- Publikační typ
- tisková chyba MeSH
BACKGROUND: Patients with advanced chronic liver disease (ACLD) are at high risk of developing hepatocellular carcinoma (HCC). Therefore, biannual surveillance is recommended. This large-scale multicenter study aimed to stratify the risk of HCC development in ACLD. METHODS: From 3016 patients with ACLD screened in 17 European and Chinese centers, 2340 patients with liver stiffness measurement (LSM) determined using different techniques (two-dimensional shear-wave elastography [2D-SWE], transient elastography, and point shear-wave elastography) and with different disease severities were included. Cox regression was used to explore risk factors for HCC. We used these data to create an algorithm, named PLEASE, but referred to in this manuscript as "the algorithm"; the algorithm was validated in internal and two external cohorts across elastography techniques. RESULTS: HCC developed in 127 (5.4%) patients during follow-up. LSM by 2D-SWE (hazard ratio: 2.28) was found to be associated with developing HCC, alongside age, sex, etiology, and platelet count (C-index: 0.8428). We thus established the algorithm with applicable cutoffs, assigning a maximum of six points: platelet count less than 150×109/l, LSM greater than or equal to 15 kPa, age greater than or equal to 50 years, male sex, controlled/uncontrolled viral hepatitis, or presence of steatotic liver diseases. Within 2 years, with a median follow-up of 13.7 months, patients in the high-risk group (≥4 points) had an HCC incidence of 15.6% (95% confidence interval [CI], 12.1% to 18.7%) compared with the low-risk group, at 1.7% (95% CI, 0.9% to 2.5%). CONCLUSIONS: Our algorithm stratified patients into two groups: those at higher risk of developing HCC and those at lower risk. Our data provide equipoise to test the prospective utility of the algorithm with respect to clinical decisions about screening patients with ACLD for incident HCC. (Funded by the German Research Foundation and others; ClinicalTrials.gov number, NCT03389152.).
- MeSH
- algoritmy MeSH
- chronická nemoc MeSH
- dospělí MeSH
- elastografie * MeSH
- hepatocelulární karcinom * epidemiologie diagnostické zobrazování diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory jater * epidemiologie diagnostické zobrazování diagnóza MeSH
- nemoci jater epidemiologie diagnostické zobrazování diagnóza MeSH
- rizikové faktory MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
OBJECTIVE: Liver stiffness measurement (LSM) is a tool used to screen for significant fibrosis and portal hypertension. The aim of this retrospective multicentre study was to develop an easy tool using LSM for clinical outcomes in advanced chronic liver disease (ACLD) patients. DESIGN: This international multicentre cohort study included a derivation ACLD patient cohort with valid two-dimensional shear wave elastography (2D-SWE) results. Clinical and laboratory parameters at baseline and during follow-up were recorded. LSM by transient elastography (TE) was also recorded if available. The primary outcome was overall mortality. The secondary outcome was the development of first/further decompensation. RESULTS: After screening 2148 patients (16 centres), 1827 patients (55 years, 62.4% men) were included in the 2D-SWE cohort, with median liver SWE (L-SWE) 11.8 kPa and a model for end stage liver disease (MELD) score of 8. Combination of MELD score and L-SWE predict independently of mortality (AUC 0.8). L-SWE cut-off at ≥20 kPa combined with MELD ≥10 could stratify the risk of mortality and first/further decompensation in ACLD patients. The 2-year mortality and decompensation rates were 36.9% and 61.8%, respectively, in the 305 (18.3%) high-risk patients (with L-SWE ≥20 kPa and MELD ≥10), while in the 944 (56.6%) low-risk patients, these were 1.1% and 3.5%, respectively. Importantly, this M10LS20 algorithm was validated by TE-based LSM and in an additional cohort of 119 patients with valid point shear SWE-LSM. CONCLUSION: The M10LS20 algorithm allows risk stratification of patients with ACLD. Patients with L-SWE ≥20 kPa and MELD ≥10 should be followed closely and receive intensified care, while patients with low risk may be managed at longer intervals.
