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1.
Sci Rep ; 12(1): 17972, 2022 Oct 26.
Article in English | MEDLINE | ID: covidwho-2087307

ABSTRACT

This study investigated whether acute liver injury (ALI) persisted and identified predictors of ALI recovery [as indicated by alanine aminotransferase (ALT) level] at hospital discharge and 2 months post-discharge for 7595 hospitalized COVID-19 patients from the Montefiore Health System (03/11/2020-06/03/2021). Mild liver injury (mLI) was defined as ALT = 1.5-5 ULN, and severe livery injury (sLI) was ALT ≥ 5 ULN. Logistic regression was used to identify predictors of ALI onset and recovery. There were 4571 (60.2%), 2306 (30.4%), 718 (9.5%) patients with no liver injury (nLI), mLI and sLI, respectively. Males showed higher incidence of sLI and mLI (p < 0.05). Mortality odds ratio was 4.15 [95% CI 3.41, 5.05, p < 0.001] for sLI and 1.69 [95% CI 1.47, 1.96, p < 0.001] for mLI compared to nLI. The top predictors (ALT, lactate dehydrogenase, ferritin, lymphocytes) accurately predicted sLI onset up to three days prior. Only 33.5% of mLI and 17.1% of sLI patients (survivors) recovered completely at hospital discharge. Most ALI patients (76.7-82.4%) recovered completely ~ 2 months post-discharge. The top predictors accurately predicted recovery post discharge with 83.2 ± 2.2% accuracy. In conclusion, most COVID-19 patients with ALI recovered completely ~ 2 months post discharge. Early identification of patients at-risk of persistent ALI could help to prevent long-term liver complications.


Subject(s)
COVID-19 , Liver Diseases , Male , Humans , COVID-19/complications , Alanine Transaminase , Aftercare , Liver Function Tests , Patient Discharge , Retrospective Studies , Liver Diseases/etiology , Liver Diseases/epidemiology , Hospitals , Ferritins , Lactate Dehydrogenases
2.
Eur J Gastroenterol Hepatol ; 34(11): 1165-1171, 2022 11 01.
Article in English | MEDLINE | ID: covidwho-2051710

ABSTRACT

BACKGROUND: Although several liver- and inflammation-based scores to predict the clinical course of patients with coronavirus disease 2019 (COVID-19) have been evaluated, no direct comparison regarding their predictive ability has been performed. METHODS: 1038 patients (608 males, age 63.5 ± 17 years) hospitalized with documented COVID-19 infection to the non-ICU ward, were included retrospectively. Clinical and laboratory characteristics on admission including evaluation of Fibrosis-4 (FIB-4) score and C-Reactive Protein (CRP) to albumin ratio (CAR) were recorded. RESULTS: One hundred and twenty-four patients (11.9%) died during hospitalization after 8 (3-72) days. In multivariate analysis, FIB-4 (hazard ratio, 1.11; 95% confidence interval (CI), 1.034-1.19; P = 0.004), was independently associated with mortality, with very good discriminative ability (area under the receiver operating characteristic curve curve, 0.76). The patients with FIB-4 &gt;2.67 (n = 377), compared to those with ≤2.67 (n = 661), had worse survival (log-rank 32.6; P &lt; 0.001). Twenty-four (6.8%) of 352 patients with possible nonalcoholic fatty liver disease (NAFLD) (defined as Hepatic Steatosis Index &gt;36) died during hospitalization. In multivariate analysis, CAR was an independent risk factor (1) for mortality (hazard ratio, 1.014; 95% CI, 1.002-1.025; P = 0.021), (2) the need for high-flow nasal cannula with or without intubation (hazard ratio, 1.016; 95% CI, 1.004-1.027; P = 0.007) and (3) development of acute kidney injury (hazard ratio, 1.017; 95% CI, 1.006-1.028; P = 0.002). In addition, the patients with possible NAFLD and CAR &gt;12 (n = 154), compared to those with CAR ≤12 (n = 198), had worse survival (log-rank 5.1; P = 0.024). CONCLUSIONS: FIB-4 was an independent factor for mortality with better performance compared to other liver function test- and inflammation-based scores in patients with COVID-19, while CAR was the only score independently associated with the clinical course in COVID-19 patients with possible NAFLD.


