Abnormal liver function tests associated with severe rhabdomyolysis

Rhabdomyolysis is a syndrome of skeletal muscle injury with release of cellular constituents such as potassium,phosphate,urate and intracellular proteins such as myoglobin into the circulation,which may cause complications including acute kidney injury,electrolyte disturbance and cardiac instability.Abnormal liver function tests are frequently observed in cases of severe rhabdomyolysis.Typically,there is an increase in serum aminotransferases,namely aspartate aminotransferase and alanine aminotransferase.This raises the question of liver injury and often triggers a pathway of investigation which may lead to a liver biopsy.However,muscle can also be a source of the increased aminotransferase activity.This review discusses the dilemma of finding abnormal liver function tests in the setting of muscle injury and the potential implications of such an association.It delves into some of the clinical and experimental evidence for correlating muscle injury to raised aminotransferases,and discusses pathophysiological mechanisms such as oxidative stress which may cause actual liver injury.Serum aminotransferases lack tissue specificity to allow clinicians to distinguish primary liver injury from muscle injury.This review also explores potential approaches to improve the accuracy of our diagnostic tools,so that excessive or unnecessary liver investigations can be avoided.

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

BACKGROUND Metabolic-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.AIM To evaluated potential implications of changes in UNL of alanine aminotransferase(ALT)in MAFLD.METHODS We 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.RESULTS Total 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).CONCLUSION Liver 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.

Effect of Ascorbic Acid Supplementation on Liver Function Tests in Hepatitis C Patients

An isolated liver function test is of little role in selection of liver disease because many harmful liver diseases may be correlated with normal levels of LFT’s. The outline of enzyme abnormalities in the perspective of patient’s commonly observed symptoms and laboratory data might be helpful in directing the subsequent diagnosis of liver diseases. Liver Function Tests (LFTs) are most generally used screening blood tests for assessment of different liver diseases and these tests provide a lot of evidence for disease processes whether for the purpose of investigation of supposed liver disease or help in observing the progress of disease action or simply by blood investigation. The evaluation of different liver enzymes simply gives diagnostic information on basic level whether patient’s principal disorder is actually hepatitis or cholestasis in source. However, it is necessary in various cases to evaluate LFTs with knowledge of liver functioning enzyme fractions. The objective of this study was to explore the effects of ascorbic acid supplementation on serum liver function tests in Hepatitis C patients. A total of 100 hepatitis C patients were selected randomly. 50 were given ascorbic acid supplementation for one month along with anti HCV treatment. The other 50 HCV patients took their normal anti HCV treatment without intake of ascorbic acid supplementation, and serum ascorbic acid level and liver function test parameters were observed before and after intake of ascorbic acid in both groups. The liver function parameters determined were aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), serum total bilirubin, direct bilirubin, indirect bilirubin and serum protein (total protein, albumin, globulin and A/G ratio). These parameters along with serum ascorbic acid were measured before and 30 days after vitamin C supplementation. Various abnormally elevated LFTs were also improved more rapidly when compared to other group which was not given ascorbic acid supplements for the period of one month. There was a significant change in levels of some liver function parameters before and after intake of ascorbic acid supplementation, and various abnormally elevated LFTs were also improved when compared to other group which was not given ascorbic acid supplements for the period of one month. The effect of Vitamin C supplementation was more marked on serum aminotransferase levels. After one-month use of ascorbic acid, serum alanine aminotransferase (p < 0.042) and serum aspartate aminotransferase (p < 0.000) levels were significantly decreased in hepatitis C patient group. In HCV group with ascorbic acid supplementation, serum total bilirubin (p < 0.046) and serum direct bilirubin (p < 0.048) were found to be less than the pre values when compared to HCV group without ascorbic acid supplementation. It was also observed that some of protein values were suggestively improved after intake of ascorbic acid supplementation.

Could quantitative liver function tests gain wide acceptance among hepatologists?

