A prospective assessment of the inter-laboratory variability of biochemical markers of fibrosis (FibroTest) and activity (ActiTest) in patients with chronic liver disease

BACKGROUND: Biochemical markers for liver fibrosis (FibroTest) and necroinflammatory features (ActiTest) are an alternative to liver biopsy in patients with chronic hepatitis C. Our aim was to assess the inter-laboratory variability of these tests, and their 6 components (gamma-glutamyl transpeptidase, alanine aminotransferase, alpha2-macroglobulin, haptoglobin, apolipoprotein A1, and total bilirubin) and to identify factors associated with this variability. RESULTS: Serum of 24 patients with chronic hepatitis C or severe alcoholic liver disease were prospectively recorded and analyzed in one reference center and in 8 additional laboratories. When gamma-glutamyl transpeptidase and alanine aminotransferase were expressed in international units, there was no significant difference between laboratories in the results of FibroTest or ActiTest; kappa statistics were greater than 0.50 with only 0.8% of cases (3/384) with a discordance of more than one stage. The main factor significantly associated with variability was the expression of gamma-glutamyl transpeptidase and alanine aminotransferase, as multiples of upper limit of reference values. The use of standardized method with pyridoxal phosphate reduced the variability of alanine aminotransferase expression, and standardized original Szasz method reduced the variability of gamma-glutamyl transpeptidase expression. CONCLUSIONS: The variability of FibroTest and ActiTest was acceptable without clinical consequences for the prediction of the stage of liver fibrosis and grade of activity. Standardized methods and assay calibration should be used and expression of alanine aminotransferase and gamma-glutamyl transpeptidase in multiples of the upper limit of reference values should not be employed.     

Transcystic or Transductal Stone Extraction during Single-Stage Treatment of Choledochocystolithiasis: A Systematic Review

Background

Choledochocystolithiasis can be managed by endoscopic retrograde cholangiopancreaticography (ERCP) or laparoscopically by transcystic (TC) or transductal (TD) stone extraction.

Objective

The aim of this study was to systematically review safety and effectiveness of combined endoscopic/laparoscopic management versus total laparoscopic management for choledochocystolithiasis with specific emphasis on TC versus TD stone extraction.

Methods

MEDLINE/PubMed, EMBASE, the Cochrane Library, and clinicaltrials.gov were searched systematically to identify trials on combined endoscopic/laparoscopic and total laparoscopic management for choledochocystolithiasis. Laparoscopic common bile duct (CBD) exploration was divided into TD and TC approach. Primary outcomes were successful stone clearance from CBD, postoperative/procedural morbidity, and mortality.

Results

Eight randomized trials with 965 patients were included. Successful bile duct clearance varied between 52.6 and 97 % in the ERCP groups, 80.4 and 100 % in the TC groups, and 58.3 and 100 % in the TD groups. There were more bile leaks after TD stone extraction (11 %) than after ERCP (1 %) and TC stone extraction (1.7 %). Total morbidity varied between 9.1 and 38.3 % in the ERCP groups, 7 and 10.5 % in the TC groups, and 18.4 and 26.7 % in the TD groups. Methodological and statistical heterogeneity among the trials precluded a meaningful meta-analysis.

Conclusion

Stone clearance rates are comparable between the three modalities, but TD stone extraction is associated with a higher risk of bile leaks and should only be performed by highly experienced surgeons. TC stone extraction seems a more accessible technique with lower complication rates. If unsuccessful, per- or postoperative endoscopic stone extraction is a viable option.     

Association between leptin, metabolic factors and liver histology in patients with chronic hepatitis C.

BACKGROUND: Steatosis is common in hepatitis C virus (HCV)-infected patients and likely accelerates fibrosis progression. Leptin, the peptide product of the obesity gene (ob), has been implicated in hepatic fibrogenesis; circulating levels of leptin correlate with body fat mass. The objective of the present study was to determine the clinical and histological correlates of serum leptin in HCV-infected patients, and to determine its utility in predicting liver histological lesions. PATIENTS AND METHODS: In 62 patients with chronic HCV, serum leptin was measured using a commercially available immunoassay. Associations between leptin, metabolic parameters, and severe hepatic fibrosis (stages 2 to 4) and steatosis (30% or greater) were determined. The utility of leptin in predicting liver histology was determined using receiver operating characteristic (ROC) curves. RESULTS: The median body mass index (BMI) was 23.2 kg/m2 (range 17.7 kg/m2 to 35.6 kg/m2); 16% of patients (n=10) had HCV genotype 3. Severe fibrosis and steatosis were present in 23% and 13% of patients, respectively. Leptin was strongly correlated with the BMI, and its levels were higher in women. BMI-corrected leptin levels were not independently associated with severe fibrosis but were significantly associated with steatosis (OR of 1.07; 95% CI 1.01 to 1.04). On it own, leptin was poorly predictive of severe steatosis (area under the ROC curve was 0.64; 95% CI 0.42 to 0.87). However, its accuracy improved with the addition of HCV genotype (area under the ROC curve was 0.86; 95% CI 0.72 to 1.00; P=0.07). CONCLUSIONS: As observed in the non-HCV setting, serum leptin correlates with BMI; higher leptin levels are found in women than men with chronic HCV. Serum leptin is a poor predictor of HCV-related fibrosis but may play a role in predicting steatosis when combined with HCV genotype.     

