- The characteristics and clinical outcome of drug-induced liver injury in a Chinese hospital: A retrospective cohort study. [Journal Article]
- Medicine (Baltimore) 2016 Aug; 95(34):e4683.
The aim of this cohort study was to determine the characteristics and clinical outcome of 287 patients with drug-induced liver injury (DILI) in a Chinese hospital.Between January 2008 and January 2013, individuals who were diagnosed with DILI were selected. The complete medical records of each case were reviewed, and factors for the outcome of patients with DILI were extracted and analyzed using univariate and multivariate analysis.Two hundred eighty-seven cases identified as DILI were included in the study. A total of 105 different drugs were considered to be related to the hepatotoxicity. The main causative group of drugs was Chinese herb (n = 111). Liver failure developed in 9 (3.1%) patients, and 2 died (0.7%). Overall, complete recovery occurred in 92 (32.1%) patients. Univariate analysis and binary logistic regression analysis identified the digestive symptoms, jaundice, total bilirubin (TBIL), and direct bilirubin (DBIL) as independent factors for the non-recovery of DILI. Then the prediction model, including digestive symptoms, jaundice, TBIL, and DBIL, was built by using binary logistic regression analysis again. Receiver operating characteristic curve validated the strong power (area under the curve (AUC) = 0.907) of prediction model for predicting the DILI non-recovery.DILI is an important cause of liver test abnormalities, and Chinese herb represented the most common drug group. The factors such as digestive symptoms, jaundice, TBIL, and DBIL have effect on DILI outcomes. The prediction model, including digestive symptoms, jaundice, TBIL, and DBIL, established in this study is really an excellent predictive tool for non-recovery of DILI patients.
- Prognostic value of the albumin-bilirubin grade in patients with hepatocellular carcinoma: validation in a Chinese cohort. [JOURNAL ARTICLE]
- Hepatol Res 2016 Aug 25.
The prognostic value of the newly raised objective liver function assessment tool, the albumin-bilirubin (ALBI) grade, in patients with hepatocellular carcinoma (HCC) has not been fully validated. We aimed to compare the performance of ALBI grade with the specific Child-Pugh score in predicting the prognosis in this study.The clinical data of 491 Child-Pugh class A patients who underwent liver resection as the initial therapy from January 2000 to December 2007 in Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. The prognostic performance of ALBI and C-P score in predicting the short and long term clinical outcomes was compared.ALBI score gained a significantly larger area under the receiver operating characteristic (ROC) curve for predicting the occurrence of severe postoperative complications than that of C-P score. With a median follow-up of 57 months,the 1-year, 3-year and 5-year overall survival (OS) rates of the patients were 92.1%, 65.8% and 45.2%, respectively. Multiple tumors, tumor size and ALBI grade were proved to be the independent prognostic factors for the overall survival in the multivariate analysis. Prognostic performance was shown to be better for ALBI when it was compared to C-P score in terms of both the AIC value and χ(2) value of likelihood ratio test.ALBI, which is featured by the simplicity and objectivity, gained a superior prognostic value than that of C-P grade in patients with HCC who underwent liver resection. Future well-designed studies with larger sample size were warranted.
- Clinical course and short-term mortality of cirrhotic patients with infections other than spontaneous bacterial peritonitis. [JOURNAL ARTICLE]
- Liver Int 2016 Aug 25.