- MeSH
- algoritmy MeSH
- chronická nemoc MeSH
- dospělí MeSH
- elastografie * MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- nemoci jater diagnóza etiologie mortalita MeSH
- prediktivní hodnota testů MeSH
- retrospektivní studie MeSH
- ROC křivka MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
Liver stiffness (LS) is a novel non-invasive parameter widely used in clinical hepatology. LS correlates with liver fibrosis stage in non-cirrhotic patients. In cirrhotic patients it also shows good correlation with Hepatic Venous Pressure Gradient (HVPG). Our aim was to assess the contribution of liver fibrosis and portal hypertension to LS in patients with advanced liver cirrhosis. Eighty-one liver transplant candidates with liver cirrhosis of various aetiologies underwent direct HVPG and LS measurement by 2D shear-wave elastography (Aixplorer Multiwave, Supersonic Imagine, France). Liver collagen content was assessed in the explanted liver as collagen proportionate area (CPA) and hydroxyproline content (HP). The studied cohort included predominantly patients with Child-Pugh class B and C (63/81, 77.8%), minority of patients were Child-Pugh A (18/81, 22.2%). LS showed the best correlation with HVPG (r=0.719, p< 0.001), correlation of LS with CPA (r=0.441, p< 0.001) and HP/Amino Acids (r=0.414, p< 0.001) was weaker. Both variables expressing liver collagen content showed good correlation with each other (r=0.574, p<0.001). Multiple linear regression identified the strongest association between LS and HVPG (p < 0.0001) and weaker association of LS with CPA (p = 0.01883). Stepwise modelling showed minimal increase in r2 after addition of CPA to HVPG (0.5073 vs. 0.5513). The derived formula expressing LS value formation is: LS = 2.48 + (1.29 x HVPG) + (0.26 x CPA). We conclude that LS is determined predominantly by HVPG in patients with advanced liver cirrhosis whereas contribution of liver collagen content is relatively low.
- MeSH
- dospělí MeSH
- elastografie MeSH
- jaterní cirhóza metabolismus patologie patofyziologie chirurgie MeSH
- játra chemie diagnostické zobrazování patologie chirurgie MeSH
- kolagen analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- portální hypertenze diagnóza patofyziologie chirurgie MeSH
- portální tlak * MeSH
- prediktivní hodnota testů MeSH
- prospektivní studie MeSH
- senioři MeSH
- transplantace jater MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Liver stiffness is a reliable non-invasive predictor of Hepatic Venous Pressure Gradient (HVPG) above 10 mm Hg. However, it failed to predict higher thresholds of HVPG. Our aim was to investigate whether liver stiffness and selected previously published non-invasive blood biomarkers could predict higher HVPG thresholds in liver transplant candidates without ongoing alcohol use. One hundred and nine liver transplant candidates with liver cirrhosis of various aetiologies underwent direct HVPG measurement, liver stiffness measurement by 2D shear-wave elastography (Aixplorer Multiwave, Supersonic Imagine, France) and assessment of blood HVPG biomarkers (osteopontin, VCAM-1, IL-6, TNF-α, IL-1ra/IL-1F3 and ELF score). The correlation between liver stiffness and HVPG was linear up to 30 mm Hg of HVPG (r = 0.765, p < 0.0001). The regression lines had similar slopes for HVPG values below and above 16 mm Hg (p > 0.05) and the correlation in patients with HVPG <16 mm Hg (r = 0.456, p = 0.01) was similar to patients with HVPG ≥ 16 mm Hg (r = 0.499, p < 0.0001). The correlation was similar in the subgroup patients with alcoholic (r = 0.718, p < 0.0001), NASH (r = 0.740, p = 0.008), cryptogenic (r = 0.648, p = 0,0377), cholestatic and autoimmune (r = 0.706, p < 0.0001) and viral cirrhosis (r = 0.756, p < 0.0001). Liver stiffness distinguished patients with HVPG above 16, and 20 mm Hg with AUROCs 0.90243, and 0.86824, sensitivity 0.7656, and 0.7027, and specificity 0.9333, and 0.8750. All studied blood biomarkers correlated better with liver stiffness than with HVPG and their AUROCs did not exceed 0.8 at both HVPG thresholds. Therefore, a composite predictor superior to liver stiffness could not be established. We conclude that liver stiffness is a clinically reliable predictor of higher HVPG thresholds in non-drinking subjects with advanced liver cirrhosis.
