Study protocol of a randomised, double-blind, placebo-controlled, two-arm parallel-group, multi-centre phase 3 pivotal trial to investigate the efficacy and safety of recombinant human alkaline phosphatase for treatment of patients with sepsis-associated acute kidney injury.

INTRODUCTION: Sepsis, the leading cause of acute kidney injury (AKI), is associated with a high morbidity and mortality. Alkaline phosphatase (ALP) is an endogenous detoxifying enzyme. A recombinant human ALP compound, ilofotase alfa, showed no safety or tolerability concerns in a phase 2 trial. Renal function improvement over 28 days was significantly greater in the ilofotase alfa group. Moreover, a significant relative reduction in 28-day all-cause mortality of >40% was observed. A follow-up trial has been designed to confirm these findings. METHODS AND ANALYSIS: This is a phase 3, global, multi-centre, randomised, double-blind, placebo-controlled, sequential design trial in which patients are randomly assigned to either placebo or 1.6 mg/kg ilofotase alfa. Randomisation is stratified by baseline modified Sequential Organ Failure Assessment (mSOFA) score and trial site. The primary objective is to confirm the survival benefit with ilofotase alfa by demonstrating a reduction in 28-day all-cause mortality in patients with sepsis-associated AKI requiring vasopressors. A maximum of 1400 patients will be enrolled at ∼120 sites in Europe, North America, Japan, Australia and New Zealand. Up to four interim analyses will take place. Based on predefined decision rules, the trial may be stopped early for futility or for effectiveness. In addition, patients with COVID-19 disease and patients with 'moderate to severe' chronic kidney disease are analysed as 2 separate cohorts of 100 patients each. An independent Data Monitoring Committee evaluates safety data at prespecified intervals throughout the trial. ETHICS AND DISSEMINATION: The trial is approved by relevant institutional review boards/independent ethics committees and is conducted in accordance with the ethical principles of the Declaration of Helsinki, guidelines of Good Clinical Practice, Code of Federal Regulations and all other applicable regulations. Results of this study will determine the potential of ilofotase alfa to reduce mortality in critically ill patients with sepsis-associated AKI and will be published in a peer-reviewed scientific journal. TRIAL REGISTRATION NUMBER: EudraCT CT Number 2019-0046265-24. US IND Number 117 605 Pre-results. CLINICALTRIALS: gov number: NCT04411472.

Evaluation of De Ritis (AST/ALT), ALP/ALT, and AST/ALP ratios as prognostic factors in patients with acute ischemic stroke.

BACKGROUND: Stroke is one of the leading causes of disability worldwide. Recently, stroke prognosis estimation has received much attention. This study investigates the prognostic role of aspartate transaminase/alanine transaminase (De Ritis, AAR), alkaline phosphatase/alanine transaminase (ALP/ALT), and aspartate transaminase/alkaline phosphatase (AST/ALP) ratios in acute ischemic stroke (AIS). METHODS: This retrospective cohort study involved patients who experienced their first-ever AIS between September 2019 and June 2021. Clinical and laboratory data were collected within the first 24 hours after admission. Functional and mortality outcomes were evaluated 90 days after hospital discharge in clinical follow-up. Functional outcome was assessed by a modified Rankin Scale (mRS). The correlation between the laboratory data and study outcomes was evaluated using univariate analysis. In addition, regression models were developed to evaluate the predictive role of AST/ALP, ALP/ALT, and AAR ratios on the study outcomes. RESULTS: Two hundred seventy-seven patients (mean age 69.10 ± 13.55, 53.1% female) were included. According to univariate analysis, there was a weak association between 3-months mRS, and both AST/ALT (r = 0.222, P < 0.001), and AST/ALP (r = 0.164, P = 0.008). Subsequently, higher levels of these ratios and absolute values of AST, ALT, and ALP were reported in deceased patients. Based on regression models adjusted with co-variable (age, gender, underlying disease, and history of smoking) AST/ALT and AST/ALP ratios had a significant independent association with 3-month mRS (CI:1.37-4.52, p = 0.003, and CI: 4.45-11,547.32, p = 0.007, respectively) and mortality (CI: 0.17-1.06, adjusted R2 = 0.21, p = 0.007, and CI: 0.10-2.91, p = 0.035, adjusted R2 = 0.20, respectively). CONCLUSIONS: Elevated AST/ALP and AAR ratios at admission were correlated with poorer outcomes at 3 months in patients with first-ever AIS. Prospective studies in larger cohorts are required to confirm our findings and to evaluate further whether the AST/ALP and De Ritis ratios may represent a useful tool for determining the prognosis of AIS patients.

