Staging liver fibrosis after severe yellow fever with ultrasound elastography in Brazil: A six-month follow-up study.

Yuri Costa Sarno Neves,Fernando Linhares Pereira,Maria Cristina Chammas,Yeh-Li Ho,Victor Augusto Camarinha De Castro-Lima,Ana Catharina Seixas Nastri,Vivian Simone De Medeiros Ogata,Davi Jorge Fontoura Solla,Jordana Machado Araujo,Michael R Holbrook

doi:10.1371/journal.pntd.0009594

Abstract

Yellow fever (YF) is a hemorrhagic disease caused by an arbovirus endemic in South America, with recent outbreaks in the last years. Severe cases exhibit fulminant hepatitis, but there are no studies regarding its late-term effects on liver parenchyma. Thus, the aim of this study was to determine the frequency and grade of liver fibrosis in patients who recovered from severe YF and to point out potential predictors of this outcome. We followed-up 18 patients who survived severe YF during a recent outbreak (January-April 2018) in Brazil using ultrasound (US) with shear-wave elastography (SWE) at 6 months after symptoms onset. No patient had previous history of liver disease. Median liver stiffness (LS) was 5.3 (4.6-6.4) kPa. 2 (11.1%) patients were classified as Metavir F2, 1 (8.3%) as F3 and 1 (8.3%) as F4; these two last patients had features of cardiogenic liver congestion on Doppler analysis. Age and cardiac failure were associated with increased LS (p = 0.036 and p = 0.024, respectively). SAPS-3 at ICU admission showed a tendency of association with significant fibrosis (≥ F2; p = 0.053). 7 patients used sofosbuvir in a research protocol, of which none showed liver fibrosis (p = 0.119). We found a low frequency of liver fibrosis in severe YF survivors. US with SWE may have a role in the follow up of patients of age and / or with comorbidities after hospital discharge in severe YF, a rare but reemergent disease.

Highlights

Yellow fever (YF) is a mosquito-borne hemorrhagic disease caused by an arbovirus of genus Flavivirus that occurs in tropical regions of South America and Africa [1]
Yellow fever (YF) is a viral disease transmitted by mosquitoes and represents an important health problem in countries of South America and Africa, with recent outbreaks in the past few years
Severe cases lead to fulminant hepatitis and death; it has been reported that surviving patients tend to recover / “regenerate” the liver after the acute phase of the disease

Summary

Introduction

Yellow fever (YF) is a mosquito-borne hemorrhagic disease caused by an arbovirus of genus Flavivirus that occurs in tropical regions of South America and Africa [1]. The pathophysiology of the disease involves viral tropism and acute direct damage to vital organs such as liver and kidneys[5,6,7], in severe cases leading to fulminant hepatitis and acute renal failure (often requiring replacement therapies)[8,9,10,11], with high in-hospital case fatality rates (of up to 67%, according to recent studies[12,13,14]). It is not clear whether liver fibrosis arises after initial insult in severe form surviving patients. The aim of this study was to determine the frequency and grade of liver fibrosis in patients who recovered from severe YF and to point out potential predictors of this outcome

Objectives

Results

Discussion

Conclusion