Multicenter Analysis of Clinical Features and Prognosis of COVID-19 Patients with Hepatic Impairment

Background/AimsRecent data indicate the presence of liver enzyme abnormalities in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical features and treatment outcomes of COVID-19 patients with abnormal liver enzymes.MethodsWe performed a retrospective, multicenter study of 874 COVID-19 patients admitted to five tertiary hospitals from February 20 to April 14, 2020. Data on clinical features, laboratory parameters, medications, and treatment outcomes were collected until April 30, 2020, and compared between patients with normal and abnormal aminotransferases.ResultsAbnormal aminotransferase levels were observed in 362 patients (41.1%), of which 94 out of 130 (72.3%) and 268 out of 744 (36.0%) belonged to the severe and non-severe COVID-19 categories, respectively. The odds ratios (95% confidence interval) for male patients, patients with a higher body mass index, patients with severe COVID-19 status, and patients with lower platelet counts were 1.500 (1.029 to 2.184, p=0.035), 1.097 (1.012 to 1.189, p=0.024), 2.377 (1.458 to 3.875, p=0.001), and 0.995 (0.993 to 0.998, p>0.001), respectively, indicating an independent association of these variables with elevated aminotransferase levels. Lopinavir/ritonavir and antibiotic use increased the odds ratio of abnormal aminotransferase levels after admission (1.832 and 2.646, respectively, both p<0.05). The median time to release from quarantine was longer (22 days vs 26 days, p=0.001) and the mortality rate was higher (13.0% vs 2.9%, p<0.001) in patients with abnormal aminotransferase levels.ConclusionsAbnormal aminotransferase levels are common in COVID-19 patients and are associated with poor clinical outcomes. Multivariate analysis of patients with normal aminotransferase levels on admission showed that the use of lopinavir/ritonavir and antibiotics was associated with abnormal aminotransferase levels; thus, careful monitoring is needed.     

Hepatocellular injury and the mortality risk among patients with COVID-19: A retrospective cohort study

BACKGROUNDClearly, infection with severe acute respiratory syndrome coronavirus 2 is not limited to the lung but also affects other organs. We need predictive models to determine patients’ prognoses and to improve health care resource allocation during the coronavirus disease 2019 (COVID-19) pandemic. While treating COVID-19, we observed differential outcome prediction weights for markers of hepatocellular injury among hospitalized patients.AIMTo investigate the association between hepatocellular injury and all-cause in-hospital mortality among patients with COVID-19.METHODSThis multicentre study employed a retrospective cohort design. All adult patients admitted to Al-Azhar University Hospital, Assiut, Egypt and Abo Teeg General Hospital, Assiut, Egypt with confirmed COVID-19 from June 1, 2020, to July 30, 2020 were eligible. We categorized our cohort into three groups of (1) patients with COVID-19 presenting normal aminotransferase levels; (2) patients with COVID-19 presenting one-fold higher aminotransferase levels; and (3) patients with COVID-19 presenting two-fold higher aminotransferase levels. We analysed the association between elevated aminotransferase levels and all-cause in-hospital mortality. The survival analysis was performed using the Kaplan–Meier method and tested by log-rank analysis.RESULTSIn total, 376 of 419 patients met the inclusion criteria, while 29 (8%) patients in our cohort died during the hospital stay. The median age was 40 years (range: 28-56 years), and 51% were males (n = 194). At admission, 54% of the study cohort had liver injury. The pattern of liver injury was hepatocellular injury with an aspartate aminotransferase (AST) predominance. Admission AST levels were independently associated with all-cause in-hospital mortality in the logistic regression analysis. A one-fold increase in serum AST levels among patients with COVID-19 led to an eleven-fold increase in in-hospital mortality (P < 0.001). Admission AST levels correlated with C-reactive protein (r = 0.2; P < 0.003) and serum ferritin (r = 0.2; P < 0.0002) levels. Admission alanine aminotransferase levels correlated with serum ferritin levels (r = 0.1; P < 0.04). Serum total bilirubin levels were independently associated with in-hospital mortality in the binary logistic regression analysis after adjusting for age and sex but lost its statistical significance in the fully adjusted model. Serum ferritin levels were significantly associated with in-hospital mortality (P < 0.01). The probability of survival was significantly different between the AST groups and showed the following order: a two-fold increase in AST levels > a one-fold increase in in AST levels > normal AST levels (P < 0.0001).CONCLUSIONLiver injury with an AST-dominant pattern predicts the severity of COVID-19. Elevated serum ferritin levels are associated with fatal outcomes.     

