Lower Total Bilirubin Research Articles

Levels of serum bilirubin in small cell lung cancer and non-small cell lung cancer patients

Elevated bilirubin has been associated with protection of cardiovascular and kidney systems, whereas decreased bilirubin may predispose respiratory diseases. However, whether serum bilirubin levels are associated with lung cancer remains unclear. Here, clinical and pathologic data of a cohort of 363 lung cancer patients along with 363 age-and gender-matched healthy subjects were collected. The association of serum bilirubin levels with lung cancer was analyzed. The levels of serum bilirubin were significantly lower in lung cancer patients. The aspartate transaminase and alkaline phosphatase levels were significantly higher in lung cancer. Multi-classification logistics regression analysis revealed low total bilirubin level [OR (95%CI), 1.12 (1.02-1.23)], aspartate transaminase [OR (95%CI), 1.12 (1.02-1.23)], and alanine transaminase [OR (95%CI), 1.12 (1.02-1.23)] were risk factors in lung cancer. Serum bilirubin levels were significantly changed among small cell lung cancer (SCLC), lung adenocarcinoma (LAC) and lung squamous cell carcinoma (LSC). Total bilirubin level, smoke history and heart disease were risk factors for subtypes. Compared with LSC, patients with smoke history had significant higher risk in LAC [OR (95% Confidence Interval, CI), 4.49 (1.70, 11.96)]. Compared with LSC, patients with smoke history [OR (95%CI), 4.49 (1.70, 11.96)] and heart disease [OR (95%CI), 4.49 (1.70, 11.96)] had significant higher risk in SCLC. Compared with SCLC, patients with low total bilirubin [OR (95%CI), 1.12 (1.02-1.23)] and heart disease [OR (95%CI), 3.52 (1.01-12.23)] had significant higher risk in LAC. Taken together, these results suggested low serum bilirubin levels are tightly associated with lung cancer, especially with LAC. Serum bilirubin levels might serve as a predictor for lung cancer patients clinically.

Low Bilirubin Levels Indicate a High Risk of Cerebral Deep White Matter Lesions in Apparently Healthy Subjects

Recent studies have reported that deep white matter lesions (DWMLs) on magnetic resonance imaging scans are related to the risk of developing impaired cognitive function in future. Bilirubin exhibits a potent antioxidant effect and an inverse relationship has been reported between bilirubin levels and the risk of several atherosclerotic diseases; however, there is limited evidence with regard to the effect of bilirubin levels on cerebrovascular diseases including DWMLs. This cross-sectional study included 1121 apparently healthy Japanese adults. The subjects were divided into three groups according to their bilirubin levels (low, <0.5 mg/dl; intermediate, ≥0.5 mg/dl and <1.0 mg/dl; and high, ≥1.0 mg/dl). The severity of DWMLs was evaluated according to Fazekas scale and their relation to bilirubin levels was examined. The association between bilirubin levels and the presence of severe DWMLs was assessed using multivariate logistic regression analysis. The analysis revealed that the low- and intermediate bilirubin groups indicated 2.36- and 1.33-fold increase in the prevalence of severe DWMLs compared with the high-bilirubin group, respectively (95% confidence interval (CI): 1.12–4.97 (the low-bilirubin group), 95% CI: 0.85–2.07 (the intermediate-bilirubin group). In conclusion, low total bilirubin levels could be associated with a high prevalence of severe DWMLs in apparent healthy subjects.

Impact of myosteatosis on skeletal muscle volume loss in patients with chronic liver disease.