The effect of Favipiravir on liver enzyme among patients with mild to moderate COVID-19 infection: A prospective cohort study.

Teratogenicity and hyperuricemia are considered as the major adverse effects of favipiravir, but less is known about other possible side effects which includes drug-induced liver damage and renal injury. In the current research, assessment of favipiravir-induced liver injury was performed by evaluating liver enzymes among patients with mild to moderate COVID-19 infection. A prospective cohort study was conducted on 66 patients diagnosed with mild to moderate COVID-19 infection who were treated with favipiravir for 5 days. During this period, a baseline assessment of liver enzymes (aspartate aminotransferase - AST, alanine transaminase - ALT and alkaline phosphatase - ALP) in addition to bilirubin before initiation of therapy and after 1 day of completion of therapy were carried out. The comparison of all measured parameters among all patients before and after receiving the treatment showed that non-significant differences were obtained in their levels. It was noticed that COVID-19 patients demonstrated high AST levels in which only 16 patients out of the all-subjected cases (66 patients) had AST levels of less than 45 U/L whereas the majority of patients showed normal ALT, ALP, and bilirubin levels. It was concluded that 5 days administration of favipiravir in mild to moderate COVID-19 patients who had no previous liver diseases did not affect the liver enzymes significantly and only transient elevations were occurred.

[Characteristics of liver function changes in 111 elderly patients with COVID-19 pneumonia].

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.

Persistent Cholestatic Injury and Secondary Sclerosing Cholangitis in COVID-19 Patients.

CONTEXT.­: COVID-19 has been associated with liver injury, and a small subset of patients recovering from severe disease have shown persistent markedly elevated liver biochemistries for months after infection. OBJECTIVE.­: To characterize persistent biliary injury after COVID-19. DESIGN.­: A search of the pathology archives identified 7 post-COVID-19 patients with persistent biliary injury, and the clinical, radiologic, and pathologic features were assessed. RESULTS.­: All patients in this cohort presented with respiratory symptoms and had a complicated clinical course with acute elevation of liver biochemistries. Alkaline phosphatase (ALP) was markedly and persistently elevated after discharge (median peak ALP, 1498 IU/L, at a median of 84 days from diagnosis). Magnetic resonance cholangiopancreatography showed 3 patients with irregularity, stricturing, and dilatation of intrahepatic ducts; no radiographic abnormalities were identified in the remaining 4 patients. Liver biopsies showed mild portal changes with features of cholestatic injury in 4 patients (bile duct injury and canalicular cholestasis) and marked biliary obstruction in 2 patients (profound cholestasis, ductular reaction, and bile infarcts), but no SARS-CoV-2 RNA was identified on in situ hybridization. On follow-up, most patients had minimal intervention and showed marked improvement of liver biochemistries but with mild persistent elevation of ALP. CONCLUSIONS.­: A subset of critically ill COVID-19 patients demonstrates marked and persistent cholestatic injury, with radiographic and histologic evidence of secondary sclerosing cholangitis, suggesting that cholestatic liver disease and secondary sclerosing cholangitis may be long-term sequelae of COVID-19 acute illness as a longstanding manifestation of critical illness.

Age-adjusted mortality and predictive value of liver chemistries in a Viennese cohort of COVID-19 patients.