The effect of liver test abnormalities on the prognosis of COVID-19

IntroductionCOVID-19 caused by the SARS-CoV-2 continues to spread rapidly across the world. In our study, we aim to investigate the relationship between the liver enzymes on admission (AST, ALT, ALP, GGT) and severity of COVID-19. We evaluated course of disease, hospital stay, liver damage and mortality.Materials and methodsOur study included 614 patients who were hospitalized with the diagnosis of COVID-19 between 03.16.20 and 05.12.20. Patients with liver disease, hematological and solid organ malignancy with liver metastases were excluded, resulting in 554 patients who met our inclusion criteria. We retrospectively evaluated liver transaminase levels, AST/ALT ratio, cholestatic enzyme levels and R ratio during hospital admission and these were compared in terms of morbidity, mortality and clinical course.ResultsMean age of 554 subjects were 66.21 ± 15.45 years, 328 (59.2%) were men. The mean values of liver enzymes on admission were AST (36.2 ± 33.6 U/L), ALT (34.01 ± 49.34 U/L), ALP (78.8 ± 46.86 U/L), GGT (46.25 ± 60.05 U/L). Mortality rate and need for intensive care unit were statistically significant in subjects that had high ALT–AST levels during their admission to the hospital (p = 0.001). According to the ROC analysis AST/ALT ratio was a good marker of mortality risk (AUC = 0.713: p = 0.001) and expected probability of intensive care unit admission (AUC = 0.636: p = 0.001). R ratio, which was used to evaluate prognosis, showed a poor prognosis rate of 26.5% in the cholestatic injury group, 36.1% in the mixed pattern group and 30% in the hepato-cellular injury group (p 0.001).ConclusionsALT–AST elevation and AST/ALT ratio >1 was associated with more severe course and increased mortality in COVID-19.     

Pattern of liver function and clinical profile in COVID-19: A cross-sectional study of 91 patients

Background– COVID-19 caused by SARS-CoV-2 leads to myriad range of organ involvement including liver dysfunction.AimTo analyse the liver function in patients with COVID-19 and their association with respect to age, sex, severity of disease and clinical features.Materials and methodsThis study was a cross-sectional study done at Rajendra Institute of Medical Sciences, Ranchi. 91 patients admitted with confirmed SARS-CoV-2 infection were included in this study and divided into asymptomatic, mild, moderate and severe groups. Liver function tests were compared among different severity groups.ResultsOf 91 patients with COVID-19, 70 (76.9%) had abnormal liver function. Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin levels was 1–2 × ULN in 33(36.3%), 34(37.3%), 12(13.2%), 6(6.6%) cases and >2 × ULN in 20(22%), 18(19.8%), 7(7.7%) and 2 (2.2%) cases respectively. Mean AST and ALP levels among different severity groups of COVID-19 was statistically significant (p < 0.05) whereas mean ALT and total bilirubin levels was statistically non-significant (p > 0.05). There was no statistical difference between males and females with regard to abnormal liver function. Liver injury was seen in 64.3% cases of hypertension and 73.3% cases of diabetes. Fever, myalgia, headache and breathlessness were found to be correlated significantly with severity of disease.ConclusionLiver injury is common in SARS-CoV-2 infection and is more prevalent in the severe disease group. Aspartate transaminase and alkaline phosphatase are better indicators of covid-19 induced liver injury than alanine transaminase and total bilirubin.     

The impact of coronavirus disease 2019 (COVID-19) on liver injury in China: A systematic review and meta-analysis

Introduction:The evidence for the incidence and severity of liver injury in Chinese patients with coronavirus disease 2019 (COVID-19) is still controversial. The purpose of this study was to summarize the incidence of liver injury and the differences between liver injury markers among different patients with COVID-19 in China.Methods:Computer searches of PubMed, Embase, China National Knowledge Infrastructure (CNKI) and medRxiv were used to obtain reports on the incidence and markers of liver injury in Chinese patients with COVID-19, from January 1, 2020 to April 10, 2020. (No. CRD42020181350)Results:A total of 57 reports from China were included, including 9889 confirmed cases of COVID-19 infection. The results of the meta-analysis showed that among the patients with early COVID-19 infection in China, the incidence of liver injury events was 24.7% (95% CI, 23.4%–26.4%). Liver injury in severe patients was more common than that in non-severe patients, with a risk ratio of 2.07 (95% CI, 1.77–2.43). Quantitative analysis showed that the severe the coronavirus infection, the higher the level of alanine aminotransferase (ALT), aspertate aminotransferase (AST), total bilirubin (TB), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), and the lower the level of albumin (ALB).Conclusion:There is a certain risk of liver injury in Chinese patients with COVID-19, and the risk and degree of liver injury are related to the severity of COVID-19.     

