key: cord-0833940-tscmmqih authors: Asai, Akira; Yasuoka, Hidetaka; Matsui, Masahiro; Okamoto, Norio; Fukunishi, Shinya; Higuchi, Kazuhide title: Exacerbation of liver dysfunction in non-alcoholic steatohepatitis patients during the coronavirus disease 2019 (COVID-19) pandemic date: 2020-12-03 journal: J Clin Biochem Nutr DOI: 10.3164/jcbn.20-136 sha: 9622f72610a3bf3f0b0dded1ae144cbbceeaaffa doc_id: 833940 cord_uid: tscmmqih Many people were forced to stay at home, including non-alcoholic steatohepatitis (NASH) patients, however it is unclear how this home-life has affected the prognosis of NASH. In this study, we examined the influences of living at home during the coronavirus disease 2019 (COVID-19) pandemic NASH patients. In this study, we compared the clinical parameters of NASH patients without COVID-19 infection 3 months before with those 3 months after the declaration of a state of emergency. In the results, the changes of aspartate transaminase and alanine aminotransferase in the 3 months before (aspartate transaminase, –3.6 ± 13.8 U/L; alanine aminotransferase, –6.8 ± 19.5 U/L) was significantly exacerbated in the 3 months after (aspartate transaminase, 2.3 ± 7.5 U/L; alanine aminotransferase, 1.7 ± 10.4 U/L). Furthermore, the changes of the fibrosis-4 index in the 3 months before (–0.27 ± 0.84) was also significantly exacerbated in the 3 months after (0.38 ± 0.96). In conclusion, liver dysfunctions in NASH patients were exacerbated due to the emergency declaration and outing restriction which accompanied COVID-19. Introduction N on-alcoholic steatohepatitis (NASH) is defined as a condition characterized by deposition of fat in at least 5% of hepatocytes in the absence of secondary causes of lipid accumulation or those attributable to consumption of alcohol. NASH is a cause of cirrhosis and hepatocellular carcinoma. (1) Over the past decade, the incidence of NASH, a lifestyle-related disease, has grown. (2, 3) Treatments with various drugs have been tried, but no evidencebased treatment has emerged. Lifestyle modifications such as exercise, diet and weight loss have been advocated as the most effective treatment. (4) From the end of 2019, coronavirus disease 2019 (COVID-19) has been an emerging infectious disease, initially mainly in China, but it has since spread all over the world. The number of COVID-19 patients dying from the severe acute respiratory syndrome caused by this virus is increasing worldwide. (5) Since this virus is considered to cause infection through contact and airborne transmission declaration of a state of emergency and outing restrictions have been applied around the world, mainly in countries where the infection is increasing. (6) Invariably, an declaration of a state of emergency was issued in Japan from April 7, 2020 to May 26, 2020 to prevent the spread of COVID-19 infections. Many people were forced to stay at home, including NASH patients, however it is unclear how this home-life has affected the prognosis of NASH. In this study, we examined the influences of living at home during the COVID-19 epidemic on NASH patients. NASH patients. This study was approved by the Institutional Review Board of the Osaka Medical College (IRB approved number: 2020-066) and was conducted in accordance with the relevant guidelines and regulations of the Osaka Medical College. Informed consent was obtained in the form of opt-out on the web-site. Those who rejected were excluded. In this study, we enrolled 259 patients who were diagnosed with NASH and had a follow-up visit at the Osaka Medical College. First, the following 199 patients were excluded: 31 patients with hepatocellular carcinoma or other cancers, 4 patients with decompensated cirrhosis, 51 patients with other liver disease (hepatitis B virus, hepatitis C virus, primary biliary cholangitis, autoimmune hepatitis, and infection), 6 patients who were diagnosed with NASH within the last 6 months, and 107 patients without blood tests. Second, 30 patients who canceled their follow-up visit themselves were excluded. Ultimately, 30 patients were eligible for this study. These patients did not have symptoms of COVID-19; which include shortness of breath, aches, nasal congestion, sore throat, cough, and fever. Clinical parameters. In these patients, the clinical parameters from blood samples taken both 6 and 3 months before, during and 3 months after the duration of declaration of a state of emergency, were compared. The fibrosis-4 (FIB-4) index was calculated by this equation. Statistical analysis. Statistical analyses were performed using JMP Pro software ver. 14 (Tokyo, Japan). Differences of quantitative values in two groups were analyzed using a Mann-Whitney U test and in three groups were Kruskal-Wallis test. The Fisher's exact test was used to analyze the nominal scales. A p value <0.05 was considered statistically significant. Four patients were diagnosed with NASH-related liver cirrhosis, with a Child-Pugh score of 5. Ten patients were treated with a combination of calorie reduction, exercise, and healthy eating. The other 20 patients received drug treatment in addition to those lifestyle modifications (Table 1A) . In these patients, 3 months before the declaration of a state of emergency, the N treatment had improved the serum AST and ALT. The fibrosis-4 (FIB-4) index score, a noninvasive fibrotic marker of the liver, (6) also decreased. However, no significant difference was observed in each parameter. Albumin, total bilirubin, total cholesterol (T-cho), platelets and prothrombin time did not change. In contrast; AST, ALT, T-cho, triglyceride, and the FIB4-index score increased in these patients in the 3 months after the declaration of a state of emergency (Table 1B) . When we compared the changes between the 3 months before and after the declaration of a state of emergency, the changes of AST, ALT, and FIB4-index in the 3 months before (AST, -3.6 ± 13.8 U/L; ALT, -6.8 ± 19.5 U/L; FIB-4 index, -0.27 ± 0.84) was significantly exacerbated in the 3 months after the declaration of a state of emergency (AST, 2.3 ± 7.5 U/L; ALT, 1.7 ± 10.4 U/L; FIB-4 index, 0.38 ± 0.96) (Fig. 1) . These results suggest that liver dysfunctions in NASH patients were exacerbated due to the emergency declaration and outing restriction which accompanied COVID-19. Although there are many diseases that are exacerbated by COVID-19 infection, this study revealed that liver dysfunctions in NASH patients, in the absence of COVID-19 infection, was exacerbated by the new lifestyle that resulted from the COVID-19 pandemic. Similar exacerbations may be detected in other lifestyle-related diseases such as diabetes, hypertension, and abnormal lipid metabolism. Also, it was reported that the malnutrition and selective IgA deficiency were detected in patients with COVID-19. (8, 9) In this study; the AST, ALT, and FIB-4 index were clearly raised suggesting that liver fibrosis may have progressed. In order to clarify this, it is important to evaluate hepatic fibrosis by pathological analysis with a liver biopsy or by measuring non-invasive liver stiffness with abdominal ultrasonography. However, it is not as easy to carry out these procedures as we did before, since visiting the hospital carries increased risk of COVID-19 infection. In future, these evaluations will need to be performed after ensuring safety against COVID-19. One of the limitations of this study is that its sample size was comparatively small. Half of the patients cancelled their follow-up visit. The influence of staying at home on the liver function of the patients who canceled is unknown and assessing liver function in these patients poses a problem in the future. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention Genetic contributions to NAFLD: leveraging shared genetics to uncover systems biology Questionnaire survey on lifestyle of patients with nonalcoholic steatohepatitis The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China Analysis of clinical features and outcomes of 161 patients with severe and critical COVID-19: a multicenter descriptive study Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease Evaluation of the nutritional status in patients with COVID-19 Association between selective IgA deficiency and COVID-19 This study was supported by OMC Internal Research Grant. No potential conflicts of interest were disclosed.This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/).