A previously healthy 27-year-old female had 3 days of fever (40°C), headache, and myalgia. She had not been previously vaccinated for YF. Initial workup revealed 2,150 leukocytes/mm , 83,000 platelets/mm , AST 8462U/L and ALT 5249U/L (Figure 1). She was icteric with a heart rate of 60 bpm. The following day, a generalized seizure led to intubation, and renal failure led to hemodialysis. Transcranial doppler ultrasound showed signs of intracranial hypertension, cranial CT scan showed diffuse hypoattenuation and loss of grey-white differentiation; abdominal doppler ultrasound, and echocardiogram were normal. This article is protected by copyright. All rights reserved.

IntroductionAn ongoing outbreak of yellow fever (YF) has been reported in Brazil with 1261 confirmed cases and 409 deaths since July 2017. To date, there is no specific treatment available for YF. Recently published papers describing in vitro and animal models suggest a potential effect of antiviral drugs (approved for the treatment of hepatitis virus) against flaviviruses, including YF. The primary aim of this study is to analyse the effect of sofosbuvir on viral kinetics and clinical outcomes among patients presenting with YF. This is a multicentre open-label randomised controlled trial with 1:1 individual allocation, stratified by severity and by recruiting centre.Methods and analysisAdults with suspected or confirmed YF infection and symptoms lasting up to 15 days are screened. Eligible and consenting patients are randomised to receive oral sofosbuvir 400 mg daily for 10 days or to receive standard clinical care. Viral kinetics are measured daily and the reduction in YF plasma viral load from the sample at inclusion to 72 hours after randomisation will be compared between active and control groups. Clinical outcomes include severity meeting criteria for intensive care support, liver transplantation, in-hospital mortality and mortality within 60 days.Ethics and disseminationEthics approval was obtained at the participating sites and at the national research ethics committee (CAAE 82673018.6.1001.0068). The trial has been submitted for ethical approval at additional potential recruiting centres. Results of the study will be published in journals and presented at scientific meetings.Trial registrationBrazilian Clinical Trials Registry (RBR-93dp9n).

Survival rates of critically ill patients with liver disease has sharply increased in recent years due to several improvements in the management of decompensated cirrhosis and acute liver failure. This is ascribed to the incorporation of evidence-based strategies from clinical trials aiming to reduce mortality. In order to discuss the cutting-edge evidence regarding critical care of patients with liver disease, a joint single topic conference was recently sponsored by the Brazilian Society of Hepatology in cooperation with the Brazilian Society of Intensive Care Medicine and the Brazilian Association for Organ Transplantation. This paper summarizes the proceedings of the aforementioned meeting and it is intended to guide intensive care physicians, gastroenterologists and hepatologists in the care management of patients with liver disease.

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Early allograft dysfunction after liver transplantation is an important cause of allograft loss. There is a lack of data on applicability of liver stiffness measurement (LSM) by elastography in early post-liver transplantation that can predict these complications. Our aim was to evaluate the diagnostic accuracy of elastography to predict early allograft dysfunction or loss after liver transplantation. Sixty-one liver transplant patients were prospectively enrolled and underwent daily LSM over the first seven post-operative days. Early allograft dysfunction and loss occurred in 27 (44.2%) and 17 (27.8%) patients, respectively. C-statistic of each day of LSM showed high accuracy and no significant difference between them. For early allograft dysfunction, LSM>2.39m/s on the first day had c-statistics=0.83, sensitivity=0.41, specificity=0.97, positive predictive value=0.92, negative predictive value=0.67, positive likelihood ratio=13.85 to rule in, while a LSM<1.65m/s had c-statistics=0.83, sensitivity=0.96, specificity=0.50, positive predictive value=0.60, negative predictive value=0.94, negative likelihood ratio=0.07 to rule out. For early allograft loss, LSM>2.25m/s had c-statistics=0.93, sensitivity=0.76, specificity=0.98, positive predictive value=0.93, negative predictive value=0.91, positive likelihood ratio=33.65 to rule in, while a LSM<1.75m/s had c-statistics=0.93, sensitivity=0.94, specificity=0.94, positive predictive value=0.50, negative predictive value =0.97, negative likelihood ratio=0.09 to rule out. These results were internally validated with the bootstrap method. No methods (Olthof criteria, MELD, MELD-5, MEAF, BAR, biomarkers) performed better than elastography to predict early allograft loss. Elastography performed over the first week after liver transplantation can accurately predict early dysfunction and allograft loss.