Risk factors cannot explain the higher prevalence rates of precancerous colorectal lesions in men.

BACKGROUND: Prevalence of (pre)cancerous colorectal lesions are higher in men than in women, although transition rates from advanced lesions to cancer is similar in both sexes. Our aim was to investigate whether the sex-specific difference in incidence of premalignant colorectal lesions might be explained by the impact of risk factors. METHODS: A cross-sectional study analysing health check-up examinations and screening colonoscopies performed within a national quality assurance program. RESULTS: A total of 25 409 patients were included in this study, 50.8% were women. Median age for both sexes was 60 years (interquartile range (IQR) 54-67). A multivariable model showed that risk factors mediated only 0.6 of the 10.4% gender gap in adenoma and 0.47 of the 3.2% gender gap in advanced adenoma detection rate. Smoking was the only independent risk factor with a varying sex-specific effect (men OR 1.46, CI 1.29, 1.64, women OR 1.76, CI 1.53, 2.06) and advanced adenomas (men OR 1.06, CI 0.80-1.42; women OR 2.08, CI 1.52-2.83). Independent risk factors for adenomas were BMI (OR 1.35 per IQR, CI 1.25-1.47) and triglyceride level (OR 1.03 per IQR, CI 1.00-1.06); for advanced adenomas physical activity (none vs regular: OR 1.54, CI 1.18-2.00, occasional vs regular: OR 1.17, CI 1.00-1.38), cholesterol level (OR 1.13 per IQR, CI 1.02-1.25), blood glucose level (OR 1.05 per IQR, CI 1.01-1.09) and alcohol score (OR 1.09 per IQR, CI 1.01-1.18). CONCLUSIONS: Risk factors cannot explain higher prevalence rates in men. Results of this study strongly underline the need for sex-specific screening recommendations.

von Willebrand factor antigen (vWF-Ag): A non-invasive predictor of treatment response and serious adverse events in HCV patients with interferon triple therapy.

BACKGROUND: Treatment of chronic hepatitis C virus (HCV) infection was revolutionized within the last years. Interferon free antiviral regimens are not accessible without limitations. Combination of peginterferon/ribavirin with first generation direct acting antivirals is less effective and associated with serious adverse events. AIM: We have shown that vWF-Ag is associated with portal hypertension and treatment response to PEG/RBV and we evaluated if vWF-Ag is a predictive marker for treatment response and safety in patients with triple therapy. METHODS: 222 HCV-GT 1 patients and DAA based triple therapy were included in this retrospective, multicenter study. RESULTS: Median vWF-Ag levels were 167.0% [IQR: 124.0-210.0%]. Significantly higher levels were seen in patients without SVR; median 190% [IQR: 146.0-259.5%] versus SVR: 142.5% [IQR: 114.3-196.8%], p<0.001. Furthermore levels of vWF-Ag were identified as independent predictor of non SVR; (OR: 1.009; 95%CI: 1.016-1.3, p=0.005). In patients with cirrhosis elevated vWF-Ag levels were associated with increased incidence of SAEs (OR: 1.016; 95%CI: 1.004-1.028; p=0.007). Best cut off for prediction of SAEs was vWF-Ag>281.5% with a sensitivity of 78% and a specificity of 90%. CONCLUSION: Baseline vWF-Ag levels predict outcome of DAA based treatment in HCV-1 patients and identify patients with a risk of SAEs. Therefore vWF-Ag may be an additional marker for selecting patients for interferon free therapeutic regimens.

Performance of 2-D shear wave elastography in liver fibrosis assessment compared with serologic tests and transient elastography in clinical routine.

Liver stiffness values assessed with 2-D shear wave elastography (SWE), transient elastography (TE) and simple serologic tests were compared with respect to non-invasive assessment in a cohort of 127 consecutive patients with chronic liver diseases. The rate of reliable liver stiffness measurements was significantly higher with 2-D SWE than with TE: 99.2% versus 74.8%, p < 0.0001 (different reliability criteria used, according to current recommendations). In univariate analysis, liver stiffness measured with 2-D SWE correlated best with fibrosis stage estimated with TE (r = 0.699, p < 0.0001), followed by Forns score (r = 0.534, p < 0.0001) and King's score (r = 0.512, p < 0.0001). However, in multivariate analysis, only 2-D SWE-measured values remained correlated with fibrosis stage (p < 0.0001). The optimal 2-D SWE cutoff values for predicting significant fibrosis were 8.03 kPa for fibrosis stage ≥2 (area under the receiver operating characteristic curve = 0.832) and 13.1 kPa for fibrosis stage 4 (area under the receiver operating characteristic curve = 0.915), respectively. In conclusion, 2-D SWE can be used to obtain reliable liver stiffness measurements in almost all patients and performs very well in predicting the presence of liver cirrhosis.