BACKGROUND AND AIMS: The coronavirus disease of 2019 (COVID-19) causes considerable mortality worldwide. We aimed to investigate the frequency and predictive role of abnormal liver chemistries in different age groups. METHODS: Patients with positive severe acute respiratory distress syndrome-coronavirus-2 (SARS-CoV-2) polymerase chain reaction (PCR) test between 03/2020-07/2021 at the Vienna General Hospital were included. Patients were stratified for age: 18-39 vs. 40-69 vs. ≥70 years (y). Aspartate aminotransferase (AST), alanine-aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and total bilirubin (BIL) were recorded. RESULTS: 900 patients (18-39 years: 32.2%, 40-69 years: 39.7%, ≥70 years: 28.1%) were included. Number of comorbidities, median D-dimer and C-reactive protein increased with age. During COVID-19, AST/ALT and ALP/GGT levels significantly increased. Elevated hepatocellular transaminases (AST/ALT) and cholestasis parameters (ALP/GGT/BIL) were observed in 40.3% (n  = 262/650) and 45.0% (n  = 287/638) of patients respectively. Liver-related mortality was highest among patients with pre-existing decompensated liver disease (28.6%, p < .001). 1.7% of patients without pre-existing liver disease died of liver-related causes, that is consequences of hepatic dysfunction or acute liver failure. Importantly, COVID-19-associated liver injury (16.0%, p < .001), abnormal liver chemistries and liver-related mortality (6.5%, p < .001) were most frequent among 40-69 years old patients. Elevated AST and BIL after the first positive SARS-CoV-2 PCR independently predicted mortality in the overall cohort and in 40-69 years old patients. CONCLUSIONS: Almost half of the COVID-19 patients exhibit abnormal hepatocellular and cholestasis-related liver chemistries with 40-69 years old patients being at particularly high risk for COVID-19-related liver injury and liver-related mortality. Elevated AST and BIL after SARS-CoV-2 infection are independent predictors of mortality, especially in patients aged 40-69 years.

A Japanese single-center experience of the efficacy and safety of asfotase alfa in pediatric-onset hypophosphatasia.

BACKGROUND: Hypophosphatasia (HPP) is a rare inherited metabolic disorder caused by mutations in the ALPL gene, which encodes tissue nonspecific alkaline phosphatase. The severity of HPP is widely diverse from the perinatal form to the adult mild form. The former represents the most severe form and was earlier associated with high mortality due to pneumonia which was caused by severe hypomineralization of the bones-such as chest deformity and fractured ribs-and muscle weakness. Enzyme replacement therapy using asfotase alfa (AA) was approved in 2015 in Japan for treating patients with HPP and has improved their pulmonary function and life prognosis. There are several practical and ethical challenges related to using orphan drugs for a rare disorder in a publicly funded healthcare system. Sharing experiences about their application is essential towards formulating guidelines to assist clinicians with decisions about their initiation and withdrawal. We report the details of AA experience in ten cases of pediatric-onset HPP in nine families from January 2015 to November 2019 (median [interquartile range] age 11.0 [7.6-12.5] years; 60% male). This is a study of a single-center cohort describing the clinical course of patients with HPP, mainly consisting of the mild childhood form of HPP, treated with AA in Japan. RESULTS: One case of perinatal form of HPP, two cases of benign prenatal form, and seven cases of childhood form were observed. The most common symptom at onset was pain. All patients had low serum alkaline phosphatase levels as compared to the age-matched reference range before the commencement of AA. All HPP patients seem to have responded to AA treatment, as evidenced by pain alleviation, increased height standard deviation, improvement in respiratory condition and 6-min walk test result improvement, disappearance of kidney calcification, alleviation of fatigue, and/or increases in bone mineralization. There were no serious adverse events, but all patients had an injection site reaction and skin changes at the injection sites. Genetic analysis showed that eight out of ten patients had compound heterozygosity. CONCLUSIONS: AA may be effective in patients with mild to severe pediatric-onset forms of HPP.