Clinical course and risk factors of death in non-SBP infections are poorly known. We assessed the prevalence of AKI and type-1 HRS, hospital, 30-d and 90-d mortality and risk factors of death in 441 decompensated patients.Analysis of 615 non-SBP infections (161 urinary infections, 95 cellulitis, 92 suspected infections, 92 bacteremias, 84 pneumonias, 21 bronchitis, 18 cholangitis, 15 spontaneous empyema, 13 secondary peritonitis, 24 other).96% of infections solved. AKI and type-1 HRS developed in 37% and 9% of infections, respectively. Overall hospital, 30-d and 90-d mortality rates were 11%, 12% and 18%, respectively. Clinical course and mortality differed markedly across infections. Endocarditis, osteoarticular infections, pneumonia, spontaneous bacteremia, cholangitis, secondary peritonitis and UTI showed higher rates of AKI. Prevalence of type-1 HRS was not significantly different among infections. Endocarditis, secondary peritonitis, pneumonia and bacteremia showed lower rates of renal impairment resolution and higher hospital mortality associated to AKI (42% vs. 12%, p<0.0001) or type-1 HRS (71% vs. 27%, p=0.003) than the rest of infections. Age (HR: 1.04), serum sodium (HR: 0.91), serum bilirubin (HR: 1.06), INR (HR: 1.91), hepatic encephalopathy (HR: 2.44), ascites (HR: 3.06) and MDR isolation (HR: 2.27) at infection diagnosis were independent predictors of death during hospitalization.Non-SBP infections constitute a heterogeneous group regarding clinical course and prognosis. Endocarditis, secondary peritonitis, pneumonia and bacteremia show worse prognosis. The combination of data of liver and renal dysfunction and of the type of infection allows the identification of patients with poor prognosis. This article is protected by copyright. All rights reserved.
- Risk assessment of gene variants for neonatal hyperbilirubinemia in Taiwan. [Journal Article]
- BMC Pediatr 2016; 16(1):144.
Hyperbilirubinemia is a common disorder during neonatal period in Taiwan. Gene variants may play an important role in the development of neonatal hyperbilirubinemia. The current study investigated the association between neonatal hyperbilirubinemia and common gene variants involving the production and metabolism of bilirubin.This prospective study enrolled 444 healthy infants born in the Chang Gung Memorial Hospital at Taipei from 2013-2015. Hyperbilirubinemia was defined as a total bilirubin ≥ 15 mg/dL. A log-binomial model was used to assess the risk of gene variants.The most common genetic variant was short heme oxygenase (HO)-1 promoter GT-allele (<24 repeats) (39.4 %), followed by GA at nt388 in hepatic solute carrier organic anion transporter 1B1 (SLCO1B1) (31.1 %), GA at nt211 in UDP-glucuronosyltransferase 1A1 (UGT1A1) (29.3 %), ABO incompatibility (16.2 %), alpha thalassemia (5.0 %), and G6PD deficiency (3.2 %). The log-binomial analysis demonstrated greater risks of hyperbilirubinemia in infants with GA at nt211 in UGT1A1 (RR = 1.548; 95 % CI = 1.096-2.187), short HO-1 promoter GT-repeat (RR = 2.185; 95 % CI = 1.527-3.125), and G6PD deficiency (RR = 1.985; 95 % CI = 1.010-3.901). The other gene variants - including blood type, alpha thalassemia, and SLCO1B1 - carried no significant risk.G6PD deficiency, short HO-1 promoter GT-repeat and GA at nt211 in UGT1A1 are risk factors of neonatal hyperbilirubinemia. The data provide clinical evidence to explain the high incidence of neonatal hyperbilirubinemia in Taiwan.
- Relationship between vitamin A deficiency and the thyroid axis in clinically stable patients with liver cirrhosis related to hepatitis C virus. [JOURNAL ARTICLE]
- Appl Physiol Nutr Metab 2016 Aug 24.:1-7.