Subject(s)
COVID-19 , Non-alcoholic Fatty Liver Disease , Aged , Aged, 80 and over , Albumins , C-Reactive Protein , Fibrosis , Humans , Inflammation/complications , Liver Cirrhosis/complications , Liver Function Tests , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/complications , Prognosis , Retrospective Studies
3.
Emerg Microbes Infect ; 11(1): 2222-2228, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1997030

ABSTRACT

ABSTRACTMulticenter case series has reported patients with hepatic injury following COVID-19 vaccination, which raised concern for the possibility of vaccine-induced liver dysfunction. We aimed to assess the impact of COVID-19 vaccination on liver function of pregnant women, who may be uniquely susceptible to vaccine-induced liver dysfunction. We conducted a retrospective cohort study at a tertiary hospital in Shanghai, China. Vaccine administration was obtained from the electronic vaccination record. Serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total bile acid (TBA) and total bilirubin (TBIL) in early pregnancy were determined by enzymatic methods. Among the 7745 included pregnant women, 3832 (49.5%) received at least two doses of an inactivated vaccine. COVID-19 vaccination was significantly associated with higher levels of maternal serum TBA. Compared with unvaccinated pregnant women, the mean TBA levels increased by 0.17 µmol/L (ß = 0.17, 95% CI, 0.04, 0.31) for women who had been vaccinated within 3 months before the date of conception. Moreover, COVID-19 vaccination was significantly associated with an increased risk of maternal hyperbileacidemia. The risk of hyperbileacidemia increased by 113% (RR = 2.13; 95% CI, 1.17-3.87) for pregnant women who had been vaccinated within 3 months before conception compared with unvaccinated pregnant women. However, when the interval from complete vaccination to conception was prolonged to more than 3 months, COVID-19 vaccination was not associated with serum TBA levels or maternal hyperbileacidemia. Our findings suggest that vaccination with inactivated COVID-19 vaccines more than 3 months before conception have no detrimental effects on maternal liver function in early pregnancy.


Subject(s)
COVID-19 Vaccines , COVID-19 , Pregnant Women , Alanine Transaminase , Aspartate Aminotransferases , Bile Acids and Salts , Bilirubin , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , China/epidemiology , Cohort Studies , Female , Humans , Liver , Liver Function Tests , Pregnancy , Retrospective Studies , Vaccines, Inactivated
4.
Zhonghua Gan Zang Bing Za Zhi ; 30(5): 527-533, 2022 May 20.
Article in Chinese | MEDLINE | ID: covidwho-1911771

ABSTRACT

Objective: To retrospectively analyze the characteristics and influencing factors of liver function changes in 111 elderly patients with COVID-19 pneumonia. Methods: 111 elderly patients with COVID-19 admitted to the Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from February 5 to March 3, 2020 were enrolled. According to the severity of disease and liver function condition, they were divided into severe group (n=40), normal group (n=71), abnormal liver function group (n=86) and normal liver function group (n=25). The indexes related to liver function changes [total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT)] and related influencing factors were analyzed. Results: Among 111 cases, 86 (77.5%) had abnormal liver function of varying degrees, and 28 (25.2%) had liver injury. The abnormal rates of TBil, AST, ALP and GGT were significantly higher in the severe group than normal group (P<0.05). There were no significant differences in age, ribavirin, glucocorticoid and the application of lopinavir-ritonavir tablets between the abnormal liver function and the normal group (P>0.05). The proportion of male was significantly higher in the abnormal liver function than normal liver function group (P<0.05). Conclusion: Elderly COVID-19 patients have a higher proportion of abnormal liver function, and patients in the severe group are more likely to have higher level of TB, AST, ALP and GGT. The abnormal liver function may be related to the direct viral infection of the liver and the inflammatory immune response of the body after infection in elderly patients.


