Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
Nestr.
Úroveň portální hypertenze vyjádřená portohepatálním gradientem (HVPG) determinuje výši rizika závažných komplikací u cirhotiků a je důležitým faktorem při rozhodování o léčbě při variceálním krvácení. Spolehlivě lze stupeň portální hypertenze změřit jen invazivně katetrizací jaterních žil. Dosud publikované práce ukazují na lineární korelaci mezi tuhostí jater změřenou shear-wave elestografií (SWE) a HVPG pouze do výše 10 mm Hg. Předpokládáme, že korelace mezi tuhostí jater a HVPG nad 12 mm Hg není lineární a že kombinací SWE a sérových markerů fibrózy bude možno nalézt korelaci i s vyššími hodnotami HVPG. Cílem je navrhnout algoritmus, kterým by bylo možno rychle a neinvazivně odlišit pacienty s významnou portální hypertenzí (HVPG 12 mm Hg a více). Studie bude provedena na 100 pacientech s pokročilou jaterní cirhózou čekajících na transplantaci jater. Před transplantací jim bude prováděna SWE, invazivní měření HVPG a vyšetření krevních markerů fibrózy. V explantovaných játrech bude stanoven obsah kolagenu.; The grade of portal hypertension, expressed as portohepatic gradient (HVPG), determines the risk of severe complications in cirrhosis and represents an important factor in decision-making in variceal bleeding. We are able to reliably assess the degree of portal hypertension only by hepatic veins cathetrisation. The data published so far show a linear correlation between liver stiffness assessed by shear-wave elastography (SWE) and HVPG lower than 10 mm Hg. We presume that the correlation between liver stiffness and HVPG >12 mm Hg is not linear and that, with liver stiffness measurement and blood fibrosis markers assessment, we would be able to find a correlation also in HVPG > 12 mm Hg. The aim of the study is to find an easy and rapid algorithm to distinguish patients with severe portal hypertension (HVPG >12 mm Hg). The study will be performed in 100 patients with advanced cirrhosis awaiting liver transplantation. They will be examined by SWE, HVPG will be measured and blood fibrosis markers will be assessed. The collagen content will be assessed in the explanted liver.
- MeSH
- Biomarkers analysis MeSH
- Elasticity Imaging Techniques MeSH
- Liver Cirrhosis diagnostic imaging complications MeSH
- Humans MeSH
- Hypertension, Portal diagnostic imaging complications MeSH
- Prognosis MeSH
- Liver Transplantation MeSH
- Check Tag
- Humans MeSH
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- hepatologie
- NML Publication type
- závěrečné zprávy o řešení grantu AZV MZ ČR
- MeSH
- Diabetes Mellitus, Type 2 MeSH
- Diabetes Mellitus MeSH
- Fibrosis MeSH
- Liver Cirrhosis MeSH
- Humans MeSH
- Liver Diseases diagnosis therapy MeSH
- Obesity MeSH
- Diagnostic Screening Programs MeSH
- Liver Transplantation MeSH
- Fatty Liver * diagnosis epidemiology physiopathology prevention & control therapy MeSH
- Check Tag
- Humans MeSH
Glekaprevir a pibrentasvir představují novou generaci přímo působících antivirotik účinných proti viru hepatitidy C (HCV). Glekaprevir je inhibitorem HCV proteázy NS3/4A, pibrentasvir je inhibitorem HCV proteinu NS5A, tzv. replikačního komplexu. Glekaprevir i pibrentasvir mají vysokou protivirovou účinnost proti všem genotypům viru hepatitidy C. Fixní kombinace glekapreviru a pibrentasviru v jedné tabletě nabízí možnost krátké léčby v trvání 8 týdnů pro dosud neléčené dospělé pacienty bez cirhózy bez ohledu na genotyp viru hepatitidy C. U pacientů s cirhózou nebo u pacientů infikovaných genotypem 3 po selhání léčby interferonovým režimem se doporučuje léčba trvající 12, resp. 16 týdnů. Kombinace glekapreviru a pibrentasviru je kontraindikována u pacientů s dekompenzovanou cirhózou jater. Glekaprevir i pibrentasvir se minimálně vylučují ledvinami, a proto jejich fixní kombinace může být bezpečně používána k léčbě pacientů s chronickým onemocněním ledvin včetně pacientů hemodialyzovaných. Kombinací glekaprevir/pibrentasvir lze léčit i pacienty po transplantaci jater a ledviny a pacienty s koinfekcí HCV/HIV. Kombinace glekapreviru a pibrentasviru vykazuje vynikající bezpečnostní profil, ve studiích fáze II a III byly nejčastějšími nežádoucími účinky (≥ 10 %) bolest hlavy a únava. Přítomnost kompenzované cirhózy nemá vliv na typ a závažnost nežádoucích účinků.