Severe muscle volume loss is a recognized negative prognostic factor in patients with chronic liver disease. However, the effect of skeletal muscle fat deposition, referred to as myosteatosis on muscle volume loss remains unclear. The aim of this study was to investigate the relationships between myosteatosis and skeletal muscle volume loss. We enrolled 362 patients with chronic liver disease (186 men, 176 women; mean age 68.4±10.0years, 94 with cirrhosis) who underwent liver biopsy and computed tomography scanning between January 2013 and February 2017. A transverse computed tomography image of each scan at the third lumbar vertebra was used to evaluate skeletal muscle tissues. Prevalence of skeletal muscle volume loss and myosteatosis were 36% and 82%, respectively. Of those with skeletal muscle volume loss, 93% have concomitant myosteatosis. Univariate analysis revealed that higher age, female, lower body mass index (BMI), higher serum albumin, lower alanine aminotransferase (ALT), lower gamma-glutamyl transpeptidase, lower total bilirubin, lower α-fetoprotein, lower skeletal muscle attenuation, and liver steatosis were significantly associated with skeletal muscle volume loss. Multivariate logistic regression analysis confirmed that lower BMI (odds ratio [OR] 5.26, 95% confidence interval [CI], 3.21-8.54; P<0.001), presence of myosteatosis (OR, 2.82; 95% CI, 1.26-6.30; P<0.001), lower ALT (OR, 2.04; 95% CI, 1.18-3.52; P=0.010), and female (OR, 1.71; 95% CI, 1.04-2.28; P=0.034) were significant independent factors associated with skeletal volume loss. Myosteatosis, low BMI, low ALT, and female are associated with skeletal muscle volume loss in patients with chronic liver disease.

Serum bilirubin level predicts postoperative overall survival in oral squamous cell carcinoma.

Aberrant level of serum bilirubin, marker of hepatobiliary and hematological disorders, was associated with patient prognosis in several human malignancies. In this study, we aim to evaluate the predictive value of serum bilirubin for clinicopathologic characteristics and survival of patients with oral squamous cell carcinoma (OSCC). This study retrospectively reviewed 129 patients with OSCC and 129 normal controls matched for age and sex. The association between levels of preoperative direct bilirubin (DBIL), indirect bilirubin (IBIL), total bilirubin (TBIL), and clinical variables was analyzed. A proportional hazards regression model was used to find out the independent predictors of survival. Significantly lower TBIL (P = .009) and IBIL (P < .001) were found in OSCC patients compared with normal controls. DBIL (P = .011) and lymph-node metastasis (P = .031) were found to be independent prognostic factors. Patients with higher DBIL (≥4.0 μmol/L) had longer overall survival than those with lower DBIL (P = .002). Patients with both lymph-node metastasis and lower DBIL showed the shortest overall survival (P = .001). Lower DBIL was associated with a poorer prognosis and may be regarded as an independent prognostic marker for patients with OSCC.

Infectious mononucleosis and hepatic function.

Abnormal hepatic function is common in infectious mononucleosis (IM). However, it remains unknown why increased transferase levels are more common than bilirubin abnormalities in IM. The current study aimed to investigate these associations in the Chinese population. A total of 95 patients with IM (47 males and 48 females) were enrolled in the current study, as well as 95 healthy controls. Patients were sorted by sex. A receiver operating characteristic (ROC) curve was used to determine cut-off values for IM diagnosis and prediction. Crude and adjusted odds ratios (OR) for IM were analyzed using binary logistic regression. It was determined that alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (GGT) levels were significantly higher in patients with IM compared with controls; however, total bilirubin (TB) levels were significantly lower in patients with IM. ROCs demonstrated that, if ALT, AST and GGT concentrations were higher than, or if TB was lower than, cut-off values, they were predictive of IM. Binary logistic regression identified that the risk of IM in patients exhibiting high levels of transferases was significantly increased, particularly in males. Crude ORs in ALT quartile 4 were 21.667 and 10.111 for males and females, respectively and adjusted ORs were 38.054 and 9.882, respectively. A significant IM risk of IM was evident in patients with low bilirubin levels and females appeared to be particularly susceptible. For example, crude ORs in quartile 1 were 8.229 and 8.257 for males and females, respectively and adjusted ORs were 8.883 and 10.048, respectively. Therefore, the current study identified a positive association between transferase levels and IM and a negative association between TB and IM. Therefore, the results of the current study indicate that high transferases are suggestive of IM, particularly in males, whereas low TB is suggestive for IM, particularly in females.

Liver Cirrhosis and/or Hepatocellular Carcinoma Occurring Late After the Fontan Procedure - A Nationwide Survey in Japan.