It has been emphasized that the assessment of residual liver function is of paramount importance to determine the following: severity of acute or chronic liver diseases independent of etiology; long-term prognosis; step-by- step disease progression; surgical risk; and efflcacy of antiviral treatment. The most frequently used tools are the galactose elimination capacity to asses hepatocyte cytosol activity, plasma clearance of indocyanine green to assess excretory function, and antipyrine clearance to estimate microsomal activity. However, a widely accepted liver test (not necessarily a laboratory one) to assess quantitative functional hepatic reserve still needs to be established, although there have been various proposals. Furthermore, who are the operators that should order these tests? Advances in analytic methods are expected to allow quantitative liver function tests to be used in clinical practice.

Liver function tests: Association with cardiovascular outcomes

An association between nonalcoholic fatty liver disease and cardiovascular disease has been repeatedly rep orted. Several studies have focused on levels of gammaglutamyltransferase (GGT) and alanine aminotransferase (ALT) in relation to cardiovascular outcomes. Evidence indicates that GGT may have a potential role for cardiovascular risk stratifi cation while the role of ALT for cardiac prognosis remains controversial. A conceptual framework that includes not only GGT and ALT but also markers of hepatocyte apoptosis such as cytokeratin-18 fragments should be developed.

Study on the Application Value of Liver Function and Serological Index Levels in the Diagnosis of Fatty Liver

Objective:To explore the application value of liver function and serological index detection in diagnosing fatty liver.Methods:Ninety patients with fatty liver disease(disease group)and ninety healthy subjects(healthy group)were selected as the subjects of this study.They all underwent liver function index testing and serological index testing.Test results were compared,and the diagnostic accuracy of single and combined tests was evaluated.Results:Liver function indicators of patients in the disease group were higher than those in the healthy group,with severe patients exhibiting higher levels than moderate patients and mild patients(P<0.05).Serological indicators in patients in the disease group were higher than those in the healthy group,with severe patients showing higher levels than moderate patients and mild patients(P<0.05).The diagnostic accuracy of liver function index testing was higher than that of serological index testing,and the accuracy of combined testing was higher than that of single testing(P<0.05).Conclusion:In diagnosing fatty liver,combining liver function testing and serological testing enables the initial diagnosis of the disease and facilitates the accurate assessment of its severity.

Establishment of age-and gender-specific pediatric reference intervals for liver function tests in healthy Han children

Background The development and growth of children influence values of liver function tests.This study aims to establish age-and gender-specific pediatric reference intervals of liver function among Han children in Changchun,China.Methods A total of 1394 healthy Han children,aged 2-14 years,were recruited from communities and schools with informed parental consent in Changchun.The levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),y-glutamyltransferase(GGT),alkaline phosphatase(ALP),total protein(TP),albumin(ALB),total bilirubin(TBIL)and direct bilirubin(DBIL)were measured on Hitachi 7600-210 automatic biochemical analyzer.The age-and gender-specific reference intervals were partitioned using Harris and Boyd's test and calculated using nonparametric rank method.The pediatric reference intervals were validated in five representative hospitals located in different areas in Changchun.Results All the analytes required some levels of age partitioning.Proteins(TP,ALB)and bilirubins(TBIL,DBIL)required no gender partitioning.In contrast,considerable gender partitioning was required for serum ALT,AST,GGT,and ALP.TP,TBIL,and DBIL showed steady increases,and AST showed apparent decreases over time,whereas ALT,GGT,ALP,and ALB demonstrated complex trends of change.ALT and GGT increased sharply in males from 11 to 14 years old.However,ALP declined in females from 13 to 14 years.All five laboratories passed the validation of reference intervals.Conclusions There were apparent age or gender variations of the reference intervals for liver function.When establishing pediatric reference intervals,partitioning according to age and gender is necessary.