Evaluation of a new balloon occlusion catheter specifically designed for measurement of hepatic venous pressure gradient.

BACKGROUND & AIMS: Despite the important clinical value of hepatic venous pressure gradient (HVPG) and its increasing use, no specific balloon occlusion catheters have been designed to cannulate liver veins. The aim of the study was to evaluate the clinical applicability of a novel balloon (NC) occlusion catheter specifically designed for HVPG measurement. METHODS: Comparison of a new CE-certified 7 French balloon occlusion catheter with a 150° angled tip and radiopaque markers (NC, Pejcl Medizintechnik, Austria), to a commonly used straight balloon catheter (SC; Boston Scientific, USA). Successful liver vein cannulation rate, need for extra equipment and total fluoroscopy time were recorded. Experts (>200) and novices (<20) in HVPG measurements were evaluated separately. RESULTS: 566 HVPG measurements taken by 11 investigators (five experts and six novices) were analysed. Overall, HVPG could be successfully measured in 98.7% of cases. The rate of successful liver vein cannulation at first attempt was significantly higher among experts when compared to novices (87.3% vs 67.3%, P < 0.001). Moreover, the rate of successful liver vein cannulation without need for any additional equipment was higher when using the NC, both among experts (NC:91.9% vs SC:80.6%, P = 0.03) and novices (NC:73.3% vs SC:50.7%, P = 0.001). The mean fluoroscopy time needed to cannulate the hepatic vein was significantly shorter in experts as compared to novices [2.37(0.10-26) vs 5.2(0.6-30.2] min, P < 0.0001), but not significantly different between catheters. CONCLUSIONS: Both novices and experts achieve higher liver vein cannulation rates using the new specifically designed catheter. The use of the novel catheter might increase rates of successful liver vein cannulation and reduce the need for additional equipment, especially in novices.

High quality of screening colonoscopy in Austria is not dependent on endoscopist specialty or setting.

BACKGROUND AND STUDY AIM: International studies have shown differences in the outcome of screening colonoscopies related to the endoscopist's specialty and setting of colonoscopy. The aim of this study was to investigate the impact of these two factors on quality parameters for screening colonoscopy in a quality-assured screening program. METHODS: Adenoma detection rate (ADR), cecal intubation rate (CIR), polypectomy rate, flat polyp detection rate, carcinoma detection rate, sedation rate, complication rates, and other parameters of 59 901 screening colonoscopies performed by 178 endoscopists were analyzed in relation to specialty (35 gastroenterologists: 10 066 colonoscopies [16.8 %]; 84 nongastroenterologists: 26 271 colonoscopies [43.9 %]; 59 surgeons: 23 564 [39.3 %]), and setting (hospital: 12 580 [21.6 %] colonoscopies; office: 45 781 [78.4 %] colonoscopies). RESULTS: The overall ADR was 20.5 % and the CIR was 95.6 %. The ADR did not show any statistical significance, either in relation to specialty or to setting. A significant difference in the CIR was found between hospital-based and office-based internists (98.5 % vs. 96.8 %, respectively; P  = 0.0005; odds ratio [OR] 2.2, 95 % confidence interval [CI] 1.4 - 3.4). Hospital-based internists had a significantly higher flat polyp detection rate (7.5 % vs. 4.1 %; P  = 0.02; OR 1.9, 95 %CI 1.1 - 3.2) and a significantly lower carcinoma detection rate (0.4 % vs. 0.6 %; P  = 0.03; OR 0.7, 95 %CI 0.5 - 1.0) compared with office-based internists. Complication rates were significantly lower among surgeons than among internists (0.1 % vs. 0.2 %; P  = 0.03; OR 0.5, 95 %CI 0.3 - 1.0). CONCLUSION: Endoscopists participating in the Austrian quality assurance program offered high quality screening colonoscopy regardless of their specialty and setting. The implementation of a standardized quality program is therefore a decisive factor in quality improvement of screening colonoscopy.

New reliability criteria for transient elastography increase the number of accurate measurements for screening of cirrhosis and portal hypertension.

