RESUMO
2023 has been marked by numerous advancements in the fields of hepatology, liver transplantation, gastroenterology, and interventional endoscopy. These developments hold the promise of changing our daily practice while enhancing the diagnosis and treatment of various hepatic and gastroenterological conditions. Additionally, the European Association for the Study of the Liver (EASL) has issued recommendations for the management of hepatitis delta, acute-on-chronic liver failure, liver diseases of pregnancy, and intrahepatic cholangiocarcinoma. Risankizumab was approved by Swiss Authorities for patients with Crohn's disease and dupilumab was approved for patients with eosinophilic esophagitis. The European Society of Gastrointestinal Endoscopy (ESGE) has revised its recommendations regarding Barrett's esophagus.
2023 a été marquée par de nombreuses avancées dans le domaine de l'hépatologie, de la transplantation hépatique, de la gastroentérologie et de l'endoscopie interventionnelle. Ces développements promettent de changer notre pratique quotidienne dans le but d'améliorer le diagnostic et le traitement de nombreuses affections hépatiques et gastroentérologiques. En outre, la Société européenne d'hépatologie (EASL) a émis des recommandations pour la prise en charge de l'hépatite delta, de l'insuffisance hépatique aiguë sur chronique, des complications hépatiques de la grossesse et du cholangiocarcinome intrahépatique. Le risankizumab a été approuvé par Swissmedic pour le traitement de la maladie de Crohn et le dupilumab pour les patients avec Åsophagite à éosinophiles. La Société européenne d'endoscopie a mis à jour ses recommandations concernant l'Åsophage de Barrett.
Assuntos
Insuficiência Hepática Crônica Agudizada , Neoplasias dos Ductos Biliares , Gastroenterologia , Feminino , Gravidez , Humanos , Ductos Biliares Intra-HepáticosRESUMO
Cirrhosis is a major health concern worldwide with a complex pathophysiology affecting various biological systems, including all aspects of haemostasis. Bleeding risk is mainly driven by portal hypertension, but in end-stage liver disease it is further increased by alterations in haemostatic components, including platelet function, coagulation, and fibrinolysis. Concurrently, patients with cirrhosis are prone to venous thromboembolic events (VTE) because of the altered haemostatic balance, in particular an increase in thrombin generation. In patients with cirrhosis, vitamin K antagonists (VKA) and low molecular weight heparins (LMWH) are currently the standard of care for VTE prevention, with VKA also being standard of care for stroke prevention in those with atrial fibrillation. However, direct oral anticoagulants (DOAC) could have specific advantages in this patient population. Clinical experience suggests that DOAC are a safe and possibly more effective alternative to traditional anticoagulants for the treatment of VTE in patients with compensated cirrhosis. In addition, emerging data suggest that primary prophylactic treatment with anticoagulants may improve clinical outcomes in patients with cirrhosis by reducing the risk of hepatic decompensation. The selection of the most appropriate DOAC remains to be clarified. This review focuses on the rationale for the use of DOAC in patients with cirrhosis, the specific effects of the different DOAC (as assessed by in vitro and in vivo pharmacokinetic and pharmacodynamic studies), as well as clinical outcomes in patients with cirrhosis on DOAC.
RESUMO
BACKGROUND: Telomeres prevent damage to coding DNA as end-nucleotides are lost during mitosis. Mutations in telomere maintenance genes cause excessive telomere shortening, a condition known as short telomere syndrome (STS). One hepatic manifestation documented in STS is porto-sinusoidal vascular disorder (PSVD). METHODS: As the etiology of many cases of PSVD remains unknown, this study explored the extent to which short telomeres are present in patients with idiopathic PSVD. RESULTS: This monocentric cross-sectional study included patients with histologically defined idiopathic PSVD. Telomere length in 6 peripheral blood leukocyte subpopulations was assessed using fluorescent in situ hybridization and flow cytometry. Variants of telomere-related genes were identified using high-throughput exome sequencing. In total, 22 patients were included, of whom 16 (73%) had short (9/22) or very short (7/22) telomeres according to age-adjusted reference ranges. Fourteen patients (64%) had clinically significant portal hypertension. Shorter telomeres were more frequent in males (p = 0.005) and patients with concomitant interstitial lung disease (p < 0.001), chronic kidney disease (p < 0.001), and erythrocyte macrocytosis (p = 0.007). Portal hypertension (p = 0.021), low serum albumin level (p < 0.001), low platelet count (p = 0.007), and hyperbilirubinemia (p = 0.053) were also associated with shorter telomeres. Variants in known STS-related genes were identified in 4 patients with VSTel and 1 with STel. CONCLUSIONS: Short and very short telomeres were highly prevalent in patients with idiopathic PSVD, with 31% presenting with variants in telomere-related genes. Telomere biology may play an important role in vascular liver disease development. Clinicians should consider measuring telomeres in any patient presenting with PSVD.
