ObjectiveData on serial liver biochemistries of patients infected by different human coronaviruses (HCoVs) are lacking. The impact of liver injury on adverse clinical outcomes in coronavirus disease ...2019 (COVID-19) patients remains unclear.DesignThis was a retrospective cohort study using data from a territory-wide database in Hong Kong. COVID-19, severe acute respiratory syndrome (SARS) and other HCoV patients were identified by diagnosis codes and/or virological results. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation was defined as ALT/AST ≥2 × upper limit of normal (ie, 80 U/L). The primary end point was a composite of intensive care unit (ICU) admission, use of invasive mechanical ventilation and/or death.ResultsWe identified 1040 COVID-19 patients (mean age 38 years, 54% men), 1670 SARS patients (mean age 44 years, 44% men) and 675 other HCoV patients (mean age 20 years, 57% men). ALT/AST elevation occurred in 50.3% SARS patients, 22.5% COVID-19 patients and 36.0% other HCoV patients. For COVID-19 patients, 53 (5.1%) were admitted to ICU, 22 (2.1%) received invasive mechanical ventilation and 4 (0.4%) died. ALT/AST elevation was independently associated with primary end point (adjusted OR (aOR) 7.92, 95% CI 4.14 to 15.14, p<0.001) after adjusted for albumin, diabetes and hypertension. Use of lopinavir–ritonavir ±ribavirin + interferon beta (aOR 1.94, 95% CI 1.20 to 3.13, p=0.006) and corticosteroids (aOR 3.92, 95% CI 2.14 to 7.16, p<0.001) was independently associated with ALT/AST elevation.ConclusionALT/AST elevation was common and independently associated with adverse clinical outcomes in COVID-19 patients. Use of lopinavir–ritonavir, with or without ribavirin, interferon beta and/or corticosteroids was independently associated with ALT/AST elevation.
In developed nations, monitoring for drug-induced liver injury through serial measurements of serum transaminases aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in at-risk ...individuals is the standard of care. Despite the need, monitoring for drug-related hepatotoxicity in resource-limited settings is often limited by expense and logistics, even for patients at highest risk. This article describes the development and clinical testing of a paper-based, multiplexed microfluidic assay designed for rapid, semiquantitative measurement of AST and ALT in a fingerstick specimen. Using 223 clinical specimens obtained by venipuncture and 10 fingerstick specimens from healthy volunteers, we have shown that our assay can, in 15 min, provide visual measurements of AST and ALT in whole blood or serum, which allow the user to place those values into one of three readout "bins" <3× upper limit of normal (ULN), 3 to 5× ULN, and >5× ULN, corresponding to tuberculosis/HIV treatment guidelines with >90% accuracy. These data suggest that the ultimate point-of-care fingerstick device will have high impact on patient care in low-resource settings.
Background
The SARS‐CoV‐2 pandemic is an ongoing global health emergency. The aim of our study was to investigate the changes of liver function and its clinical significance in COVID‐19 patients.
...Method
This retrospective, single‐centre study was conducted on 115 confirmed cases of COVID‐19 in Zhongnan hospital of Wuhan University from 18 January 2020 to 22 February 2020. Liver function and related indexes were analysed to evaluate its relationship with disease progression in COVID‐19 patients.
Results
Part of the COVID‐19 patients presented with varying degrees of abnormality in liver function indexes. However, the levels of ALT, AST, TBIL, GGT and LDH in COVID‐19 patients were not significantly different when compared with hospitalised community‐acquired pneumonia patients, and the levels of albumin is even significantly higher. The levels of ALT, AST, TBIL, LDH and INR showed statistically significant elevation in severe COVID‐19 cases compared with that in mild cases. However, the clinical significance of the elevation is unremarkable. Majority of severe COVID‐19 patients showed significantly decreasing in albumin level and continuously decreasing in the progress of illness. Most of the liver function indexes in COVID‐19 patients were correlated with CRP and NLR, the markers of inflammation. Logistic regression analysis further identified NLR as the independent risk factor for severe COVID‐19, as well as age.
Conclusions
Although abnormalities of liver function indexes are common in COVID‐19 patients, the impairment of liver function is not a prominent feature of COVID‐19, and also may not have serious clinical consequences.