Subject(s)
COVID-19 , Liver Diseases , Aged , Alkaline Phosphatase , Aspartate Aminotransferases , Bilirubin , Humans , Liver Function Tests , Male , Retrospective Studies , gamma-Glutamyltransferase
5.
J Viral Hepat ; 29(9): 823-834, 2022 09.
Article in English | MEDLINE | ID: covidwho-1896011

ABSTRACT

Abnormal liver function tests (A-LFTs) during admission for coronavirus disease-19 (COVID-19) are frequent, but its evolution after COVID-19 resolution remains unexplored. We evaluated factors related to A-LFTs during COVID-19 and assessed the liver outcome after patients' discharge. This is a observational study including: (1) retrospective analysis of variables related to A-LFTs during COVID-19; and (2) follow-up evaluation with blood test, transient elastography and liver biopsy in those with persistent A-LFTs. A-LFTs were defined according to CTCAEv4.0. Among 595 patients, 366 (61.5%) showed A-LFTs. The ratio of partial pressure of oxygen and inspired oxygen fraction (P/F) below 200, ferritin ≥1000 ng/mL, male gender and antibiotic and immunomodulatory treatments were related to A-LFTs. Follow-up evaluation was performed in 153 individuals. Persistent A-LFTs at follow-up was similar in patients with/without A-LFTs during admission (14.1% vs. 4.9%, p = 0.104). Fifteen (93%) and 58 (39%) patients with/without A-LFTs at follow-up showed metabolic fatty liver disease criteria (p < 0.001), which were histologically confirmed. In conclusion, A-LFTs during COVID-19 were related to infection severity. Abnormalities remitted at follow-up in >80% of patients, and no correlation between A-LFTs at admission and at follow-up was found. Most patients with A-LFTs at follow-up had non-invasive and histologically proven fatty liver disease.


Subject(s)
COVID-19 , Liver Diseases , Follow-Up Studies , Humans , Liver Diseases/diagnosis , Liver Function Tests , Male , Oxygen , RNA, Viral , Retrospective Studies , SARS-CoV-2
6.
Front Cell Infect Microbiol ; 12: 864933, 2022.
Article in English | MEDLINE | ID: covidwho-1822356

ABSTRACT

Objective: The longitudinal effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the liver are unknown. This study aimed to characterize dynamic changes in liver function test abnormalities in patients with COVID-19 at the acute phase and recovery phase. Methods: A prospective cohort study involved patients with COVID-19 who were admitted to Shenzhen Third People's Hospital between January 11, 2020, and April 27, 2020. Patients underwent liver function tests at hospitalization and at the outpatient visit at the 1-month, 3-month, 6-month, and 12-month follow-ups. Results: Among 461 patients, 28.4% of patients had any kind of liver function tests abnormality at admission, manifested as elevated ALT (13.0%), AST (17.6%), and GGT (15.8%) levels. The trajectory analysis indicated a marked improvement in liver function after discharge, with any kind of liver function test abnormalities of 25.1% at 1 month, 13.2% at 3 months, 16.7% at 6 months, and 13.2% at 12 months after discharge. Persistent liver function abnormalities were observed in patients with pre-existing conditions during follow-up. A significantly higher prevalence of ultrasound determined fatty liver disease was found in those patients with more frequent LFT abnormalities at follow-up. Conclusion: In this study of patients with COVID-19, liver damage in COVID-19 was usually temporary and could return to normal at the end of the 12-month follow-up.


Subject(s)
COVID-19 , Liver Diseases , Aftercare , Humans , Liver Function Tests , Patient Discharge , Prospective Studies , SARS-CoV-2
7.
World J Gastroenterol ; 27(42): 7350-7361, 2021 Nov 14.
Article in English | MEDLINE | ID: covidwho-1526866

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection is known to cause abnormal hepatic enzymes. The long term consequences of such elevations are uncertain. AIM: To assessed the prevalence and prognostic value of initial liver enzymes in a large cohort of COVID-19 patients. METHODS: We reviewed electronic medical records of 10614 COVID-19 patients without known chronic liver disease who were admitted to our health system from March 1, 2020, to April 30, 2020. We analyzed baseline demographics and liver chemistries. The primary outcome was in-hospital mortality, and the secondary outcome was a composite of in-hospital mortality or need for mechanical ventilation. RESULTS: Subjects with abnormal liver tests had increased risks of mortality and composite outcome when compared to patients with normal measurements on unadjusted analysis and after adjustment for demographic factors. CONCLUSION: In our diverse patient population, liver enzyme abnormalities are associated with increased mortality and the need for mechanical ventilation in subjects without chronic liver disease. Cholestasis patients are at the greatest risk for poor outcomes.