Assuntos
Encurtamento do Telômero , Humanos , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Encurtamento do Telômero/genética , Idoso , Adulto , Prevalência , Telômero/genética , Hipertensão Portal/genética , Hibridização in Situ Fluorescente , Proteínas de Ligação a Telômeros/genética , Telomerase/genéticaRESUMO
BACKGROUND AND AIM: Direct-acting antivirals (DAAs) have revolutionised the management of chronic hepatitis C. We analysed the use of different generations of DAAs over time in Switzerland and investigated factors predictive of treatment failure. METHODS: This retrospective study was conducted within the framework of the Swiss Association for the Study of the Liver and the Swiss Hepatitis C Cohort Study; it included all patients with chronic hepatitis C treated with DAAs between January 2015 and December 2019 at eight Swiss referral centres. RESULTS: A total of 3088 patients were included; 57.3% were male, and the median age was 54 years. Liver cirrhosis was present in 23.9% of the cohort, 87.8% of whom were compensated. The overall sustained virological response (SVR) rate (defined as undetectable HCV RNA at week 12 after the first course of DAA-based treatment) was 96.2%, with an increase over time. The rate of treatment failure dropped from 8.3% in 2015 to 2.5% in 2019. Multivariable analysis revealed that female sex, the use of the latest generation of pangenotypic DAA regimens, Caucasian origin, and genotype (gt) 1 were associated with SVR, whereas the presence of active hepatocellular carcinoma (HCC), gt 3, and increasing liver stiffness were associated with treatment failure. Notably, the presence of active HCC during treatment increased the risk of DAA failure by a factor of almost thirteen. CONCLUSIONS: SVR rates increased over time, and the highest success rates were identified after the introduction of the latest generation of pangenotypic DAA regimens. Active HCC, gt 3 and increasing liver stiffness were associated with DAA failure.
Assuntos
Antivirais , Hepatite C Crônica , Cirrose Hepática , Resposta Viral Sustentada , Humanos , Hepatite C Crônica/tratamento farmacológico , Suíça/epidemiologia , Masculino , Feminino , Antivirais/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , Hepacivirus/genética , Falha de Tratamento , Genótipo , Carcinoma Hepatocelular , Neoplasias Hepáticas , AdultoRESUMO
Alternative medicines such as phytotherapy and herbal preparations have been widely used over the past 5 decades. However, they are still poorly known in Western medicine, and because they are considered as natural products, they are often omitted in the review of medication. One of the most used herbal preparations in Europe is Iberogast®, a formulation of 9 medicinal plant extracts, including Greater Celandine that has proven effective in the treatment of functional dyspepsia and irritable bowel syndrome. Safety and tolerability of Iberogast® were extensively evaluated in double-blind and randomized studies vs placebo, but rare and usually mild adverse symptoms have been reported in the literature. We report a 32-year-old female with no previous medical history who presented to the emergency department with abdominal pain, jaundice, and pruritus. The blood tests revealed an acute severe hepatitis with marked increase of direct bilirubin. After exclusion of other possible acute liver injury etiologies, we retained the diagnosis of Iberogast®-associated drug-induced liver injury. Patient's symptoms resolved spontaneously 5 weeks after treatment interruption. Despite the general safety of Iberogast®, occasional cases of drug-induced liver injury have been documented. Based on these observations, we recommend that the use of herbal and phytotherapeutic products should be part of the standard investigation of the medical history, as they could be relevant information in the diagnosis process of acute liver injury.