key: cord-0923590-irizjp8m authors: Ji, Dong; Qin, Enqiang; Xu, Jing; Zhang, Dawei; Cheng, Gregory; Wang, Yudong; Lau, George title: Non-alcoholic fatty liver diseases in patients with COVID-19: A retrospective study date: 2020-04-08 journal: J Hepatol DOI: 10.1016/j.jhep.2020.03.044 sha: bef1b448d5ef09f58ee7e241e89c78f7ec57c756 doc_id: 923590 cord_uid: irizjp8m nan A retrospective study To the Editor: Liver injury has been observed in patients with COVID-19, at an incidence ranging from 14-53%. [1] [2] [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. From January 20 through February 17, 2020, consecutive patients admitted to 2 designated COVID-19 Hospitals in China with confirmed COVID-19 and information on NAFLD status were studied. The diagnosis and clinical management of patients with COVID-19 were conducted in accordance with the practice guidelines issued by The Chinese National Health Commission. 4 COVID-19 was confirmed by the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequences in the throat swab by reverse transcription PCR. Liver injury was defined as hepatocellular if the alanine aminotransferase (ALT) level was >30 IU/L for males and >19 IU/L for females 5 The criteria of discharge include all the following conditions: body temperatures remain normal over 3 days, significant improvement of respiratory symptoms, resolution of pulmonary imaging of inflammation, and repeated tests at least 24 hours apart confirms SARS-CoV-2 clearance. used for HSI was taken either at complete recovery on discharge or from records of the patients before and within 12 months of the diagnosis of COVID-19. The patients were followed till discharged with recovery or disease progression. The study was approved by the Ethics Committees of FYSPH (20200303006) and the Fifth Medical Center of PLAGH (2020005D). The significance of clinical characteristics on admission were assessed by univariate and multivariate logistic regression analysis to investigate the independent risk factors of disease progression. p values <0.05 were considered significant. Two hundred and two consecutive patients with confirmed COVID-19 and information relating to NAFLD status were studied. Liver injury was observed in 101 (50%) and 152 (75.2%) patients on admission and during hospitalization, respectively. Almost all liver injury was mild with hepatocellular pattern, only 2.6% (4/152) had ductular or mixed pattern. Sixty-seven (33.2%) patients had persistent abnormal liver function from admission to last follow-up. Thirty-nine (19.3%) and 163 (80.7%) had progressive and stable disease, respectively. Patients with progressive disease were older, had higher BMI, and a higher percentage of comorbidity and NAFLD ( Similar to other reports, our study showed that liver injury in patients with COVID-19 was frequent but mild in nature. [1] [2] [3] The pattern of liver injury was mostly hepatocellular rather than cholestatic. This is of interest as it had been shown that biliary cells have high expression of angiotensin-converting enzyme (ACE2) receptor with a high affinity for the spike protein of SARS-CoV-2. 7 In other respiratory viral infection, hepatitis has been related to the collateral damage mediated by virus-specific effector cells generated in response to the pulmonary infection. 8 The postmortem liver biopsy in one of our patients showed only microvesicular steatosis, accompanied by overactivation of T cells, suggesting that liver injury in COVID-19 is likely immune mediated rather than being the result of direct cytopathic damage, as described for other viral respiratory diseases. 9 The majority of patients in our series with persistent liver injury had NAFLD and high BMI. Patients with NAFLD also had a higher risk of progression to severe COVID-19 and longer viral shedding time. With increasing global prevalence of NAFLD, this may suggest a large proportion of our population could be at risk of severe COVID-19. The underlying mechanism is unknown but might be related to impaired innate immunity to the virus. In particular, there are abundant ACE2 receptors in the small intestine and clinically, patients complain of abdominal pain and diarrhea. Circulation of the virus via the hepatic reticular system is expected, given the rich supply of blood to the liver from the small bowel. The liver contains the largest number of macrophages (Kupffer cells) in the body and is a potent cytokine producer. Impaired hepatic innate immune status might play a critical role in COVID-19 outcome. We postulate that in patients with NAFLD, the polarization status of hepatic macrophages might be skewed from inflammation-promoting M1 macrophages to inflammationsuppressing M2 macrophages, leading to progression of COVID-19. 10 However, a better understanding of the role of NAFLD in COVID-19 may have therapeutic implications. This work is funded by the Capital characteristic clinic project of Beijing Municipal Science and Technology Commission (Z181100001718034). We acknowledge all health-care workers involved in the diagnosis and treatment of patients with COVID-19 in our hospital. Liver injury during highly pathogenic human coronavirus infections Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series Chinese Clinical Guidance for COVID-19 Pheumonia Diagnosis and Treatment Low alanine aminotransferase cut-off for predicting liver outcomes; a nationwide population-based longitudinal cohort study Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection Kupffer cell-dependent hepatitis occurs during influenza infection Pathological findings of COVID-19 associated with acute respiratory distress syndrome Macrophages in obesity and non-alcoholic fatty liver disease: crosstalk with metabolism The authors declare no conflicts of interest that pertain to this work.Please refer to the accompanying ICMJE disclosure forms for further details.Authors' contributions DJ, DZ, JX, and EQ treated the patients.DJ, GC, YW and GL processed statistical data and drafted the manuscript. DJ and GL had the idea for and designed the study. Supplementary data to this article can be found online at https:// doi.org/10.1016/j.jhep.2020.03.044.