Gadoxetic acid-enhanced MRI-derived functional liver imaging score (FLIS) and spleen diameter predict outcomes in ACLD.

BACKGROUND & AIMS: Functional liver imaging score (FLIS) - derived from gadoxetic acid-enhanced MRI - correlates with liver function and independently predicts liver-related mortality in patients with chronic liver disease (CLD), while splenic craniocaudal diameter (SCCD) is a marker of portal hypertension. The aim of this study was to investigate the accuracy of a combination of FLIS and SCCD for predicting hepatic decompensation, acute-on-chronic liver failure (ACLF), and mortality in patients with advanced CLD (ACLD). METHODS: We included 397 patients with CLD who underwent gadoxetic acid-enhanced liver MRI. The FLIS was calculated by summing the points (0-2) of 3 hepatobiliary-phase features: hepatic enhancement, biliary excretion, and portal vein signal intensity. Patients were stratified into 3 groups according to liver fibrosis severity and presence/history of hepatic decompensation: non-ACLD, compensated ACLD (cACLD), and decompensated ACLD (dACLD). RESULTS: SCCD showed excellent intra- and inter-reader agreement. Importantly, SCCD was an independent risk factor for hepatic decompensation in patients with cACLD (per cm; adjusted hazard ratio [aHR] 1.13; 95% CI 1.04-1.23; p = 0.004). Patients with cACLD and a FLIS of 0-3 points and/or a SCCD of >13 cm were at increased risk of hepatic decompensation (aHR 3.07; 95% CI 1.43-6.59; p = 0.004). In patients with dACLD, a FLIS of 0-3 was independently associated with an increased risk of ACLF (aHR 2.81; 95% CI 1.16-6.84; p = 0.02), even after adjusting for other prognostic factors. Finally, a FLIS and SCCD-based algorithm was independently predictive of transplant-free mortality and stratified the probability of transplant-free survival (TFS) in ACLD (p <0.001): FLIS 4-6 and SCCD ≤13 cm (5-year TFS of 84%) vs. FLIS 4-6 and SCCD >13 cm (5-year TFS of 70%) vs. FLIS 0-3 (5-year TFS of 24%). CONCLUSION: The FLIS and SCCD are simple imaging markers that provide complementary information for risk stratification in patients with compensated and decompensated ACLD. LAY SUMMARY: Magnetic resonance imaging (MRI) can be used to assess the state of the liver. Previously the functional liver imaging score, which is based on MRI criteria, was developed as a measure of liver function and to predict the risk of liver-related complications or death. By combining this score with a measurement of spleen diameter, also using MRI, we generated an algorithm that could predict the risk of adverse liver-related outcomes in patients with advanced chronic liver disease.

MRI-defined sarcopenia predicts mortality in patients with chronic liver disease.

BACKGROUND & AIMS: To explore whether sarcopenia, diagnosed by an abbreviated magnetic resonance imaging (MRI) protocol is a risk factor for hepatic decompensation and mortality in patients with chronic liver disease (CLD). METHODS: In this retrospective single-centre study we included 265 patients (164 men, mean age 54 ± 16 years) with CLD who had undergone MRI of the liver between 2010 and 2015. Transverse psoas muscle thickness (TPMT) was measured on unenhanced and contrast-enhanced T1-weighted and T2-weighted axial images. Sarcopenia was defined by height-adjusted and gender-specific cut-offs in women as TPMT < 8 mm/m and in men as TPMT < 12 mm/m respectively. Patients were further stratified into three prognostic stages according to the absence of advanced fibrosis (FIB-4 < 1.45, non-advanced CLD), compensated-advanced CLD (cACLD) and decompensated-advanced CLD (dACLD). RESULTS: The inter-observer agreement for the TPMT measurements (κ = 0.98; 95% confidence interval [95% CI]:0.96-0.98), as well as the intra-observer agreement between the three image sequences (κ = 0.99; 95% CI: 0.99-1.00) were excellent. Sarcopenia was not predictive of first or further hepatic decompensation. In patients with cACLD and dACLD, sarcopenia was a risk factor for mortality (cACLD: hazard ratio (HR):3.13, 95% CI: 1.33-7.41, P = .009; dACLD:HR:2.45, 95% CI: 1.32-4.57, P = .005) on univariate analysis. After adjusting for the model of end-stage liver disease (MELD) score, albumin and evidence of clinical significant portal hypertension, sarcopenia (adjusted HR: 2.76, 95% CI: 1.02-7.42, P = .045) remained an independent risk factor for mortality in patients with cACLD. CONCLUSION: Sarcopenia can be easily evaluated by a short MRI exam without the need for contrast injection. Sarcopenia is a risk factor for mortality, especially in patients with cACLD.