Subject(s)
COVID-19 , Liver Diseases , Hospital Mortality , Humans , Liver Diseases/diagnosis , Liver Diseases/epidemiology , Liver Function Tests , SARS-CoV-2
8.
Inflammopharmacology ; 29(6): 1795-1805, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1505910

ABSTRACT

Hydroxychloroquine has attracted attention in the treatment of COVID-19. Many conflicting findings have been reported regarding the efficacy and safety of this drug, which has been used safely in the rheumatological diseases for years. However, these studies lacked measurement methods that allow accurate assessment of hydroxychloroquine and its metabolite levels. The aim of this study was to measure hydroxychloroquine and its metabolite levels in whole blood samples of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren's syndrome (SS) and scleroderma (Scl) by a robust, simple and accurate validated tandem mass spectrometric method, and to investigate the relationship between these levels with drug-related adverse effects and disease activity scores. The validated LC-MS/MS method was applied to measure blood hydroxychloroquine and its metabolite levels of patients with RA, SLE, SS, Scl. Various haematological and biochemical parameters were measured with Beckman-Coulter AU 5800 and Beckman Coulter LH 780 analyzers, respectively. QTc intervals were calculated with Bazett's formula, and the patients were followed up by clinicians in terms of clinical findings and adverse effects. Hydroxychloroquine levels of patients were similar to previous studies. There was a negative correlation between disease activity scores and hydroxychloroquine levels, while the highest correlation was between QTc interval, creatinine and GFR levels with desethylchloroquine. Bidetylchloroquine had the highest correlation with RBC count and liver function tests. Our findings showed that hydroxychloroquine and its metabolite levels were associated with disease activity scores, renal, hepatic function, QTc prolongation, and hematological parameters.


Subject(s)
Antimalarials/adverse effects , Antimalarials/blood , COVID-19/complications , Connective Tissue Diseases/complications , Hydroxychloroquine/adverse effects , Hydroxychloroquine/blood , Adult , Aged , Chromatography, High Pressure Liquid , Creatinine/blood , Electrocardiography , Erythrocyte Count , Female , Glomerular Filtration Rate/drug effects , Humans , Kidney Function Tests , Liver Function Tests , Long QT Syndrome/chemically induced , Male , Middle Aged , Tandem Mass Spectrometry , Young Adult
9.
Ann Hepatol ; 26: 100553, 2021 12.
Article in English | MEDLINE | ID: covidwho-1482445

ABSTRACT

INTRODUCTION AND OBJECTIVES: In many studies, varying degrees of liver damage have been reported in more than half of the COVID-19 patients. The aim of this study is to determine the effect of liver biochemical parameters abnormality on mortality in critical COVID-19 patients who have been followed in the ICU since the beginning of the pandemic process. MATERIALS AND METHODS: In this study 533 critical patients who admitted to the ICU due to COVID-19 were included. The patients were divided into three groups according to their ALT, AST, and total bilirubin levels at their admission to the ICU. Group 1 was formed of patients with normal liver biochemical parameters values; Group 2 was formed of patients with liver biochemical parameters abnormality; Group 3 was formed of patients with liver injury. RESULTS: 353 (66.2%) of all patients died. Neutrophil, aPTT, CRP, LDH, CK, ALT, AST, bilirubin, procalcitonin and ferritin values in Group 2 and Group 3 were found to be statistically significantly higher than Group 1. It was detected that the days of stay in ICU of the patients in Group 1 was statistically significantly longer than others group. It was found that the patients in Groups 2 and 3 had higher total, 7-day, and 28-day mortality rates than expected. CONCLUSIONS: The study showed that liver disfunction was associated with higher mortality and shorter ICU occupation time.


