- Impact of hepatic function on serum procalcitonin for the diagnosis of bacterial infections in patients with chronic liver disease: A retrospective analysis of 324 cases. [JOURNAL ARTICLE]
- Medicine (Baltimore) 2016 Jul; 95(30):e4270.
Although procalcitonin (PCT) is a valid marker for early diagnosis of bacterial infections, it is unclear whether its accuracy in predicting bacterial infections is affected by impaired liver function. This study aimed to assess the impact of compromised liver function on the diagnostic value of PCT.This retrospective study was conducted between January 2013 and May 2015. A total of 324 patients with chronic liver disease were enrolled. Routine laboratory measurements and PCT were performed. Patients were divided into 3 groups according to clinical diagnosis: chronic hepatitis (group 1), decompensated cirrhosis (group 2), and acute-on-chronic liver failure/chronic liver failure (group 3). The correlation between PCT and liver function was analyzed. The area under the receiver operating characteristic (AUCROC) curve of PCT was analyzed according to infection status and liver function.PCT was more accurate than white blood cell count (P < 0.001) and percentage of neutrophils (P < 0.001) in detecting bacterial infections in patients with impaired liver function. In patients without infection, PCT had a moderate positive correlation with serum total bilirubin (TBIL) (r = 0.592), and a weak correlation with model for end-stage liver disease score (r = 0.483) and international normalized ratio (r = 0.389). The AUCROC and optimum thresholds of PCT and for predicting bacterial infections at different levels of TBIL were 0.907 (95% CI 0.828-0.958) and 0.38 ng/mL, respectively, for TBIL <5 mg/dL, 0.927 (95% CI 0.844-0.974) and 0.54 ng/mL (5 mg/dL ≤TBIL<10 mg/dL), 0.914 (95% CI 0.820-0.968) and 0.61 ng/mL (10 mg/dL ≤TBIL<20 mg/dL), 0.906 (95% CI 0.826-0.958) and 0.94 ng/mL (TBIL ≥20 mg/dL), respectively.This study demonstrated that PCT was a valuable marker of bacterial infection in patients with chronic liver diseases. TBIL affected PCT threshold, so different cut-offs should be used according to different TBIL values.
- Attenuation of Carbon Tetrachloride-Induced Hepatic Toxicity by a Dietary Supplement. [JOURNAL ARTICLE]
- J Diet Suppl 2016 Jul 29.:1-11.
Advanced liver disease (ALD) is often characterized with overt malnutrition and liver fibrosis. In this study, a dietary supplement (DS) was first developed, including branch chain amino acids, fat soluble vitamins, zinc, medium chain triglycerides, soy lecithin, L-carnitine, and n-3 polyunsaturated fatty acids. Benefits of DS were then tested using an ALD rat model treated with carbon tetrachloride (CCl4) for 6, 8, and 10 weeks, respectively. Our study showed that CCl4-induced drop of serum albumin and ratio of branch chain to aromatic amino acids were significantly prevented at all three time points. DS also mitigated CCl4-induced elevation of classical liver function markers (alanine aminotransferase, aspartate aminotransferase, and bilirubin) at certain time points, depending on specific liver function markers. Moreover, CCl4-induced liver fibrosis was strongly inhibited at all three time points in a transforming growth factor beta (TGF-β) independent manner. These findings indicated multi-faceted benefits of DS in this animal model, suggesting that it could be a useful adjunctive treatment of ALD in clinic.
- Antioxidant and Hepatoprotective Potentiality of Randia dumetorum Lam. Leaf and Bark via Inhibition of Oxidative Stress and Inflammatory Cytokines. [Journal Article]
- Front Pharmacol 2016.:205.
Randia dumetorum Lam. (RD) (Rubiaceae) is traditionally used by some tribes of Assam and Manipur of North East India for the treatment of liver ailments. In this context, to scientifically validate this indigenous traditional knowledge, we have evaluated the antioxidant and hepatoprotective activity of RD leaf and bark. The methanol extracts of RD leaf and bark were evaluated for in vitro antioxidant activity which exhibited good antioxidant activity in terms of reducing power assay, total antioxidant assay and DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging assay. Total phenolic and flavonoid content were found to be 112 ± 3.24 mg and 138 ± 2.46 mg gallic acid equivalents/g extract and 2.6 ± 0.26 mg and 3.34 ± 0.31 mg rutin equivalents/g extract respectively for RD leaf and bark methanol extracts. The in vivo hepato protective activity of the RD leaf and bark extract was evaluated against carbon tetrachloride (CCl4) induced hepatic damage in male wistar rats. CCl4 administration induced hepatic damage in rats resulted in increased levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, thiobarbituric acid reacting substances, albumin, bilirubin, TNF-α, IL-1β and decreased levels of total protein and antioxidant enzymes like superoxide dismutase, catalase, and glutathione reductase. RD leaf and bark methanol extracts pre-treatment exhibited protection against CCl4 induced hepatotoxicity by reversing all the abnormal parameters to significant levels. Histopathological results revealed that RD leaf and bark extracts at 400 mg/kg protects the liver from damage induced by CCl4. The results of this study scientifically validate the traditional use of RD leaf and bark for the treatment of liver ailments.
