Reply to: “Liver fibrosis and adverse outcomes in COVID-19”

Dear Editor,

We appreciate Dr. Jianmin Huang letter [1] and interest in our work, as well as the important comments provided for our retrospective cohort study entitled “Liver fibrosis in patients with metabolic associated fatty liver disease is a risk factor for adverse outcomes in COVID-19” published in Digestive and Liver Disease.

We agree with the comments made regarding descriptive data; in Table 2 we presented the data as mean ± SD, however it would certainly be more appropriate to use median for their description. Here we provide the median values for D-Dimer, CPK and troponins in patients with fatty liver in the group of no fibrosis vs fibrosis:

	No fibrosis	Fibrosis	p value
D-dimer	595 (416–1011)	640 (425–955)	p = 0.970
CPK	127 (65–229)	313 (101–611)	p < 0.001
Troponins	4.2 (3.15–6.3)	6.7 (5–12.5)	p = 0.001

We did find a change in troponin description, that was significantly different according to the presence of fibrosis. We performed the same multivariate analysis including troponins, however, this did not affect the conclusions nor the main findings mentioned in the paper, as liver fibrosis remained associated with poor prognosis (AKI, mechanical ventilation and mortality), independently of several biochemical markers, including troponins. In this cohort, troponins were also significantly associated with mortality, but not orotracheal intubation or acute kidney injury.

With regards to the second comment, the main aim of our study was to evaluate the association between the presence of liver fibrosis evaluated by non-invasive scores in patients with fatty liver diagnosed by CT scan and clinical outcomes in patients admitted for COVID-19. Our study did not intend to attain new prognostic markers nor evaluate the performance of the different markers in patients with COVID-19, as would be adding AST/ALT ratio, in which case we would have used a different design. The reason why transaminases were not added to the models, was the fact that both ALT and AST are already present in the two used fibrosis scores, thus creating collinearity in the model, which would be unfitting.

Finally, as Huang J referred, the severity of COVID-19 is associated with poor prognosis. Although COVID-19 can be classified into 4 subtypes (mild, moderate, severe, and critical) according to the World Health Organization, our cohort only included hospitalized patients, consequently, only severe and critical subtypes were included. Therefore, in our cohort, it is not feasible to evaluate liver fibrosis in the full spectrum of COVID-19. However, our analysis shows that patients with severe fibrosis measured by NFS/APRI score have a significant risk [OR: 2.59 (1.18–5.66)] to have a critical presentation of the disease, and therefore worse prognosis, compared with patients without severe fibrosis. And the proportion of patients with liver fibrosis was 35.6% in patients that required mechanical ventilation compared with 16.2% in those without mechanical ventilation (p = 0.006).

We hope this information is able to address the questions raised and preclude misinterpretation of the study results.

Sincerely,

Astrid Ruiz-Margáin, Alejandro Campos-Murguía, José Alberto González-Regueiro, Berenice Monserrat Román-Calleja, Deyanira Kúsulas Delint, Ricardo Ulises Macías-Rodríguez.

Declaration of Competing Interest

The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.