Glecaprevir and pibrentasvir represent the next‑generation of antivirals indicated for treatment of hepatitis C. Glecaprevir is an HCV NS3/4A protease inhibitor, pibrentasvir is the inhibitor of NS5A replication complex. Glecaprevir as well as pibrentasvir have a high antiviral activity against all HCV genotypes. The fixed‑dose combination of glecaprevir and pibrentasvir in one pill represents a possibility of a short, 8‑weeks treatment for treatment‑naive patients without cirrhosis regardless of HCV genotype. In patients with cirrhosis or in patients with liver cirrhosis and genotype 3 in whom an interferon‑based treatment had failed, 12 and 16 weeks of therapy are indicated, respectively. The regimen is contraindicated in patients with decompensated liver cirrhosis. Glecaprevir and pibrentasvir have a minimal kidney excretion, it is possible to administer the combination to the patients with kidney disease including patients on maintenance hemodialysis. The combination can be used in kidney and liver transplant recipients and patients with HIV coinfection. The glecaprevir/pibrentasvir combination has an excellent safety profile, the most common side effects in phase II and III clinical trials (≥ 10%) were headache and fatigue. The presence of compensated liver cirrhosis does not increase the frequency of adverse events.
- MeSH
- Antiviral Agents * pharmacology therapeutic use MeSH
- Benzimidazoles pharmacokinetics therapeutic use MeSH
- Quinoxalines pharmacology therapeutic use MeSH
- Drug Combinations MeSH
- Hepatitis C * drug therapy virology MeSH
- Drug Evaluation MeSH
- Liver Cirrhosis * drug therapy MeSH
- Drug Interactions MeSH
- Humans MeSH
- Meta-Analysis as Topic MeSH
- Drug-Related Side Effects and Adverse Reactions MeSH
- Randomized Controlled Trials as Topic MeSH
- Sulfonamides pharmacology therapeutic use MeSH
- Check Tag
- Humans MeSH
BACKGROUND/AIMS: Chronic hepatitis C (HCV) virus infection reactivates under immunosuppressive drugs and therefore has a negative impact on long-term survival of kidney transplant recipients. Treatment-induced clearance of hepatitis C virus (HCV) in kidney transplant candidates prevents virus reactivation after transplantation. Paritaprevir/Ritonavir/Ombitasvir with Dasabuvir (PrOD) represents a highly effective treatment regimen for HCV genotype 1 (GT1), also suitable for patients with end-stage renal disease (ESRD). Serious drug-drug interactions may represent a limiting factor of this regimen. The aim of this retrospective study was to evaluate safety, efficacy and drug-drug interactions management associated with PrOD treatment in the Czech real-world cohort. METHODS: Emphasizing concomitant medication adjustment, we described the treatment course with PrOD regimen in 23 patients (4 with CKD4 and 19 on maintenance haemodialysis) infected with HCV GT1 (21 GT1b, 2 GT1a), 18 males and 5 females with an average age of 53.7 years. Six patients had compensated liver cirrhosis and 3 of them were liver transplant recipients. RESULTS: All 23 patients completed the 12-week treatment and achieved sustained virological response 12 weeks after the treatment (SVR12 rate 100%). None of the patients presented with a significant decrease in haemoglobin level, white blood cell and platelet count during the treatment period. The most frequent adverse events were nausea, hypotension, diarrhoea, and hyperkalemia. Four patients presented with a serious adverse event unrelated to the antiviral drugs (salmonellosis, non-functional kidney graft rejection, early gastric cancer, renal cyst infection, initiation of haemodialysis). Concomitant medication had to be modified with the treatment initiation in 10 out of 23 (43.5%) patients (calcium channel blockers, ACE inhibitors, statins, diuretics, tacrolimus); four patients required further adjustment of antihypertensive drugs or tacrolimus dosage on-treatment. CONCLUSION: PrOD regimen demonstrated an excellent efficacy and good tolerability. Both prospective adjustment of concomitant medication and further on-treatment adjustment allowed for a safe treatment course.
- MeSH
- Anilides therapeutic use MeSH
- Antihypertensive Agents therapeutic use MeSH
- Antiviral Agents adverse effects therapeutic use MeSH
- Hepatitis C, Chronic complications drug therapy virology MeSH
- Kidney Failure, Chronic therapy virology MeSH
- Genotype MeSH
- Hepacivirus drug effects genetics MeSH
- Carbamates therapeutic use MeSH
- Drug Therapy, Combination MeSH
- Middle Aged MeSH
- Humans MeSH
- Macrocyclic Compounds therapeutic use MeSH
- Renal Insufficiency therapy virology MeSH
- Ritonavir therapeutic use MeSH
- Sulfonamides therapeutic use MeSH
- Uracil analogs & derivatives therapeutic use MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Keywords
- ombitasvir, dasabuvir, paritaprevir,
- MeSH
- Anilides pharmacology therapeutic use MeSH
- Antiviral Agents * pharmacology therapeutic use MeSH
- Drug Combinations MeSH
- Hepatitis C * drug therapy MeSH
- Drug Evaluation MeSH
- Carbamates pharmacology therapeutic use MeSH
- Clinical Studies as Topic MeSH
- Drug Therapy, Combination MeSH
- Humans MeSH
- Macrocyclic Compounds pharmacology therapeutic use MeSH
- Ritonavir pharmacology therapeutic use MeSH
- Sulfonamides pharmacology therapeutic use MeSH
- Uracil pharmacology therapeutic use MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Keywords
- grazoprevir,
- MeSH
- Antiviral Agents * therapeutic use MeSH
- Hepatitis C, Chronic * drug therapy MeSH
- Drug Combinations MeSH
- Hepatitis B * drug therapy MeSH
- Hepatitis C * drug therapy MeSH
- Hepatitis E * epidemiology complications MeSH
- Clinical Studies as Topic MeSH
- Drug Interactions MeSH
- Publication type
- Interview MeSH
