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.

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.

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.

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.

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.

HBV genotype characterization and distribution in patients with HBV-related liver diseases in Zhejiang Province, P. R. China: possible association of co-infection with disease prevalence and severity

BACKGROUND: There are 8 well-documented genotypes of hepatitis B virus (HBV) at this time point. Genotyping can be accomplished based on a partial sequence of hepatitis B virus (HBV) genome such as the pre-S or S gene. Several methods have been developed and used for HBV genotyping including direct sequencing, restriction fragment length polymorphism, line probe assay and enzyme-linked immunoassay. Recently, a novel, rapid and cost-effective genotyping method based on PCR amplification assay using type-specific primers that can identify all six major genotypes has been developed. This study was undertaken to characterise HBV genotypes and investigate the association between the prevalence of different genotypes and the severity of HBV-induced liver diseases. METHODS: Serum samples from carriers of HBV and patients with HBV-related liver diseases from Zhejiang Province were screened for viral serological markers using commercially available radioimmunoassay (RIA) and enzyme linked immunosorbent assay (ELISA) kits. Serum HBV DNA load was determined by real-time detection PCR. A type-specific primer based the nested-PCR method was employed in the HBV genotyping. The genotype results obtained were confirmed by direct sequencing of nested PCR amplicons of the pre-S region. Ten samples of each genotype (B and C) were sequenced. RESULTS: The survey on a cohort of 125 HBV carriers in and around Hangzhou City, Zhejiang Province showed the existence of HBV genotypes A (0.8%), B (48%), C (40.8%), D (0.8%), mixed B and C (9.6%) and an absence of E and F genotypes. Distribution of HBV genotypes in patients with liver diseases revealed a statistically insignificant higher prevalence of genotype B in mild chronic hepatitis (CH). Among the three genotypes B, C and mixed B/C infections 11 (73.3%), 3 (20%) and 1 (6.7%), (P< 0.05), respectively in subjects with moderate CH, genotype B was significantly predominant. The infection patterns for genotypes B, C and B/C mixed in (i) liver cirrhosis (LC) 4 (23.5%), 10 (58.8%) and3 (17.7%) and (ii) hepatocellular carcinoma (HCC) 2 (28.6%), 5(71.4%) and 0 (0.0%) respectively revealed a marked association of C genotype with liver disease; however, the association was statistically insignificant (P >0.05). Differences in positive rate of HBeAg for the three genotypes B, 16(30.8%), C, 27(51.9%), and mixed B/C, 9(17.3%) were significant (P < 0. 05 ) , with genotype C showing predominance. CONCLUSIONS : These findings show an interesting distribution of HBV A-D genotypes in Zhejiang Province. Furthermore, our results indicate a novel and markedly high prevalence of mixed B/C genotype infections in subjects with severe CH and LC, and a possible association of mixed B/C infections with the severity of liver diseases in this region of China's Mainland.

Ursodeoxycholic acid as a means of preventing atherosclerosis,steatosis and liver fibrosis in patients with nonalcoholic fatty liver disease

BACKGROUND Atherosclerotic cardiovascular disease(ASCVD)is the leading cause of mortality in patients with nonalcoholic fatty liver disease(NAFLD).Weight loss is a key factor for successful NAFLD and CVD therapy.Ursodeoxycholic acid(UDCA),which is one of the first-line therapeutic agents for treatment of NAFLD,is reported to have a beneficial effect on dyslipidemia and ASCVD risk because of antioxidant properties.AIM To evaluate the effects of 6 mo of UDCA treatment on hepatic function tests,lipid profile,hepatic steatosis and fibrosis,atherogenesis,and ASCVD risk in men and women with NAFLD,as well as to assess the impact of>5%weight reduction on these parameters.METHODS An open-label,multicenter,international noncomparative trial was carried out at primary health care settings and included 174 patients with ultrasound-diagnosed NAFLD who received 15 mg/kg/d UDCA for 6 mo and were prescribed lifestyle modification with diet and exercise.The efficacy criteria were liver enzymes,lipid profile,fatty liver index(FLI),noninvasive liver fibrosis tests(nonalcoholic fatty liver disease fibrosis score and liver fibrosis index),carotid intima-media thickness(CIMT),and ASCVD risk score.To test statistical hypotheses,the Wilcoxon test,paired t-test,Fisher’s exact test,and Pearson's chi-squared test were used.RESULTS The alanine aminotransferase(ALT)level changed by-14.1 U/L(-31.0;-5.3)from baseline to 3 mo and by-6.5 U/L(-14.0;0.1)from 3 to 6 mo.The magnitude of ALT,aspartate transaminase,and glutamyltransferase decrease was greater during the first 3 mo of treatment compared to the subsequent 3 mo(P<0.001,P<0.01,P<0.001,respectively).At 6 mo,in the total sample,we observed a statistically significant decrease in body weight and levels of FLI:84.9±10.4 vs 72.3±17.6,P<0.001,total cholesterol:6.03±1.36 vs 5.76±1.21,Р<0.001,lowdensity lipoprotein:3.86±1.01 vs 3.66±0.91,Р<0.001,and triglyceride:3.18(2.00;4.29)vs 2.04(1.40;3.16),Р<0.001.No effect on nonalcoholic fatty liver disease fibrosis score or liver fibrosis index was found.The CIMT decreased significantly in the total sample(0.985±0.243 vs 0.968±0.237,P=0.013),whereas the highdensity lipoprotein(Р=0.036)and 10-year ASCVD risk(Р=0.003)improved significantly only in women.Fifty-four patients(31%)achieved>5%weight loss.At the end of the study,the FLI decreased significantly in patients with(88.3±10.2 vs 71.4±19.6,P<0.001)and without>5%weight loss(83.5±10.3 vs 72.8±16.7,P<0.001).The changes in ALT,aspartate transaminase,glutamyltransferase,total cholesterol,and low-density lipoprotein levels were similar between the subgroups.CONCLUSION UDCA normalizes liver enzymes greatly within the first 3 mo of treatment,improves lipid profile and hepatic steatosis independent of weight loss,and has a positive effect on CIMT in the total sample and 10-year ASCVD risk in women after 6 mo of treatment.

