High levels of serum interleukin-6 increase mortality of hepatitis B virus-associated acute-on-chronic liver failure

BACKGROUND Patients with hepatitis B virus-associated acute-on-chronic liver failure(HBVACLF)present a complex and poor prognosis.Systemic inflammation plays an important role in its pathogenesis,and interleukin-6(IL-6)as a pro-inflammatory cytokine is related with severe liver impairment and also plays a role in promoting liver regeneration.Whether serum IL-6 influences HBV-ACLF prognosis has not been studied.AIM To determine the impact of serum IL-6 on outcome of patients with HBV-ACLF.METHODS We performed a retrospective study of 412 HBV-ACLF patients.The findings were analyzed with regard to mortality and the serum IL-6 level at baseline,as well as dynamic changes of serum IL-6 within 4 wk.RESULTS The serum IL-6 level was associated with mortality.Within 4 wk,deceased patients had significantly higher levels of IL-6 at baseline than surviving patients[17.9(7.3-57.6)vs 10.4(4.7-22.3),P=0.011].Patients with high IL-6 levels(>11.8 pg/mL)had a higher mortality within 4 wk than those with low IL-6 levels(≤11.8 pg/mL)(24.2%vs 13.2%,P=0.004).The odds ratios calculated using univariate and multivariate logistic regression were 2.10(95%confidence interval[CI]:1.26-3.51,P=0.005)and 2.11(95%CI:1.15-3.90,P=0.017),respectively.The mortality between weeks 5 and 8 in patients with high IL-6 levels at 4 wk was 15.0%,which was significantly higher than the 6.6%mortality rate in patients with low IL-6 levels at 4 wk(hazard ratio=2.39,95%CI:1.05-5.41,P=0.037).The mortality was 5.0%in patients with high IL-6 levels at baseline and low IL-6 levels at 4 wk,7.5%in patients with low IL-6 levels both at baseline and at 4 wk,11.5%in patients with low IL-6 levels at baseline and high IL-6 levels at 4 wk,and 16.7%in patients with high IL-6 levels both at baseline and at 4 wk.The increasing trend of the mortality rate with the dynamic changes of IL-6 was significant(P for trend=0.023).CONCLUSION A high level of serum IL-6 is an independent risk factor for mortality in patients with HBV-ACLF.Furthermore,a sustained high level or dynamic elevated level of serum IL-6 indicates a higher mortality.

A New Prognostic Model Covering All Stages of Intrahepatic Cholangiocarcinoma

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is the second most common primary hepatic malignancy that causes a poor survival.We aimed to identify its prognostic factors and to develop a nomogram that will predict survival of ICC patients among all stages.Methods:A total of 442 patients with pathology-proven ICC registered at the Fifth Medical Center of PLA General Hospital between July 2007 and December 2019 were enrolled.Subjects were followed for survival status until June 30,2020.A prognostic model visualized as a nomogram was constructed in the training cohort using multivariate cox model,and was then validated in the validation cohort.Results:The median age was 55 years.With a median follow-up of 50.4 months,337 patients died.The median survival was 11.6 months,with 1-,3-and 5-year survival rates of 48.3%,22.7%and 16.2%,respectively.Factors associated with overall survival were multiple tumors,lymph node involvement,vascular invasion,distant metastasis,decreased albumin,elevated lactate dehydrogenase(LDH),decreased iron,elevated fi-brinogen,elevated CA125 and elevated CA19-9.A nomo-gram predicting survival of ICC patients at the time of di-agnosis achieved a Harrel’s c-statistic of 0.758,significantly higher than the 0.582 of the TNM stage alone.Predicted median survivals of those within the low,mid and high-risk subgroups were 35.6,12.1 and 6.2 months,respectively.Conclusions:A nomogram based on imaging data and serum biomarkers at diagnosis showed good ability to predict survival in patients with all stages of ICC.Further studies are needed to validate the prognostic capability of our new model.