The effects of vasopressin and its analogues on the liver and its disorders in the critically ill:

Purpose of review: Vasopressin and terlipressin, a long-acting V1a analogue, are increasingly used in intensive care. The main clinical indications are the treatment of patients with septic shock and of patients with cirrhosis, who develop variceal bleeding, the hepatorenal syndrome or both. In this review, we summarize the effects of these drugs on splanchnic hemodynamics and organ function.Recent findings: A recent systematic meta-analysis of randomized trials suggests that terlipressin may improve renal function in hepatorenal syndrome and thereby reduce mortality by 34%. Moreover, a recent study reported that association of terlipressin and albumin was more effective than terlipressin alone. In patients with variceal bleeding, the bleeding control is significantly improved by early administration of terlipressin. The place of vasopressin in the treatment of patients with septic shock is still discussed, but compared with norepinephrine, vasopressin showed at least an equal efficacy. Summary: The use of vasopressin and its synthetic analogues has shown beneficial effects in the management of patients with cirrhosis, especially in the context of variceal bleeding, the hepatorenal syndrome or both. In both cases, the use of terlipressin improved survival. Therefore, in these clinical indications, terlipressin is a part of recommendations. The role of vasopressin in patients with septic shock remains to be precisely evaluated

The noninvasive diagnosis of esophageal varices and its application in clinical practice

Here, we review recent improvements made to different noninvasive tests used for the diagnosis of esophageal varices (EV) in the light of the recent Baveno VI recommendation and with an emphasis on clinical application. Like for fibrosis tests, these noninvasive EV tests can be classified as direct markers when they provide a visualization of EV (including all imaging procedures like endoscopy or radiology) and as indirect markers when they do not (blood markers or elastometry). Clinical descriptors expressed as percentages, especially the spared endoscopy rate and the missed high-risk esophageal varices (HREV) rate, are more eloquent in this setting than classical statistical descriptors like accuracy. Single biomarkers are insufficient, generally due to a missed HREV rate exceeding the acceptable limit of 5% indicated in the Baveno VI consensus. Thus, biomarker combinations are currently garnering the most interest. The Baveno VI recommendation states that in alcoholic and viral cirrhoses, screening endoscopy can be safely set aside for patients with liver stiffness<20kPa and platelets>150G/L. The Baveno rule\u27s mean missed HREV rate is<5% but its spared endoscopy rate is<20%. New combinations or stepwise algorithms show promise but must be validated. Going forward, the Baveno rule provides a simple noninvasive method to rule out HREV in clinical practice but the need for further research continues. The noninvasive diagnosis of HREV will be significantly improved by new, simple and affordable combinations

Cirrhosis Diagnosis and Liver Fibrosis Staging: Transient Elastometry Versus Cirrhosis Blood Test.

INTRODUCTION: Elastometry is more accurate than blood tests for cirrhosis diagnosis. However, blood tests were developed for significant fibrosis, with the exception of CirrhoMeter developed for cirrhosis. We compared the performance of Fibroscan and CirrhoMeter, and classic binary cirrhosis diagnosis versus new fibrosis staging for cirrhosis diagnosis. METHODS: The diagnostic population included 679 patients with hepatitis C and liver biopsy (Metavir staging and morphometry), Fibroscan, and CirrhoMeter. The prognostic population included 1110 patients with chronic liver disease and both tests. RESULTS: Binary diagnosis: AUROCs for cirrhosis were: Fibroscan: 0.905; CirrhoMeter: 0.857; and P=0.041. Accuracy (Youden cutoff) was: Fibroscan: 85.4%; CirrhoMeter: 79.2%; and P<0.001. Fibrosis classification provided 6 classes (F0/1, F1/2, F2±1, F3±1, F3/4, and F4). Accuracy was: Fibroscan: 88.2%; CirrhoMeter: 88.8%; and P=0.77. A simplified fibrosis classification comprised 3 categories: discrete (F1±1), moderate (F2±1), and severe (F3/4) fibrosis. Using this simplified classification, CirrhoMeter predicted survival better than Fibroscan (respectively, χ=37.9 and 19.7 by log-rank test), but both predicted it well (P<0.001 by log-rank test). Comparison: binary diagnosis versus fibrosis classification, respectively, overall accuracy: CirrhoMeter: 79.2% versus 88.8% (P<0.001); Fibroscan: 85.4% versus 88.2% (P=0.127); positive predictive value for cirrhosis by Fibroscan: Youden cutoff (11.1 kPa): 49.1% versus cutoffs of F3/4 (17.6 kPa): 67.6% and F4 classes (25.7 kPa): 82.4%. CONCLUSIONS: Fibroscan\u27s usual binary cutoffs for cirrhosis diagnosis are not sufficiently accurate. Fibrosis classification should be preferred over binary diagnosis. A cirrhosis-specific blood test markedly attenuates the accuracy deficit for cirrhosis diagnosis of usual blood tests versus transient elastometry, and may offer better prognostication