Progressive liver injury and increased mortality risk in COVID-19 patients: A retrospective cohort study in China

BACKGROUND Liver injury is common and also can be fatal,particularly in severe or critical patients with coronavirus disease 2019(COVID-19).AIM To conduct an in-depth investigation into the risk factors for liver injury and into the effective measures to prevent subsequent mortality risk.METHODS A retrospective cohort study was performed on 440 consecutive patients with relatively severe COVID-19 between January 28 and March 9,2020 at Tongji Hospital,Wuhan,China.Data on clinical features,laboratory parameters,medications,and prognosis were collected.RESULTS COVID-19-associated liver injury more frequently occurred in patients aged≥65 years,female patients,or those with other comorbidities,decreased lymphocyte count,or elevated D-dimer or serum ferritin(P<0.05).The disease severity of COVID-19 was an independent risk factor for liver injury(severe patients:Odds ratio[OR]=2.86,95%confidence interval[CI]:1.78-4.59;critical patients:OR=13.44,95%CI:7.21-25.97).The elevated levels of on-admission aspartate aminotransferase and total bilirubin indicated an increased mortality risk(P<0.001).Using intravenous nutrition or antibiotics increased the risk of COVID-19-associated liver injury.Hepatoprotective drugs tended to be of assistance to treat the liver injury and improve the prognosis of patients with COVID-19-associated liver injury.CONCLUSION More intensive monitoring of aspartate aminotransferase or total bilirubin is recommended for COVID-19 patients,especially patients aged≥65 years,female patients,or those with other comorbidities.Drug hepatotoxicity of antibiotics and intravenous nutrition should be alert for COVID-19 patients.     

The relative expression of hepatocellular and cholestatic liver enzymes in adult patients with liver disease

Introduction and objectivesHepatocellular liver injury is characterized by elevations in serum alanine (ALT) and aspartate (AST) aminotransferases while cholestasis is associated with elevated serum alkaline phosphatase (ALP) levels. When both sets of enzymes are elevated, distinguishing between the two patterns of liver disease can be difficult. The aim of this study was to document the predicted ranges of serum ALP values in patients with hepatocellular liver injury and ALT or AST values in patients with cholestasis.Materials and methodsLiver enzyme levels were documented in adult patients with various types and degrees of hepatocellular (non-alcoholic fatty liver disease, hepatitis B and C, alcohol and autoimmune hepatitis) and cholestatic (primary biliary cholangitis and primary sclerosing cholangitis) disease.ResultsIn 5167 hepatocellular disease patients with ALT (or AST) values that were normal, 1–5×, 5–10× or >10× elevated, median (95% CI) serum ALP levels were 0.64 (0.62–0.66), 0.72 (0.71–0.73), 0.80 (0.77–0.82) and 1.15 (1.0–1.22) fold elevated respectively. In 252 cholestatic patients with ALP values that were normal, 1–5× or >5× elevated, serum ALT (or AST) values were 1.13 (0.93–1.63), 2.47 (2.13–2.70) and 4.57 (3.27–5.63) fold elevated respectively. In 56 patients with concurrent diseases, ALP levels were beyond predicted values for their hepatitis in 38 (68%) and ALT (or AST) values beyond predicted values for their cholestatic disorder in 24 (43%).ConclusionsThese data provide health care providers with predicted ranges of liver enzymes in patients with hepatocellular or cholestatic liver disease and may thereby help to identify patients with concurrent forms of liver disease.     

