Su Lin

Interleukin-6 as an early diagnostic marker for bacterial sepsis in patients with liver cirrhosis

OBJECTIVE Liver cirrhosis is associated with frequent bacterial infections that increase the mortality rate. However, the early diagnosis and treatment of these infections are often difficult. In this retrospective-prospective observational study, the serum levels of interleukin-6 (IL-6) and procalcitonin (PCT) were measured in 233 cirrhotic patients to evaluate the early diagnostic and prognostic values of IL-6 and PCT for cirrhotic patients. METHODS Cirrhotic patients admitted to the Liver Research Center of the First Affiliated Hospital of Fujian Medical University between 1 October 2012 and 30 June 2014 were enrolled. They showed no evidence of infection on admission, and all had first onset of fever and met the systemic inflammatory response syndrome criteria 72 hours after admission. The serum IL-6 and PCT levels were determined on admission, at the onset of fever (0 hour) and 24 and 48 hours after fever onset. RESULTS A total of 233 cirrhotic patients, including 183 men and 50 women, with a median age of 56 (46-65) years were enrolled. A training group of 159 patients was retrospectively enrolled from 1 October 2012 to 31 December 2013, and a validation group of 74 patients was prospectively enrolled from 1 January 2014 to 30 June 2014. Among these patients, 134 were diagnosed with bacterial sepsis, 96 of whom were in the training group and 38 of whom were in the validation group; infections were ultimately ruled out in 99 patients: 63 training patients and 36 validation patients. At 0 hour, the IL-6 and PCT levels as well as the proportion of neutrophils were much higher in septic patients than in nonseptic ones. The IL-6 level and proportion of neutrophils peaked upon the onset of fever, 24 hours before the PCT levels and white blood cell count, and then sharply declined. The area under the receiver operating characteristic curve of IL-6 for diagnosing sepsis was largest at the onset of fever (area under the receiver operating characteristic curve, 0.983; 95% confidence interval, 0.967-0.999). The threshold of IL-6 for diagnosis was 135 pg/mL, with a sensitivity of 94.8% and a specificity of 93.7%. These diagnostic values were also confirmed in the validation group, with a sensitivity of 97.4% and specificity of 80.6%. Eleven (11.5%) patients died, and 85 (88.5%) patients recovered in the sepsis group of training patients after a 4-week follow-up. The IL-6 level was significantly higher in the nonsurvival group than that in the survival group (1813.00 vs 472.10 pg/mL, P = .004) at the onset of sepsis. The cutoff value for predicting prognosis was 1105 pg/mL, with a sensitivity of 81.8% and a specificity of 76.5%. CONCLUSIONS The serum IL-6 levels increased earlier than the PCT in septic cirrhotic patients. The direct measurement of the serum IL-6 level can help to rapidly detect bacterial infection, thus allowing for early therapeutic decisions and prognostic predictions.

Serum Ceruloplasmin Levels Correlate Negatively with Liver Fibrosis in Males with Chronic Hepatitis B: A New Noninvasive Model for Predicting Liver Fibrosis in HBV-Related Liver Disease

Aims This study aimed to investigate associations between ceruloplasmin (CP) levels, inflammation grade and fibrosis stages in patients with chronic hepatitis B (CHB) and to establish a noninvasive model to predict cirrhosis. Methods Liver biopsy samples and sera were collected from 198 CHB patients randomized into a training group (n=109) and a validation group (n=89). CP levels were determined using nephelometric immunoassays. Relationships between CP and liver inflammation and fibrosis were analyzed by Spearman rank correlation. Receiver operator characteristic (ROC) curves were used to evaluate the diagnostic value of CP for determining liver fibrosis in CHB. The liver pathology-predictive model was built using multivariate logistic regression analysis to identify relevant indicators. Results CP levels were lower in males than in females, lower in patients with inflammation stage G4 compared to other stages and lower in cirrhotic compared to non-cirrhotic patients. Using area under the curve (AUC) values, CP levels distinguished different stages of inflammation and fibrosis. Multivariate analysis showed that CP levels were all significantly associated with cirrhosis in males. A model was developed combining routine laboratory markers APPCI (alpha-fetoprotein [AFP], prothrombin time, and platelets [PLT] with CP) to predict fibrosis in CHB patients. The APPCI had a significantly greater AUC than FIB-4 (aspartate aminotransferase [AST]/ alanine aminotransferase [ALT]/PLT/age), APRI (AST/PLT ratio index), GPI (globin/PLT), and APGA (AST/PLT/gammaglutamyl transpeptidase [GGT]) models (all P-values<0.001). Conclusions CP levels correlate negatively and indirectly with inflammation and fibrosis stages in male CHB patients. The APPCI model uses routine laboratory variables with CP to accurately predict liver fibrosis in CHB.

