Reply to: ‘NAFLD or comorbidities, that is the question’
Authors: Dong Ji, Dawei Zhang, George Lau
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 NAFLD or comorbidities, that is the questionJournal of HepatologyVol. 73Issue 3PreviewIn this study,1 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%,2 with a high variability between different regions. In northeastern China, where the study was conducted, the reported prevalence is 26.9%.3 Full-Text PDF We thank Ponziani et al. for their interest in our manuscript and for their thoughtful comments.1Ponziani F.R. Gasbarrini A. Pompili M. NAFLD or comorbidities, that is the question.J Hepatol. 2020; 73: 723Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar 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. Secondly, the 2 hospitals in our study are in Anhui (Eastern China) and Beijing (Northern China), not in Northeastern China (Liaoning, Jilin, Heilongjiang provinces), therefore using the 27.6% prevalence might not be relevant.2Zhou 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 (403) Google Scholar We agree that hepatic steatosis index (HIS) is affected by inflammatory activities. To reduce over-diagnoses, we used the lowest alanine aminotransferase (ALT)/aspartate aminotransferase (AST) value from the medical records of the patients in the preceding 12 months before the COVID-19 diagnosis. If the patient had no ALT/AST records in the preceding 12 months, the lowest value during the current admission and follow-up was used to calculate HSI. Also, the mean AST and ALT values were not significantly different between the stable and progressive groups. If inflammation led to elevation of transaminases and subsequently over diagnosis of HIS as suggested, again it should affect both the stable and progressive groups equally. In our cohort, 6/202 (3%) of patients fulfilled the criteria of excessive alcohol intake (≥30 g/d for man and ≥20 g/d for women), with 5/163(3.1%) and 1/39 (2.6%) in the stable and progressive groups, respectively (p = 1.000), as shown in Table 1.3Vilar-Gomez E. Chalasani N. Non-invasive assessment of non-alcoholic fatty liver disease: clinical prediction rules and blood-based biomarkers.J Hepatol. 2018; 68: 305-315Abstract Full Text Full Text PDF PubMed Scopus (421) Google Scholar Only 2/76 (2.6%) patients with excessive alcohol intake had NAFLD, and 4/126 (3.2%) with excessive alcohol intake did not have NAFLD (p = 1.000). Nonetheless, we acknowledge the limitation of non-invasive assessment of NAFLD.4Ji 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 (392) Google Scholar However, with the priority concern being the safety of the medical staff and the patients with COVID-19, further non-invasive or invasive assessments (such as liver biopsy) were not undertaken. In the near future, we hope that efforts to create a "big data" collection, such as the "APCOLIS" study (APASL Covid Liver Injury Spectrum) (https://www.surveymonkey.com/r/covid-liver) will enhance our understanding of the role of NAFLD/MAFLD in COVID-19.5Lau G. Sharma M. APASL Covid-19 Working Task ForceClinical practice guidance for hepatology and liver transplant providers during the COVID-19 pandemic: APASL expert panel consensus recommendations.Hepatol Int. 2020; 14: 415-428Crossref PubMed Scopus (63) Google Scholar Though HIV infection was defined as a comorbidity, none of the patients in our cohort had positive HIV serology or documented HIV infection in the past. Fig. 1 showed that after multivariate analysis, male sex (odds ratio [OR] 3.1; 95% CI 1.1–9.4), age >60 years (OR 4.8; 95% CI 1.5–16.2), higher BMI (OR 1.3; 95% CI 1.0–1.8), underlying comorbidity (OR 6.3; 95% CI 2.3–18.8) and NAFLD (OR 6.4; 95% CI 1.5–31.2) were associated with progression of illness. This work is funded by the Capital Characteristic Clinic Project of Beijing Municipal Science and Technology Commission (Z181100001718034). DJ and DZ wrote the manuscript; GL provided guidance and proof-read the manuscript; all authors revised and approved the final version. We declare no competing interests. Please refer to the accompanying ICMJE disclosure forms for further details. We acknowledge all patients and health-care workers involved in the diagnosis and treatment of patients with COVID-19 in our hospitals. Download .pdf (.16 MB) Help with pdf files disclosures.pdf