Metabolic dysfunction associated fatty liver disease increases risk of severe Covid-19

Background and aimsLiver involvement is common in COVID-19. Elevated aspartate and alanine amino transaminase (AST/ALT) and borderline increase in serum bilirubin and serum alkaline phosphatase (ALP) are the commonest findings. Patients with associated co morbid conditions like obesity, cardiovascular disease, renal disease, malignancy, hypertension and old age are prone to develop severe disease. Limited data is available in patients with COVID-19 and metabolic dysfunction associated fatty liver disease (MAFLD).The aim of this review is to analyse the effect of MAFLD on severity of COVID-19.MethodsWe systematically searched the PubMed database till May 20, 2020 and retrieved all the articles published on COVID-19 and fatty liver/MAFLD/NAFLD.ResultsLimited studies done had shown four to six fold high risk of severe COVID-19 in patients with MAFLD. Patients with MAFLD and associated obesity, severe fibrosis and age <60 yrs are more prone to develop severe COVID-19.ConclusionMAFLD is associated with 4–6 fold increase in severity of COVID-19 compared to non MAFLD patients. Physician and hepatologist should follow these patients cautiously and preventive measures to be taken strictly in these high risk patients.     

Coronavirus Disease 2019 and Liver Injury: A Retrospective Analysis of Hospitalized Patients in New York City

Background and AimsCoronavirus disease 2019 (COVID-19) is a global threat, affecting more than 100 million people and causing over 2 million deaths. Liver laboratory test abnormalities are an extrapulmonary manifestation of COVID-19, yet characterization of hepatic injury is incomplete. Our objective was to further characterize and identify causes of liver injury in patients with COVID-19.MethodsWe conducted a retrospective cohort study of 551 patients hospitalized with COVID-19 at NewYork-Presbyterian Hospital/Columbia University Irving Medical Center between March 1, 2020 and May 31, 2020. We analyzed patient demographics, liver laboratory test results, vital signs, other relevant test results, and clinical outcomes (mortality and intensive care unit admission).ResultsAbnormal liver laboratory tests were common on hospital admission for COVID-19 and the incidence increased during hospitalization. Of those with elevated serum alanine aminotransferase and/or alkaline phosphatase activities on admission, 58.2% had a cholestatic injury pattern, 35.2% mixed, and 6.6% hepatocellular. Comorbid liver disease was not associated with outcome; however, abnormal direct bilirubin or albumin on admission were associated with intensive care unit stay and mortality. On average, patients who died had greater magnitudes of abnormalities in all liver laboratory tests than those who survived. Ischemic hepatitis was a mechanism of severe hepatocellular injury in some patients.ConclusionsLiver laboratory test abnormalities are common in hospitalized patients with COVID-19, and some are associated with increased odds of intensive care unit stay or death. Severe hepatocellular injury is likely attributable to secondary effects such as systemic inflammatory response syndrome, sepsis, and ischemic hepatitis.     

Liver function tests and metabolic-associated fatty liver disease: Changes in upper normal limits,does it really matter?

BACKGROUNDMetabolic-associated fatty liver disease (MAFLD) is the commonest cause of abnormal liver function tests (LFTs). Current upper normal of limit (UNL) of LFTs was derived from a “healthy” population, where undiagnosed MAFLD and viral hepatitis might be suspected. AIMTo evaluated potential implications of changes in UNL of alanine aminotransferase (ALT) in MAFLD.METHODSWe retrospectively assessed consecutive first referrals with a diagnosis of MAFLD from 2010 to 2017. The conventional UNL of ALT was 45 IU/L for men and 34 IU/L for women, while a low UNL of ALT was 30 IU/L for men and 19 IU/L for women. The UNL of aspartate aminotransferase (AST) was 40 IU/L.RESULTSTotal 436 patients were enrolled; of these, 288 underwent liver biopsy. Setting a lower UNL reduced the percentage of those with significant disease despite normal ALT; specifically, patients with advanced fibrosis (F ≥ F3) or definite “metabolic-associated steato-hepatitis (MASH)” (NAS ≥ 5) within normal ALT decreased from 10% to 1% and from 28% to 4% respectively. However, the proportion of those with elevated ALT and no evidence of advanced fibrosis or “definite MASH” increased from 39% to 47% and from 3% to 19%. Overall, LFTs performed poorly in distinguishing “definite MASH” from simple steatosis (receiver operating characteristic areas under the curves 0.59 for ALT and 0.55 for AST).CONCLUSIONLiver function tests might both under- and overestimate MASH-related liver disease. Reducing the UNL might not be beneficial and imply an increase in healthcare burden. Risk stratification in MAFLD should rely on a combination of risk factors, not on LFTs alone.     