Abnormal liver chemistries as a predictor of COVID-19 severity and clinical outcomes in hospitalized patients.

BACKGROUND: Abnormal liver chemistries are common findings in patients with Coronavirus Disease 2019 (COVID-19). However, the association of these abnormalities with the severity of COVID-19 and clinical outcomes is poorly understood. AIM: We aimed to assess the prevalence of elevated liver chemistries in hospitalized patients with COVID-19 and compare the serum liver chemistries to predict the severity and in-hospital mortality. METHODS: This retrospective, observational study included 3380 patients with COVID-19 who were hospitalized in the Johns Hopkins Health System (Baltimore, MD, United States). Demographic data, clinical characteristics, laboratory findings, treatment measures, and outcome data were collected. Cox regression modeling was used to explore variables associated with abnormal liver chemistries on admission with disease severity and prognosis. RESULTS: A total of 2698 (70.4%) had abnormal alanine aminotransferase (ALT) at the time of admission. Other more prevalent abnormal liver chemistries were aspartate aminotransferase (AST) (44.4%), alkaline phosphatase (ALP) (16.1%), and total bilirubin (T-Bil) (5.9%). Factors associated with liver injury were older age, Asian ethnicity, other race, being overweight, and obesity. Higher ALT, AST, T-Bil, and ALP levels were more commonly associated with disease severity. Multivariable adjusted Cox regression analysis revealed that abnormal AST and T-Bil were associated with the highest mortality risk than other liver injury indicators during hospitalization. Abnormal AST, T-Bil, and ALP were associated with a need for vasopressor drugs, whereas higher levels of AST, T-Bil, and a decreased albumin levels were associated with mechanical ventilation. CONCLUSION: Abnormal liver chemistries are common at the time of hospital admission in COVID-19 patients and can be closely related to the patient's severity and prognosis. Elevated liver chemistries, specifically ALT, AST, ALP, and T-Bil levels, can be used to stratify risk and predict the need for advanced therapies in these patients.

Clinical and laboratory characteristics of patients with novel coronavirus disease-2019 infection and deep venous thrombosis.

OBJECTIVE: Early reports suggest that patients with novel coronavirus disease-2019 (COVID-19) infection carry a significant risk of altered coagulation with an increased risk for venous thromboembolic events. This report investigates the relationship of significant COVID-19 infection and deep venous thrombosis (DVT) as reflected in the patient clinical and laboratory characteristics. METHODS: We reviewed the demographics, clinical presentation, laboratory and radiologic evaluations, results of venous duplex imaging and mortality of COVID-19-positive patients (18-89 years) admitted to the Indiana University Academic Health Center. Using oxygen saturation, radiologic findings, and need for advanced respiratory therapies, patients were classified into mild, moderate, or severe categories of COVID-19 infection. A descriptive analysis was performed using univariate and bivariate Fisher's exact and Wilcoxon rank-sum tests to examine the distribution of patient characteristics and compare the DVT outcomes. A multivariable logistic regression model was used to estimate the adjusted odds ratio of experiencing DVT and a receiver operating curve analysis to identify the optimal cutoff for d-dimer to predict DVT in this COVID-19 cohort. Time to the diagnosis of DVT from admission was analyzed using log-rank test and Kaplan-Meier plots. RESULTS: Our study included 71 unique COVID-19-positive patients (mean age, 61 years) categorized as having 3% mild, 14% moderate, and 83% severe infection and evaluated with 107 venous duplex studies. DVT was identified in 47.8% of patients (37% of examinations) at an average of 5.9 days after admission. Patients with DVT were predominantly male (67%; P = .032) with proximal venous involvement (29% upper and 39% in the lower extremities with 55% of the latter demonstrating bilateral involvement). Patients with DVT had a significantly higher mean d-dimer of 5447 ± 7032 ng/mL (P = .0101), and alkaline phosphatase of 110 IU/L (P = .0095) than those without DVT. On multivariable analysis, elevated d-dimer (P = .038) and alkaline phosphatase (P = .021) were associated with risk for DVT, whereas age, sex, elevated C-reactive protein, and ferritin levels were not. A receiver operating curve analysis suggests an optimal d-dimer value of 2450 ng/mL cutoff with 70% sensitivity, 59.5% specificity, and 61% positive predictive value, and 68.8% negative predictive value. CONCLUSIONS: This study suggests that males with severe COVID-19 infection requiring hospitalization are at highest risk for developing DVT. Elevated d-dimers and alkaline phosphatase along with our multivariable model can alert the clinician to the increased risk of DVT requiring early evaluation and aggressive treatment.