Subject(s)
COVID-19/diagnosis , Liver Diseases/diagnosis , Liver Function Tests , Liver/metabolism , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/blood , COVID-19/mortality , Critical Illness , Female , Hospital Mortality , Humans , Intensive Care Units , Length of Stay , Liver Diseases/blood , Liver Diseases/mortality , Male , Middle Aged , Predictive Value of Tests , Prognosis , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Turkey
10.
BMC Infect Dis ; 21(1): 818, 2021 Aug 16.
Article in English | MEDLINE | ID: covidwho-1477280

ABSTRACT

BACKGROUND: Liver injuries have been reported in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate the clinical role played by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: In this multicentre, retrospective study, the parameters of liver function tests in COVID-19 inpatients were compared between various time-points in reference to SARS-CoV-2 shedding, and 3 to 7 days before the first detection of viral shedding was regarded as the reference baseline. RESULTS: In total, 70 COVID-19 inpatients were enrolled. Twenty-two (31.4%) patients had a self-medication history after illness. At baseline, 10 (14.3%), 7 (10%), 9 (12.9%), 2 (2.9%), 15 (21.4%), and 4 (5.7%) patients already had abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), albumin, and total bilirubin (TBIL) values, respectively. ALT and AST abnormal rates and levels did not show any significant dynamic changes during the full period of viral shedding (all p > 0.05). The GGT abnormal rate (p = 0.008) and level (p = 0.033) significantly increased on day 10 of viral shedding. Meanwhile, no simultaneous significant increases in abnormal ALP rates and levels were observed. TBIL abnormal rates and levels significantly increased on days 1 and 5 of viral shedding (all p < 0.05). Albumin abnormal decrease rates increased, and levels decreased consistently from baseline to SARS-CoV-2 clearance day (all p < 0.05). Thirteen (18.6%) patients had chronic liver disease, two of whom died. The ALT and AST abnormal rates and levels did not increase in patients with chronic liver disease during SARS-CoV-2 shedding. CONCLUSIONS: SARS-CoV-2 does not directly lead to elevations in ALT and AST but may result in elevations in GGT and TBIL; albumin decreased extraordinarily even when SARS-CoV-2 shedding ended.


Subject(s)
COVID-19/complications , Liver/virology , Adult , Aged , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Biomarkers/blood , COVID-19/blood , COVID-19/epidemiology , Female , Humans , Liver/pathology , Liver Function Tests/methods , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index
11.
Medicine (Baltimore) ; 100(30): e26719, 2021 Jul 30.
Article in English | MEDLINE | ID: covidwho-1475908

ABSTRACT

ABSTRACT: Liver dysfunction in patients with COVID-19 (coronavirus disease 2019) has been described. However, it is not clear if the presence of abnormal liver function tests at presentation was related to underlying undiagnosed liver disease, or a result of the viral infection.We retrospectively examined the first 554 consecutive polymerase chain reaction positive SARS-CoV-2 patients admitted from February 2020 to April 2020 to our academic medical centre. We reviewed their clinical data, chest radiography and laboratory studies obtained within 24 hour of admission.Despite similar hemodynamic parameters, we found significant aspartate transaminase elevation (64 ±â€Š141 vs 35 ±â€Š23 U/L, P < .001) in those with pneumonia compared to those without. Elevated liver enzymes were seen in 102 patients (18.4%). They presented with higher temperatures (38.5 ±â€Š0.9 vs 37.5 ±â€Š0.8 degC, P = .011), higher total white cell counts (6.95 ±â€Š2.29 vs 6.39 ±â€Š2.19 x109/L, P = .021), serum ferritin (240 ±â€Š274 vs 165 ±â€Š198 ng/ml, P = .002) and lactate dehydrogenase (632 ±â€Š912 vs 389 ±â€Š107 U/L, P < .001). These patients were more likely to require intensive care (6.9% vs 2.7% P = .036) and mechanical ventilation (5.9% vs 2.2%, P = .046). Migrant workers from dormitories had a higher rate of baseline liver function test abnormalities (88/425 vs 14/129, P = .01), which were more likely to persist at the time of discharge.Despite relatively mild COVID-19 disease, there was a significant prevalence of liver dysfunction, particularly amongst migrant workers. Elevated liver enzymes were associated with more severe disease, despite similar haemodynamic characteristics. Future studies should explore whether pre-existing liver disease may predispose to more severe COVID-19 disease.


