J. Vergniol

Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study

Background: Transient elastography (FibroScan) is a new, non-invasive, rapid, and reproducible method allowing evaluation of liver fibrosis by measurement of liver stiffness. In cirrhotic patients, liver stiffness measurements range from 12.5 to 75.5 kPa. However, the clinical relevance of these values is unknown. The aim of this prospective study was to evaluate the accuracy of liver stiffness measurement for the detection of cirrhosis in patients with chronic liver disease. Methods: A total of 711 patients with chronic liver disease were studied. Aetiologies of chronic liver diseases were hepatitis C virus or hepatitis B virus infection, alcohol, non-alcoholic steatohepatitis, other, or a combination of the above aetiologies. Liver fibrosis was evaluated according to the METAVIR score. Results: Stiffness was significantly correlated with fibrosis stage (ru200a=u200a0.73, p<0.0001). Areas under the receiver operating characteristic curve (95% confidence interval) were 0.80 (0.75–0.84) for patients with significant fibrosis (F>2), 0.90 (0.86–0.93) for patients with severe fibrosis (F3), and 0.96 (0.94–0.98) for patients with cirrhosis. Using a cut off value of 17.6 kPa, patients with cirrhosis were detected with a positive predictive value and a negative predictive value (NPV) of 90%. Liver stiffness was significantly correlated with clinical, biological, and morphological parameters of liver disease. With an NPV >90%, the cut off values for the presence of oesophageal varices stage 2/3, cirrhosis Child-Pugh B or C, past history of ascites, hepatocellular carcinoma, and oesophageal bleeding were 27.5, 37.5, 49.1, 53.7, and 62.7 kPa, respectively. Conclusion: Transient elastography is a promising non-invasive method for detection of cirrhosis in patients with chronic liver disease. Its use for the follow up and management of these patients could be of great interest and should be evaluated further.

Changes of non-invasive markers and FibroScan values during HCV treatment

Summary.u2002 The recent advent of non‐invasive methods for assessment of fibrosis allows serial assessments in all patients with hepatitis C. The aim of this prospective study was to evaluate changes in liver fibrosis, as measured with non‐invasive methods, in a large cohort of HCV‐infected patients with and without treatment. From May 2003 through March 2006, all previously untreated HCV‐infected patients were enrolled in this study. Liver fibrosis was staged with FibroScan and Fibrotest at inclusion, then every year in untreated patients, and at the end of treatment and 6u2003months later in treated patients. The study population consisted of 416 patients, of whom 112 started treatment after enrolment. In the treatment group, FibroScan and Fibrotest values were significantly higher before and after treatment than in untreated patients at baseline and after 1u2003year. However, there was no significant difference between treated and untreated patients at the end of follow‐up. FibroScan and Fibrotest values fell in all treated patients, whatever their virological response. In multivariate analysis, treatment was the only factor independently associated with a fall in the FibroScan value. In conclusion, whatever the virological response, treatment for HCV infection is associated with an improvement of FibroScan and Fibrotest values. Further studies are needed to compare these non‐invasive methods with liver biopsy. These non‐invasive methods, and especially FibroScan, should be useful for assessing treatment efficacy in clinical trials of new drugs.

Non-invasive tests for fibrosis and liver stiffness predict 5-year survival of patients chronically infected with hepatitis B virus.

Liver stiffness and non‐invasive tests predict overall survival in chronic hepatitis C. However, in patients chronically infected with hepatitis B virus (HBV), only the association between liver stiffness and the risk of hepatocellular carcinoma has been published.

Staging chronic hepatitis C in seven categories using fibrosis biomarker (FibroTest™) and transient elastography (FibroScan®).

BACKGROUND & AIMSnFibroTest™ (FT) and Transient Elastography (TE) have been validated as non-invasive markers of METAVIR fibrosis stages from F0 to F4 using biopsy, and as prognostic markers of liver related mortality in patients with chronic hepatitis C. The aim was to extend the validation of FT and TE as markers of critical steps defined by occurrence of cirrhosis without complications (F4.1), esophageal varices (F4.2), and severe complications (F4.3): primary liver cancer, variceal bleeding, or decompensation (ascites, encephalopathy, or jaundice).nnnMETHODSnThe updated individual data of 3927 patients (1046 cirrhotics) without complications at baseline were pooled from three prospective cohorts called EPIC, Paris, and Bordeaux cohorts.nnnRESULTSnAt 5 years, among 501 patients without varices at baseline (F4.1) varices occurred in 19 patients [F4.2 incidence of 4.0% (95% CI 2.2-5.8)]. The predictive performance (AUROC) of FT was 0.77 (0.66-0.84; p<0.001). At 10 years severe complications occurred in 203 patients, [F4.3 incidence of 13.4% (9.6-17.1)], including primary liver cancer in 84 patients [6.4% (3.5-9.3)]. FT was predictive (Cox adjusted on treatment) of severe complications [AUROC 0.79 (76-82); p<0.0001], including primary liver cancer [AUROC 0.84 (80-87); p<0.0001]. Similarly TE was predictive of severe complications [AUROC 0.77 (72-81); p<0.0001], including primary liver cancer [AUROC 0.86 (81-90); p<0.0001].nnnCONCLUSIONSnFibroTest™ and TE increase were associated with the occurrence of all severe complications including hepatocellular carcinoma, hepatic insufficiency, and variceal bleeding. FibroTest™ increase was also associated with the occurrence of esophageal varices.