Impact of the COVID-19 pandemic on endoscopic retrograde cholangiopancreatography: a single center experience.

BACKGROUND: the COVID-19 pandemic has impacted on several aspects of health care services worldwide. The aim of the study was to determine its influence on the case volume, success rate and complication rate of endoscopic retrograde cholangiopancreatography (ERCP). METHOD: all patients who underwent ERCP one-year before and after applying COVID-19 safety measures at the Qena University Hospital were included. Data were collected from the patients' records, analyzed and compared. RESULTS: a total of 250 patients underwent ERCP between April 1st, 2019 and March 31st, 2021, and the mean age of participants was 52 ± 18 years. There was a 5 % increase in case volume after applying COVID-19 safety measures (128 vs 122) and the total procedure time was significantly shorter (42 vs 46 minutes, p = 0.04). There was no significant difference in the overall success rate and complication rate. Procedure success significantly correlated with cannulation attempts and total procedure time in both groups, and serum bilirubin and cannulation time in the pre-COVID-19 patients and alkaline phosphatase (ALP) in post-COVID patients. ERCP-related complications significantly correlated with cannulation attempts in both groups, and ALP, international normalized ratio (INR), cannulation time and total procedure time in pre-COVID-19 patients, and platelet count and amylase in post-COVID patients. Two patients were confirmed COVID-19 cases at the time of ERCP; therapeutic targets were achieved in both with a smooth post-ERCP recovery. Three out of nine ERCP team members caught a mild to moderate COVID-19 infection and recovered after receiving proper management. CONCLUSION: our result show that there was no negative impact of using COVID-19 safety measures and precautions on the case-volume, indications, overall outcome or complication rate of ERCP.

Cholangiopathy After Severe COVID-19: Clinical Features and Prognostic Implications.

INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 virus, is a predominantly respiratory tract infection with the capacity to affect multiple organ systems. Abnormal liver tests, mainly transaminase elevations, have been reported in hospitalized patients. We describe a syndrome of cholangiopathy in patients recovering from severe COVID-19 characterized by marked elevation in serum alkaline phosphatase (ALP) accompanied by evidence of bile duct injury on imaging. METHODS: We conducted a retrospective study of COVID-19 patients admitted to our institution from March 1, 2020, to August 15, 2020, on whom the hepatology service was consulted for abnormal liver tests. Bile duct injury was identified by abnormal liver tests with serum ALP > 3x upper limit of normal and abnormal findings on magnetic resonance cholangiopacreatography. Clinical, laboratory, radiological, and histological findings were recorded in a Research Electronic Data Capture database. RESULTS: Twelve patients were identified, 11 men and 1 woman, with a mean age of 58 years. Mean time from COVID-19 diagnosis to diagnosis of cholangiopathy was 118 days. Peak median serum alanine aminotransferase was 661 U/L and peak median serum ALP was 1855 U/L. Marked elevations of erythrocyte sedimentation rate, C-reactive protein, and D-dimers were common. Magnetic resonance cholangiopacreatography findings included beading of intrahepatic ducts (11/12, 92%), bile duct wall thickening with enhancement (7/12, 58%), and peribiliary diffusion high signal (10/12, 83%). Liver biopsy in 4 patients showed acute and/or chronic large duct obstruction without clear bile duct loss. Progressive biliary tract damage has been demonstrated radiographically. Five patients were referred for consideration of liver transplantation after experiencing persistent jaundice, hepatic insufficiency, and/or recurrent bacterial cholangitis. One patient underwent successful living donor liver transplantation. DISCUSSION: Cholangiopathy is a late complication of severe COVID-19 with the potential for progressive biliary injury and liver failure. Further studies are required to understand pathogenesis, natural history, and therapeutic interventions.