Fontan-associated liver disease (FALD) is an important late complication involving liver dysfunction, such as liver cirrhosis (LC) and hepatocellular carcinoma (HCC), in patients undergoing the Fontan procedure. However, the prevalence, clinical manifestation, and methods of diagnosis of FALD are still not well established.Methods and Results:This study comprised 2 nationwide surveys in Japan. First, the prevalence of LC and/or HCC in patients undergoing the Fontan procedure was determined. Second, clinical manifestations in patients with LC and/or HCC were analyzed, along with data from blood tests, echocardiography, and right heart catheterization. In the 1st survey, of the 2,700 patients who underwent the Fontan procedure, 31 were diagnosed with LC and/or HCC (1.15%), and 5 died due to liver diseases (mortality: 0.19%). In the 2nd survey, data were collected from 17 patients (12 with LC, 2 with HCC, and 3 with LC+HCC. Of these 17 patients, 5 died (mortality: 29.4%). The mean age at diagnosis of LC and HCC was 23 and 31 years, respectively. Computed tomography followed by ultrasound was most frequently used for diagnosis. Blood tests revealed low platelet counts, increased hemoglobin, aspartate aminotransferase, γ-guanosine triphosphate, and total bilirubin levels, and an elevated international normalized ratio of prothrombin time. LC and/or HCC in patients undergoing the Fontan procedure were not rare late complications and were associated with high mortality rates.

Characteristics of Hepatocellular Carcinoma Aggressiveness Factors in Turkish Patients

A large cohort of hepatocellular carcinoma (HCC) patients from several collaborating Turkish institutions were examined for the tumor parameters of maximum diameter (MTD), portal vein thrombosis (PVT), and α-fetoprotein (AFP) levels. A relationship was found between MTD and blood platelet levels. Patients with large ≥5 cm tumors who had normal platelet levels had significantly larger tumors, higher percent of PVT, and significantly lower blood total bilirubin and liver cirrhosis than similar ≥5 cm tumor patients having thrombocytopenia. A comparison of patients with and without PVT showed significantly larger tumors, greater multifocality, blood AFP, and C-reactive protein levels, and, interestingly, lower HDL levels in the patients with PVT. Fifty-eight percent of the total cohort had AFP levels ≤100 IU/mL (and 42.1% had values ≤20 IU/mL). These patients had significantly smaller tumors, less tumor multifocality and percent PVT, lower total bilirubin, and less cirrhosis. There was considerable geographic heterogeneity within Turkey in the patterns of HCC presentation, with areas of higher and lower hepatitis B virus, hepatitis D virus, cirrhosis, and tumor aggressiveness parameters. Turkish patients thus have distinct patterns of presentation, but the biological relationships between MTD and both platelets and bilirubin levels are similar to the relationships that have been reported in other ethnic patient groups.

Interactive association of serum uric acid and total bilirubin with renal dysfunction among community-dwelling subjects.

Chronic kidney disease is a major public health concern. Serum uric acid (SUA) at high levels was oxidative stress agents, and total bilirubin (T-BiL) at mildly increased levels was potent antioxidants, but whether SUA and T-BiL produce an additive interaction for the risk of renal dysfunction remains unclear. The subjects comprised 567 men aged 71±8 (mean±standard deviation) years and 853 women aged 70±8years from a rural village. We examined the relationship between SUA and T-BiL, and renal function was evaluated by estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease Study Group equation. Stepwise multiple regression analysis using eGFR as an objective variable, adjusted for risk factors as explanatory variables, showed that SUA (β=-0.358, p<0.001) as well as age (β=-0.534, p<0.001), drinking status (β=0.119, p<0.001), and the presence of antihypertensive medication (β=-0.058, p=0.005) were significantly and independently associated with eGFR, but T-BiL was not associated with eGFR. While in the group with the highest tertile of SUA, T-BiL (β=0.081, p=0.032) was significantly and independently associated with eGFR, and in the group with the lowest to middle tertile of SUA, T-BiL was not associated with eGFR. In addition, interaction between SUA and T-BiL (F=8.512, p=0.004) as well as age, drinking status, the presence of antihypertensive medication, SUA, and T-BiL was a significant and independent determinant for eGFR. Our data demonstrated that low T-BiL could be important as a potential risk factor for renal dysfunction in those with high SUA.

Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT-0401 and REVERSE randomised clinical studies.

