Acute Brucellosis and Cirrhosis: The Triggering Event of Fatal Liver Decompensation

Cirrhotic patients are known to be particularly susceptible to infectious complications that may vary according to regional endemic patterns. Brucellosis, a common zoonosis with worldwide distribution, exhibits a predilection for the reticuloendothelial system and thus resulting in hepatic involvement. We describe three cirrhotic patients in whom acute brucellosis and/or its treatment served as the triggering factor of hepatic decompensation, with deleterious effects. The patients suffered from alcoholic cirrhosis and culture-proven brucellosis. All patients came from an area endemic to brucellosis. The first patient exhibited a relapsing brucellosis course with progressive deterioration of his fragile liver function. The second patient progressed rapidly to jaundice, possibly partly attributed to antibiotic pharmacotoxicity, and died during liver transplantation. The third patient eventually succumbed to diffuse intravascular coagulation. Brucellosis can be a triggering event of fatal liver decompensation in cirrhotic patients. Enhancing health literacy of the patients, particularly in endemic areas, is of paramount importance for prevention of exposure to similar pathogens

Early Start of Oral Clarithromycin Is Associated with Better Outcome in COVID-19 of Moderate Severity: The ACHIEVE Open-Label Single-Arm Trial

Introduction The anti-inflammatory effect of macrolides prompted the study of oral clarithromycin in moderate COVID-19. Methods An open-label non-randomized trial in 90 patients with COVID-19 of moderate severity was conducted between May and October 2020. The primary endpoint was defined at the end of treatment (EOT) as no need for hospital re-admission and no progression into lower respiratory tract infection (LRTI) for patients with upper respiratory tract infection and as at least 50% decrease of the respiratory symptoms score without progression into severe respiratory failure (SRF) for patients with LRTI. Viral load, biomarkers, the function of mononuclear cells and safety were assessed. Results The primary endpoint was attained in 86.7% of patients treated with clarithromycin (95% CIs 78.1-92.2%); this was 91.7% and 81.4% among patients starting clarithromycin the first 5 days from symptoms onset or later (odds ratio after multivariate analysis 6.62; p 0.030). The responses were better for patients infected by non-B1.1 variants. Clarithromycin use was associated with decreases in circulating C-reactive protein, tumour necrosis factor-alpha and interleukin (IL)-6; by increase of production of interferon-gamma and decrease of production of interleukin-6 by mononuclear cells; and by suppression of SARS-CoV-2 viral load. No safety concerns were reported. Conclusions Early clarithromycin treatment provides most of the clinical improvement in moderate COVID-19

Evinacumab for Homozygous Familial Hypercholesterolemia

BACKGROUND Homozygous familial hypercholesterolemia is characterized by premature cardiovascular disease caused by markedly elevated levels of low-density lipoprotein (LDL) cholesterol. This disorder is associated with genetic variants that result in virtually absent (null–null) or impaired (non-null) LDL-receptor activity. Loss-offunction variants in the gene encoding angiopoietin-like 3 (ANGPTL3) are associated with hypolipidemia and protection against atherosclerotic cardiovascular disease. Evinacumab, a monoclonal antibody against ANGPTL3, has shown potential benefit in patients with homozygous familial hypercholesterolemia. METHODS In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned in a 2:1 ratio 65 patients with homozygous familial hypercholesterolemia who were receiving stable lipid-lowering therapy to receive an intravenous infusion of evinacumab (at a dose of 15 mg per kilogram of body weight) every 4 weeks or placebo. The primary outcome was the percent change from baseline in the LDL cholesterol level at week 24. RESULTS The mean baseline LDL cholesterol level in the two groups was 255.1 mg per deciliter, despite the receipt of maximum doses of background lipid-lowering therapy. At week 24, patients in the evinacumab group had a relative reduction from baseline in the LDL cholesterol level of 47.1%, as compared with an increase of 1.9% in the placebo group, for a between-group least-squares mean difference of –49.0 percentage points (95% confidence interval [CI], –65.0 to –33.1; P 0.001); the between-group least-squares mean absolute difference in the LDL cholesterol level was –132.1 mg per deciliter (95% CI, –175.3 to –88.9; P 0.001). The LDL cholesterol level was lower in the evinacumab group than in the placebo group in patients with null–null variants (–43.4% vs. +16.2%) and in those with non-null variants (–49.1% vs. –3.8%). Adverse events were similar in the two groups. CONCLUSIONS In patients with homozygous familial hypercholesterolemia receiving maximum doses of lipid-lowering therapy, the reduction from baseline in the LDL cholesterol level in the evinacumab group, as compared with the small increase in the placebo group, resulted in a between-group difference of 49.0 percentage points at 24 weeks. (Funded by Regeneron Pharmaceuticals; ELIPSE HoFH ClinicalTrials.gov number, NCT03399786.