Elevated transaminases and hypoalbuminemia in Covid-19 are prognostic factors for disease severity.

Prognostic markers are needed to understand the disease course and severity in patients with Covid-19. There is evidence that Covid-19 causes gastrointestinal symptoms and abnormalities in liver enzymes. We aimed to determine if hepatobiliary laboratory data could predict disease severity in patients with Covid-19. In this retrospective, single institution, cohort study that analyzed patients admitted to a community academic hospital with the diagnosis of Covid-19, we found that elevations of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (AP) at any time during hospital admission increased the odds of ICU admission by 5.12 (95% CI: 1.55-16.89; p = 0.007), 4.71 (95% CI: 1.51-14.69; p = 0.01) and 4.12 (95% CI: 1.21-14.06, p = 0.02), respectively. Hypoalbuminemia found at the time of admission to the hospital was associated with increased mortality (p = 0.02), hypotension (p = 0.03), and need for vasopressors (p = 0.02), intubation (p = 0.01) and hemodialysis (p = 0.002). Additionally, there was evidence of liver injury: AST was significantly elevated above baseline in patients admitted to the ICU (54.2 ± 15.70 U/L) relative to those who were not (9.2 ± 4.89 U/L; p = 0.01). Taken together, this study found that hypoalbuminemia and abnormalities in hepatobiliary laboratory data may be prognostic factors for disease severity in patients admitted to the hospital with Covid-19.

Evaluation of serum hepatic enzyme activities in different COVID-19 phenotypes.

Coronavirus disease 2019 (COVID-19) is a newly emerging infectious disease. Our understanding of the clinical characteristics of liver damage and the relationship with disease severity in COVID-19 is still limited. To investigate the serum hepatic enzyme activities in different phenotypes of COVID-19 patients, evaluate their relationship with the illness severity and analyze the correlation of glycyrrhizin treatment and abnormal liver enzyme activities, one hundred and forty-seven patients with COVID-19 were enrolled in a retrospective study that investigated hepatic dysfunction. Liver alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactic dehydrogenase (LDH), Y-glutamyl transferase (GGT), superoxide dismutase (SOD), and alkaline phosphatase (ALP) were analyzed in these patients. Patients with diammonium glycyrrhizinate (DG) treatment were further investigated. Of the 147 patients, 56 (38.1%) had abnormal ALT activity and 80 (54.4%) had abnormal AST activity. The peak of abnormal hepatic enzyme activities occurred at 3 to 6 days after on admission. Serum AST and LDH levels were elevated, while the SOD level was decreased in severe and critical patients, compared with mild cases. DG treatment may alleviate the abnormal liver enzyme activities in non-critical COVID-19 patients. Abnormal liver functions may be observed in patients with COVID-19, and were associated with SARS-CoV-2-induced acute liver damage. Glycyrrhizin treatment may be an effective therapeutic approach for the outcome of abnormal hepatic enzyme activities in severe COVID-19 cases. Serum hepatic enzyme tests may reflect the illness severity and should be monitored.

Evaluation of hepatic enzymes activities in COVID-19 patients.