On-sky results of the adaptive optics MACAO for the new IR-spectrograph CRIRES at VLT

The adaptive optics MACAO has been implemented in 6 focii of the VLT observatory, in three different flavors. We present in this paper the results obtained during the commissioning of the last of these units, MACAO-CRIRES. CRIRES is a high-resolution spectrograph, which efficiency will be improved by a factor two at least for point-sources observations with a NGS brighter than R=15. During the commissioning, Strehl exceeding 60% have been observed with fair seeing conditions, and a general description of the performance of this curvature adaptive optics system is done.Comment: SPIE conference 2006, Advances in adaptive optics, 12 pages, 11 figure

Simple blood fibrosis tests reduce unnecessary referrals for specialized evaluations of liver fibrosis in NAFLD and ALD patients

BACKGROUND: Liver fibrosis evaluation is mandatory in non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) to decide the patient management. Patients with these diseases are usually under the care of non-liver specialists who refer them to specialized centers where the most accurate fibrosis tests are available. We aimed to evaluate whether simple blood fibrosis tests available to all physicians help to reduce the rate of unnecessary referral of NAFLD and ALD patients without advanced fibrosis. METHODS: NAFLD and/or ALD patients newly referred to our center for a non-invasive evaluation of liver fibrosis were retrospectively included. The FibroMeter (FM, combination of blood markers and Fibroscan results) was defined as the reference test for specialized evaluation of liver fibrosis. A FM result <0.384 indicated the absence of advanced fibrosis and thus an "unnecessary referral". RESULTS: 558 patients were included (NAFLD: 283, ALD: 156, mixed NAFLD+ALD: 119). FM was <0.384 (unnecessary referral) in 58.8% of patients. FIB4 was <1.30 in 45.2% and eLIFT <8 in 47.7% of the patients. 84.9% of patients with FIB4 <1.30 and 85.3% of patients with eLIFT <8 had also FM <0.384. Therefore, using FIB4 or eLIFT as first-line evaluation of liver fibrosis decreased by three-fold the rate of unnecessary referral. The negative predictive value of FIB4 and eLIFT was >80% whatever the underlying cause of chronic liver disease. CONCLUSION: The use of eLIFT by non-liver specialists for NAFLD and ALD patients can improve the relevance of referrals for specialized evaluation of liver fibrosis

Factors limiting complete tumor ablation by radiofrequency ablation

The purpose of this study was to determine radiological or physical factors to predict the risk of residual mass or local recurrence of primary and secondary hepatic tumors treated by radiofrequency ablation (RFA). Eighty-two patients, with 146 lesions (80 hepatocellular carcinomas, 66 metastases), were treated by RFA. Morphological parameters of the lesions included size, location, number, ultrasound echogenicity, computed tomography density, and magnetic resonance signal intensity were obtained before and after treatment. Parameters of the generator were recorded during radiofrequency application. The recurrence-free group was statistically compared to the recurrence and residual mass groups on all these parameters. Twenty residual masses were detected. Twenty-nine lesions recurred after a mean follow-up of 18 months. Size was a predictive parameter. Patients\u27 sex and age and the echogenicity and density of lesions were significantly different for the recurrence and residual mass groups compared to the recurrence-free group (p < 0.05). The presence of an enhanced ring on the magnetic resonance control was more frequent in the recurrence and residual mass groups. In the group of patients with residual lesions, analysis of physical parameters showed a significant increase (p < 0.05) in the time necessary for the temperature to rise. In conclusion, this study confirms risk factors of recurrence such as the size of the tumor and emphasizes other factors such as a posttreatment enhanced ring and an increase in the time necessary for the rise in temperature. These factors should be taken into consideration when performing RFA and during follow-up

Combination of blood tests for significant fibrosis and cirrhosis improves the assessment of liver-prognosis in chronic hepatitis C