Clinical Significance of Liver Function Abnormality in Patients with COVID-19: A Single-center Experience from Western India

Background and AimsThe impact of coronavirus disease-2019 (COVID-19) on liver function remains to be fully elucidated. This study was designed to investigate such and determine the clinical significance in determining mortality risk.MethodsA retrospective study was conducted in patients with COVID-19 from March 2020 to July 2020. Clinical details were retrieved from electronic medical records to obtain clinical characteristics, medical history, laboratory tests, therapeutic intervention, and outcome data.ResultsA total of 184 patients with COVID-19 were included (median age: 45.5 years), comprised of 62.5% men. In total, 22 (12.0%) patients had severe infection and 162 (88.0%) had mild to moderate infection. Overall, 95 (51.6%) showed abnormal liver function test (LFT) and 17 (9.2%) showed normal LFT at admission. The median age, hospital stay, and LFT were significantly higher in severe vs. non-severe infection (p<0.001). Out of 12 deaths, the majority were due to severe infection (n=11). Deaths were also due to acute respiratory distress syndrome (n=5), cardiac reasons (n=3), and sepsis with multiorgan failure (n=3). The median age, hospital stay and number of intensive care unit admissions were higher in patients having abnormal LFT compared to normal LFT. Incidence of elevated aspartate aminotransferase (42.8% and 40.4%), alanine transaminase (43.7% and 41.6%), and hypoalbuminemia (71.4% and72.7%) at admission and discharge were more common in severe infection. The mean survival was significantly lower in severe infection compared to those with non-severe disease (17.2 vs. 52.3 days; p<0.001).ConclusionsIncidence of abnormal liver function was higher in patients with severe COVID-19 and was associated with prolonged hospital stay; mortality was associated with severity of COVID-19. For ruling out the risk of liver injury, it is crucial to vigilantly monitor the liver function parameters in patients with COVID-19 admitted to hospital.     

重型和危重型新型冠状病毒肺炎患者肝功能损害回顾性分析

目的 探讨不同性别和年龄组肝重型和危重型冠状病毒疾病-19(COVID-19)病毒感染患者肝功能相关指标、治疗药物和疾病转归情况,为临床诊治该类肝损害提供经验。方法 2020年1月22日～2月22日我院收治的重型和危重型COVID-19感染患者27例,回顾性分析其临床特征、不同性别和年龄组入院首次肝功能相关指标、治疗药物和疾病转归情况。结果 在27例重型和危重型COVID-19感染患者中,男性22例(81.5%),女性5例(18.5%);年龄为29～91岁,中位年龄为56.0(44.0～68.0)岁。其中<60岁中青年组16例(59.3%),>60岁老年组11例(40.7%);26例(96.3%)患者出现血清ALT、AST、GGT、ALP、TBIL、PTA、DBIL和LDH水平异常;男性组与女性组血清ALT、AST、GGT、ALP、TBIL、PTA、DBIL和LDH水平比较,差异无统计学意义(P＞0.05);中青年组与老年组血清ALT、AST、GGT、ALP、TBIL、DBIL和LDH水平比较,差异无统计学意义(P＞0.05),但老年组PTA水平显著低于中青年组,差异有统计学意义(P＜0.05);22例(81.5%)接受了联合抗病毒药物,18例(66.7%)接受了联合抗炎、调节免疫类中成药物,14例(51.9%)接受了联合护肝药物;自发病起1个月时间内,本组生存率为96.3%。结论 重型和危重型COVID-19感染患者病程早期容易出现肝损害,不同性别和年龄患者肝损伤差异不大。在中西药应用过程中出现肝损害,其与药物应用有关还是病毒感染本身的作用,还有待进一步探讨。     