Liver dysfunction-related COVID-19:A narrative review

The coronavirus 2019 disease(COVID-19)is caused by a novel coronavirus,severe acute respiratory syndrome coronavirus 2.This disease was designated by the World Health Organization as a pandemic on March 11,2020,which is not seen before.There are no classical features among the cases of the disease owing to the involvement of nearly all body tissues by the virus.Hepatic involvement is one of the characteristics of the COVID-19 course.There are six possible mechanisms of such involvement:Direct virus injury,drug-induced effect,inflammatory cytokine storm,hypoxia-ischemic destruction,abnormalities in liver function tests,and pre-existing chronic liver diseases.Liver abnormalities are seen commonly in the severe or critical stage of COVID-19.Therefore,these abnormalities determine the COVID-19 severity and carry a high rate of morbidity and mortality.The elderly and patients with comorbidities like diabetes mellitus and hypertension are more vulnerable to liver involvement.Another issue that needs to be disclosed is the liver manifestations following the COVID-19 vaccination,such as autoimmune hepatitis.Of note,complete vaccination with third and fourth booster doses is necessary for patients with previous chronic liver diseases or those who have been subjected to liver transplantation.This review aims to explore the various aspects of liver dysfunction during the COVID-19 course regarding the epidemiological features,predisposing factors,pathophysiological mechanisms,hepatic manifestations due to COVID-19 or following vaccination,role of liver function tests in the assessment of COVID-19 severity,adverse effects of the therapeutic agents for the disease,and prognosis.

Influence of diet intake on liver function test

ＩｎｆｌｕｅｎｃｅｏｆｄｉｅｔｉｎｔａｋｅｏｎｌｉｖｅｒｆｕｎｃｔｉｏｎｔｅｓｔＣＨＥＮＧＳｈｕＱｕａｎ，ＺＨＡＮＧＪｉＦａｎｇ，ＺＨＡＮＧＺｉＦｕ，ＱＩＡＮＭｅｉＹａｎ，ＧＵＯＸｉａｏＬｉｎｇ，ＳＨＡＮＧＷｅｎＺｈａｎｇａｎｄＬＩＤｕｏ...

Measurement of hepatic functional mass by means of ^(13)C-methacetin and ^(13)C-phenylalanine breath tests in chronic liver disease: Comparison with Child-Pugh score and serum bile acid levels

AIM: To evaluate and compare the clinical usefulness of 13C-phenylalanine and 13C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these results with those of conventional tests, Child-Pugh score and serum bile acid levels.METHODS: One hundred and forty patients (50 HCV-related chronic hepatitis, 90 liver cirrhosis patients) and 40 matched healthy controls were studied. Both breath test and routine liver test, serum levels of cholic and chenodeoxycholic acid conjugates were evaluated.RESULTS: Methacetin breath test, expressed as 60 min cumulative percent of oxidation, discriminated the hepatic functional capacity not only between controls and liver disease patients, but also between different categories of chronic liver disease patients. Methacetin breath test was correlated with liver function tests and serum bile acids.Furthermore, methacetin breath test, as well as serum bile acids, were highly predictive of Child-Pugh scores. The diagnostic power of phenylalanine breath test was always less than that of methacetin breath test.CONCLUSION: Methacetin breath test represents a safe and accurate diagnostic tool in the evaluation of hepatic functional mass in chronic liver disease patients.

Measurement of liver function for patients with cirrhosis by ^13C-methacetin breath test compared with Child-Pugh score and routine liver function tests

^13C-methacetin breath test was used for the evaluation of liver function, as for quantitative data could be achieved using this method, it had the characteristics of safety, quantification, and repetition and got recognition gradually through the world. We began this ^13C- methacetin test to assess liver function of patients with cirrhosis from January 2002. The aim of this study was to explore the characteristic of this test for liver function evaluation and explore the correlation of this method with some clinical liver biochemical parameters and Child-Pugh score.