BACKGROUND: Recent longitudinal studies have emphasised the prognostic value of noninvasive tests of liver fibrosis and cross-sectional studies have shown their combination significantly improves diagnostic accuracy. AIM: To compare the prognostic accuracy of six blood fibrosis tests and liver biopsy, and evaluate if test combination improves the liver-prognosis assessment in chronic hepatitis C (CHC). METHODS: A total of 373 patients with compensated CHC, liver biopsy (Metavir F) and blood tests targeting fibrosis (APRI, FIB4, Fibrotest, Hepascore, FibroMeter) or cirrhosis (CirrhoMeter) were included. Significant liver-related events (SLRE) and liver-related deaths were recorded during follow-up (started the day of biopsy). RESULTS: During the median follow-up of 9.5 years (3508 person-years), 47 patients had a SLRE and 23 patients died from liver-related causes. For the prediction of first SLRE, most blood tests allowed higher prognostication than Metavir F [Harrell C-index: 0.811 (95% CI: 0.751-0.868)] with a significant increase for FIB4: 0.879 [0.832-0.919] (P = 0.002), FibroMeter: 0.870 [0.812-0.922] (P = 0.005) and APRI: 0.861 [0.813-0.902] (P = 0.039). Multivariate analysis identified FibroMeter, CirrhoMeter and sustained viral response as independent predictors of first SLRE. CirrhoMeter was the only independent predictor of liver-related death. The combination of FibroMeter and CirrhoMeter classifications into a new FM/CM classification improved the liver-prognosis assessment compared to Metavir F staging or single tests by identifying five subgroups of patients with significantly different prognoses. CONCLUSIONS: Some blood fibrosis tests are more accurate than liver biopsy for determining liver prognosis in CHC. A new combination of two complementary blood tests, one targeted for fibrosis and the other for cirrhosis, optimises assessment of liver-prognosis

Acoustic radiation force impulse: a new ultrasonographic technology for the widespread noninvasive diagnosis of liver fibrosis:

Background/aims: As a module of a standard ultrasound imaging device, acoustic radiation force impulse (ARFI) is a new technology for liver stiffness evaluation (LSE). We aimed to evaluate accuracy, feasibility, reproducibility, and training effect of ARFI for liver fibrosis evaluation.Methods: One hundred and one patients with chronic liver disease had LSE by Fibroscan and ARFI. LSE by ARFI was performed in the two liver lobes by two operators: an expert and a novice. Correlation and agreement were evaluated by the Pearson (Rp) and intraclass (Ric) correlation coefficients. The independent reference for liver fibrosis was fibrosis blood tests. Results: ARFI results, ranging from 0.7 to 4.6 m/s, were well correlated with Fibroscan results (Rp=0.76). Fibroscan had a significantly higher area under the receiver operating characteristic curve (AUROC) than ARFI for the perprotocol diagnosis of significant fibrosis: 0.890±0.034 versus 0.795±0.047 (P=0.04). However, LSE failure occurred in zero patients using ARFI versus six patients using Fibroscan (P=0.03). Thus, on an intention-to-diagnose basis, Fibroscan and ARFI AUROCs for the diagnosis of significant fibrosis were not different: 0.791±0.049 versus 0.793±0.046 (P=0.98). Interobserver agreement was very good (Ric=0.84) and excellent for ARFI interquartile range (IQR)≤0.30 (Ric=0.91). Indeed, agreement was independently predicted only by ARFI IQR, but not by LSE result as earlier observed for Fibroscan. ARFI AUROC was 0.876±0.057 in patients with ARFI IQR ratio≤0.30, and Fibroscan AUROC was 0.912±0.034 in patients with Fibroscan IQR ratio less than 0.21 (P=0.59). Intersite ARFI agreement between the two liver lobes was fair (Ric=0.60). There was no training effect for LSE by ARFI. Conclusion: ARFI is highly feasible and reproducible, and provides diagnostic accuracy similar to Fibroscan. This new device seems noteworthy for the widespread noninvasive diagnosis of liver fibrosis

Treatment of liver fibrosis: Clinical aspects

SummaryThe main objective of antifibrotic treatment is to avoid the complications of chronic liver disease where its cause cannot be treated. Three main therapeutic endpoints can be targeted: cause; comorbidity; and fibrosis. Antifibrotic treatment is any intervention independent of cause that is intended to modify the course and/or level of fibrosis through direct action on the mechanisms of fibrosis. Several modalities are here considered: reduction of fibrosis course; reversion of fibrosis; and reversion of cirrhosis. Semiquantitative histological staging and morphometry are complementary techniques for monitoring fibrosis. The degree of fibrosis should preferentially be estimated by fibrosis progression based on measurements taken at baseline and during treatment, rather than by raw static measurements. Surrogate markers are the only tools for assessing drug efficacy in clinical practice, and are especially useful for checking compliance and identifying poor or non-responders. We propose to define non-response as no decrease in fibrosis progression. The renin–angiotensin system is a good candidate target for antifibrotic treatment, and angiotensin-II type-1 receptor blockers, such as sartans, are probably effective. Clinical trials are currently ongoing using marketed drugs, while new multitargeted drugs are likely to emerge from basic research