SummaryBackgroundThe goal of hepatorenal syndrome type 1 (HRS‐1) treatment is to improve renal function. Terlipressin, a synthetic vasopressin analogue, is a systemic vasoconstrictor used for the treatment of HRS‐1, where it is available.AimTo compare the efficacy of terlipressin plus albumin vs. placebo plus albumin in patients with HRS‐1.MethodsPooled patient‐level data from two large phase 3, randomised, placebo‐controlled studies were analysed for HRS reversal [serum creatinine (SCr) value ≤133 μmol/L], 90‐day survival, need for renal replacement therapy and predictors of HRS reversal. Patients received intravenous terlipressin 1–2 mg every 6 hours plus albumin or placebo plus albumin up to 14 days.ResultsThe pooled analysis comprised 308 patients (terlipressin: n = 153; placebo: n = 155). HRS reversal was significantly more frequent with terlipressin vs. placebo (27% vs. 14%; P = 0.004). Terlipressin was associated with a more significant improvement in renal function from baseline until end of treatment, with a mean between‐group difference in SCr concentration of −53.0 μmol/L (P < 0.0001). Lower SCr, lower mean arterial pressure and lower total bilirubin and absence of known precipitating factors for HRS were independent predictors of HRS reversal and longer survival in terlipressin‐treated patients.ConclusionsTerlipressin plus albumin resulted in a significantly higher rate of HRS reversal vs. albumin alone in patients with HRS‐1. Terlipressin treatment is associated with improved renal function. (ClinicalTrials.gov identifier: OT‐0401, NCT00089570; REVERSE, NCT01143246).

Differential impact of serum total bilirubin level on cerebral atherosclerosis and cerebral small vessel disease.

BackgroundA low serum total bilirubin (T-bil) level is associated with an increased risk of atherosclerosis. However, the differential impact of the serum T-bil level on cerebral atherosclerosis and cerebral small vessel disease (SVD) is still unclear.MethodsWe evaluated serum T-bil levels from 1,128 neurologically healthy subjects. Indices of cerebral atherosclerosis (extracranial arterial stenosis [ECAS] and intracranial arterial stenosis [ICAS]), and indices of SVD (silent lacunar infarct [SLI], and moderate-to-severe white matter hyperintensities [msWMH]) were evaluated by the use of brain magnetic resonance imaging (MRI) and MR angiography.ResultsIn logistic regression analysis after adjusting for confounding variables, subjects within middle T-bil (odds ratio [OR]: 0.63; 95% CI: 0.41–0.97) and high T-bil tertiles (OR: 0.54; 95% CI: 0.33–0.86) showed a lower prevalence of ECAS than those in a low T-bil tertile. Although subjects with a high T-bil tertile had a lower prevalence of ICAS than those with a low T-bil tertile, the statistical significance was marginal after adjusting for confounding variables. There were no significant differences in the proportions of subjects with SLI and msWMH across serum T-bil tertile groups.ConclusionsThe serum T-bil level is negatively associated with cerebral atherosclerosis, especially extracranial atherosclerosis, but not with SVD.

Predictive factors for bile leakage after hepatectomy for hepatic tumors: a retrospective multicenter study with 631 cases at Yokohama Clinical Oncology Group (YCOG).

International Study Group of Liver Surgery (ISGLS) proposed the standardized definition for bile leakage (BL) after hepatectomy (Hx) at 2011 to precisely perceive incidence and predictive factors of this critical condition. We conducted a multicenter retrospective study using the ISGLS definition of BL after Hx. Perioperative data regarding 631 patients undergoing elective Hx for hepatic tumors without biliary reconstruction performed between January 2009 and December 2011 were analyzed. BL was observed in 30 patients (4.8%). (Grade A, 8 (1.3%); B, 21(3.3%); C, 1 (0.2%)). Five independent predictors (diagnosis of liver metastases, prolonged operation, high risk procedures defined as Hx with broad exposure of the hilar Glissonean sheath, low platelet count and high serum total bilirubin on postoperative day 1) for grade B/C BL were elucidated by the multivariate analysis. When the study cohorts were divided into groups by number of accompanying these predictors, the more the accompanying independent predictors, the higher the incidence of BL. Notably, incidence of BL exceeded 40% in patients with four or more of these predictors. Risk stratification for BL after Hx can be achievable using independent predictors clarified in this study. However, proper management for high risk patients remains to be elucidated.