Six Minute Walk Test to assess functional capacity in chronic liver disease patients

AIM: To examine the utility of Six Minute Walk Test (6MWT) in patients with chronic liver disease (CLD). METHODS: Two hundred and fifty subjects between the ages of 18 and 80 (mean 47) years performed 6MWT and the Six Minute Walk Distance (6MWD) was measured. RESULTS: The subjects were categorized into four groups. Group A (n = 45) healthy subjects (control); group B (n = 49) chronic hepatitis B patients; group C (n = 54) chronic hepatitis C patients; group D (n = 98) liver cirrhosis patients. The four groups differed in terms of 6MWDs (P < 0.001). The longest distance walked was 421 ± 47 m by group A, then group B (390 ± 53 m), group C (357 ± 72 m) and group D (306 ± 111 m). The 6MWD correlated with age (r = -0.482, P < 0.01), hemoglobin (r = +0.373, P < 0.001) and albumin (r = +0.311, P < 0.001) levels. The Child-Pugh classification was negatively correlated with the 6MWD in cirrhosis (group D) patients (r = -0.328, P < 0.01). At the end of a 12 mo follow-up period, 15 of the 98 cirrhosis patients had died from disease complications. The 6MWD for the surviving cirrhotic patients was longer than for non-survivors (317 ± 101 vs 245 ± 145 m, P = 0.021; 95% CI 11-132). The 6MWD was found to be an independent predictor of survival (P = 0.024). CONCLUSION: 6MWT is a useful tool for assessing physical function in CLD patients. We suggest that 6MWD may serve as a prognostic indicator in patients with liver cirrhosis.

Indocyanine green clearance test and model for end-stage liver disease score of patients with liver cirrhosis

BACKGROUND: The indocyanine green (ICG) clearance test (clearance rate (K) and retention rate at 15 minutes (R(15))) is a sensitive indicator to evaluate liver function. The model for end-stage liver disease (MELD) score has emerged as a useful tool for estimating the mortality of patients awaiting liver transplantation and has recently been validated on patients with liver diseases of various etiologies and severity. In this study, we investigated the correlation between the ICG clearance test and MELD score of patients with liver cirrhosis. METHODS: From June 2007 to March 2008, 52 patients with liver cirrhosis admitted to our center were classified into Child-Pugh class A (8 patients), B (14) and C (30). The ICG clearance test (K value and R(15)) was performed by ICG pulse spectrophotometry (DDG-3300K), and the MELD scores of patients were calculated. RESULTS: As the Child-Pugh classification of liver function gradually deteriorated, the K value decreased, while R(15) and MELD score increased. There were significant statistical differences in K value, R(15) and MELD score in patients with different Child-Pugh classifications. Significant correlations were found between the parameters of the ICG clearance test (K value and R(15)) and MELD score. A negative correlation was observed between K value and MELD score (r=-0.892, P < 0.05), while a positive correlation was observed between R(15) and MELD score (r=0.804, P < 0.05). CONCLUSIONS: The ICG clearance test and MELD score are good parameters for evaluating liver function. Moreover, K value and R(15) have significant correlations with MELD score, especially the K value, which may be a convenient and appropriate indicator to evaluate liver function of patients with liver cirrhosis.