SARS-CoV-2 or Coronavirus disease 2019 (COVID-19) outbreak which caused by the severe acute respiratory syndrome, has rapidly spread over the world. The exact mechanism how this virus will affect the liver remained elusive. The aim of this study was to evaluate the liver function in patients with severe acute respiratory syndrome coronavirus 2 and potential causes of hepatic enzymes disease in these patients. Clinical characteristics and laboratory findings were collected from patients with COVID-19 who were admitted to the corona center in Erbil city/Kurdistan region of Iraq, from March 10 to July 10, 2020. Serum was collected from patients with COVID-19 and liver enzyme tests were measured. Liver alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL) were analyzed in these patients. Of the 74 patients, 25 (34.7%) had abnormal ALT activity, 28 (40%) had abnormal AST activity, 12 (20.3%) had abnormal ALP activity, and 39 (52.7%) had abnormal total bilirubin P-value < 0.05. The inflammatory biomarkers CRP and IL-6 in COVID-19 patients with abnormal liver function test (4.9 ± 1.0 mg/dl) and (231.2 ± 35.7 pg/ml) respectively. The levels of both biomarkers were statistically significantly higher than COVID-19 patients with normal liver function test (2.1 ± 0.5 mg/dl) and (2.1 ± 0.5 mg/dl) respectively, P-value < 0.05. However, CRP and IL-6 were not statistically significant different between male and female COVID-19 patients P-value < 0.05. In conclusion, we found that most of the patients with SARS-CoV-2 have abnormal hepatic enzyme activities and that is might related to virus replication in the liver.

Effects of a Serum Heating Procedure for Inactivating COVID-19 on Common Biochemical Tests.

BACKGROUND: COVID-19 has recently been declared an epidemic by the WHO, and there is an urgent need for affected countries and laboratories to assess and treat people at risk of COVID-19. A heat procedure has been suggested for specimen inactivation. This study was designed to evaluate the effect of serum heating on biochemical indexes, and providing a basis for accurate detection results of the COVID-19 patients. METHODS: We collected 29 normal cases of two tubes of 5 mL whole blood. One tube was analyzed directly, and the other was analyzed after heating at 56°C 30 minutes. RESULTS: A total of 34 serum biochemical index quantitative results were obtained, 28/34 indexes were not significantly affected by the heat inactivation and remained clinically interpretable. As the thermal inactivation for these indexes showed good correlation, ALB (p = 0.04, Pearson R = 0.91, 2.6% mean increase), CysC (p = 0.03, Pearson R = 0.98, 9.9% mean increase), CO2CP (p < 0.001, Pearson R = 0.96, 13% mean decrease), they were still inter-pretable. Four biochemical indexes ALP, CK, CK-MB, and insulin were inactivated and showed significant statistical differences (p < 0.001). CONCLUSIONS: Our study showed CK, CK-MB, ALP, and insulin were sensitive to heat and will be inhibited or degrade after heating, indicating that the rapid decrease of this indexes in the COVID-19 patients may be caused by sample heat inactivation. For safety and diagnostic accuracy, we recommend the use of a point-of-care device for blood gases, electrolytes, troponin, and liver and renal function tests within a ISL 2 or above biosafety cabinet with level 3 or above biosafety laboratory practice.

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. AIM: To 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 METHODS: This 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. RESULTS: Of 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. CONCLUSION: Liver 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.

Transient benign hyperphosphatasemia due to COVID-19: the first case report.

OBJECTIVES: Coronavirus disease (COVID-19) rapidly spread worldwide in a few months and was declared as a worldwide pandemic by WHO in March 2020. Transient benign hyperphosphatasemia (THI) is a benign condition associated with marked elevation of alkaline phosphatase (ALP) without any other kidney, bone, and liver pathologies. CASE PRESENTATION: Herein, we report a previously healthy 16-month-old female patient who developed a secondary transient benign hyperphosphatasemia associated with SARS-CoV-2. Patient whole family's SARS-CoV-2 real-time reverse transcription-polymerase chain reaction (RT-PCR) results were positive. Since THI is a diagnosis of exclusion, other reasons that may cause ALP elevation should be ruled out. ALP activity decreased and turned to normal ranges within the following month. THI has been reported to be in association with various conditions. Its relationship with many viruses has been reported previously. CONCLUSIONS: If ALP elevation is detected in patients with COVID 19 due to the increasing number of infections, THI should be considered if there is no other accompanying pathology.