Vitamin A deficiency (VAD) and altered thyroid function are commonly encountered in patients with liver cirrhosis. The link between vitamin A metabolism and thyroid function has been previously identified. The aim of this study was to explore the association between VAD and the thyroid axis in clinically stable patients with cirrhosis related to hepatitis C virus (HCV). One hundred and twelve patients with clinically stable HCV-related cirrhosis and 56 healthy controls matched for age, sex, and socioeconomic status were recruited for this study. Vitamin A status, liver function, thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), reverse triiodothyronine (rT3), anti-thyroid peroxidase antibodies (anti-TPO), and thyroid volume were evaluated. The prevalence of VAD among patients with HCV-related cirrhosis was 62.5% compared with 5.4% among controls (P < 0.001). Patients with HCV-related cirrhosis had significantly higher FT4, FT3, TSH, and thyroid volume than did healthy controls. Of the 112 patients initially recruited, 18 were excluded (patients with subclinical hypothyroidism and/or anti-TPO positive), so a total of 94 patients with HCV-related cirrhosis were divided into 2 groups according to vitamin A status: VAD and normal vitamin A. Patients with VAD had significantly lower vitamin A intake and serum albumin and higher serum bilirubin, FT4, FT3, and TSH than patients with normal vitamin A status. Multiple logistic regression analysis revealed that VAD was associated with Child-Pugh score (β = 0.11, P = 0.05) and TSH (β = -1.63, P = 0.02) independently of confounding variables. We conclude that VAD may be linked to central hyperthyroidism in patients with clinically stable HCV-related liver cirrhosis.
- Association of Admission Laboratory Values and the Timing of Endoscopic Retrograde Cholangiopancreatography With Clinical Outcomes in Acute Cholangitis. [JOURNAL ARTICLE]
- JAMA Surg 2016 Aug 24.
Acute cholangitis (AC), particularly severe AC, has historically required urgent endoscopic decompression, although the timing of decompression is controversial. We previously identified 2 admission risk factors for adverse outcomes in AC: total bilirubin level greater than 10 mg/dL and white blood cell count greater than 20 000 cells/µL.To validate previously identified prognostic factors in AC, evaluate the effect of timing of endoscopic retrograde cholangiopancreatography on clinical outcomes, and compare recent experience with AC vs an historical cohort.A retrospective analysis (2008-2015) of patients with AC (validation cohort, n = 196) was conducted at 2 academic medical centers to validate predictors of adverse outcome. Timing of endoscopic retrograde cholangiopancreatography and outcome were stratified by severity using the Tokyo Guidelines for acute cholangitis diagnosis. Outcomes for the validation cohort were compared with the derivation cohort (1995-2005; n = 114). Data analysis was conducted from July 1, 2015, to September 9, 2015.Death and a composite outcome of death or organ failure.The median age of patients in the derivation cohort was 54 years (interquartile range, 40-65 years) and in the validation cohort was 59 years (45-67 years). Multivariate logistic regression analysis of the validation cohort confirmed white blood cell count of more than 20 000 cells/µL (odds ratio, 3.4; 95% CI, 1.2-9.5; P = .02) and total bilirubin level of more than 10 mg/dL (odds ratio, 5.4; 95% CI, 1.8-16.4; P = .003) as independent risk factors for poor outcomes. In the validation cohort, timing of endoscopic retrograde cholangiopancreatography was not significantly different between those with and without an adverse outcome, even when stratified by AC severity (moderate: median, 0.6 hours [interquartile range (IQR), 0.5-0.9] vs 1.7 hours [IQR, 0.7-18.0] and severe: median, 10.6 hours [IQR, 1.2-35.1] vs 25.5 hours [IQR, 15.5-58.5] for those with and without adverse events, respectively). Patients in the validation cohort had a shorter hospital length of stay (median, 7 days [IQR, 4-10 days] vs 9 days [IQR, 5-16 days]) and lower rate of intensive care unit admission (26% vs 82%), despite a higher rate of severe cholangitis (n = 131 [67%] vs n = 29 [25%]). There were no significant differences in the composite outcome between the validation and derivation cohorts (22 [18.6%] vs 44 [22.4%]; P = .47). Adjusted analysis demonstrated decreased mortality in the validation cohort (odds ratio, 0.3; 95% CI, 0.1-0.7; P = .01).White blood cell count greater than 20 000 cells/µL and total bilirubin level greater than 10 mg/dL are independent prognostic factors for adverse outcomes in AC. Consideration should be given to include these criteria in the Tokyo Guidelines severity assessment. Timing of endoscopic retrograde cholangiopancreatography does not appear to affect clinical outcomes in these patients. Management of AC has improved with time, with an overall shorter hospital length of stay, lower rate of intensive care unit admission, and a decreased adjusted mortality, demonstrating improvements in care efficiency and delivery.