- MeSH
- biologické markery krev MeSH
- dospělí MeSH
- elastografie metody MeSH
- fibróza patologie MeSH
- jaterní cirhóza patologie MeSH
- játra patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lineární modely MeSH
- portální hypertenze patologie MeSH
- portální tlak fyziologie MeSH
- prospektivní studie MeSH
- pružnost fyziologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- venae hepaticae patologie MeSH
- venózní tlak fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Publikační typ
- abstrakt z konference MeSH
Terlipresin byl poprvé vyroben před 54 lety v tehdejším Československu. Jedná se o lék s výrazným vazokonstrikčním a protikrvácivým účinkem, který působí vazokonstrikci především splanchnického řečiště s následným snížením portálního tlaku a průtoku v portosystémových kolaterálách. Nevyžaduje kontinuální podání a je možné ho podávat frakcionovaně. V klinické praxi je užíván především při akutním krvácení z jícnových varixů a hepatorenálním syndromu. Mezi další indikace terlipresinu patří krvácení z portální gastropatie, krvácení z trávicího a urogenitálního ústrojí u dětí i dospělých a lokální použití během gynekologických operací na děložním čípku. Léčba akutního varikózního krvácení terlipresinem je dnes dána jasně stanovenými postupy a měla by být zahájena již při prvním kontaktu s pacientem. Terlipresin v této indikaci snižuje mortalitu i riziko recidivy krvácení. U jedinců s hepatorenálním syndromem je terlipresin preferovaným lékem, který snižuje mortalitu a zlepšuje funkci ledvin u hepatorenálního syndromu 1. i 2. typu. Pro diagnózu hepatorenálního syndromu neexistuje jednoznačně doporučené dávkovací schéma terlipresinu ani doporučená doba léčby. Rekurence onemocnění po vysazení terlipresinu je obvykle řešena opětovným nasazením léku. Hlavním nežádoucím účinkem terlipresinu je myokardiální, splanchnická a akrální ischemie.
Terlipressin was first synthesized more than 54 years ago in former Czechoslovakia. This drug has potent vasoconstrictive and antibleeding effects, which reduce portal pressure and flow in portosystemic shunts, and can be administered in individual doses rather than continuously. Terlipressin is used in clinical practice primarily to treat acute variceal bleeding and hepatorenal syndrome. Other indications include bleeding due to portal gastropathy and bleeding from the gastrointestinal and urogenital tracts in children and in adults, and this drug is also locally applied during gynecological operations on the uterine cervix. Acute variceal bleeding is currently treated according to clearly established procedures and should be initiated upon first contact with the patient. Use of terlipressin in this indication reduces mortality and the risk of bleeding recurrence. Terlipressin is the preferred drug for treatment of hepatorenal syndrome and reduces mortality and improves kidney function in patients with hepatorenal syndrome type 1 and 2. There is no recommended dosage schedule of terlipressin in hepatorenal syndrome patients and the treatment duration is not clearly established. Recurrence of hepatorenal syndrome after discontinuation of terlipressin is usually resolved by re-administration of the drug. The main side effects of terlipressin are myocardial, splanchnic, and acral ischemia.
- Klíčová slova
- krvácení z varixů, krvácení z jícnových varixů,
- MeSH
- děložní krvácení farmakoterapie MeSH
- ezofageální a žaludeční varixy komplikace MeSH
- gastrointestinální krvácení farmakoterapie MeSH
- hepatorenální syndrom * farmakoterapie MeSH
- hodnocení léčiv MeSH
- krvácení * farmakoterapie MeSH
- lidé MeSH
- portální hypertenze * farmakoterapie MeSH
- terlipresin MeSH
- vasopresiny farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