- Association of Serum Bilirubin with SYNTAX Score and Future Cardiovascular Events in Patients Undergoing Coronary Intervention. [Journal Article]
- Acta Cardiol Sin 2016 Jul; 32(4):412-9.
Bilirubin has emerged as an important endogenous antioxidant molecule, and increasing evidence shows that bilirubin may protect against atherosclerosis. The SYNTAX score has been developed to assess the severity and complexity of coronary artery disease. The aim of this study was to evaluate whether serum bilirubin levels are associated with SYNTAX scores and whether they could be used to predict future cardiovascular events in patients undergoing coronary intervention.Serum bilirubin levels and other blood parameters in patients with at least 12-h fasting states were determined. The primary endpoint was any composite cardiovascular event within 1 year, including death, nonfatal myocardial infarction, and target-vessel revascularization.In total, 250 consecutive patients with stable coronary artery disease (mean age 70 ± 13) who had received coronary intervention were enrolled. All study subjects were divided into two groups: group 1 was defined as high SYNTAX score (> 22), and group 2 was defined as low SYNTAX score (≤ 22). Total bilirubin levels were significantly lower in the high SYNTAX score group than in the low SYNTAX score group (0.51 ± 0.22 vs. 0.72 ± 0.29 mg/dl, p < 0.001). By multivariate analysis, serum total bilirubin levels were identified as an independent predictor for high SYNTAX score (adjusted odds ratio: 0.28, 95% confidence interval 0.04-0.42; p = 0.004). Use of the Kaplan-Meier analysis demonstrated a significant difference in 1-year cardiovascular events between high (> 0.8 mg/dl), medium (> 0.5, ≤ 0.8 mg/dl), and low (≤ 0.5 mg/dl) bilirubin levels (log-rank test p = 0.011).Serum bilirubin level is associated with SYNTAX score and predicts future cardiovascular events in patients undergoing coronary intervention.
- [Diagnostic criteria for HBV-related acute-on-chronic pre-liver failure]. [English Abstract, Journal Article]
- Zhonghua Gan Zang Bing Za Zhi 2016 May 20; 24(5):363-7.
To investigate the diagnostic criteria for HBV-related acute-on-chronic pre-liver failure (pre-ACLF) which can effectively predict the risk of liver failure.A total of 1279 patients with severe icteric chronic hepatitis B (CHB) and/or severe acute exacerbation of CHB were enrolled. The influence of serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil), international normalized ratio (INR) of prothrombin time, sex, and age on the incidence rate of acute-on-chronic liver failure (ACLF) was analyzed, the diagnostic criteria for pre-ACLF and predictive model for ACLF were developed. The chi-square test was used for comparison of categorical variables, and the independent samples t-test was used for continuous data; multivariate logistic regression analysis was performed to evaluate the risk of liver failure.The baseline serum levels of ALT, AST, and TBil, and INR were independent risk factors for liver failure (P < 0.05). The diagnostic criteria for pre-ACLF were as follows: (1) INR≥1.30; (2) AST≥10×upper limit of normal (ULN) and obvious jaundice (TBil≥51.3 μmol/L), or TBil≥342.0 μmol/L. These criteria had a positive predictive value of 45.9%, a negative predictive value of 89.8%, a sensitivity of 69.1%, and a specificity of 76.9%. The predictive model for the risk of ACLF was PY = 1=e(X)/(1+e(X)) (PY represented positive results of logistic regression analysis), X = -10.245+0.026×AST(ULN)-0.025×AST(ULN)+0.046×TBil(mg/dl) + 4.642×INR+0.049×age(years). The patients with higher PY values tended to have a higher incidence rate of ACLF. The incidence rate of ACLF was 75.3% in patients with PY≥0.60, more than 50% in patients with a PY value of 0.40-0.59, and 1.8% in patients with PY < 0.10 (P < 0.01).The diagnostic criteria for pre-ACLF and predictive model can effectively evaluate the risk of HBV-related ACLF.
- [Role and clinical significance of Th17/Treg balance in patients with severe exacerbation of hepatitis B]. [English Abstract, Journal Article]
- Zhonghua Gan Zang Bing Za Zhi 2016 May 20; 24(5):341-6.