Effect of Vitamin K on Coagulopathy of Liver Disease: A Single Center Retrospective Review

▪Introduction: Liver disease is often marked by changes in hemostasis. Vitamin K is frequently administered to cirrhotic patients with an elevated INR to improve their coagulopathy, though strong evidence justifying this approach is lacking. Questions regarding the efficacy of vitamin K have been gathering based on an increased understanding of the rebalanced hemostasis of liver disease. This study evaluated the effect of vitamin K on the INR 24-72 hours after administration.Methods: This retrospective chart review used the VA Informatics and Computing Infrastructure (VINCI) database to identify 886 admissions for patients with liver disease who received vitamin K between January 1, 2001 and March 31, 2014. Patients were included if they had a coded diagnosis of cirrhosis, acute hepatitis, non-alcoholic steatohepatitis, hepatocellular carcinoma, or end stage liver disease. Charts for patients with one of those diagnoses who received vitamin K at the LSCDVAMC were included.All data was collected from the Computerized Patient Record System (CPRS). Medication route and dosing was determined from the pharmacy administration record. Patients were excluded if they received heparin, LMWH, FFP, or if they did not have an INR value before the administration of vitamin K or 24-72 hours after the dose was given.Results: A total 886 individual admissions were identified, 333 admissions met inclusion criteria for analysis. The mean INR on admission for the included encounters was 1.88 (95% CI 1.798 - 1.955) the lowest INR was 0.86 and the highest was 5.99. In the 333 admissions analyzed the mean decrease in the INR was 0.08 (95% CI 0.028 - 0.132). 180 encounters had a repeat INR during the hospitalization. The mean decrease in INR from admission to the second post-vitamin K INR was 0.123 (95% CI 0.058 - 0.187). Of the 333 included patient encounters 37 had a change in INR (increase or decrease) >0.4, of which in 11 the INR increased and in 24 the INR decreased (mean change in INR 0.313; 95% CI -0.139 to 0.765). The average INR of those 37 encounters was 2.83 (95% CI 2.497 - 3.171). There was no significant difference in albumin in encounters when the INR increased vs. decreased in response to vitamin K. There was a trend towards higher total bilirubin (TBILI) when the INR did not decrease in response to vitamin K. Mean TBILI was 5.9 in INR responders (95% CI 5.011 - 6.789) and was 6.66 (95% CI 5.219 - 8.101) in the encounters where the INR increased despite vitamin K.Conclusion: Vitamin K administration to improve the coagulopathy of patients with liver disease is common and often administered in response to an elevated INR. This is the largest retrospective review to date evaluating the effect of vitamin K on the INR of patients with liver disease. While a statistically significant decrease in INR of 0.08 was found, it is unclear if such a difference from vitamin K would be clinically significant. Moreover, only a very small portion of the patients included in this study (24/333) had an INR decrease of greater than 0.4. A limitation of our study is that patient centered outcomes, such as bleeding events, were not assessed. Future research should evaluate if there is a role for vitamin K in liver disease patients with a significantly elevated INR and low total bilirubin. DisclosuresNo relevant conflicts of interest to declare.

Interactive effect of serum uric acid and total bilirubin for cardiovascular disease in Chinese patients with type 2 diabetes.

Serum uric acid (SUA) at high levels and bilirubin at low levels were potent antioxidant but it was uncertain that whether SUA and total bilirubin (TBIL) had additive interaction for the risk of CVD in type 2 diabetes mellitus (T2DM). We conducted a cross-sectional survey of 6713 inpatients with T2DM and admitted to 81 tertiary care hospitals. CVD was defined as having either prior coronary heart disease or stroke or peripheral arterial disease. Binary logistic regression was used to estimate odds ratios of SUA and TBIL for CVD. The effect size of additive interaction was estimated by three measures, i.e., relative excess risk due to interaction, attributable proportion due to interaction and synergy index. Among 6713 patients with T2DM, 561 (8.36%) suffered from CVD. Using ≥283 umol/L (median) to define high SUA and <11.5 umol/L (n = 2290 or 34.11%) to define low TBIL, copresence of both factors (n = 621 or 9.25%) was associated with 5.18-fold (95% CI, 4.00–6.72) risk of CVD with significant additive interactions in multivariable analysis as compared to absence of both risk factors. The copresence of both high SUA and low TBIL was associated with a large increased risk of CVD in high-risk Chinese patients with type 2 diabetes.