Staging chronic hepatitis B into seven categories, defining inactive carriers and assessing treatment impact using a fibrosis biomarker (FibroTest®) and elastography (FibroScan®)

BACKGROUND & AIMSnThe first aim was to extend the validation of FibroTest® (FT) and transient elastography (TE) as markers of occurrence of cirrhosis without complications (F4.1), oesophageal varices (F4.2), and severe complications (F4.3) in patients with chronic hepatitis B (CHB). The second aim was to validate a previous definition of an inactive carrier based on normal FT and ActiTest® (normal-FT-AT). The third aim was to assess the long-term dynamics of fibrosis in patients with sustained virological response.nnnMETHODSnThe 10-year updated individual data of 1434 patients were pooled from two prospective cohorts.nnnRESULTSnOf the 1312 patients without a history of complications, varices had occurred after 10 years in 14 patients (F4.2, incidence of 1.7%, 95% CI [0.6-2.8]), and severe complications in 25 (F4.3 3.7% [1.8-5.7]), including hepatocellular carcinoma (HCC) in 21 (3.7% [1.5-5.8]). Using Cox-multivariate analysis adjusted for treatment, viral load, HBeAg status and ALT, FT, and TE were predictive of liver complications (n=37; AUROC=0.83 [0.71-0.90]; p<0.0001) and (n=8/844; AUROC=0.82 [0.72-0.89]; p<0.0001) respectively. Normal FT-AT better identified patients with lower fibrosis progression than the ALT-based standard: 3/163 (1.8%) vs. 16/181 (8.8%; p=0.004) in the Paris cohort, and 5/195 (2.6%) vs. 15/228 (6.6%; p=0.05) in the Bordeaux cohort. Of the 582 responders, 23 had complications (incidence 6.2% [3.2-9.1]) including 19 HCC (5.8% [2.6-9.0]) and 10 with varices (2.6% [0.8-4.4]). Of the 138 responders with advanced fibrosis, only 31% (15-47%) had fibrosis regression.nnnCONCLUSIONSnFibroTest® and TE identified three categories of cirrhosis with increasing morbidity. Normal FibroTest® and ActiTest® were better able to identify inactive hepatitis B carriers than the standard definition. Despite virological response, the overall incidence of cirrhosis increased, with a remaining 5.8% risk of HCC.

Liver stiffness measurements for evaluation of central venous pressure in congenital heart diseases

Objective Transient elastography (TE; Fibroscan, Echosens, France) is a non-invasive and reproducible approach to assess liver stiffness (LS). LS has been reported to be associated with fibrosis but central venous pressure (CVP) can also influence LS values. We sought to evaluate the correlation between LS and CVP in a large cohort of children and adults with congenital heart disease. Methods All patients referred in our institution between 2012 and 2013 for diagnostic or interventional right heart catheterisation (RHC) were prospectively enrolled excluding patients with acute heart failure, chronic alcohol abuse, chronic liver disease, severe obesity and ascites. Patients underwent LS measurement and CVP measurement by RHC under general anaesthesia within the same or subsequent day. Results Sixty children (7.4±5.5u2005years) and 36 adults (38±16u2005years) were included. Median CVP was 6u2005mmu2005Hg (range 3–15), median LS was 5u2005kPa (range 2.8–47.2). LS significantly correlated with CVP (r=0.75, p<10−4). In the two subgroups (ie, children and adults), correlation was r=0.68 and r=0.84 (p<10−4), respectively. In the overall population, the area under the curve of LS for identification of CVP >10u2005mmu2005Hg was 0.972 (95% CI 0.855 to 1; p<0.05). Optimal cut-off value of LS for detection of CVP >10u2005mmu2005Hg was 8.8u2005kPa (sensitivity=91.67%, specificity=96.25%). Conclusions LS measurement using TE is a rapid and reliable method to evaluate CVP in patients with congenital heart disease.