AST/ALT比值在慢性肝病患者中的特点和判断预后价值

目的 分析不同病因、不同病情的慢性肝病患者天冬氨酸氨基转移酶和丙氨酸氨基转移酶比值(AST/ALT)的特点,评价AST/ALT比值判断慢性肝病患者预后方面的价值.方法 对534例不同病因的肝硬化、原发性肝癌患者的住院资料进行分析,比较各类患者AST/ALT比值的特点.运用接受者运行曲线(ROC)及曲线下面积,比较AST/ALT比值与终末期肝病模型(MELD)、Child-Turcotte-Pugh(CTP)分级(CC)和评分(CS)在判断慢性肝病患者中短期预后方面的准确性;运用非参数相关分析,计算Spearman相关系数,分析三者之间的相关性.结果 在原发性肝癌患者,AST/ALT比值明显高于肝硬化患者(P＜0.05);病毒性肝病患者和非病毒性肝病患者的AST/ALT比值无明显差异(P=0.852).死亡患者的AST/ALT比值明显高于生存患者的平均值(P=0.000);随着CTP分级的升高,AST/ALT比值也逐渐升高,A、B、C三级之间的AST/ALT比值具有显著差异(P＜0.05).AST/ALT比值和MELD、CS及CC在判断慢性肝病患者生存3个月的ROC曲线下面积分别是0.88、0.92、0.69和0.59,判断生存1年时间的ROC曲线下面积分别为0.64、0.77、0.65和0.63;AST/ALT比值与MELD、CS和CC三者之间的相关系数分别是0.185、0.291和0.297(P=0.000).结论 AST/ALT比值随着肝脏病变的加重而逐渐升高.AST/ALT比值和MELD在判断慢性肝病患者短期预后方面是较好的指标.AST/ALT比值和MELD、CS、CC三者之间具有显著相关性.     

甲状腺功能亢进症316例肝功能某些指标变化的分析

目的探讨甲状腺功能亢进症（甲亢）患者与肝功能的一些指标变化关系。方法对316例甲亢患者行甲功、肝功能检测,指标包括丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）、谷胺酰转肽酶（GGT）、碱性磷酸酶（ALP）、血清总胆红素（TBL）;比较分析甲亢性肝功能损害和甲亢无肝功能损害两组之间的游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、促甲状腺素（TSH）水平;并分析甲亢患者肝功能变化的情况。结果甲亢性肝损害组TSH、FT3、FT4比无肝损害甲亢组高（P〈0．05）,甲亢性肝功能损害时主要以ALP、ALT、AST的异常增高为主;并且FT3、FT4分别与ALP、ALT、AST存在正相关关系,P〈0．05。结论甲亢性肝功能损害（特别是ALP变化）与甲状腺激素水平有密切关系,能否用ALP来协助甲亢诊断和治疗观察值得探讨。     

The AST/ALT ratio as an indicator of cirrhosis in patients with PBC.

OBJECTIVES: A non-invasive, simple and non-expensive test to predict cirrhosis would be highly desirable. The aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio has been proven to be such an indicator of cirrhosis in alcoholic liver disease, hepatitis C. AIM: To test whether the AST/ALT ratio is a marker of cirrhosis also in patients with primary biliary cirrhosis (PBC). METHODS: The study consisted of 160 patients. In 126 patients, we had clinical and laboratory data at the time of diagnosis and follow-up with outcome: liver-related death, liver transplantation and survival. In 121 patients, we had laboratory data and liver histology. RESULTS: We found that the AST/ALT ratio was significantly higher in cirrhotic patients than in non-cirrhotic patients. A high AST/ALT ratio was significantly associated with esophageal varices and ascites. In a multivariate analysis, bilirubin and ALP were predictors of poor prognosis. CONCLUSION: The AST/ALT ratio seems to be of clinical value as a hint to the diagnosis of cirrhosis in patients with PBC but not as a prognostic factor.     

Abnormal liver tests and non-alcoholic fatty liver disease predict disease progression and outcome of patients with COVID-19

Background and aimsCoronavirus disease 2019 (COVID-19) is a serious public health issue that became rapidly pandemic. Liver injury and comorbidities, including metabolic syndrome, are associated with severe forms of the disease. This study sought to investigate liver injury, clinical features, and risk factors in patients with mild, moderate, and severe COVID-19.MethodsWe retrospectively included all consecutive patients hospitalized with laboratory-confirmed COVID-19 between February, 22 and May 15, 2020 at the emergency rooms of a French tertiary hospital. Medical history, symptoms, biological and imaging data were collected.ResultsAmong the 1381 hospitalizations for COVID-19, 719 patients underwent liver tests on admission and 496 (68.9%) patients displayed abnormal liver tests. Aspartate aminotransferase was most commonly abnormal in 57% of cases, followed by gamma-glutamyl transferase, alanine aminotransferase, albumin, alkaline phosphatase, and total bilirubin in 56.5%, 35.9%, 18.4%, 11.4%, and 5.8%. The presence of hepatocellular type more than 2xULN was associated with a higher risk of hospitalization and a worse course of severe disease (odd ratio [OR] 5.599; 95%CI: 1.27–23.86; p = 0.021; OR 3.404; 95% CI: 2.12–5.47; p < 0.001, respectively). A higher NAFLD fibrosis score was associated with a higher risk of hospitalization (OR 1.754; 95%CI: 1.27–2.43, p < 0.001). In multivariate analyses, patients with high fibrosis-4 index had a 3-fold greater risk of severe disease (p < 0.001).ConclusionAbnormal liver tests are common in patients with COVID-19 and could predict the outcome. Patients with non-alcoholic fatty liver disease and liver fibrosis are at higher risk of progressing to severe COVID-19.     