A study of multiple biliary hamartomas based on 1697 liver biopsies.

Objective Multiple biliary hamartomas (MBHs) are rare benign malformations of the intrahepatic bile ducts. There are only a handful of clinical studies based on large populations on the incidence of MBHs. Materials and methods A series of 1697 consecutive liver needle biopsies was examined for the occurrence of MBHs. Results A total of six patients (0.35%, four men and two women, a 2 : 1 ratio) were confirmed by histology to have MBHs. Of the total of 1697 patients, 59 (3.5%) patients were younger than 18 years of age, 828 patients (48.8%) were between 18 and 38 years of age, and 810 patients (47.7%) were older than 38 years of age. Of the six MBHs patients, one was 17 years of age and the other five patients were older than 39 years of age. The median (range) age of the patients was 42 (17–63) years. Although nearly half (48.8%) of the biopsied patients were between 18 and 38 years of age, no MBH was found in this group. All MBHs patients were diagnosed with fibrosis/cirrhosis by initial ultrasound scanning; however, only two patients were confirmed to have cirrhosis by histological examination. Of those two patients with cirrhosis, one had concomitant congenital hepatic fibrosis and the other had concomitant cirrhotic hepatitis B. The latter patient developed hepatocellular carcinoma 1 year after biopsy. No kidney cysts were found in any of the six MBHs patients. MRI scanning was performed in four patients and the results were consistent with the histological diagnosis. Conclusion MBHs are not common in patients who undergo liver biopsy and, in this study, the occurrence was higher in the older age group.

A new model for predicting liver cirrhosis in chronic hepatitis B virus carriers with low serum alanine transaminase activity

OBJECTIVES To develop a cirrhosis-predicted model in chronic hepatitis B virus carriers with alanine transarninase (ALT) less than two times the upper limit of normal (ULN). METHODS Treatment-naive patients (n=278), who had undergone liver biopsies, were randomly divided into two groups - a training group and a validation group. Thirteen bio-clinical parameters were analyzed. A liver cirrhosis-predicting model (PPT model) was constructed using multivariate analysis. The diagnostic value of the model was analyzed by the receiving operating characteristics (ROC) method and compared with other available models. RESULTS A PPT model to predict liver cirrhosis was derived from three independent predictors of liver fibrosis [platelet count (PLT), prothrombin time (PT) and total bile acid (TBA)]. PPT model predicted cirrhosis with an area under the ROC (AUROC) curve of 0.83, a positive predictive value of 86.7% and a negative predictive value of 95.2%. Compared with APRI, FIB-4, age-AST model, AP index and APGA model, PPT model had the highest correlation coefficient (r=0.49) and greater predictive performance (AUROC of 0.83). CONCLUSIONS The PPT model was accurate in predicting cirrhosis and may reduce the need for liver biopsy in chronic hepatitis B virus carriers with ALT less than two times ULN.

Hemorrhagic Complications Following Abdominal Paracentesis in Acute on Chronic Liver Failure: A Propensity Score Analysis.