- Anti-inflammatory Signaling During Ex Vivo Liver Perfusion Improves the Preservation of Pig Liver Grafts Before Transplantation. [JOURNAL ARTICLE]
- Liver Transpl 2016 Aug 24.
Normothermic ex vivo liver perfusion (NEVLP) improves graft preservation by avoiding cold ischemic injury. We investigated whether the protective effects of NEVLP can be further improved by applying strategies targeted on reducing the activation of pro-inflammatory cytokines during perfusion.Livers retrieved under heart beating conditions were perfused for 4 hours. Following preservation period, pig liver transplantation was performed. In group-1 (n=5) anti-inflammatory strategies (alprostadil, n-acetylcysteine, CO and sevoflurane, subnormothermic temperature (33°C)) were applied. This was compared to a perfused control group (group-2) where livers (n=5) were perfused at 37ºC without anti-inflammatory agents, similar to the setup used in current European clinical trials, and to a control group preserved with static cold storage (group-3). During 3-day follow-up, markers of reperfusion injury, bile duct injury, and liver function were examined.AST levels during perfusion were significantly lower in the study vs. control group at 1hr (52±6 vs. 162±86 U/L; p=0.01), 2hr (43±5 vs. 191±111 U/L; p=0.008) and 3hr (24±16 vs. 218±121 U/L; p=0.009). During perfusion group-1 vs group-2 had reduced IL-6, TNFα, and galactosidase levels, and increased IL-10 levels. After transplantation, group-1 had lower AST peak levels compared to group-2 and group-3 (1400±653 vs. 2097±1071 vs 1747±841.6 U/L; p=0.5) without reaching significance. Bilirubin levels were significantly lower in group-1 vs group-2 at day 1 (3.6±1.5 vs. 6.60±1.5 µmol/l; p=0.02) and 3 (2±1.1 vs. 9.7±7.6 µmol/l; p=0.01). A trend towards decreased hyaluronic acid, as a marker of improved endothelial cell function, was observed at 1, 3 and 5hrs after reperfusion in group-1 vs group-2. Only one early death occurred in each group (80% Survival).Addition of anti-inflammatory strategies further improves warm perfused preservation. This article is protected by copyright. All rights reserved.
- Nomograms incorporated serum direct bilirubin level for predicting prognosis in stages II and III colorectal cancer after radical resection. [JOURNAL ARTICLE]
- Oncotarget 2016 Aug 19.
An elevated serum bilirubin has been reported to be associated with a reduced risk of some cancer; however, the prognostic significance of serum bilirubin in colorectal cancer wasn't fully understood. The purpose of this study was to evaluate whether serum bilirubin could predict the prognosis of patients in stages II and III colorectal cancer. A retrospective cohort of 986 patients with colorectal cancer who received surgical resection between January 2005 and December 2010 was included in the study. Levels for serum bilirubin were obtained from medical records. Survival analysis was used to evaluate the predictive value of bilirubin. Serum direct bilirubin (DBIL) was validated as a significant prognostic factor by univariate cox regression test for both overall survival (OS) and disease free survival (DFS) (P < 0.05). X-tile program identified 3.6 as optimal cutoff values for DBIL in terms of OS and DFS. Patients were then divided into DBIL high (DBIL ≥ 3.60 μmol/l) and low group (DBIL < 3.60 μmol/l) according to the optimal cutoff. High DBIL had higher percentage of lymph node metastasis and lymphovascular invasion as compared with low DBIL levels (P < 0.05). Multivariate cox regression analyses confirmed that high DBIL level was an independently prognostic factor for both OS (HR: 1.337, 95% CI: 1.022-1.748, P = 0.034) and DFS (HR: 1.312, 95% CI: 1.049-1.643, P = 0.018). In addition, nomograms on OS and DFS were established according to all significant factors, and c-indexes were 0.715 (95% CI: 0.683-0.748) and 0.704 (95% CI: 0.678-0.730), respectively. Nomograms based on OS and DFS can be recommended as practical models to evaluate prognosis for CRC patients.
