EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis

EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis.

Hyponatraemia, defined as a serum sodium concentration !135 mmol/l, is the most common disorder of body fluid and electrolyte balance encountered in clinical practice. It can lead to a wide spectrum of clinical symptoms, from subtle to severe or even life threatening, and is associated with increased mortality, morbidity and length of hospital stay in patients presenting with a range of conditions. Despite this, the management of patients remains problematic. The prevalence of hyponatraemia in widely different conditions and the fact that hyponatraemia is managed by clinicians with a broad variety of backgrounds have fostered diverse institution- and speciality-based approaches to diagnosis and treatment. To obtain a common and holistic view, the European Society of Intensive Care Medicine (ESICM), the European Society of Endocrinology (ESE) and the European Renal Association – European Dialysis and Transplant Association (ERA–EDTA), represented by European Renal Best Practice (ERBP), have developed the Clinical Practice Guideline on the diagnostic approach and treatment of hyponatraemia as a joint venture of three societies representing specialists with a natural interest in hyponatraemia. In addition to a rigorous approach to methodology and evaluation, we were keen to ensure that the document focused on patient-important outcomes and included utility for clinicians involved in everyday practice.

/pdf/clinical-practice-guideline-on-diagnosis-and-treatment-of-509w3449ob.pdf

Clinical practice guideline on diagnosis and treatment of hyponatraemia

Vasopressin antagonists increase the serum sodium concentration in patients who have euvolemia and hypervolemia with hyponatremia in the short term (≤30 days), but their safety and efficacy with longer term administration is unknown. SALTWATER was a multicenter, open-label extension of the Study of Ascending Levels of Tolvaptan in Hyponatremia (SALT-1 and SALT-2). In total, 111 patients with hyponatremia received oral tolvaptan for a mean follow-up of 701 days, providing 77,369 patient-days of exposure. All patients had hyponatremia at randomization in SALT-1 and SALT-2, and 85% continued to have hyponatremia at entry in SALTWATER. The most common adverse effects attributed to tolvaptan were pollakiuria, thirst, fatigue, dry mouth, polydipsia, and polyuria. Six drug-related adverse effects led to study discontinuation. The increase in serum sodium exceeded the desired 1 mmol/L per h at initiation in five patients. Hypernatremia (>145 mmol/L) led to discontinuation in one patient. Mean serum sodium increased from 130.8 mmol/L at baseline to >135 mmol/L throughout the observation period (P < 0.001 versus baseline at most points). Responses were comparable between patients with euvolemia and those with heart failure but more modest in patients with cirrhosis. In conclusion, prolonged administration of tolvaptan maintains an increased serum sodium with an acceptable margin of safety.

Oral Tolvaptan Is Safe and Effective in Chronic Hyponatremia

Antiviral therapeutics with profiles of high potency, low resistance, panserotype, and low toxicity remain challenging, and obtaining such agents continues to be an active area of therapeutic development. Due to their unique three-dimensional structural features, spirooxindoles have been identified as privileged chemotypes for antiviral drug development. Among them, spiro-pyrazolopyridone oxindoles have been recently reported as potent inhibitors of dengue virus NS4B, leading to the discovery of an orally bioavailable preclinical candidate (R)-44 with excellent in vivo efficacy in a dengue viremia mouse model. This review highlights recent advances in the development of biologically active spirooxindoles for their antiviral potential, primarily focusing on the structure–activity relationships (SARs) and modes of action, as well as future directions to achieve more potent analogues toward a viable antiviral therapy.

Therapeutic Potential of Spirooxindoles as Antiviral Agents.

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.22293

Slobodan Milutinovic

Papers

Effects of satavaptan, a selective vasopressin V2 receptor antagonist, on ascites and serum sodium in cirrhosis with hyponatremia: A randomized trial