989 NEW FIBROSCAN PROBE FOR OBESE PATIENTS. A PILOT STUDY OF FEASIBILITY AND PERFORMANCES IN PATIENTS WITH BMI ≥ 30 kg/m2

Liver stiffness measurement (LSM) failure rate ranges between 2 and 10% when using FibroScan® and is generally due to obese patients. The aim of this prospective study was to evaluate a new probe for the FibroScan® designed to overcome this limitations in terms of feasibility compared to the M (standard) probe.100 patients with a BMI 30 kg/m2 were recruited (27 men, mean age 52 years, mean BMI 41 (30−64) kg/m2. LSM was attempted with the M (central US frequency: 5MHz, diameter: 7mm, measurement depths: 25−65mm below the skin surface) and XL (2.5MHz, 10mm, 35−75mm) probes using an ultrasound imaging system to optimize the measurement point.The feasibility of LSM with both probes is presented in Table 1 (Fisher’s exact test, Wilcoxon signed rank test). LSM was significantly (p< 0.05) correlated with platelets (Spearman: −0.24), phosphatase alkaline (0.25) and glycemia (0.45) but not to prothrombin time, total bilirubin, GGT or transaminases. It was significantly correlated with non invasive markers: FIB-4 (0.26), Forns (0.27) and Virahep-C (0.30). Due to the presence of non hepatic tissue in the volume explored with the M probe in overweighed patients, LSM was lower with XL probe than M Probe.

Serial combination of non-invasive tools improves the diagnostic accuracy of severe liver fibrosis in patients with NAFLD.

The accuracy of available non‐invasive tools for staging severe fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) is still limited.

Sexual quality of life is impaired in patients with chronic hepatitis C

Chronic hepatitis C (CHC) patients often have altered quality of life. Few data are available about sexual impairment (SI) in CHC. From 2011 to 2013, we included consecutive CHC outpatients. Exclusion criteria were: antiviral therapy, co-infection, age <18 or >75, transplantation, alcohol consumption, Eastern Cooperative Oncology Group >1. Non-CHC subjects were healthy blood donors. Sexual questionnaires for men and women were adapted from the International Index of Erectile Function and Female Sexual Function Index, respectively, and concerned the past 30 days. Two hundred eighty-one patients were compared with 1086 blood donors. SI was more frequent in CHC patients. Men with CHC had worse desire, confidence, erections, climax and satisfaction (P<0.001). Women with CHC had worse desire, arousal, climax, satisfaction, lubrication and comfort (P<0.001). In multivariate analysis, factors associated with SI in men were CHC (odds ratio (OR)=4.45, 95% confidence interval (CI) 2.46–8.06), age (OR=1.06, 95% CI 1.03–1.09), no intercourse (OR=8.74, 95% CI 4.65–16.04) and unemployment (OR=2.14, 95% CI 1.16–3.95). Factors associated with a worse global sexual life in women were CHC (OR=7.96, 95% CI 4.07–15.58) and no intercourse (OR=21.39, 95% CI 11.03–41.48). The study results were corroborated by propensity score-matching analysis. Sexual life is impaired in men and women with CHC. In clinical practice, sexual quality of life should be evaluated and treated.

Risk of Incident Cancer in Inflammatory Bowel Disease Patients Starting Anti-TNF Therapy While Having Recent Malignancy.

Background:Patients with inflammatory bowel disease (IBD) and history of malignancy within the last 5 years are usually contraindicated for receiving anti–tumor necrosis factor (anti-TNF) agents. The aim of this study is to assess survival without incident cancer in a cohort of IBD patients exposed to anti-TNF while having previous malignancy within past 5 years. Methods:Data from IBD patients with previous malignancy diagnosed within the last 5 years before starting an anti-TNF agent were collected through a Groupe dEtude Thérapeutiques des Affections Inflammatoires du tube Digestif multicenter survey. Inclusion date corresponded to the first anti-TNF administration after cancer diagnosis. Results:Twenty centers identified 79 cases of IBD patients with previous malignancy diagnosed 17 months (median; range: 1–65) before inclusion. The most frequent cancer locations were breast (n = 17) and skin (n = 15). After a median follow-up of 21 (range: 1–119) months, 15 (19%) patients developed incident cancer (8 recurrent and 7 new cancers), including 5 basal-cell carcinomas. Survival without incident cancer was 96%, 86%, and 66% at 1, 2, and 5 years, respectively. Crude incidence rate of cancer was 84.5 (95% CI, 83.1–85.8) per 1000 patient-years. Conclusions:In a population of refractory IBD patients with recent malignancy, anti-TNF could be used taking into account a mild risk of incident cancer. Pending prospective and larger studies, a case-by-case joint decision taken with the oncologist is recommended for managing these patients in daily practice.