Heavy metals have been reported to affect liver function. However, there is currently little and inconsistent knowledge about the effects of combined and individual urinary metals on specific ...parameters of liver function in the general population. Therefore, this study aimed to investigate their associations.
This study involved 807 general population from the China National Human Biomonitoring of Zhejiang Province 2017–2018. Concentrations of urinary metals, including Chromium (Cr), Cobalt (Co), Nickle (Ni), Arsenic (As), Selenium (Se), Molybdenum (Mo), Cadmium (Cd), Thallium (Tl) and Lead (Pb) were measured. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein (TP), albumin (ALB), direct bilirubin (DBIL), total bilirubin (TBIL) as liver function biomarkers. Multivariable linear regression and weighted quantile sum (WQS) regression were employed to explore the associations of urinary metals with liver function biomarkers. Subgroup analysis stratified by gender and age, excluding smokers and drinkers for sensitivity analysis.
Both statistical models indicated that urinary metals were positively associated with ALT and AST, while negatively with TP, ALB, DBIL and TBIL. In the WQS analysis, each quartile increase in the ln-transformed levels of metal mixtures was associated with 4.11 IU/L (95% CI: 1.07, 7.15) higher ALT and 3.00 IU/L (95% CI: 1.75, 4.25) higher AST, as well as, with 0.67 g/L (95% CI: 1.24, −0.11) lower TP, 0.74 g/L (95% CI: 1.09, −0.39) lower ALB, 0.38 μmol/L (95% CI: 0.67, −0.09) lower DBIL, and 1.56 μmol/L (95% CI: 2.22, −0.90) lower TBIL. The association between urinary metals and ALT was primarily driven by Cd (55.8%), Cr contributed the most to the association with AST (20.2%) and TBIL (45.2%), while the association with TP was primarily driven by Ni (38.2%), the association with ALB was primarily driven by As (32.8%), and the association with DBIL was primarily driven by Pb (30.9%). The associations between urinary metals and liver function might differ by sex and age.
Urinary metals were significantly associated with liver function parameters. Further studies are required to clarify the relationship between heavy metals and liver function.
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•Urinary metals were significantly associated with liver function biomarkers individually in the general population.•Both statistical models indicated that urinary metals were positively associated with ALT and AST, and negatively associated with TP, ALB, DBIL, and TBIL.•The associations between urinary metals and liver function might differ by sex and age.
Background: Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) persist in the environment and are found in relatively high concentrations in animal livers. Studies in humans have reported ...inconsistent associations between PFOA and liver enzymes. Objectives: We examined the cross-sectional association between serum PFOA and PFOS concentrations with markers of liver function in adults. Methods: The C8 Health Project collected data on 69,030 persons; of these, a total of 47,092 adults were included in the present analysis. Linear regression models were fitted for natural log (In)-transformed values of alanine transaminase (ALT), γ-glutamyltransferase (GGT), and direct bilirubin on PFOA, PFOS, and potential confounders. Logistic regression models were fitted comparing deciles of PFOA or PFOS in relation to high biomarker levels. A multilevel analysis comparing the evidence for association of PFOA with liver function at the individual level within water districts to that at the population level between water districts was also performed. Results: ln-PFOA and ln-PFOS were associated with ln-ALT in linear regression models PFOA: coefficient, 0.022; 95% confidence interval (CI): 0.018, 0.025; PFOS: coefficient, 0.020; 95% CI: 0.014, 0.026 and with raised ALT in logistic regression models with a steady increase in the odds ratio (OR) estimates across deciles of PFOA and PFOS; PFOA: OR = 1.10; 95% CI: 1.07, 1.13; PFOS: OR = 1.13; 95% CI: 1.07, 1.18. There was less consistent evidence of an association of PFOA and GGT or bilirubin. The relationship with bilirubin appears to rise at low levels of PFOA and to fall again at higher levels. Conclusions: These results show a positive association between PFOA and PFOS concentrations and serum ALT level, a marker of hepatocellular damage.
Coronavirus disease 2019 (COVID-19) poses a major health threat to healthy individuals and those with comorbidities, but its impact on patients with cirrhosis is currently unknown. Herein, we aimed ...to evaluate the impact of COVID-19 on the clinical outcome of patients with cirrhosis.