- Diagnosis of HCC for patients with cirrhosis using miRNA profiles of the tumor-surrounding tissue - A statistical model based on stepwise penalized logistic regression. [JOURNAL ARTICLE]
- Exp Mol Pathol 2016 Aug 20.
The presence of hepatocellular carcinoma (HCC) is a significant complication of cirrhosis because it changes the prognosis and the treatment of the patients. By now, contrast-enhanced CT and MR scans are the most reliable tools for the diagnosis of HCC; however, in some cases, a biopsy of the tumor is necessary for the final diagnosis. The aim of the study was to develop a diagnostic tool using the microRNA (miRNA) profiles of the tissue surrounding the HCC tumor combined with clinical parameters in statistical models. At a transplantation setting, 32 patients with HCC and cirrhosis (B) were compared to 22 patients suffering from cirrhosis only (A). The diagnosis and exclusion of HCC was confirmed following the histopathological examination of the explanted liver. The HCC patients were significantly older than the patients with cirrhosis only (B: 60.6 and A: 49.9, p<0.001) and showed higher levels of ALT (A: 0.76 μkat/l, B: 1.02 μkat/, p=0.006) and AFP (A: 5.8ng/ml, B: 70.3ng/ml, p<0.001), whereas the bilirubin levels were higher in the cirrhosis only group (p=0.002). Using age (cut-off 50.23years) and AFP (cut-off 4.2ng/ml) thresholds, the levels of expression of miR-1285-3p and miR-943 differentiated between the patients with HCC and cirrhosis from those with cirrhosis only with an accuracy of 96.3%. This is the first report about the use of stepwise penalized logistic regression and decision tree analyses of miRNA expressions in the tumor-surrounding tissue combined with clinical parameters for the diagnosis of HCC.
- Liver cirrhosis and thyroid function: Friend or foe? [JOURNAL ARTICLE]
- Acta Clin Belg 2016 Aug 24.:1-6.
The liver plays a central role in thyroid hormone metabolism, transport, and clearance. A normal function of both the thyroid gland and the liver is therefore necessary to maintain normal thyroid hormone levels and action. Data regarding thyroid function in patients with liver cirrhosis are scarce and variable. The most consistent finding is a decreased free triiodothyronine (fT3) level, which correlates with the severity of liver disease and has been proposed as a prognostic factor for liver-related complications.To evaluate thyroid hormone values in patients with stable liver cirrhosis and to compare them with healthy controls without liver disease. We also assessed the prevalence of thyroid autoimmunity and whether liver function tests correlated with thyroid function.We performed a prospective case-control study in an endocrinological setting. Twenty-nine patients with stable cirrhosis (20 males and 9 females, mean age 60.97 ± 7.17 years) were included in the case group and 50 healthy subjects (22 males and 28 females, mean age 61.70 ± 13.00 years) in the control group. We excluded patients with confounding factors known to influence thyroid function. Levels of serum thyroid-stimulating hormone (TSH), fT3, free thyroxine (fT4) and anti-TPO-antibodies (TPO-Ab) were measured. These thyroid hormone values were compared in both groups. Biochemical indices of liver function (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [AP], gamma-glutamyl transpeptidase [GGT], INR, total bilirubin, and albumin levels) were correlated with thyroid function tests.fT3 en fT4 levels were significantly lower in patients with cirrhosis than in healthy subjects (p = 0.001 and 0.002, respectively). TSH levels were not statistically significantly different in the two groups. The level of TPO-Ab was not increased in patients with cirrhosis compared to healthy controls. fT3 correlated negatively with the Child-Pugh score.These results indicate that, compared to healthy controls, patients with cirrhosis have decreased fT3 and fT4 levels and comparable TSH levels and may be consistent with findings of limited acquired central hypothyroidism as observed in the non-thyroidal illness syndrome (NTIS). fT3 levels correlated negatively with Child-Pugh score, a measure of severity of liver dysfunction. We did not find an increased prevalence of thyroid autoimmunity in these patients.