Prevalence of liver injury and correlation with clinical outcomes in patients with COVID-19: systematic review with meta-analysis.

OBJECTIVE: Liver involvement of SARS-CoV-2 infection has been reported in several papers, but without homogeneous findings. We aimed to systematically review the prevalence of liver involvement in patients with SARS-CoV-2 infection at their hospital admission, and its correlation with disease severity and clinical outcomes in patients with or without pre-existing chronic liver disease. MATERIALS AND METHODS: We systematically searched PubMed, Embase, Web of Science, Medline, PMC, clinical trial registries, and other Coronavirus family publications for studies reporting data on SARS-CoV-2 infection or COVID-19 and liver function tests (LFTs) alterations, as well as clinical course of patients with chronic liver disease or cirrhosis. Case reports, preprints, editorials, reviews were excluded. We also revised literature to describe the background of liver involvement during SARS-CoV-2 infection. RESULTS: 36 studies, including 20724 patients with SARS-CoV-2 infection, were included. The pooled prevalence of LFTs abnormalities at admission was 46.9% (AST 26.5%, ALT 22.8%, GGT 22.5%, ALP 5.7%, tBIL 8.0%). ALT, AST, tBIL were independent predictors of disease severity (ALT OR 1.54, 95% CI 1.17-2.03; AST OR 3.17, 95% CI 2.10-4.77; tBIL OR 2.32, 95% CI 1.18-4.58) and in-hospital mortality (ALT OR 1.48, 95% CI 1.12-1.96; AST OR 4.39, 95% CI 2.68-7.18; tBIL OR 7.75, 95% CI 2.28-26.40). Heterogeneity among studies was high. The few available data also reported that COVID-19 was associated with increased risk of liver decompensation and mortality in patients with liver cirrhosis. CONCLUSIONS: LFTs alterations were reported in up to 47% of unselected patients with COVID-19 and were associated with severe disease or in-hospital mortality. In cirrhotic patients, COVID-19 was associated with high risk of liver decompensation or mortality.

The liver in COVID-19: prevalence, patterns, predictors, and impact on outcomes of liver test abnormalities.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused a global pandemic unprecedented in over a century, with ≈35 million cases, and more than 1 million deaths globally. Though predominantly a lower respiratory illness, other organ injuries are well-recognized. Among these, liver injury is of major interest. OBJECTIVE: To define prevalence, pattern, predictors, and impact of liver injury among patients hospitalized with COVID-19. METHODS: Demographic, clinical, and biochemical data were collected retrospectively among patients admitted to St. Luke's University Hospital with COVID-19 between 1 March and 18 April 2020. Association of liver tests (LTs) with mortality and need for mechanical ventilation, adjusted for demographic, clinical and biochemical predictors, was examined. RESULTS: Data were available on 551 patients. Prevalence of any or ≥3 × upper limit of normal transaminase elevation on was 61.2 and 9.4% on admission, and 72.1 and 22.4% at peak. Bilirubin and alkaline phosphatase elevations were less common on admission (11.4 and 12.6%, respectively), and at peak (17.7 and 22%, respectively). All liver test (LT) elevations were consistently predicted by inflammatory markers. Hyperbilirubinemia predicted mortality on admission and at peak. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) had opposite impact on mortality with AST positively, and ALT negatively associated with mortality. Hence, besides hyperbilirubinemia, AST:ALT ratio emerged as the best marker for mortality among the LTs. CONCLUSION: LT elevations among patients presenting with COVID-19 are very common, though majority are mild. Admission and peak bilirubin ≥1 mg/dl, as well as admission and peak AST:ALT ratio were significant predictors of mortality, along with age, myocardial injury, and chronic medical illness.