Autoimmune liver diseases in systemic rheumatic diseases

Systemic rheumatic diseases(SRDs)are chronic,inflammatory,autoimmune disorders with the presence of autoantibodies that may affect any organ or system.Liver dysfunction in SRDs can be associated with prescribed drugs,viral hepatitis,alternative hepatic comorbidities and coexisting autoimmune liver diseases(AILDs),requiring an exclusion of secondary conditions before considering liver involvement.The patterns of overlap diseases depend predominantly on genetic determinants with common susceptible loci widely distributing in both disorders.In AILDs,it is important to identify the overlapping SRDs at an early stage since such a coexistence may influence the disease course and prognosis.Commonly co-occurring SRDs in AILDs are Sjögren syndrome(SS),rheumatoid arthritis(RA)or systemic lupus erythematosus(SLE)in autoimmune hepatitis(AIH),and SS,RA or systemic sclerosis in primary biliary cholangitis.Owing to different disease complications and therapies,it is imperative to differentiate between SLE liver involvement and SLE-AIH overlap disease.Therapeutic options can be personalized to control coexisting conditions of liver autoimmunity and rheumatic manifestations in AILD-SRD overlap diseases.The collaboration between hepatologists and rheumatologists can lead to significant advances in managing such a complex scenario.In this review,we provide a comprehensive overview on coexisting AILDs in different SRDs and the therapeutic approach in managing these overlap diseases.

Abnormal liver enzymes: A review for clinicians

Liver biochemical tests are some of the most commonly ordered routine tests in the inpatient and outpatient setting,especially with the automatization of testing in this technological era.These tests include aminotransferases,alkaline phosphatase,gamma-glutamyl transferase,bilirubin,albumin,prothrombin time and international normalized ratio(INR).Abnormal liver biochemical tests can be categorized based on the pattern and the magnitude of aminotransferases elevation.Generally,abnormalities in aminotransferases can be classified into a hepatocellular pattern or cholestatic pattern and can be further sub-classified based on the magnitude of aminotransferase elevation to mild[<5×upper limit of normal(ULN)],moderate(>5-<15×ULN)and severe(>15×ULN).Hepatocellular pattern causes include but are not limited to;non-alcoholic fatty liver disease/non-alcoholic steatohepatitis,alcohol use,chronic viral hepatitis,liver cirrhosis(variable),autoimmune hepatitis,hemochromatosis,Wilson’s disease,alpha-1 antitrypsin deficiency,celiac disease,medication-induced and ischemic hepatitis.Cholestatic pattern causes include but is not limited to;biliary pathology(obstruction,autoimmune),other conditions with hyperbilirubinemia(conjugated and unconjugated).It is crucial to interpret these commonly ordered tests accurately as appropriate further workup,treatment and referral can greatly benefit the patient due to prompt treatment which can improve the natural history of several of the diseases mentioned and possibly reduce the risk of progression to the liver cirrhosis.