BACKGROUND & AIMS: Transient elastography (TE) can non-invasively diagnose cirrhosis and portal hypertension (PHT). New TE reliability criteria suggest classifying measurements as very reliable (IQR/M < 0.1), reliable (IQR<0.3 or >0.3, if TE < 7.1 kPa) and poorly reliable (IQR/M > 0.3, if TE > 7.1 kPa). Compare traditional (reliable: success rate >60% + IQR/M ≤ 0.30) and new TE quality criteria (accurate: very reliable + reliable) regarding their diagnostic accuracy for cirrhosis and PHT and to identify potential confounders (age, aetiology, necroinflammatory activity, steatosis, siderosis, cholestasis, aminotransferases) of TE performance. METHODS: Patients undergoing simultaneous measurements of TE, portal pressure (hepatic venous pressure gradient, HVPG) and liver biopsy were analysed. RESULTS: Among 226 patients (48.7 ± 13.1 years, 74.7% male, 75.7% viral aetiology, 57% F3/F4), traditional TE quality criteria identified 71.6% reliable measurements, while new criteria yielded in 83.2% accurate results. Reliable TE values according to both criteria significantly correlated with fibrosis stage (r = 0.648 vs. r = 0.636) and HVPG (r = 0.836 vs. r = 0.846). Diagnostic accuracy for cirrhosis (cut-off >14.5 kPa) was 76.5% (AUC: 0.863) and 75.0% (AUC: 0.852) for traditional and new TE criteria, respectively, while for predicting HVPG ≥ 10 mmHg (>16.1 kPa), the accuracies were 88.9% (AUC: 0.957) and 89.8% (AUC: 0.962). New TE criteria allowed a better discrimination of reliable and non-reliable results for prediction of fibrosis and CSPH. Only aetiology and aminotransferases were independent confounders of the correlation of TE and fibrosis stage, while no confounder affected the correlation of TE and HVPG. CONCLUSIONS: New reliability criteria for TE measurements increase the number of patients with accurate measurements without affecting diagnostic performance for detecting cirrhosis and portal hypertension. Aetiology of liver disease and aminotransferases should be considered when assessing liver fibrosis by TE.

Endoscopists with low adenoma detection rates benefit from high-definition endoscopy.

BACKGROUND: An endoscopists adenoma detection rate (ADR) of less than 20 % correlates with high risk for occurrence of interval cancer. The impact of high-definition (HD) imaging on the ADR is discussed controversially. We aimed to investigate whether detection rates of individual endoscopists increase within 1 year before and 1 year after the switch from standard to HD endoscopy. METHODS: This cohort study analyzed 6,330 screening colonoscopies (2,968 with standard and 3,362 with HD) performed by 42 endoscopists between November 2007 and March 2013 within a nationwide quality assurance program for screening colonoscopy. RESULTS: The ADR of endoscopists with a low ADR (<20 %) increased significantly higher (from 11.8 to 18.1 %, p = 0.003) than of those with a high ADR (≥ 20 %) (from 28.6 to 30.7 %, p = 0.439) after switch from standard to HD colonoscopes (p = 0.0076). The proportion of endoscopists with an ADR < 20 % decreased from 45 to 42.9 % (p = 0.593). There was no significant increase in age- and sex-adjusted detection rates of adenomas (20.2 vs 23.7 %; p = 0.089), advanced adenomas (4.7 vs 5.5 %; p = 0.479), flat adenomas (2.7 vs 3.1 %; p = 0.515), polyps (38.8 vs 41.5 %; p = 0.305), proximal polyps (18.5 vs 20 %; p = 0.469) and hyperplastic polyps (15 vs 17.2 %; p = 0.243) of endoscopists after switch to HD colonoscopes. There was no difference in detection rates of flat polyps (5.5 vs 5.5 %; p = 0.987). CONCLUSIONS: The use of HD scopes is associated with marginal improvement in adenoma detection rates limited to those endoscopists with low adenoma detection rates prior to its introduction.

A greater proportion of liver transplant candidates have colorectal neoplasia than in the healthy screening population.