Subject(s)
Aspartate Aminotransferases/blood , COVID-19/complications , L-Lactate Dehydrogenase/blood , Liver Diseases/etiology , Adult , COVID-19/blood , Female , Ferritins/blood , Humans , Leukocyte Count , Liver Diseases/blood , Liver Function Tests , Male , Middle Aged , Retrospective Studies , Risk Factors , Singapore
12.
Int J Antimicrob Agents ; 59(1): 106462, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1474605

ABSTRACT

OBJECTIVES: The use of antibiotics was common in some countries during the early phase of the coronavirus disease 2019 (COVID-19) pandemic, but adequate evaluation remains lacking. This study aimed to evaluate the effect of early antibiotic use in patients with non-severe COVID-19 admitted without bacterial infection. METHODS: This multi-centre retrospective cohort study included 1,373 inpatients with non-severe COVID-19 admitted without bacterial infection. Patients were divided into two groups according to their exposure to antibiotics within 48 h of admission. The outcomes were progression to severe COVID-19, length of stay >15 days and mortality rate. A mixed-effect Cox model and random effect logistic regression were used to explore the association between early antibiotic use and outcomes. RESULTS: During the 30-day follow-up period, the proportion of patients who progressed to severe COVID-19 in the early antibiotic use group was almost 1.4 times that of the comparison group. In the mixed-effect model, the early use of antibiotics was associated with higher probability of developing severe COVID-19 and staying in hospital for >15 days. However, there was no significant association between early use of antibiotics and mortality. Analysis with propensity-score-matched cohorts displayed similar results. In subgroup analysis, patients receiving any class of antibiotic were at increased risk of adverse health outcomes. Azithromycin did not improve disease progression and length of stay in patients with COVID-19. CONCLUSIONS: It is suggested that antibiotic use should be avoided unless absolutely necessary in patients with non-severe COVID-19, particularly in the early stages.


Subject(s)
Anti-Bacterial Agents/therapeutic use , COVID-19/drug therapy , Adult , Aged , Antiviral Agents/therapeutic use , Bacterial Infections , COVID-19/etiology , COVID-19/mortality , Female , Fever/drug therapy , Fever/virology , Humans , Kidney Function Tests , Length of Stay , Liver Function Tests , Male , Middle Aged , Mortality , Retrospective Studies , Treatment Outcome
13.
Iran J Med Sci ; 46(4): 237-255, 2021 07.
Article in English | MEDLINE | ID: covidwho-1395708

ABSTRACT

Background: The outbreak of the coronavirus disease-2019 (COVID-19) has become a global public health challenge. Assessing the effect of COVID-19 on liver injury is of great importance. A systematic review and meta-analysis were conducted to establish the characteristics of liver function tests in COVID-19 patients. Methods: A systematic search of publications from December 2019 up to April 2020 in Web of Science, Scopus, and Medline (via PubMed) databases was performed. Both cross-sectional and case series studies reporting an association between liver injury and COVID-19 infection were included. The data were analyzed using the STATA software (version 11.0) and the random-effects model for I2>50% was used to pool the results. Results: In this meta-analysis, 42 articles comprising a total of 6,557 COVID-19 patients were studied. The prevalence of increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels was 30% and 21% in non-severe patients and 38% and 48% in severe patients, respectively. Patients with severe COVID-19 infection were 4.22, 4.96, and 4.13 times more likely to have elevated AST, ALT, and lactate dehydrogenase (LDH) levels, respectively. Conclusion: Elevation in liver function tests was higher in patients with severe than non-severe COVID-19 infection. Given the widespread use of drugs that increases the risk of hepatotoxicity, healthcare providers should be aware of changes in liver enzymes in COVID-19 patients. The inclusion of other studies from outside China could confirm the pattern of elevation in liver function tests in COVID-19 patients across the globe. Preprint of this article is available on medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.20.20108357v1.