Advances in preoperative assessment of liver function

BACKGROUND： Postoperative liver failure remains a lifethreatening complication. Preoperative evaluation of liver function is essential in reducing the complications after hepatectomy. However, it is difficult to accurately evaluate liver function before surgery because of the limitations of the liver function tests available. Recent advances in liver function tests improved the ability to assess liver function. The present review was to analyze these methods and their advantages.DATA SOURCES： MEDLINE was searched using the terms of ＂liver function test＂, ＂liver function evaluation＂ and ＂galactosyl serum albumin＂. Relevant articles published in English and Chinese from 1961 to 2014 were reviewed.RESULTS： Although serological tests are used frequently in practice, they reflect the degree of total liver damage or function, not the remnant of liver function. Child-Pugh score and model for end-stage liver disease（MELD） score assess whole liver function, and are particularly useful in determining whether patients with hepatocellular carcinoma and cirrhosis are candidates for resection or transplantation, but cannot determine the safe extent or removal. The indocyanine green and other metabolic quantitative liver function tests can evaluate functional hepatocytes, making them more accurate in predicting liver function. Computed tomography（CT）volumetry can provide anatomic information on the remnant liver volume but not on functional volume. 99mTc-galactosyl serum albumin scintigraphy, combined with single photon emission computed tomography, CT and three-dimensional reconstruction, may be a better quantitative measure of liver function, especially of remnant liver function.CONCLUSIONS： Tests used to evaluate liver functional reserve and to predict surgical risk have limitations. 99mTc-galactosylserum albumin scintigraphy, which can more accurately evaluate the whole and regional liver function, may be promising in predicting resection margins and risks of liver failure.

Liver function in COVID-19 infection

Coronavirus disease 2019(COVID-19)disease affects multiple organs,including anomalies in liver function.In this review we summarize the knowledge about liver injury found during severe acute respiratory syndrome coronavirus 2(SARSCoV-2)infection with special attention paid to possible mechanisms of liver damage and abnormalities in liver function tests allowing for the evaluation of the severity of liver disease.Abnormalities in liver function observed in COVID-19 disease are associated with the age and sex of patients,severity of liver injury,presence of comorbidity and pre-treatment.The method of antiviral treatment can also impact on liver function,which manifests as increasing values in liver function tests.Therefore,analysis of variations in liver function tests is necessary in evaluating the progression of liver injury to severe disease.

Age, Gender Pattern and Liver Function Markers in Hepatitis B and C Seropositive Participants Attending a Health Facility in Yaba-Lagos, Nigeria

Background: Individuals with sero-positivity for Hepatitis B and C have been reported. Most seropositive individuals appear healthy. Liver function markers such as AST, ALT, ALP, Bilirubin and total protein levels are markers for assessing liver impairment. This study (i)assessed seroprevalence of HBV, HCV and both HBV and HCV (ii) HBV and or HCV seropositivity and age or gender, (iii) assess gender and liver function markers and (iv) update data on liver function and simple diagnostic markers. Materials and Methods: This was a prospective, cross sectional study of asymptomatic individuals presenting at the Clinical Diagnostic Laboratory of Nigerian Institute of Medical Research (NIMR), Yaba, Lagos, Nigeria from January 2018 to August 2020. Markers of liver function were investigated on hepatitis B and or C sero-positive and negative participants using TC Matrix Chemistry analyser (Teco Diagnostics, USA) and Biobase reagent Kits. Data were analyzed using descriptive and inferential statistics. Results: Out of 475 participants, 60.4% were males and 39.6% females. 53% of males and 32.5% of females were sero-positive for HBV while 32.5% of males and 14.5% of females were sero-positive for HCV. 75.3% and 76.1% of Age group 20 - 40 years were sero-positive for Hepatitis B and C respectively. Mean AST levels of 17.49 ± 13.69, 33.46 ± 93.42 and 19.82 ± 12.54 respectively among those sero-positive for HBV, HCV, and both HBV and HCV. Mean ALT levels of 17.68 ± 14.32, 40.26 ± 13.86 and 20.04 ± 12.78 respectively for HBV, HCV and both HBV and HCV sero-positive cases. Mean ALP levels were 77.52 ± 34.0 for HBV sero-positive cases, 82.04 ± 38.45 in HCV and 77.95 ± 30.48 in both HBV and HCV sero-positive cases. Mean Total Bilirubin levels of HBV, HCV and both HBV and HCV sero-positive cases were 13.25 ± 14.52, 14.98 ± 20.74, 10.58 ± 4.91 respectively while Mean Total protein levels were 77.24 ± 6.27 in HBV, 77.87 ± 5.56 in HCV and 77.0 ± 5.99 in both HBV and HCV sero-positive cases. ALP, bilirubin and total protein were all within normal reference values in HBV, HCV and HBV/HCV dual infections. AST and ALT values were significantly elevated in HCV seropositivity compared to HBV single and HBV/BCV dual seropositivity. Conclusion: 30% prevalence of HBV, HCV and both HBV and HCV were observed. Age 20 - 40 years was significantly higher in seropositivity for hepatitis B, C and B and C dual seropositivity. More males than females showed seropositivity for hepatitis B and C. There was no significant difference between gender and liver function markers. AST and ALT remain reliable markers of liver function.