AbstarctPatients with acute on chronic liver failure (ACLF) usually present with severe coagulopathy. Abdominal paracentesis is often performed in these patients. The aim of this study was to analyze the prevalence of hemorrhagic events after paracentesis and the predictive factors of this condition in ACLF populations.ACLF patients who underwent paracentesis were retrospectively enrolled within a 5-year period. A propensity score (PS) matching analysis was used to select matched cases from the overall nonhemorrhagic group to be used as the control group. Hemorrhagic complications and risk factors were examined using logistic regression analysis.A total of 602 abdominal paracenteses were carried out on 218 ACLF patients and 18 (2.99%) hemorrhagic complications were identified. The MELD scores were higher in hemorrhagic patients than overall patients before PS matching (25.77±6.65 vs 21.04 ± 7.93, P = 0.013). We matched 18 cases with bleeding events to 72 unique cases without. The hemorrhagic group had significantly lower fibrinogen levels and higher PT levels than nonhemorrhagic cases. Logistic regression analysis revealed that lower fibrinogen levels could independently predict hemorrhagic complications (OR: 0.128, 95% CI: 0.023–0.697, P = 0.017). The best cut-off value for reliable measurement of fibrinogen levels was 0.70 g/L, with a sensitivity of 76.4% and a specificity of 80.0%. The area under curve was 0.733 (95% CI 0.604–0.862, P value 0.002).Severe hemorrhagic complications occur more commonly in ALCF patients than previously thought. A low fibrinogen level is an independent predictor of bleeding events in patients with MELD >25.

Serum interleukin-6 in the diagnosis of bacterial infection in cirrhotic patients: A meta-analysis

Background: The diagnostic accuracy of interleukin-6 (IL-6) in predicting bacterial infection in cirrhotic patients remains unclear. The aim of this meta-analysis is to explore the potential diagnostic value of IL-6 in cirrhotic patients. Methods: We systematically searched PubMed, Embase (via OvidSP), Web of Science, the Cochrane Library, and Scopus for studies published from inception to October 2015. Studies were enrolled if they included assessment of the accuracy of IL-6 in the diagnosis of bacterial infection in cirrhotic patients and provided sufficient data to construct a 2 × 2 contingency table. Results: Totally, 535 studies were searched in the initial database and finally 6 studies involving 741 patients were included for the final analysis. The pooled sensitivity, specificity and diagnostic odds ratio were 0.85 (95% confidence interval [CI], 0.64–0.94), 0.91 (95% CI, 0.80–0.96) and 52.89 (95% CI, 15.21–183.86), respectively. The pooled positive likelihood ratio was 8.99 (95% CI, 4.13–19.55) and the pooled negative likelihood ratio was 0.17 (95% CI, 0.07–0.43). The area under the receiver operating characteristic curve was 0.94 (95% CI, 0.92–0.96). Conclusion: This meta-analysis suggests IL-6 has a high diagnostic value for the differentiation of bacterial infection in patients with cirrhosis.

Letter: the liver to abdominal area ratio – a novel imaging score for prognostication in cirrhosis

low BMD were excluded. Mean age at diagnosis was 39.2 years, and 75.8% of patients were female. A significant proportion (75.2%) had an abnormal BMD at diagnosis, with osteoporosis present in 23.2% of patients and osteopaenia in 51.7%. A previous history of fracture prior to the diagnosis was present in 13.1% of patients. Half of the fractures (n = 10 patients) occurred in patients below the age of 50, with six of them occurring before 40 years of age. Patients with more advanced Marsh staging at diagnosis were more likely to have an abnormal BMD at both the hip and spine (chi-squared P = 0.023 at the hip and 0.001 at the spine). The reasons for this could include a greater degree of intestinal injury leading to a higher degree of malabsorption, or that this Marsh staging may also represent a more severe chronic inflammatory process, with resultant abnormal BMD. 6 BMI at diagnosis was an important determinant between normal densitometry at the hip (26.82 kg/m CI 1.18), osteopaenia (24.26 kg/m CI 0.99) and osteoporosis (22.99 kg/m CI 1.38) (one-way ANOVA P = 0.0004). One might argue that a lower BMI may be due to malabsorption. However, various chronic inflammatory conditions where malabsorption is not a feature are also associated with a lower BMI and weight loss. 6 It is important to note that more than 90% of total body vitamin D is obtained via sunlight exposure, not through intestinal absorption. Considering that none of our patients were house-bound and there is an average of 3121 h of sunlight per year, with an average of 8.5 h of sunlight per day, our patients should have had adequate sunlight exposure. Thus, our study confirms the role of chronic inflammation as a cause for an abnormal BMD in this group of patients. In view of the high prevalence of abnormal BMD at the time of diagnosis in patients with CD, as well as the occurrence of fractures in patients below the age of 50, our results support recommendations that all adult CD patients should have a DEXA bone scan either at diagnosis or within 1 year of diagnosis.