BACKGROUND & AIMS: Various types of liver disease are associated with an increased prevalence of colorectal adenomas. We investigated whether cirrhosis is a risk factor for colorectal neoplasia by analyzing colonoscopy findings from 2 cohorts of patients awaiting liver transplantation. METHODS: We performed a retrospective analysis to compare findings from colorectal cancer screenings of 567 adult patients with cirrhosis placed on the waitlist for liver transplantation with those from controls (matched for age, sex, body mass index, smoking, and diabetes). Rates of adenoma and advanced adenoma detection were adjusted owing to differences in rates of polypectomies performed in the 2 cohorts. RESULTS: Adenomas were detected in a significantly higher percentage of patients with cirrhosis (29.3%) than in controls (21.5%) (P = .0057; relative risk [RR], 1.36; 95% confidence interval [CI], 1.09-1.69); and patients with cirrhosis had a higher rate of advanced adenoma detection than controls (13.9% vs 7.7%; P = .0015; relative risk, 1.82; 95% CI, 1.25-2.64). A greater percentage of patients with alcoholic cirrhosis had neoplasias (34.3%) than controls (25.3%; P = .0350; RR, 1.36), and rates of advanced adenoma detection were 16.7% vs 10.2% (P = .0409; RR, 1.63). Adenomas were detected in 27.8% of patients with viral cirrhosis vs 15.9% of controls (P = .0061; RR, 1.74), with rates of advanced adenoma detection of 13.6% vs 5.0% (P = .0041; RR, 2.73). Similar proportions of patients with cirrhosis of other etiologies and controls were found to have colorectal neoplasias. CONCLUSIONS: Based on a retrospective analysis of colonoscopy findings from patients awaiting liver transplantation, those with alcoholic or viral cirrhosis are at higher risk of developing colorectal neoplasia and should be considered for earlier colonoscopy examination.

Sex is a stronger predictor of colorectal adenoma and advanced adenoma than fecal occult blood test.

Due to high costs and limited availability of screening colonoscopy, some screening programs require a positive fecal occult blood test (FOBT) before screening colonoscopy is remunerated. As male sex is a strong predictor of adenoma and advanced adenoma, we evaluated whether a positive FOBT or male sex is a stronger risk factor for adenoma and advanced adenoma. FOBT and screening colonoscopy results from 18.665 consecutive patients participating in a "national health check program" between 2009 and 2011 were included in this cohort study. Age-corrected adenoma detection rates (ADR), advanced adenoma detection rates (AADR) and carcinoma detection rates were calculated for men and women according to FOBT result separately. ADR and AADR in FOBT-positive men (34.6 and 11.8 %) and FOBT-negative men (29.1 and 7.6 %) were higher than ADR and AADR in FOBT-positive women (20 and 6.9 %) and in FOBT-negative women (17.6 and 4.4 %), (p = 0.0003). Men with negative FOBT were at higher risk of having an adenoma and advanced adenoma than women with positive FOBT (p < 0.0001). Odds ratios of a positive FOBT for ADR and AADR were 1.3 (1.1-1.5) (p = 0.0047) and 1.6 (1.2-2.1) (p < 0.0001), respectively. Odds ratios of male sex to predict ADR and AADR were significantly higher with 1.9 (1.8-2.1) and 1.8 (1.6-2), respectively (p < 0.001). Male sex is a stronger predictor for colorectal adenoma and advanced adenoma than positive FOBT. These results should be taken into account analyzing FOBT-based screening programs.

Meta-analysis: ARFI elastography versus transient elastography for the evaluation of liver fibrosis.

AIMS: This meta-analysis aims to compare the diagnostic performance of acoustic radiation force impulse (ARFI) elastography and transient elastography (TE) in the assessment of liver fibrosis using liver biopsy (LB) as 'gold-standard'. METHODS: PubMed, Medline, Lilacs, Scopus, Ovid, EMBASE, Cochrane and Medscape databases were searched for all studies published until 31 May 2012 that evaluated the liver stiffness by means of ARFI, TE and LB. Information abstracted from each study according to a fixed protocol included study design and methodological characteristics, patient characteristics, interventions, outcomes and missing outcome data. RESULTS: Thirteen studies (11 full-length articles and 2 abstracts) including 1163 patients with chronic hepatopathies were included in the analysis. Inability to obtain reliable measurements was more than thrice as high for TE as that of ARFI (6.6% vs. 2.1%, P < 0.001). For detection of significant fibrosis, (F ≥ 2) the summary sensitivity (Se) was 0.74 (95% CI: 0.66-0.80) and specificity (Sp) was 0.83 (95% CI: 0.75-0.89) for ARFI, while for TE the Se was 0.78 (95% CI: 0.72-0.83) and Sp was 0.84 (95% CI: 0.75-0.90). For the diagnosis of cirrhosis, the summary Se was 0.87 (95% CI: 0.79-0.92) and Sp was 0.87 (95% CI: 0.81-0.91) for ARFI elastography, and, respectively, 0.89 (95% CI: 0.80-0.94) and 0.87 (95% CI: 0.82-0.91) for TE. The diagnostic odds ratio of ARFI and TE did not differ significantly in the detection of significant fibrosis [mean difference in rDOR = 0.27 (95% CI: 0.69-0.14)] and cirrhosis [mean difference in rDOR = 0.12 (95% CI: 0.29-0.52)]. CONCLUSION: Acoustic radiation force impulse elastography seems to be a good method for assessing liver fibrosis, and shows higher rate of reliable measurements and similar predictive value to TE for significant fibrosis and cirrhosis.