Rebanding for Slippage After Gastric Banding: Should We Do It?

Background

Laparoscopic adjustable gastric banding (LAGB) is a commonly performed bariatric procedure. LAGB is frequently complicated by slippage. Possible treatment for slippage is rebanding, but long-term effects are unknown. The aim of this study was to investigate whether rebanding after gastric band slippage is associated with weight loss failure.

Methods

This was a post hoc analysis of a prospectively collected database of 627 consecutive LAGB patients. Rebanding for slippage was performed in 81 patients. The effect of rebanding on weight loss was evaluated by three analyses: (1) in 81 rebanded patients, weight loss was compared before and after rebanding, separately for patients in whom primary LAGB was successful or unsuccessful; (2) 81 rebanded patients were matched to 81 patients without slippage for prognostic variables and compared for weight loss after rebanding; (3) multivariate logistic regression was performed whether rebanding was independently associated with weight loss failure.

Results

The chance of a fair result of rebanding for patients following primary successful (n?=?34) and unsuccessful LAGB (n?=?22) was 62 and 27 % after median follow-up of 113 and 97 months, respectively. There was no difference in weight loss failure between 81 rebanded patients and 81 matched patients: 54 vs 59 % (P?=?0.43). In multivariate analysis, rebanding was not significantly associated with weight loss failure: adjusted odds ratio 1.42; 95 % confidence interval 0.85–2.38; P?=?0.18.

Conclusion

In general, rebanding after LAGB has no negative effect on weight loss. However, patients in whom LAGB was unsuccessful prior to rebanding have poor long-term weight loss results.     

Sirolimus and tacrolimus trough concentrations and dose requirements after kidney transplantation in relation to CYP3A5 and MDR1 polymorphisms and steroids

BACKGROUND: CYP3A5 and MDR1 polymorphisms have been shown to influence tacrolimus blood concentrations and dose requirements. The aim is to determine whether these polymorphisms also affect sirolimus trough concentrations and dose requirements after kidney transplantation. METHODS: Eighty-five renal transplant recipients receiving sirolimus were included. Twenty-four were treated with a combined sirolimus-tacrolimus regimen. Eighty-one patients received steroids. Sirolimus and tacrolimus were adjusted to a target therapeutic window. CYP3A5 (intron 3) and MDR1 (exons 12, 21, 26) genotypes were correlated to the adjusted trough concentrations and dose requirements for both sirolimus and tacrolimus. RESULTS: There were no significant correlation between adjusted sirolimus trough concentrations or dose requirements and genetic polymorphisms. In a multiple regression model, adjusted-prednisone dose was involved with a positive or negative effect when considering sirolimus dose requirements or adjusted concentrations, respectively. In the subgroup of patients treated by tacrolimus and sirolimus, adjusted tacrolimus doses were higher in patients carrying at least one CYP3A5 *1 allele (median 0.083 vs. 0.035 mg/kg for CYP3A5*3/*3 patients, P<0.05). Adjusted-prednisolone dose and CYP3A5 polymorphism explained up to 61% of the variability in tacrolimus dose requirements. CONCLUSIONS: Unlike tacrolimus, sirolimus adjusted trough concentrations and dose requirements seem not affected by CYP3A5 and MDR1 polymorphisms. Adjusted-prednisone dose has a significant impact on tacrolimus and sirolimus dose requirements.     

Cohort mortality study among French asphalt workers

BACKGROUND: In conjunction with the European cohort study among asphalt workers coordinated by the International Agency for Research on Cancer (IARC), we studied the mortality of 15,011 French men who were followed for 17 years for a total of 175,062 persons-years. This group contained 2,506 subjects who had ever been employed as asphalt workers: they contributed 30,692 person-years of risk. A reference group was composed of 6,675 subjects (i.e., 61,856 persons-years) who had been employed only in building or ground construction. METHODS: Mortality ratios standardized for age and period were computed with their 95% confidence intervals (CI) from the age and period mortality rates of all French men for the years covered by the study (1979-1996). We also compared the mortality of exposed workers and the reference group with Poisson regression models after adjustment for age, calendar period, and either duration of employment or length of follow-up. RESULTS: Mortality from lung cancer was equivalent to the expected rate [SMR = 1.01 95% CI (0.6-1.6)], but was 40% greater than among the non-exposed reference group [RR = 1.4 95% CI (0.7-2.8)]. We also found an excess of gastrointestinal cancers, especially of the esophagus [SMR = 1.94, 95% CI (0.9-3.6)] and stomach [SMR = 2.2, 95% CI (0.8-4.7)]. Comparison with the internal reference group confirmed these findings, especially for stomach cancer [RR = 2.8, 95% CI (0.7-11.4)]. CONCLUSIONS: Although our results are not statistically significant, they suggest that road-paving workers may have a slightly higher rate of lung cancer and a moderately higher rate of stomach cancer than their non-exposed counterparts. The excess of lung cancer may be due to potential confounding factors, including the occupational risk factor of coal tar exposure and the lifestyle risk factor of smoking. A nested case-control study is under way that will make it possible to control for smoking and other potential carcinogenic exposures; this is necessary before any definitive conclusions can be drawn.