Effectiveness of Ledipasvir-Sofosbuvir Combination in Patients With Hepatitis C Virus Infection and Factors Associated With Sustained Virologic Response

The combination of ledipasvir and sofosbuvir has been approved for treatment of genotype 1 hepatitis C virus (HCV) infection, including an 8-week regimen for treatment-naïve patients without cirrhosis and a baseline level of HCV RNA <6 million IU/mL. We analyzed data from a multicenter, prospective, observational study to determine real-world sustained virologic responses 12 weeks after treatment (SVR12) with regimens containing ledipasvir and sofosbuvir and identify factors associated with treatment failure. We collected data from 2099 participants in the HCV-TARGET study with complete virologic data (per-protocol population). We analyzed data from 1788 patients receiving ledipasvir-sofosbuvir (282 for 8 weeks, 910 for 12 weeks, 510 for 24 weeks, and 86 for a different duration) and 311 receiving ledipasvir-sofosbuvir plus ribavirin (212 for 12 weeks and 81 for 24 weeks, 18 for other duration) to estimate SVR12 (with 95% confidence interval [CI]), and logistic regression methods to identify factors that predicted an SVR12. The overall study population was 25% black, 66% with HCV genotype 1A infection, 41% with cirrhosis, 50% treatment-experienced, and 30% receiving proton pump inhibitors at start of treatment. In the per-protocol population, SVR12s were achieved by 96% of patients receiving ledipasvir-sofosbuvir for 8 weeks (95% CI, 93%-98%), 97% receiving the drugs for 12 weeks (95% CI, 96%-98%), and 95% receiving the drugs for 24 weeks (95% CI, 93%-97%). Among patients also receiving ribavirin, SVR12 was achieved by 97% of the patients receiving the drugs for 12 weeks (95% CI, 94%-99%) and 95% receiving the drugs for 24 weeks (95% CI, 88%-99%). Of the 586 patients who qualified for 8 weeks of treatment, only 255 (44%) received the drugs for 8 weeks. The rate of SVR12 among those who qualified for and received 8 weeks of therapy was similar in those who qualified for 8 weeks but received 12weeks therapy (96%; 95% CI, 92%-99% vs 98%; 95% CI,95%-99%). Factors that predicted SVR12 were higher albumin (≥3.5 g/dL), lower total bilirubin (≤1.2 g/dL), absence of cirrhosis, and absence of proton pump inhibitor use. Regimens containing ledipasvir and sofosbuvir are highly effective for a broad spectrum of patients with HCV genotype 1 infection treated in different clinical practice settings. Expanded use of 8-week treatment regimens for eligible patients is supported by these real-world results. Modification of proton pump inhibitor use may increase rates of SVR. ClinicalTrials.gov no. NCT01474811.

Clinical factors that affect the outcomes after anatomical versus non-anatomical resection for hepatocellular carcinoma.

For hepatocellular carcinoma (HCC), the superiority of anatomical resection (AR) over non-anatomical resection (NR) is still controversial. In this study, we assessed the potential benefits of AR for HCC. We enrolled 173 consecutive patients with HCC who underwent hepatectomy in our hospital from August 2003 to May 2013 and compared the outcomes for the AR group (n=125) with those for the NR group (n=48). The median observational period was 790days. The 1- and 2-year overall survival (OS) rates were 92.1 and 85.8%, respectively; the 1- and 2-year disease-free survival (DFS) rates were 78.2 and 63.0%, respectively. The AR and NR groups did not significantly differ in the OS or DFS. However, the 2-year DFS was significantly better for the AR group than the NR group among HCV patients (68.2 vs. 32.2%; P=0.004) and patients with alpha-fetoprotein (AFP) within the normal range (<20ng/ml; 76.7 vs. 60.9%; P=0.031), total bilirubin <0.8mg/dl (70.8 vs. 47.0%; P=0.034), and tumors 2-5cm in diameter (82.0 vs. 62.5%; P=0.025). If a patient is HCV-negative, has low AFP, low total bilirubin, or a tumor diameter of 2-5cm, AR is recommended.

Relationship Between the Serum Total Bilirubin and Inflammation in Patients With Psoriasis Vulgaris.

