RESUMEN
Portal hypertension often precedes the development of advanced fibrosis in patients with Metabolic dysfunction-associated steatotic liver disease (MASLD) and may accelerate disease progression to cirrhosis. We aimed to evaluate whether prioritization tools accurately predict survival in patients with MASLD and clinically significant portal hypertension (CSPH). We retrospectively identified patients diagnosed with esophageal or gastric varices (EGV). Laboratory results, endoscopy reports and outcomes of patients with MASLD were compared to patients with advanced stage chronic liver disease (CLD) of other etiologies. During the study period 326 patients were diagnosed with EGV. 88 (26.9%) had MASLD, 113 (34.6%) viral hepatitis (VH), 63 (19.3%) alcoholic liver disease (ALD) and 62 (19%) both VH and ALD (VHALD). EGV bleeding events were significantly more frequent in patients with MASLD (36.3%), compared to VH (28.3%), ALD (30.1%) and VHALD (25.8%), respectively (p < 0.01). Mean Model for End-Stage Liver Disease (MELD)-Na score surrounding 1 year of first event of EGV bleeding was significantly lower in MASLD patients compared to all other etiologies (p = 0.02). At a MELD-Na score of 11-20, cumulative survival rate was significantly lower in MASLD patients compared to all other etiologies (log rank p < 0.01). MASLD patients present with EGV bleeding at lower MELD-Na scores compared to other etiologies of CLD. MELD-Na score may therefore underestimate disease severity and risk of death in patients with MASLD and CSPH.
Asunto(s)
Enfermedad Hepática en Estado Terminal , Várices Esofágicas y Gástricas , Hígado Graso , Hipertensión Portal , Hepatopatías Alcohólicas , Humanos , Enfermedad Hepática en Estado Terminal/complicaciones , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Hipertensión Portal/complicaciones , Várices Esofágicas y Gástricas/complicaciones , Hígado Graso/complicaciones , Hepatopatías Alcohólicas/complicacionesRESUMEN
BACKGROUND AND AIMS: HDV infection leads to the most aggressive form of human viral hepatitis for which there is no FDA-approved therapy. PEG IFN-lambda-1a (Lambda) has previously demonstrated a good tolerability profile in HBV and HCV patients compared to PEG IFN-alfa. The goal of Phase 2 LIMT-1 trial was to evaluate the safety and efficacy of Lambda monotherapy in patients with HDV. APPROACH AND RESULTS: An open-label study of Lambda 120 or 180 mcg, administered once weekly by subcutaneous injections for 48 weeks, followed by 24 weeks of posttreatment follow-up. Thirty-three patients were allocated to Lambda 180 mcg (n=14) or 120 mcg (n=19). Baseline mean values: HDV RNA 4.1 log10 IU/mL (SD±1.4); ALT 106 IU/L (35-364); and bilirubin 0.5 mg/dL (0.2-1.2). Intention-to-treat rates of virologic response to Lambda 180 mcg and 120 mcg, 24 weeks following treatment cessation were 5 of 14(36%) and 3 of 19 (16%), respectively. The posttreatment response rate of 50% was seen in low BL viral load (≤4 log10) on 180 mcg. Common on-treatment adverse events included flu-like symptoms and elevated transaminase levels. Eight (24%) cases of hyperbilirubinemia with or without liver enzyme elevation, leading to drug discontinuation, were mainly observed in the Pakistani cohort. The clinical course was uneventful, and all responded favorably to dose reduction or discontinuation. CONCLUSIONS: Treatment with Lambda in patients with chronic HDV may result in virologic response during and following treatment cessation. Clinical phase 3 development of Lambda for this rare and serious disease is ongoing.
Asunto(s)
Antivirales , Hepatitis D Crónica , Humanos , Antivirales/efectos adversos , Hepatitis D Crónica/tratamiento farmacológico , Quimioterapia Combinada , Interferón-alfa/efectos adversos , Polietilenglicoles/efectos adversos , Hiperbilirrubinemia/inducido químicamente , Interleucinas/genética , Proteínas Recombinantes/efectos adversos , Resultado del TratamientoRESUMEN
Sex and gender can affect the prevalence and prognosis of diseases. Our aim was to assess similarities and differences for males and females who underwent an upper endoscopy, with regards to indications and results. We reviewed all upper endoscopy reports from 2012 to 2016. Data regarding demographics, indications, and procedure findings were collected. The upper endoscopy findings were compared regarding the most common indications: gastroesophageal reflux, abdominal pain, gastrointestinal bleeding, and anemia. We investigated 12,213 gastroscopies among males (age, 56.7 ± 17.4) and 15,817 among females (age, 56.0 ± 17.3, p = 0.002). Males who underwent an upper endoscopy for gastroesophageal reflux had higher rates of esophagitis (7.7% vs. 3.4%, p < 0.001) and Barret's esophagus (4.4% vs. 1.5%, p < 0.001). Females who underwent an upper endoscopy for abdominal pain had a higher rate of hiatal hernia, whereas males had higher rates of esophagitis, helicobacter pylori infection, gastritis, gastric ulcer, duodenitis, and duodenal ulcer (p < 0.001). Gastrointestinal bleeding as an indication for upper endoscopy showed that helicobacter, duodenitis, and duodenal ulcers are more common among males compared to females (p < 0.001). Males with anemia who underwent an upper endoscopy had higher rates of esophagitis (p = 0.021) gastritis (p = 0.002), duodenitis (p < 0.001), and duodenal ulcer (p < 0.001). We found significant differences regarding the pathological gastroscopy findings between males and females in relation to the different indications.
