Arterial Calcifications in Patients with Liver Cirrhosis Are Linked to Hepatic Deficiency of Pyrophosphate Production Restored by Liver Transplantation

International audienceLiver fibrosis is associated with arterial calcification (AC). Since the liver is a source of inorganic pyrophosphate (PPi), an anti-calcifying compound, we investigated the relationship between plasma PPi ([PPi]pl), liver fibrosis, liver function, AC, and the hepatic expression of genes regulating PPi homeostasis. To that aim, we compared [PPi]pl before liver transplantation (LT) and 3 months after LT. We also assessed the expression of four key regulators of PPi in liver tissues and established correlations between AC, and scores of liver fibrosis and liver failure in these patients. LT candidates with various liver diseases were included. AC scores were assessed in coronary arteries, abdominal aorta, and aortic valves. Liver fibrosis was evaluated on liver biopsies and from non-invasive tests (FIB-4 and APRI scores). Liver functions were assessed by measuring serum albumin, ALBI, MELD, and Pugh–Child scores. An enzymatic assay was used to dose [PPi]pl. A group of patients without liver alterations from a previous cohort provided a control group. Gene expression assays were performed with mRNA extracted from liver biopsies and compared between LT recipients and the control individuals. [PPi]pl negatively correlated with APRI (r = −0.57, p = 0.001, n = 29) and FIB-4 (r = −0.47, p = 0.006, n = 29) but not with interstitial fibrosis index from liver biopsies (r = 0.07, p = 0.40, n = 16). Serum albumin positively correlated with [PPi]pl (r = 0.71; p < 0.0001, n = 20). ALBI, MELD, and Pugh–Child scores correlated negatively with [PPi]pl (r = −0.60, p = 0.0005; r = −0.56, p = 0.002; r = −0.41, p = 0.02, respectively, with n = 20). Liver fibrosis assessed on liver biopsies by FIB-4 and by APRI positively correlated with coronary AC (r = 0.51, p = 0.02, n = 16; r = 0.58, p = 0.009, n = 20; r = 0.41, p = 0.04, n = 20, respectively) and with abdominal aorta AC (r = 0.50, p = 0.02, n = 16; r = 0.67, p = 0.002, n = 20; r = 0.61, p = 0.04, n = 20, respectively). FIB-4 also positively correlated with aortic valve calcification (r = 0.40, p = 0.046, n = 20). The key regulator genes of PPi production in liver were lower in patients undergoing liver transplantation as compared to controls. Three months after surgery, serum albumin levels were restored to physiological levels (40 [37–44] vs. 35 [30–40], p = 0.009) and [PPi]pl was normalized (1.40 [1.07–1.86] vs. 0.68 [0.53–0.80] µmol/L, p = 0.0005, n = 12). Liver failure and/or fibrosis correlated with AC in several arterial beds and were associated with low plasma PPi and dysregulation of key proteins involved in PPi homeostasis. Liver transplantation normalized these parameters

Functional Alterations Due to COVID-19 Lung Lesions—Lessons From a Multicenter V/Q Scan-Based Registry

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Cost-Utility Analysis of Transarterial Radioembolization With Yttrium-90 Resin Microspheres Compared With Sorafenib in Locally Advanced and Inoperable Hepatocellular Carcinoma

International audiencePurpose: The SARAH (Sorafenib Versus Radioembolization in Advanced Hepatocellular Carcinoma) trial (ClinicalTrials.gov Identifier NCT01482442) did not show a significant survival benefit for patients treated with transarterial radioembolization (TARE) compared with continuous oral sorafenib. The improved toxicity profile of patients treated with TARE in the trial, however, could result in a quality of life benefit in economic evaluations. Our objective was to perform a cost-utility analysis of TARE versus sorafenib for locally advanced and inoperable hepatocellular carcinoma.Methods: This study used patient-level data of the SARAH trial regarding resource use, progression-free and overall survival, and quality of life for the within-trial period for the patients who received at least 1 dose of sorafenib or 1 treatment with TARE according to their randomization arm. Data were extrapolated by using a partitioned survival model that incorporated costs and health outcomes, measured in life-years and quality-adjusted life-years (QALYs).Findings: The use of TARE resulted in an average loss of 0.036 life-year and a gain of 0.006 QALY compared with sorafenib. The aerage cost for the TARE arm was €17,179 (95% CI, 9,926-24,280) higher than the sorafenib arm, for an incremental cost-effectiveness ratio of €3,153,086/QALY. The probabilistic sensitivity analysis revealed a 50% risk that the TARE strategy was dominated. TARE was consistently dominated by sorafenib or had an incremental cost-effectiveness ratio more than €450,000/QALY in all sensitivity analyses.Implications: This economic evaluation of SARAH found that using radioembolization with yttrium-90 microspheres for the treatment of hepatocellular carcinoma was not a cost-effective option at the usually accepted willingness-to-pay thresholds

Health-related quality of life in locally advanced hepatocellular carcinoma treated by either radioembolisation or sorafenib (SARAH trial)

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