Psoriasis is a chronic and recurrent inflammatory skin disease. Previous studies have shown that bilirubin has anti-inflammation and antioxidant effects. However, the various roles of bilirubin in psoriasis patients are still unclear. To investigate the serum total bilirubin (TB) level in the individuals with psoriasis vulgaris and further evaluate the relationship between serum TB concentration and C-reactive protein (CRP) to clarify the effect of bilirubin on inflammation. A total of 214 patients with psoriasis vulgaris and 165 age- and gender-matched healthy control subjects were recruited. The peripheral leukocyte count (white blood cell, WBC) and differential, serum biochemical and immunologic indexes including serum TB, immunoglobulin (Ig) G, IgA, IgM, complement C3 and C4 , as well as serum CRP concentrations were measured. Results showed that the serum TB level decreased significantly and peripheral WBC, neutrophil, and serum CRP concentrations increased significantly in patients with psoriasis vulgaris. Meanwhile, the serum CRP was negatively correlated with serum TB levels but positively correlated with peripheral WBC and the Psoriasis Area and Severity Index (PASI). Logistic regression analysis showed that the serum TB was a protective factor for psoriasis vulgaris. The present study suggests that lower serum TB is associated with the enhancement of the inflammatory response in psoriasis vulgaris. Therefore, lower serum TB has a prognostic significance for worsening psoriasis vulgaris. Bilirubin may play a crucial role in inflammation by contributing to the inhibition of the inflammatory response.

(406) - Microarray Analysis of Endobronchial Lung Transplant Biopsies: Detection of T-cell Mediated Inflammation in a Safer Biopsy

s S155 Takayama,1 Y. Naka.1 1Surgery, Columbia University Medical Center, New York, NY; 2Biostatistics, Columbia University Medical Center, New York, NY; 3Medicine, Columbia University Medical Center, New York, NY. Purpose: Implantable left ventricular assist devices (iVAD) have been widely used for patients with end-stage heart failure as a bridge to heart transplantation (HTx). There is an increasing population of patients who require bridging with a temporary ventricular assist device (tVAD), either with or without an iVAD. Outcome of these patients after HTx is unknown. Methods: Between January 2007 and April 2015 there were 430 patients cared for at this institution who underwent OHT. Patients were further grouped by the algorithm of support device prior to their HTX as no bridge (Group A, n= 248), single bridge with tVAD (Group B, n= 17), single bridge with iVAD (Group C, n= 148) and multiple bridges with tVAD and iVAD (Group D, n= 17). Primary outcome was survival after HTX. Results: Patients in group B were more likely to be younger compared to the others (A:52±13, B:46±16, C:54±13, D:54±11, years, respectively, p= 0.059) and have lower body mass index (A:25.4±5.0, B:23.6±4.6, C:27.0±4.7, D:25.6±6.3, kg/m2, respectively, p= 0.008). Patients bridged with iVAD (bridge groups C and D) had lower total bilirubin at the time of HTX (A:1.2±1.0, B:1.1±0.8, C:0.9±0.8, D:0.8±0.3, p= 0.078). In-hospital mortality rate after HTx was not significantly different between groups (A: 8.5%, B: 11.8%, C:11.7%, D:11.7%, p= 0.660). The 1-year survival for group D was comparable to groups A and C, while 1-year survival for group B is significantly lower than any other groups (90.2%, 70.6%, 88.3% and 87.8%, respectively, p= 0.018). Conclusion: Post HTx survival in patients requiring multiple bridges was similar to those in non-bridge or single bridge with iVAD patients.

(405) - Outcome of Patients Having Multiple Mechanical Circulatory Support Devices before Orthotopic Heart Transplantation