In this multicentre retrospective study, patients with cirrhosis and a confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection were enrolled between 1st and 31th March 2020. Clinical and biochemical data at diagnosis of COVID-19 and at the last outpatient visit were obtained through review of medical records.
Fifty patients with cirrhosis and confirmed SARS-CoV-2 infection were enrolled (age 67 years, 70% men, 38% virus-related, 52% previously compensated cirrhosis). At diagnosis, 64% of patients presented fever, 42% shortness of breath/polypnea, 22% encephalopathy, 96% needed hospitalization or a prolonged stay if already in hospital. Respiratory support was necessary in 71%, 52% received antivirals, 80% heparin. Serum albumin significantly decreased, while bilirubin, creatinine and prothrombin time significantly increased at COVID-19 diagnosis compared to last available data. The proportion of patients with a model for end-stage liver disease (MELD) score ≥15 increased from 13% to 26% (p = 0.037), acute-on-chronic liver failure and de novo acute liver injury occurred in 14 (28%) and 10 patients, respectively. Seventeen patients died after a median of 10 (4–13) days from COVID-19 diagnosis, with a 30-day-mortality rate of 34%. The severity of lung and liver (according to CLIF-C, CLIF-OF and MELD scores) diseases independently predicted mortality. In patients with cirrhosis, mortality was significantly higher in those with COVID-19 than in those hospitalized for bacterial infections.
COVID-19 is associated with liver function deterioration and elevated mortality in patients with cirrhosis.
Coronavirus disease 2019 (COVID-19) poses a major health threat to healthy individuals and those with comorbidities. Herein, we assessed its impact on patients with cirrhosis. Infection with COVID-19 was associated with liver function deterioration and elevated mortality in patients with cirrhosis.
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•50 patients with cirrhosis and SARS-CoV-2 infection were studied, with an overall 30-day mortality rate of 34%.•Mortality was higher in patients with respiratory failure and in those with worsening liver function at COVID-19 diagnosis.•30-day mortality rates were higher in patients with cirrhosis and COVID-19 than in those with bacterial infections.•No major adverse events were related to the thromboprophylaxis with heparin (given to 80% of patients) or antiviral treatments.
...we aimed to perform a meta-analysis to estimate the prognosis of patients with COVID-19 stratified according to liver injury. Abnormal liver function in patients with COVID-19 is possibly ...multifactorial; that is, drug-induced liver injury (DILI), severe acute respiratory syndrome coronavirus 2 replications in the liver10 and interorgan cross-talk in acute inflammation.9 Published studies on COVID-19 have shown that 37.2%–76.3% of patients have abnormal liver function.2 9 Similarly, the prevalence of liver injury is reported in about 21.5%–45.71% of patients.2 10 Generally, 7.14%–64.15% of patients with COVID-19 had increased aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT) and bilirubin levels, whereas albumin was decreased to 27.9–33.0 g/L in non-survivor patients.6 Besides, patients with COVID-19 with chronic liver disease (CLD) might develop decompensated liver as a systemic inflammatory response induced by COVID-19.1 We found that the prevalence of CLD was 4% (95% CI 1.5 to 6.4, I2=89%) among patients with COVID-19, with cirrhosis and hepatitis B being the most common. (A) Severity. 2 4 5 9 (B) Mortality. 6-9 To conclude, patients with COVID-19 have a high prevalence of liver injury, and patients with COVID-19 with liver injury are at an increased risk of severity and mortality. ...special attention should be given to any liver dysfunction while treating patients with COVID-19.
Abstract Background13 C-liver function breath tests can facilitate the assessment of hepatic function in-vivo and may help surgeons to identify candidates for safe liver surgery. However, their ...acceptance into clinical practice is dependent on evaluation of technical efficacy and repeatability. The aims of this study were to evaluate the within-subject repeatability of the LiMAx (maximum liver function capacity) test in healthy individuals and in surgical patients to determine liver function in the perioperative workup. Material and methods The LiMAx test, which is based on intravenous injection of13 C-methacetin at a dosage of 2 mg/kg body weight was performed in eighty-six healthy subjects to determine a reference range. Twenty-four subjects underwent repeat LiMAx testing the following day to assess within-subject repeatability. Twenty-one patients undergoing elective extra-abdominal surgery under general anesthesia (GA group) received pre- and post-operative examinations. Results The normal range of LiMAx was found to be 430 ± 86 μg/kg/h and revealed a one-sided cut-off value of 315 μg/kg/h. The intraclass correlation coefficient of the repeat LiMAx tests was 0.85 (95% confidence interval 0.69–0.93) in the control group and 0.81 (95% confidence interval 0.60–0.92) in the group of patients with GA. Conclusions The LiMAx test shows excellent reproducibility in subjects with normal liver function. GA has no effect on test results.