The influence of aminotransferase levels on liver stiffness assessed by Acoustic Radiation Force Impulse Elastography: a retrospective multicentre study.

BACKGROUND: Acoustic Radiation Force Impulse Elastography is a new method for non-invasive evaluation of liver fibrosis. AIM: To evaluate the impact of elevated alanine aminotransferase levels on liver stiffness assessment by Acoustic Radiation Force Impulse Elastography. METHODS: A multicentre retrospective study including 1242 patients with chronic liver disease, who underwent liver biopsy and Acoustic Radiation Force Impulse. Transient Elastography was also performed in 512 patients. RESULTS: The best Acoustic Radiation Force Impulse cut-off for predicting significant fibrosis was 1.29 m/s in cases with normal alanine aminotransferase levels and 1.44 m/s in patients with alanine aminotransferase levels>5 × the upper limit of normal. The best cut-off for predicting liver cirrhosis were 1.59 and 1.75 m/s, respectively. Acoustic Radiation Force Impulse cut-off for predicting significant fibrosis and cirrhosis were relatively similar in patients with normal alanine aminotransferase and in those with alanine aminotransferase levels between 1.1 and 5 × the upper limit of normal: 1.29 m/s vs. 1.36 m/s and 1.59 m/s vs. 1.57 m/s, respectively. For predicting cirrhosis, the Transient Elastography cut-offs were significantly higher in patients with alanine aminotransferase levels between 1.1 and 5 × the upper limit of normal compared to those with normal alanine aminotransferase: 12.3 kPa vs. 9.1 kPa. CONCLUSION: Liver stiffness values assessed by Acoustic Radiation Force Impulse and Transient Elastography are influenced by high aminotransferase levels. Transient Elastography was also influenced by moderately elevated aminotransferase levels.

von Willebrand factor as new noninvasive predictor of portal hypertension, decompensation and mortality in patients with liver cirrhosis.

UNLABELLED: von Willebrand factor antigen (vWF-Ag) is elevated in patients with liver cirrhosis, but the clinical significance is unclear. We hypothesized that vWF-Ag levels may correlate with portal pressure, measured by hepatic venous pressure gradient (HVPG), and predict clinically significant portal hypertension (CSPH; HVPG ≥ 10 mmHg), decompensation and mortality. Portal hemodynamics were assessed by HVPG measurement, whereas vWF-Ag levels were measured by enzyme-linked immunosorbent assay. During follow-up, complications of liver cirrhosis, death or transplantation were recorded. Two hundred and eighty-six patients (205 male and 81 female; mean age, 56 years) with liver cirrhosis were included. vWF-Ag correlated with HVPG (r = 0.69; P < 0.0001) and predicted CSPH independently of Child Pugh score. Higher vWF-Ag levels were associated with varices (odds ratio [OR] = 3.27; P < 0.001), ascites (OR = 3.93; P < 0.001) and mortality (hazard ratio: 4.41; P < 0.001). Using a vWF-Ag cut-off value of ≥ 241%, the AUC for detection of CSPH in compensated patients was 0.85, with a positive predictive value and negative predictive value of 87% and 80%, respectively. Compensated patients had 25% mortality after 53 months if the vWF-Ag was <315% compared to 15 months in patients with vWF-Ag >315% (P < 0.001). Decompensated patients had a mortality of 25% after 37 and 7 months if their vWF-Ag was <315% and >315%, respectively (P = 0.002). In compensated patients with a vWF-Ag >315% median time to decompensation or death was 32 months compared with 59 months in patients with vWF-Ag <315%. vWF-Ag equals Model for End-Stage Liver Disease (MELD) in mortality prediction (area under the curve [AUC] = 0.71 for vWF-Ag versus AUC = 0.65 for MELD; P = 0.2). CONCLUSION: vWF-Ag is a new, simple and noninvasive predictor of CSPH. A vWF-Ag cut-off value at 315% can clearly stratify patients with compensated and decompensated liver cirrhosis in two groups with completely different survival. vWF-Ag may become a valuable marker for the prediction of mortality in patients with liver cirrhosis in clinical practice.