Indocyanine green kinetics to assess liver function: Ready for a clinical dynamic assessment in major liver surgery?

Indocyanine green(ICG) kinetics(PDR/R15) used to quantitatively assess hepatic function in the perioperative period of major resective surgery and liver transplantation have been the object of an extensive, updated and critical review. New, non invasive bedside monitors(pulse dye densitometry technology) make this opportunity widely available in clinical practice. After having reviewed basic concepts of hepatic clearance, we analysed the most common indications ICG kinetic parameters have nowadays in clinical practice, focusing in particular on the diagnostic and prognostic role of PDR and R15 in the perioperative period of major liver surgery and liver transplantation. As recently pointed out, even if of extreme interest, ICG clearance parameters have still some limitations, to be considered when using these tests.

Non-invasive assessment of choledocholithiasis in patients with gallstones and abnormal liver function

AIM:To find a non-invasive strategy for detecting choledocholithiasis before cholecystectomy,with an acceptable negative rate of endoscopic retrograde cholangiopancreatography.METHODS:All patients with symptomatic gallstones were included in the study.Patients with abnormal liver functions and common bile duct abnormalities on ultrasound were referred for endoscopic retrograde cholangiopancreatography.Patients with normal ultrasoundwere referred to magnetic resonance cholangiopancreatography.All those who had a negative magnetic resonance or endoscopic retrograde cholangiopancreatography underwent laparoscopic cholecystectomy with intraoperative cholangiography.RESULTS:Seventy-eight point five percent of patients had laparoscopic cholecystectomy directly with no further investigations.Twenty-one point five percent had abnormal liver function tests,of which 52.8%had normal ultrasound results.This strategy avoided unnecessary magnetic resonance cholangiopancreatography in 47.2%of patients with abnormal liver function tests with a negative endoscopic retrograde cholangiopancreatography rate of 10%.It also avoided un-necessary endoscopic retrograde cholangiopancreatography in 35.2%of patients with abnormal liver function.CONCLUSION:This strategy reduces the cost of the routine use of magnetic resonance cholangiopancreatography,in the diagnosis and treatment of common bile duct stones before laparoscopic cholecystectomy.

Measurement of serum paraoxonase-1 activity in the evaluation of liver function

Paraoxonase-1 (PON1) is an esterase and lactonase synthesized by the liver and found in the circulation associated with high-density lipoproteins. The physiological function of PON1 seems to be to degrade specific oxidized cholesteryl esters and oxidized phospholipids in lipoproteins and cell membranes. PON1 is, therefore, an antioxidant enzyme. Alterations in circulating PON1 levels have been reported in a variety of diseases involving oxidative stress including chronic liver diseases. Measurement of serum PON1 activity has been proposed as a potential test for the evaluation of liver function. However, this measurement is still restricted to research and has not been extensively applied in routine clinical chemistry laboratories. The reason for this restriction is due to the problem that the substrate commonly used for PON1 measurement, paraoxon, is toxic and unstable. The recent development of new assays with non-toxic substrates makes this proposal closer to a practical development. The present editorial summarizes PON1 biochemistry and function, its involvement with chronic liver impairment, and some aspects related to the measurement of PON1 activity in circulation.