Subject(s)
COVID-19/complications , Liver Diseases/virology , Liver Function Tests , Alanine Transaminase , Aspartate Aminotransferases , Humans , L-Lactate Dehydrogenase , Liver/enzymology , Liver Diseases/epidemiology
14.
BMJ Open Gastroenterol ; 8(1)2021 05.
Article in English | MEDLINE | ID: covidwho-1388491
16.
Hepatol Commun ; 6(2): 270-280, 2022 02.
Article in English | MEDLINE | ID: covidwho-1384171

ABSTRACT

Liver test abnormalities are frequently observed in patients with coronavirus disease 2019 (COVID-19) and are associated with worse prognosis. However, information is limited about pathological changes in the liver in this infection, so the mechanism of liver injury is unclear. Here we describe liver histopathology and clinical correlates of 27 patients who died of COVID-19 in Manaus, Brazil. There was a high prevalence of liver injury (elevated alanine aminotransferase and aspartate aminotransferase in 44% and 48% of patients, respectively) in these patients. Histological analysis showed sinusoidal congestion and ischemic necrosis in more than 85% of the cases, but these appeared to be secondary to systemic rather than intrahepatic thrombotic events, as only 14% and 22% of samples were positive for CD61 (marker of platelet activation) and C4d (activated complement factor), respectively. Furthermore, the extent of these vascular findings did not correlate with the extent of transaminase elevations. Steatosis was present in 63% of patients, and portal inflammation was present in 52%. In most cases, hepatocytes expressed angiotensin-converting enzyme 2 (ACE2), which is responsible for binding and entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), even though this ectoenzyme was minimally expressed on hepatocytes in normal controls. However, SARS-CoV-2 staining was not observed. Most hepatocytes also expressed inositol 1,4,5-triphosphate receptor 3 (ITPR3), a calcium channel that becomes expressed in acute liver injury. Conclusion: The hepatocellular injury that commonly occurs in patients with severe COVID-19 is not due to the vascular events that contribute to pulmonary or cardiac damage. However, new expression of ACE2 and ITPR3 with concomitant inflammation and steatosis suggests that liver injury may result from inflammation, metabolic abnormalities, and perhaps direct viral injury.


Subject(s)
COVID-19/complications , Liver Diseases/pathology , Liver Diseases/virology , Liver/pathology , Liver/virology , Adult , Aged , Aged, 80 and over , Brazil , COVID-19/mortality , COVID-19/pathology , COVID-19/physiopathology , Female , Humans , Liver/physiopathology , Liver Diseases/diagnosis , Liver Diseases/physiopathology , Liver Function Tests , Male , Middle Aged
17.
Turk J Ophthalmol ; 51(4): 231-242, 2021 08 27.
Article in English | MEDLINE | ID: covidwho-1380043

ABSTRACT

Immunomodulatory agents are often used in the systemic treatment of non-infectious uveitis. These drugs consist of corticosteroids, conventional immunosuppressives, and biological agents. As it is known that they suppress the immune system, the most important concern associated with immunomodulatory therapy (IMT) is the increased risk of infection. The World Health Organization declared COVID-19 a pandemic on 11 March 2020. Although severe acute respiratory distress syndrome secondary to SARS-CoV-2 infection may develop in all people, patients who receive IMT may be at higher risk in terms of both the transmission of the infection and more severe disease course. Therefore, guidelines on the management of patients receiving IMT due to uveitis during the pandemic are needed. In this review, we examined the immunomodulatory drugs used in the treatment of uveitis in terms of infectious complications and the data of patients who received IMT during the COVID-19 pandemic and discussed recommendations for the use of these drugs. According to the latest information, patients who receive IMT may continue their treatment as long as there are no disruptions in regular complete blood count (especially white blood cell count >4,000/µL) and liver and kidney function tests. Patients diagnosed with COVID-19 should be managed with a multidisciplinary approach.


Subject(s)
COVID-19/epidemiology , Glucocorticoids/therapeutic use , Immunomodulation , Immunosuppressive Agents/therapeutic use , SARS-CoV-2 , Uveitis/drug therapy , COVID-19/transmission , Clinical Decision-Making , Disease Transmission, Infectious/prevention & control , Humans , Kidney Function Tests , Leukocyte Count , Liver Function Tests , Ophthalmology , Risk Assessment
18.
Viruses ; 13(9)2021 08 27.
Article in English | MEDLINE | ID: covidwho-1374535