Open-Label Study of the Stability of Sublingual Nitroglycerin Tablets in Simulated Real-Life Conditions.

Contemporary practice favors refilling sublingual nitroglycerin (SL NTG) every 3 to 6 months. This recommendation is based on antiquated data that does not consider the reformulated tablet and the improved manufacturing process. Our objective was to investigate the stability of SL NTG over time using simulated real-life scenarios in comparison to controlled storage conditions. This was an open-label study of 100- and 25-count commercial SL NTG bottles stored in either controlled temperature and relative humidity conditions, or carried in a pocket or purse. SL NTG potency (chemical stability) was assessed using high performance liquid chromatography and physical stability was assessed by changes in tablet weights over time through the labeled expiration date. Both chemical and physical stability of SL NTG were affected by environmental and physical factors. High temperature storage resulted in the most rapid loss of potency. Tablets carried in a pant pocket lost potency faster than those carried in a purse. Potency was also dependent on headspace of the bottle. Tablets stored in the original bottle in a temperate environment could be expected to maintained potency for more than 2 years when carried in a purse, irrespective of package size. When carried in a pant pocket, potency of a 25-count bottle was maintained for 2 years, whereas potency of a 100-count bottle fell below acceptable limits at 12 months. In conclusion, since potency is dependent on temperature, headspace, and carrying practices, frequency of SL NTG refills should be based on individual patient behavior.

State of the art in vivo imaging techniques for laboratory animals.

In recent decades, imaging devices have become indispensable tools in the basic sciences, in preclinical research and in modern drug development. The rapidly evolving high-resolution in vivo imaging technologies provide a unique opportunity for studying biological processes of living organisms in real time on a molecular level. State of the art small-animal imaging modalities provide non-invasive images rich in quantitative anatomical and functional information, which renders longitudinal studies possible allowing precise monitoring of disease progression and response to therapy in models of different diseases. The number of animals in a scientific investigation can be substantially reduced using imaging techniques, which is in full compliance with the ethical endeavours for the 3R (reduction, refinement, replacement) policies formulated by Russell and Burch; furthermore, biological variability can be alleviated, as each animal serves as its own control. The most suitable and commonly used imaging modalities for in vivo small-animal imaging are optical imaging (OI), ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), and finally the methods of nuclear medicine: positron emission tomography (PET) and single photon emission computed tomography (SPECT).

Liver regeneration after different degrees of portal vein ligation.

BACKGROUND: Selective portal vein ligation (PVL) is followed by ipsilateral atrophy and contralateral hypertrophy of the liver lobes. Although the atrophy-hypertrophy complex induced by PVL is a well-documented phenomenon, the effect of different degrees of extended portal vein occlusion on liver regeneration is not known. The aim of this study was to assess the effects of different degrees of portal occlusion on portal pressure and liver regeneration. MATERIALS AND METHODS: Male Wistar rats (n = 96; 220-250 g) were randomized into three groups and underwent 70%, 80%, or 90% portal vein ligation, respectively. The portal pressure was measured immediately and 24, 48, 72, 120, and 168 h after PVL (n = 6/group/time point). The hepatic lobes and the spleen were weighed, and liver regeneration ratio was calculated. Changes in liver histology and the mitotic activity were assessed on hematoxylin-eosin stained slides. RESULTS: Higher degree of portal occlusion triggered a stronger regenerative response (regeneration ratio of PVL 70%168h = 2.23 ± 0.13, PVL 80%168h = 3.11 ± 0.37, PVL 90%168h = 4.68 ± 0.48) PVL led to an immediate increase in portal pressure, the value of which changed proportionally to the mass of liver tissue deprived of portal perfusion (PVL 70%acute = 17 ± 2 mm Hg, PVL 80%acute = 19 ± 1 mm Hg, PVL 90%acute = 26 ± 4 mm Hg). Findings in histology showed necro-apoptotic lesions in the atrophic liver lobes and increased mitotic cell count in the hypertrophic lobes. The mitotic cell count of PVL 90% peaked earlier and at a significantly higher value than of PVL 70% and PVL 80% (PVL 9024h%: 96.0 ± 3.5 PVL 70%48h: 64.0 ± 2.1, PVL 80%48h: 56.3 ± 4.0). The mitotic index after 24 h showed a strong correlation with the acute portal hypertension. CONCLUSIONS: A higher degree of portal vein occlusion leads to a greater regenerative response, presumably triggered by the proportional increase in portal pressure, which supports the role of the so-called "blood-flow" theory of PVL-triggered liver regeneration.