RESUMEN
The advent of direct-acting antivirals (DAAs) has transformed the landscape of hepatitis C virus (HCV) management. We aimed to prospectively (real-time) evaluate the feasibility of using a response-guided therapy approach, based on mathematical modeling of early viral kinetics, to reduce the duration of DAAs therapy. Patients were treated with DAAs according to the physicians' preference. HCV was measured at baseline and at day 2 and weeks 1, 2 and 4 after treatment initiation. The primary endpoint was the proportion of patients with sustained-virological response (SVR) at 12 and/or 24 weeks post-treatment. Twenty-nine patients (mean age 54 ± 16, 44% females, 73% with HCV genotype 1), were enrolled and all completed therapy. Treatment duration was shortened in 11 of the 29 patients (38%). SVR was achieved in 28 of the 29 patients (97%). Relapse occurred post treatment in a single case of a non-cirrhotic male with genotype 3, who was treated with sofosbuvir/velpatasvir for 6 weeks. Virus sequencing did not identify baseline or treatment emergent resistance associated substitutions. Real-time mathematical modeling of early HCV kinetics can be utilized for shortening DAAs duration in approximately 40% of patients without compromising treatment efficacy.Clinical trial registration: ClinicalTrials.gov Identifier: NCT03603327.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Adulto , Anciano , Estudios de Factibilidad , Femenino , Hepatitis C Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Resultado del Tratamiento , Carga ViralRESUMEN
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Asunto(s)
Antivirales/uso terapéutico , Inhibidores del Citocromo P-450 CYP3A/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Respuesta Virológica Sostenida , 2-Naftilamina , Anilidas/uso terapéutico , Carbamatos/uso terapéutico , Ciclopropanos/uso terapéutico , Esquema de Medicación , Quimioterapia Combinada , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Lactamas Macrocíclicas/uso terapéutico , Persona de Mediana Edad , Prolina/análogos & derivados , Prolina/uso terapéutico , Ritonavir/uso terapéutico , Simvastatina/efectos adversos , Sulfonamidas/uso terapéutico , Uracilo/análogos & derivados , Uracilo/uso terapéutico , ValinaRESUMEN
BACKGROUND: Seasonal variations of 25-hydroxyvitamin D, PTH and calcium levels are not well characterized in primary hyperparathyroidism (PHPT). Our objectives were to characterize seasonal changes in these parameters in PHPT patients, and to assess whether these seasonal changes affect clinical decision making. METHODS: This is a retrospective study based on the electronic medical records of Clalit Health service in the south of Israel between 2000 and 2012. Patients 18years and older with PHPT (PTH>upper limit of norm (ULN) and serum calcium>10.5mg%) were included. Patients with renal failure or on Thiazide diuretics were excluded. All serum levels of calcium, PTH and 25-hydroxyvitamin D were collected and then stratified according to season. RESULTS: 792 patients were classified as PHPT (72.2% female) and had a total of 2659 PTH tests, 1395 25-hydroxyvitamin D tests and 7426 calcium test. Fifty six percent of 25-hydroxyvitamin D levels were <50nmol/L. Seasonality was demonstrated in all three parameters: mean 25-hydroxyvitamin D was 13% higher in the summer compared to the winter (P<0.001), median PTH values showed opposite trend with a fall of about 8.4% in summer compared to winter (P<0.001). Calcium levels were higher during the autumn with a rise of about 0.2mg/dL in the mean calcium levels compared to spring and summer (P<0.001). The odds ratio of calcium level above 11.5mg/dL is highest in the autumn (OR=1.275, P=0.018). CONCLUSION: We show seasonal variation in serum 25-hydroxyvitamin D, PTH, and calcium levels in patients with PHPT. These seasonal variations cause transition to pathological values that may influence diagnosis and treatment of PHPT patients.