ABSTRACT

Infection with SARS-CoV-2, the virus responsible for the global COVID-19 pandemic, causes a respiratory illness that can severely impact other organ systems and is possibly precipitated by cytokine storm, septic shock, thrombosis, and oxidative stress. SARS-CoV-2 infected individuals may be asymptomatic or may experience mild, moderate, or severe symptoms with or without pneumonia. The mechanisms by which SARS-CoV-2 infects humans are largely unknown. Mouse hepatitis virus 1 (MHV-1)-induced infection was used as a highly relevant surrogate animal model for this study. We further characterized this animal model and compared it with SARS-CoV-2 infection in humans. MHV-1 inoculated mice displayed death as well as weight loss, as reported earlier. We showed that MHV-1-infected mice at days 7-8 exhibit severe lung inflammation, peribronchiolar interstitial infiltration, bronchiolar epithelial cell necrosis and intra-alveolar necrotic debris, alveolar exudation (surrounding alveolar walls have capillaries that are dilated and filled with red blood cells), mononuclear cell infiltration, hyaline membrane formation, the presence of hemosiderin-laden macrophages, and interstitial edema. When compared to uninfected mice, the infected mice showed severe liver vascular congestion, luminal thrombosis of portal and sinusoidal vessels, hepatocyte degeneration, cell necrosis, and hemorrhagic changes. Proximal and distal tubular necrosis, hemorrhage in interstitial tissue, and the vacuolation of renal tubules were observed. The heart showed severe interstitial edema, vascular congestion, and dilation, as well as red blood cell extravasation into the interstitium. Upon examination of the MHV-1 infected mice brain, we observed congested blood vessels, perivascular cavitation, cortical pericellular halos, vacuolation of neuropils, darkly stained nuclei, pyknotic nuclei, and associated vacuolation of the neuropil in the cortex, as well as acute eosinophilic necrosis and necrotic neurons with fragmented nuclei and vacuolation in the hippocampus. Our findings suggest that the widespread thrombotic events observed in the surrogate animal model for SARS-CoV-2 mimic the reported findings in SARS-CoV-2 infected humans, representing a highly relevant and safe animal model for the study of the pathophysiologic mechanisms of SARS-CoV-2 for potential therapeutic interventions.


Subject(s)
Coronavirus Infections/pathology , Coronavirus Infections/virology , Murine hepatitis virus/physiology , Animals , Biomarkers , Biopsy , COVID-19/pathology , COVID-19/virology , Coronavirus Infections/mortality , Disease Models, Animal , Female , Genome, Viral , Humans , Immunohistochemistry , Liver Function Tests , Mice , Mortality , Organ Specificity , SARS-CoV-2/physiology , Viral Load
19.
Eur J Gastroenterol Hepatol ; 33(9): 1194-1200, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1354344

ABSTRACT

OBJECTIVE: Coronavirus disease-19 (COVID-19) infection is a global health threat. To inform the liver community on the potential relevance of COVID-19, we performed a systematic review and meta-analysis of published data on liver injury in patients with COVID-19 infection. METHODS: We searched PubMed and Google Scholar through 22 March according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled data were analyzed by using random-effects meta-analyses. RESULTS: A total of 14 studies combining data from 2.871 patients were identified. The prevalence of pre-existing liver disease was reported at 3.1%. The pooled prevalence of elevated aspartate aminotransferase (AST) and alanine transaminase (ALT) levels were 26% [95% confidence interval (CI), 20-32%] and 19% (95% CI, 14-26%), respectively. Only two studies reported the prevalence of elevated liver function tests according to normal ward versus ICU and here the frequency of elevated levels of AST was 50% and 62% versus ALT 40.8% and thus quantitatively higher in ICU-treated patients. Mean levels of absolute AST levels were 33 U/L (95% CI, 30.21-36.09), while mean ALT levels were 31 U/L (95% CI, 27.52-34.57). Cholestatic liver function tests were only incompletely reported in 510 patients. Here, mean levels of alkaline phosphatase were 71 U/L across three studies, and mean levels of gamma-glutamyl transferase were 40.6 U/L across four studies. CONCLUSIONS: Emerging data on LFTs in COVID-19 are heterogeneous indicating mild LFTs involvement in every fourth to fifth patients with numerical more prevalent AST over ALT elevations. Prospective studies are needed to define the clinical relevance of liver injury in COVID-19.


Subject(s)
COVID-19 , Liver Diseases , Alanine Transaminase , Aspartate Aminotransferases , Humans , Liver , Liver Function Tests , SARS-CoV-2
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