To investigate the role of Th17/Treg balance in immune mechanism in severe exacerbation of hepatitis B.The clinical data of 41 patients with chronic hepatitis B were collected, and according to the conditions during hospitalization, these patients were divided into exacerbation group (19 patients) and improvement group (22 patients). On admission, at weeks 1 and 2 of treatment, and at the end of treatment, flow cytometry was used to measure the frequencies of Th17 and Treg cells in peripheral blood, and enzyme-linked immunosorbent assay was used to determine the serum levels of interleukin-17 (IL-17), interleukin-10 (IL-10), and transforming growth factor-β (TGF-β). The dynamic changes in the frequencies of Th17 and Treg cells were compared between the two groups, and the correlation between clinical indices for hepatitis and cytokines was analyzed. The t-test was used for comparison between groups, a one-way analysis of variance was used for comparison within one group across different time points, and Pearson correlation analysis was performed.With disease progression, the exacerbation group showed an increase in the frequency of Th17 cells and a relatively low frequency of Treg cells; compared with the improvement group, the exacerbation group had a higher frequency of Th17 cells and a lower frequency of Treg cells. Th17/Treg ratio gradually increased with exacerbation and decreased with improvement in conditions; in the exacerbation group and the improvement group, Th17/Treg ratio was positively correlated with total bilirubin and negatively correlated with prothrombin activity. In the exacerbation group and the improvement group, Th17 cells were positively correlated with IL-17, and Treg cells were positively correlated with IL-10 and TGF-β.Th17 and Treg cells play important roles in severe exacerbation of hepatitis B, and Th17/Treg ratio may be used as an immunobiological marker for the judgment of severity during severe exacerbation of hepatitis B.
- Leukapheresis in patients newly diagnosed with acute myeloid leukemia. [JOURNAL ARTICLE]
- Transfus Apher Sci 2016 Jul 14.
Hyperleukocytosis is present in 5 to 20 percent of patients with newly diagnosed acute myeloid leukemia (AML). The management of hyperleukocytosis, when symptoms of leukostasis occur, includes intensive supportive care and interventions for rapid cytoreduction. Leukapheresis is a rapid and effective means of cytoreduction and has been used in AML patients. In the current study, we evaluated the outcomes of 68 newly diagnosed AML patients that underwent leukapheresis and the effects of leukapheresis on various laboratory parameters. A total of 127 leukapheresis cycles were performed. The median number of leukapheresis cycles was 2 (range, 1-8). The overall survival for all patients was 4.2 months (95% CI 1.2-9.7 months). The median overall survival for patients who achieved complete remission after induction chemotherapy was significantly higher (19.1 months [95% CI 12.1-41.8 months]) than patients that did not achieve complete remission (0.46 months [95% CI 0.33-0.99 months]). Stepwise logistic regression demonstrated that elevated number of peripheral blasts, low platelet count and elevated bilirubin at AML diagnosis were predictive of death within a week. Leukapheresis was effective in reducing the peripheral blood leukocytes and leukemia blasts and was a safe procedure with regard to organ function, coagulation parameters, red blood cells and platelet count. The high initial response rates in newly diagnosed AML patients fit to receive intensive chemotherapy suggest that leukapheresis could be beneficial in reducing the complications associated with hyperleukocytosis until systemic intensive chemotherapy commences.
- [Prognostic analysis of acute-on-chronic liver failure after withdrawal of nucleos(t)ide analogues for antiviral treatment of chronic hepatitis B]. [English Abstract, Journal Article]
- Zhonghua Gan Zang Bing Za Zhi 2016 Apr; 24(4):252-7.
To investigate the prognostic factors for acute-on-chronic liver failure (ACLF) after the withdrawal of nucleos(t)ide analogues (NAs) for the antiviral treatment of chronic hepatitis B (CHB).The clinical data of 67 hospitalized patients with ACLF after withdrawal of NAs for the antiviral treatment of CHB were analyzed retrospectively.The HBeAg status before initial treatment and after recurrence, course of the antiviral treatment, duration from the withdrawal of NAs to recurrence, and type of NAs before and after withdrawal were not associated with the prognosis of ACLF. The Cox univariate regression analysis showed that serum bilirubin, international normalization ratio, serum creatinine, model of end-stage of liver disease (MELD) score, hepatic encephalopathy, and concurrent infection were associated with the 12-week death. The Cox multivariate regression analysis showed that MELD score and hepatic encephalopathy were independent predictors for 12-week death. The area under the receiver operating characteristic curve for the MELD score to predict 12-week death was 0.906, with an optimal cutoff value of 32, a sensitivity of 82.9%, a specificity of 88.5%, a positive predictive value of 91.9%, and a negative predictive value of 76.7%.MELD score and hepatic encephalopathy are closely associated with the prognosis of patients with ACLF after withdrawal of NAs for the antiviral treatment of CHB.