COVID-19 and Indirect Liver Injury: A Narrative Synthesis of the Evidence

The liver is frequently affected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. The most common manifestations are mildly elevated alanine aminotransferase and aspartate aminotransferase, with a prevalence of 16-53% among patients. Cases with severe coronavirus disease 2019 (COVID-19) seem to have higher rates of acute liver dysfunction, and the presence of abnormal liver tests at admission signifies a higher risk of severe disease during hospitalization. Patients with chronic liver diseases also have a higher risk of severe disease and mortality (mainly seen in patients with metabolic-associated fatty liver disease). Several pathways of damage have been proposed in the liver involvement of COVID-19 patients; although, the end-cause is most likely multifactorial. Abnormal liver tests have been attributed to the expression of angiotensin-converting enzyme 2 receptors in SARS-CoV-2 infection. This enzyme is expressed widely in cholangiocytes and less in hepatocytes. Other factors attributed to liver damage include drug-induced liver injury, uncontrolled release of proinflammatory molecules (“cytokine storm”), pneumonia-associated hypoxia, and direct damage by the infection. Hepatic steatosis, vascular thrombosis, fibrosis, and inflammatory features (including Kupffer cell hyperplasia) are the most common liver histopathological findings in deceased COVID-19 patients, suggesting important indirect mechanisms of liver damage. In this translational medicine-based narrative review, we summarize the current data on the possible indirect mechanisms involved in liver damage due to COVID-19, the histopathological findings, and the impact of these mechanisms in patients with chronic liver disease.     

Liver overload in Brazilian triathletes after half-ironman competition is related muscle fatigue

Triathlon competition is dependent on the athletes’ ability to perform each discipline at optimal time, without excessive fatigue influencing the next one. Objectives: Determine the effects of a long distance triathlon on biochemistry parameters related to liver function. Design and methods: Blood samples from six athletes were collected before (T = 0) and immediately after the triathlon competition (T = 1). AST, ALT and alkaline phosphatase (ALP) values were assessed. Results: Significant changes after triathlon competition were found for AST and ALP and no significant changes were found for ALT over time.Conclusions: A series of metabolically alterations, mainly related to energy production and also to muscle and skeletal adaptations occurs during and after strenuous exercise. The altered status of those metabolical changes cannot directly reflect the intensity of any possible muscular or hepatic damage or overload and elevated AST/ALT ratio is better associated to skeletal muscle lesion during competition.     

Increased liver markers are associated with higher risk of type 2 diabetes

AIM: To investigate the association between liver markers and the risk of type 2 diabetes (T2DM) and impaired fasting glucose (IFG).METHODS: A total of 8863 participants (3408 men and 5455 women) over 30 years of age were analyzed from the fifth Korean National Health and Nutrition Examination Survey (2010-2011). The associations of serum liver markers such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST/ALT, and gamma-glutamyltransferase (GGT) with T2DM and IFG were analyzed using logistic regression models. Participants were divided into sex-specific quartiles on the basis of liver markers.RESULTS: The prevalence of T2DM and IFG were 11.3% and 18.3%. Increasing quartiles of ALT and GGT were positively and AST/ALT were negatively correlated with T2DM and IFG. Analysis of the liver marker combinations showed that if any two or more markers were in the highest risk quartile, the risks of both T2DM and IFG increased significantly. The risk was greatest when the highest ALT and GGT and lowest AST/ALT quartile were combined, with the risk of T2DM at 3.21 (95%CI: 1.829-5.622, P < 0.001) in men and 4.60 (95%CI: 3.217-6.582, P < 0.001) in women. Men and women with the highest AST and ALT and lowest AST/ALT quartile had a 1.99 and 2.40 times increased risk of IFG.CONCLUSION: Higher levels of GGT and ALT and lower AST/ALT within the physiological range are independent, additive risk factors of T2DM and IFG.