Prognostic nomogram for acute-on-chronic hepatitis B liver failure

Background & Aims To establish an effective prognostic nomogram for acute-on-chronic hepatitis B liver failure (ACHBLF). Materials and Methods The nomogram was based on clinical data of 203 ACHBLF patients who admitted to the First Affiliated Hospital of Fujian Medical University from 2009 to 2014. The area under the receiver-operating characteristic curve (AUC) and calibration curve were carried out to verify the predictive accuracy ability of the nomogram. The result was validated in internal and external validation cohorts. Kaplan-Meier survival curve was used in survival analysis. Results We developed a new prognostic nomogram to predict 3-month mortality based on risk factors selected by multivariate analysis. This nomogram consisted three independent factors: age, liver to abdominal area ratio (LAAR) and model for end-stage liver disease (MELD) score. The AUC of this nomogram for survival prediction was 0.877 (95% CI 0.831–0.923), which was higher than that of MELD score, MELD-Na and Child-Turcotte-Pugh (CTP). Good agreement of calibration plot for the probability of survival at 3-month was shown between the prediction by nomogram and actual observation. These results were supported by internal and external validation studies. Conclusions The ACHBLF nomogram could predict the short-term survival for ACHBLF patients.

Letter: is HIV infection an important factor for liver fibrosis?

SIRS, We read the article by Dr Lui et al. with interest. The authors compared liver stiffness and hepatic steatosis between HIV-infected patients and HIV-uninfected healthy controls, and then drew the conclusion that HIV-infected patients were at more risk for liver fibrosis and cirrhosis. HIV-related mechanisms and fatty liver disease might play important roles. In this case–control study, although the authors tried to match the age, gender and alcohol consumption status between two groups, interestingly, the HIV-infected group still had a significantly higher BMI and higher prevalence of metabolic syndrome, which have been proven to be associated with fatty liver disease and the prognosis of NASH. 3 According to the ‘burnt-out’ theory, patients with advanced NASH could have less hepatic fat deposition. In Dr Lee’s cohort, the significance of HIV infection in liver fibrosis could be an over-estimate, because it was hard to exclude the possibility of NAFLD-related fibrosis. If the authors had matched for metabolic syndrome between two groups, this result would be more convincing.

Efficacy and safety of autologous stem cell transplantation for decompensated liver cirrhosis: A retrospective cohort study

AIM To evaluate the long-term efficacy and safety of autologous stem cell transplantation (SCT) for decompensated liver cirrhosis. METHODS Consecutive patients with decompensated liver cirrhosis were included and assigned into the SCT group and non-transplantation (non-SCT) group according to whether they received SCT treatment. Patients were followed up for ten years. The long-term survival rate and incidence of hepatocellular carcinoma (HCC) were compared between groups. RESULTS A total of 159 patients were enrolled, including 27 cases in the SCT group and 132 cases in the non-SCT group. The baseline characteristics were significantly different between the two groups. Propensity score matching (PSM) was used to match SCT and non-SCT patients. After PSM, 92 subjects were enrolled in the final analysis, including 23 cases in the SCT group and 69 cases in the non-SCT group. The overall mortality was 73.9% and 55.1%, and the median survival period was 48 and 64 mo, respectively. However, no significant difference was found in the long-term survival rate between the two groups (P > 0.05). In addition, the incidence of HCC was higher in the SCT group than in the non-SCT group (47.8% vs 21.7%, P < 0.05). After adjusting for other covariates, SCT (OR = 3.065, 95%CI: 1.378-6.814) and age (OR = 1.061, 95%CI: 1.021-1.102) were independently correlated with the development of HCC in this decompensated liver cirrhosis cohort. CONCLUSION Autologous SCT may fail to improve the long-term efficacy and increase the incidence of HCC for decompensated liver cirrhosis. Close monitoring of HCC is strongly recommended in patients undergoing autologous SCT.