess the prognostic value of pretreatment albumin-bilirubin(ALBI)on short-term mortality(30 days)and overall survival(OS).The aim of this study was to construct a prognosis model of non-Hodgkin lymphoma-associated secondary hemophagocytic lymphohistiocytosis(NHL-s HLH)patients with hepatic injuries by the combination of ALBI score and serum ferritin parameters.Material and methodsThis retrospective study included 168 NHL-s HLH patients with hepatic injuries between February 1,2014,and February 1,2020.Multivariable logistic/Cox models and restricted cubic spline models were conducted to evaluate the relationships between the ALBI score and short-term and OS.The predictive performance of the ALBI score was assessed and compared using time-dependent receiver operating characteristic(ROC)analysis.ResultsAmong 168 adult NHL-s HLH patients,82(48.8%)patients died within 30 days after admission,and 144(85.7%)patients died during the follow-up period.Multivariate logistic regression indicated that ALBI grade could be an independent risk factor for predicting the prognosis of patients with 30-day mortality and overall survival(odds ratios [OR]30 days 5.37,95% confidence interval 2.41-12.64,P < 0.001;hazard ratios [HR]OS 1.52,95% confidence interval 1.06-2.18,P = 0.023),respectively.The restricted cubic spline curve displayed a linear and positive relationship between the ALBI score and risk of mortality(P for nonlinearity =0.503).Furthermore,receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC)for predicting mortality by integrative analysis of the ALBI score and ferritin was significantly improved compared to the ALBI score(AUC 30 days: 0.820 vs 0.693,P = 0.001;AUC1 year: 0.754 vs 0.681,P = 0.043)or ferritin(AUC30 days: 0.820 vs 0.724,P = 0.005;AUC1 year: 0.754 vs 0.658,P = 0.031)alone.ConclusionsIn conclusion,the ALBI score could be a useful indicator of 30-day mortality and overall survival for NHL-s HLH patients with hepatic injuries,and the combination analysis of the ALBI score and ferritin provides incremental prognostic value for clinical use.Part threeComparison of two nomogram models based on aspartate transaminase-to-alanine transaminase ratio and albumin-bilirubin for prediction survival in adults secondary hemophagocytic lymphohistiocytosisObjectiveRecent progress in adults secondary hemophagocytic lymphohistiocytosis(s HLH)patients with associated with high morbidity and mortality allows us to explore the clinical characteristics and develop a clinical model for predicting survival of patients.We sought to non-invasive availably serological-based biomarker in routine clinical practice,i.e.,the aspartate transaminase/alanine transaminase(AST/ALT,De Ritis)ratio and albumin-bilirubin(ALBI),to predict short-term survival and overall survival(OS),respectively,and compare to the value of two multi-parametric prognostic nomogram model(De Ritis nomogram and ALBI nomogram).Material and methodsWe retrospectively collected clinical and laboratory data from our hospital database of 173 patients with NHL-s HLH.Independent prognostic liver enzymes(De Ritis)and ALBI markers were identified according to multivariable Cox analysis and two multi-parametric prognostic nomogram prognostic models were developed incorporating the identified factors.The predictive accuracy of De Ritis nomogram and ALBI nomogram was assessed using a calibration plot,concordance index(C-index)and decision curve.Decision curve analysis and Time-dependent ROC(td ROC)compared the performance between models.The best cut-off value of nomogram score was determined by the survival receiver operating characteristic curve(ROC).Patients were divided into high-risk and low-risk based on the best cut-off value and the difference in survival between subgroups was analyzed using Kaplan-Meier survival analysis.ResultsA total of 173 NHL-s HLH patients were included for analysis.The median De Ritis ratio and ALBI score of 173 patients were-1.38(-1.78 to-0.97)and 1.52(0.96-2.39),respectively.Five independent prognostic factors were identified and entered into the De Ritis nomogram and four factors into the ALBI nomogram.The C-index of the De Ritis nomogram for OS is 0.72 and 0.73 of ALBI nomogram,respectively(P=0.871).These models calibration curves for probability of 30-,90-,and 365-day overall survival(OS)showed optimal agreement between nomogram prediction and actual observation.The td ROC curve and DCA show these models have good predictive accuracy and discriminatory power.Two nomogram predictive models are similar in terms of survival prediction performance.The total score of each NHL-s HLH patient was calculated based on nomogram,and patients were divided into high-risk and low-risk subgroups,respectively.Survival times were obviously shorter in patients with high-risk groups.ConclusionWe established two novel nomograms that all can provide similarly individual prediction of short-term survival and OS for NHL-s HLH patients.Further patients were collected for external verification.