Acoustic holography (AH), a promising approach for cell patterning, emerges as a powerful tool for constructing novel invitro 3D models that mimic organs and cancers features. However, understanding ...changes in cell function post-AH remains limited. Furthermore, replicating complex physiological and pathological processes solely with cell lines proves challenging. Here, we employed acoustical holographic lattice to assemble primary hepatocytes directly isolated from mice into a cell cluster matrix to construct a liver-shaped tissue sample. For the first time, we evaluated the liver functions of AH-patterned primary hepatocytes. The patterned model exhibited large numbers of self-assembled spheroids and superior multifarious core hepatocyte functions compared to cells in 2D and traditional 3D culture models. AH offers a robust protocol for long-term in vitro culture of primary cells, underscoring its potential for future applications in disease pathogenesis research, drug testing, and organ replacement therapy.
Non-alcoholic steatohepatitis (NASH) is a chronic, progressive fibrotic liver disease that can lead to cirrhosis. While liver biopsy is considered the reference standard for the histologic diagnosis ...of NASH and staging of fibrosis, its use in clinical practice is limited. Non-invasive tests (NITs) are increasingly being used to identify and stage liver fibrosis in patients with NASH, and several can assess liver-related outcomes. We report changes in various NITs in patients treated with obeticholic acid (OCA) or placebo in the phase III REGENERATE study.
Patients with NASH and fibrosis stage F2 or F3 (n = 931) were randomized (1:1:1) to receive placebo, OCA 10 mg, or OCA 25 mg once daily. Various NITs based on clinical chemistry and/or imaging were evaluated at baseline and throughout the study.
Rapid, sustained reductions from baseline in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase levels, as well as in Fibrosis-4 (FIB-4), FibroTest, FibroMeter, and FibroScan-AST scores were observed in OCA-treated vs. placebo-treated patients. Reduction in liver stiffness by vibration-controlled transient elastography was observed in the OCA 25 mg group vs. the placebo group at Month 18. NIT changes were associated with shifts in histologic fibrosis stage. The greatest improvements were observed in patients with ≥1-stage fibrosis improvement; however, improvements in ALT, AST, FIB-4, and FibroTest were also observed in OCA-treated patients whose histologic fibrosis remained stable.
Based on the REGENERATE Month 18 interim analysis, rapid and sustained improvements in various NITs were observed with OCA treatment. Dynamic changes in selected NITs separated histologic responders from non-responders. These results suggest that NITs may be useful in assessing histologic response to OCA therapy.
NCT02548351
Non-alcoholic steatohepatitis (NASH) is a chronic, progressive liver disease that can lead to cirrhosis. To diagnose and assess liver fibrosis (scarring) in patients with NASH, non-invasive tests (NITs) are increasingly being used rather than liver biopsy, which is invasive, expensive, and can be risky. In the REGENERATE study, which is evaluating the effects of obeticholic acid vs. placebo in patients with NASH, various NITs were also evaluated. This analysis shows that improvements in levels of certain blood components, as well as favorable results of ultrasound imaging and proprietary tests of liver function, were associated with improvements in liver fibrosis after treatment with obeticholic acid, suggesting that NITs may be useful alternatives to liver biopsy in assessing NASH patients’ response to therapy.
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•Reduced ALT, AST, GGT, FIB-4, and FibroTest scores were seen with OCA vs. placebo.•Reduced liver stiffness by VCTE was observed in OCA vs. placebo arms at Month 18.•NIT changes in OCA treatment arms were associated with shifts in fibrosis stage.•The antifibrotic effect of OCA might be measurable with commonly used NITs.
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