- Chrysin, a flavonoid attenuates histological changes of hyperammonemic rats: A dose dependent study. [JOURNAL ARTICLE]
- Biomed Pharmacother 2016 May 24.:345-354.
Chrysin (5,7-dihydroxyflavone) is a major component of some traditional medicinal herbs present in honey, propolis and many plant extracts. The study was aimed to illuminate the effect of chrysin in the pathogenesis of ammonium chloride (NH4Cl) induced hyperammonemic rat model in a dose dependent manner. Rats were injected with NH4Cl (100mg/kg b.w.) by intraperitonially (i.p) thrice a week for 8 consecutive weeks for the induction of experimental hyperammonemia. Hyperammonemic rats were treated with chrysin by orally at a dose of 25, 50 & 100mg/kg b.w. respectively. Protective effect of chrysin against hyperammonemia was evaluated by performing biochemical estimations and morphopathological investigations of hematoxylin and eosin stained sections of liver, brain and kidney tissues. Supplementation of chrysin reinstated the levels of blood ammonia, plasma urea, uric acid, total bilirubin, creatinine, brain glutamate, glutamine, nitric oxide (NO) and the activities of Na(+)/K(+)-ATPase, and liver marker enzymes. On the other hand increased level of plasma urea was observed in chrysin treated rats as compared with hyperammonemic rats. Chrysin administration caused distortion of hepatic, brain and kidney architecture as shown by histological examination. Chrysin at a dose (100mg/kg b.w.) showed an utmost decline in the level of all biochemical estimations. Both biochemical and morphological studies clearly revealed that chrysin protects against cell injury induced by ammonia intoxication in a dose-response manner with respect to endogenous antioxidants and hypoammonemic effects.
- Low-dose versus standard-dose ritonavir-boosted atazanavir in virologically suppressed Thai adults with HIV (LASA): a randomised, open-label, non-inferiority trial. [Journal Article]
- Lancet HIV 2016 Aug; 3(8):e343-50.
Thai patients with HIV have higher exposure to HIV protease inhibitors than do white people and dose reduction might be possible. We compared the efficacy of low-dose with standard-dose ritonavir-boosted atazanavir in virologically suppressed Thai patients with HIV.In this randomised, open-label, non-inferiority trial, we recruited patients aged 18 years or older who were receiving ritonavir-boosted protease-inhibitor-based antiretroviral therapy (ART) with HIV plasma viral loads of less than 50 copies per mL, an alanine aminotransferase concentration of less than 200 IU/L, and a creatinine clearance of at least 60 mL/min from 14 hospitals in Thailand. We excluded patients who had active AIDS-defining disease or opportunistic infections, had a history of an HIV viral load of 1000 copies per mL or more after 24 weeks of any ritonavir-boosted protease-inhibitor-based ART, used concomitant medications that could interact with the study drugs, were pregnant or lactating, had illnesses that might change the effect of the study drugs, or had a history of sensitivity to the study drugs. A biostatistician at the study coordinating centre randomly allocated patients (1:1) to switch the protease inhibitor for oral atazanavir 200 mg and ritonavir 100 mg or for atazanavir 300 mg and ritonavir 100 mg once daily, both with two nucleoside or nucleotide reverse transcriptase inhibitors at recommended doses. Randomisation was done with a minimisation schedule, stratified by recruiting centre, use of tenofovir, and use of indinavir as a component of the preswitch regimen. The primary endpoint was the proportion of patients with viral loads of less than 200 copies per mL at week 48, and we followed up patients every 12 weeks. Treatments were open label, the non-inferiority margin was -10%, and all patients who received at least one dose of study medication were analysed. This trial is registered with ClinicalTrials.gov, number NCT01159223.Between July 6, 2011, and Dec 23, 2013, we randomly assigned 559 patients: 279 to receive atazanavir 200 mg and ritonavir 100 mg (low dose) and 280 to atazanavir 300 mg and ritonavir 100 mg (standard dose). At week 48, 265 (97·1%) of 273 in the low-dose group and 267 (96·4%) of 277 in the standard-dose group had viral loads of less than 200 copies per mL (difference 0·68; 95% CI -2·29 to 3·65). Seven (3%) of 273 in the low-dose group and 21 (8%) of 277 in the standard-dose group discontinued their assigned treatment (p=0·01). 46 (17%) of 273 participants in the low-dose group and 97 (35%) of 277 in the standard-dose group had total bilirubin grade 3 or higher toxicity (≥3·12 mg/dL; p<0·0001).A switch to low-dose atazanavir should be recommended for Thai patients with well controlled HIV viraemia while on regimens based on boosted protease inhibitors.The National Health Security Office and Kirby Institute for Infection and Immunity in Society.