s S155 Takayama,1 Y. Naka.1 1Surgery, Columbia University Medical Center, New York, NY; 2Biostatistics, Columbia University Medical Center, New York, NY; 3Medicine, Columbia University Medical Center, New York, NY. Purpose: Implantable left ventricular assist devices (iVAD) have been widely used for patients with end-stage heart failure as a bridge to heart transplantation (HTx). There is an increasing population of patients who require bridging with a temporary ventricular assist device (tVAD), either with or without an iVAD. Outcome of these patients after HTx is unknown. Methods: Between January 2007 and April 2015 there were 430 patients cared for at this institution who underwent OHT. Patients were further grouped by the algorithm of support device prior to their HTX as no bridge (Group A, n= 248), single bridge with tVAD (Group B, n= 17), single bridge with iVAD (Group C, n= 148) and multiple bridges with tVAD and iVAD (Group D, n= 17). Primary outcome was survival after HTX. Results: Patients in group B were more likely to be younger compared to the others (A:52±13, B:46±16, C:54±13, D:54±11, years, respectively, p= 0.059) and have lower body mass index (A:25.4±5.0, B:23.6±4.6, C:27.0±4.7, D:25.6±6.3, kg/m2, respectively, p= 0.008). Patients bridged with iVAD (bridge groups C and D) had lower total bilirubin at the time of HTX (A:1.2±1.0, B:1.1±0.8, C:0.9±0.8, D:0.8±0.3, p= 0.078). In-hospital mortality rate after HTx was not significantly different between groups (A: 8.5%, B: 11.8%, C:11.7%, D:11.7%, p= 0.660). The 1-year survival for group D was comparable to groups A and C, while 1-year survival for group B is significantly lower than any other groups (90.2%, 70.6%, 88.3% and 87.8%, respectively, p= 0.018). Conclusion: Post HTx survival in patients requiring multiple bridges was similar to those in non-bridge or single bridge with iVAD patients.

Demethylation of tumor necrosis factor-α converting enzyme predicts poor prognosis in acute-on-chronic hepatitis B liver failure

Tumor necrosis factor-α converting enzyme (TACE) has been demonstrated to be involved in liver inflammation. However, the significance of TACE methylation in acute-on-chronic hepatitis B liver failure (ACHBLF) has not been demonstrated. This study aims to evaluate TACE methylation status in ACHBLF and determine its predictive value for prognosis. Forty-five patients with ACHBLF, 80 with chronic hepatitisB (CHB) and 54 healthy controls (HCs) were enrolled. The methylation status of TACE promoter was determined by methylation-specific polymerase chain reaction. The TACE mRNA expression was determined by quantitative real-time polymerase chain reaction. The plasma levels of TACE, TNF-α, sTNFRI, sTNFRII were measured by enzyme-linked immunosorbent assay. TACE methylation was significantly lower in patients with ACHBLF than those with CHB (χ(2)=24.69, P<0.01) and HCs (χ(2)=35.93, P<0.01). Meanwhile, TACE methylation was significantly lower in CHB patients than HCs (χ(2)=4.03, P<0.05). TACE methylation was significantly inversely associated with its mRNA expression (r=-0.68; P<0.01). The plasma levels of TACE, TNF-α, sTNFRI, sTNFRII were significantly higher in patients with ACHBLF than those with CHB (P<0.05, respectively) and HCs (P<0.05, respectively). In patients with ACHBLF, significantly higher prothrombin activity, lower total bilirubin and MELD score were found in TACE methylated group than unmethylated group (P<0.05). ACHBLF patients with methylated TACE showed significantly better survival than those without (P<0.01). This study showed that demethylation of TACE promoter occurred in ACHBLF and might serve as a potential prognostic marker.

The Comparative Efficacy and Safety of Entecavir and Lamivudine in Patients with HBV-Associated Acute-on-Chronic Liver Failure: A Systematic Review and Meta-Analysis.

Background. Currently, both of entecavir and lamivudine are effective for patients with HBV-associated acute-on-chronic liver failure (ACLF). However, there is no consensus on the efficacy of entecavir versus lamivudine for patients with HBV-associated ACLF. The aim of the study was to compare the efficacy and safety of entecavir with that of lamivudine for HBV-associated ACLF patients. Methods. Publications on entecavir versus lamivudine in HBV-associated ACLF patients were comprehensively identified. Odds ratio and mean difference were used to measure the effect. Results. Ten studies, totaling 1254 patients, were eligible. No significant differences between the two drugs presented in the 1-, 2-, 3-, or 6-month survival rates. However, after 12 months of treatment, patients prescribed entecavir had a statistically higher survival rate (p = 0.008) and lower total bilirubin (p < 0.0001) and alanine aminotransferase (p = 0.04) levels compared to patients prescribed lamivudine. More patients achieved HBV negative levels when taking entecavir as measured at 1-, 3-, and 12-month time points and had a lower rate of HBV recurrence. Conclusion. While entecavir and lamivudine are both relatively safe and well tolerated, entecavir was more efficacious in terms of survival rate and clinical improvement in long-term treatment. Further prospective randomized controlled trials are needed to validate these results.