NAFLD or comorbidities, that is the question
Authors: Francesca Romana Ponziani, Antonio Gasbarrini, Maurizio Pompili
Journal: Journal of Hepatology (2020)

Non-alcoholic fatty liver diseases in patients with COVID-19: A retrospective studyJournal of HepatologyVol. 73Issue 2PreviewLiver injury has been observed in patients with COVID-19, at an incidence ranging from 14–53%.1–3 We examined the liver injury patterns and implication of non-alcoholic fatty liver diseases (NAFLD) on clinical outcomes in Chinese patients with COVID-19. Full-Text PDF Reply to: 'NAFLD or comorbidities, that is the question'Journal of HepatologyVol. 73Issue 3PreviewWe thank Ponziani et al. for their interest in our manuscript and for their thoughtful comments.1 They raised the concern that the 37.6% prevalence of non-alcoholic fatty liver disease (NAFLD) in our cohorts was rather high compared to the 26.9% reported in Northeastern China and suggested that we may have over-diagnosed NAFLD. If NAFLD was over-diagnosed, the prevalence should be similar in the stable and progressive groups, as opposed to the marked difference, 25.8% vs. 87.2 %, respectively, observed in our study. Full-Text PDF In this study,1Ji D. Qin E. Xu J. Zhang D. Cheng G. Wang Y. et al.Non-alcoholic fatty liver diseases in patients with COVID-19: a retrospective study.J Hepatol. 2020; 73: 451-453Abstract Full Text Full Text PDF PubMed Scopus (387) Google Scholar Ji et al. describe the implication of non-alcoholic fatty liver disease (NAFLD) on clinical outcomes in patients with SARS-CoV-2 infection. They reported that the prevalence NAFLD was 37.6%, which is a high percentage with respect to the population included in the study. Indeed, the prevalence of NAFLD in China ranges from 15% to 40%,2Fan J.G. Kim S.U. Wong V.W. New trends on obesity and NAFLD in Asia.J Hepatol. 2017; 67: 862-873Abstract Full Text Full Text PDF PubMed Scopus (760) Google Scholar with a high variability between different regions. In northeastern China, where the study was conducted, the reported prevalence is 26.9%.3Zhou F. Zhou J. Wang W. Zhang X.J. Ji Y.X. Zhang P. et al.Unexpected rapid increase in the burden of NAFLD in China from 2008 to 2018: a systematic review and meta-analysis.Hepatology. 2019; 70: 1119-1133Crossref PubMed Scopus (398) Google Scholar This higher prevalence of NAFLD could be explained by an over-diagnosis, mainly due to the use of indirect methods. In the absence of histological data, NAFLD was identified using the hepatic steatosis index (HSI) and/or abdominal ultrasound examination. It is not specified in how many patients either or both methods were used. HSI is affected by inflammatory activity and fibrosis and has poor performance in populations with moderate to severe steatosis.4Fedchuk L. Nascimbeni F. Pais R. Charlotte F. Housset C. Ratziu V. et al.Performance and limitations of steatosis biomarkers in patients with nonalcoholic fatty liver disease.Aliment Pharmacol Ther. 2014; 40: 1209-1222Crossref PubMed Scopus (317) Google Scholar,5Guiu B. Crevisy-Girod E. Binquet C. Duvillard L. Masson D. Lepage C. et al.Prediction for steatosis in type-2 diabetes: clinico-biological markers versus 1H-MR spectroscopy.Eur Radiol. 2012; 22: 855-863Crossref PubMed Scopus (27) Google Scholar Nevertheless, cut-offs above that of 36 used by the authors in this study showed the best sensitivity/specificity for NAFLD detection.4Fedchuk L. Nascimbeni F. Pais R. Charlotte F. Housset C. Ratziu V. et al.Performance and limitations of steatosis biomarkers in patients with nonalcoholic fatty liver disease.Aliment Pharmacol Ther. 2014; 40: 1209-1222Crossref PubMed Scopus (317) Google Scholar No information about other possible confounding factors was provided, the most common one being excessive alcohol intake (≥30 g for men and ≥20 g for women).6European Association for the Study of the Liver, European Association for the Study of Diabetes, European Association for the Study of ObesityEASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease.Obes Facts. 2016; 9: 65-90Crossref PubMed Scopus (324) Google Scholar Nevertheless, HIV infection was reported among patient comorbidities but was not considered in the analysis, as reported in Table 1, representing a further confounding factor for both clinical outcomes and indirect diagnosis of NAFLD. Besides these considerations, as also stated by the authors, SARS-CoV-2 infection is frequently associated with the increase in transaminases and gamma-glutamyl transferase serum levels.7Zhang C. Shi L. Wang F.S. Liver injury in COVID-19: management and challenges.Lancet Gastroenterol Hepatol. 2020; 5: 428-430Abstract Full Text Full Text PDF PubMed Scopus (1326) Google Scholar,8Xu L. Liu J. Lu M. Yang D. Zheng X. Liver injury during highly pathogenic human coronavirus infections.Liver Int. 2020; 40: 998-1004Crossref PubMed Scopus (609) Google Scholar This is the main bias, potentially leading to the increase in HSI with the consequent overestimation of the prevalence of NAFLD in this population of patients. Nevertheless, the association between NAFLD, increased risk of disease progression and longer viral shedding time could be explained by advanced age, higher body mass index and prevalence of comorbidities (e.g. diabetes, arterial hypertension, cardiovascular disease) in the group of patients classified as having "NAFLD". Indeed, the unfavorable clinical outcome of SARS-CoV-2 infection in more frail patients is well-known all over the world.9Guan W.J. Liang W.H. Zhao Y. Liang H.R. Chen Z.S. Li Y.M. et al.Comorbidity and its impact on 1590 patients with Covid-19 in China: a nationwide analysis.Eur Respir J. 2020; 55: 2000547Crossref PubMed Scopus (8) Google Scholar,10Grasselli G. Zangrillo A. Zanella A. Antonelli M. Cabrini L. Castelli A. et al.Baseline Characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region, Italy.JAMA. 2020; 323: 1574-1581Crossref PubMed Scopus (3862) Google Scholar Overall, the conclusions of this study should be treated with caution and only larger series that include patients with a previous diagnosis of NAFLD before SARS-CoV-2 infection will provide clarity regarding outcomes. The authors received no financial support to produce this manuscript. FRP wrote the letter, AG and MP revised and approved the final version of the letter. The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details. Download .pdf (.24 MB) Help with pdf files disclosures.pdf