Etiology and management of liver injury in patients with COVID-19

The outbreak of novel coronavirus disease 2019(COVID-19)has resulted in global emergence.With the expansion of related research,in addition to respiratory symptoms,digestive system involvement such as nausea,vomiting,and diarrhea have also been reported with COVID-19.Besides,abnormal liver function is also frequent in biochemical tests of COVID-19 patients,which is correlated with the severity and mortality of the disease course.The etiology of liver injury in patients with COVID-19 might include viral immunologic injury,drug-induced liver injury,the systemic inflammatory response,hypoxic hepatitis,and the exacerbation of preexisting liver disease.Although liver injuries in COVID-19 are often transient and reversible,health workers need to pay attention to preexisting liver disease,monitor liver function,strengthen supportive treatment,and reduce the chance of drug-induced liver injury.This article reviews the epidemiological characteristics,etiology,management,and preventive strategies for liver injury in patients with COVID-19.

Elevated liver enzymes portends a higher rate of complication and death in SARS-CoV-2

BACKGROUND Severe acute respiratory syndrome coronavirus 2,or coronavirus disease-2019(COVID-19),has infected millions worldwide since its discovery in Wuhan,China in December 2019,but little is still known about the disease process.Preliminary research in China notes liver function tests(LFTs)abnormalities are common in COVID-19 patients,suggesting decreased hepatic function,and that abnormalities in LFTs are related to complicated disease course and negative outcomes.However,there has been limited large-scale data assessing COVID-19’s association with liver dysfunction and negative outcomes.AIM To investigate how COVID-19 affects the liver function and disease course in patients infected with the virus treated at Henry Ford Hospital from March to September 2020.METHODS A total of 8028 patients infected with COVID-19 were identified and included in the study at a single academic center.Data from medical charts on laboratory testing including aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(AP),and bilirubin levels,past history of liver disease,and disease course indicators including hospital admission,intensive care unit(ICU)admission,intubation,and death were recorded and analyzed.Elevated liver enzymes were defined as ALT/AST greater than 60,AP greater than 150,or bilirubin greater than 1.5,super-elevated liver enzymes were defined as ALT/AST greater than 120,AP greater than 300,or bilirubin greater than 3.0.RESULTS A total of 8028 COVID-19 patients were identified and included in the study.Data from medical charts on LFTs(namely,AST,ALT,AP,and bilirubin levels),past history of liver disease,and disease course indicators(hospital/ICU admission,intubation,death)were recorded and analyzed.LFTs from 3937 patients were available for interpretation.45% were found to have elevated or super-elevated LFT.When compared to COVID-19 patients without elevated LFTs,this cohort was found to have significantly higher odds of hospital admittance,ICU admission,intubation,and death(all P<0.001).248(3.1%)had a history of liver disease.Those with elevated and super elevated LFTS had significantly higher odds of having a past history of liver disease(P<0.001).CONCLUSION The findings from this study suggest that in patients who have tested positive for COVID-19,those with elevated and super elevated liver enzyme levels have significantly higher odds of hospital admittance,ICU admittance,intubation and death in comparison to those COVID-19 patients without elevated liver enzyme levels.

Post-COVID-19 cholangiopathy:Systematic review

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic has had a profound impact on global health,primarily characterized by severe respiratory illness.However,emerging evidence suggests that COVID-19 can also lead to secondary sclerosing cholangitis(SC),referred to as post-COVID-19 cholangiopathy.AIM To synthesize currently reported cases to assess the current state of knowledge on post-COVID-19 cholangiopathy.METHODS Medical Subject Headings and Health Sciences Descriptors were used to retrieve relevant studies,which were combined using Boolean operators.Searches were conducted on electronic databases including Scopus,Web of Science,and MEDLINE(PubMed).Studies published in English,Spanish,or Portuguese were included,with no restrictions on the publication date.Additionally,the reference lists of retrieved studies were manually searched.Simple descriptive analyses were used to summarize the results.Then the data were extracted and assessed based on Reference Citation Analysis(https://www.referencecitationanalysis.com/).RESULTS The initial search yielded a total of 192 articles.After screening,85 articles were excluded due to duplication,leaving 107 articles for further review.Of these,63 full-length articles met the inclusion criteria and were included in the analyses.Most of the patients were male and exhibited elevated liver function tests(93.8%).Magnetic resonance imaging revealed duct thickening with contrast enhancement(47.7%),as well as beading of the intrahepatic ducts(45.7%)with peribiliary contrast enhancement on diffusion(28.7%).Liver biopsy results confirmed SC in most cases(74.4%).Sixteen patients underwent liver transplantation,with three CONCLUSION Post-COVID-19 cholangiopathy is a serious condition that is expected to become increasingly concerning in the coming years,particularly considering long COVID syndromes.Although liver transplantation has been proposed as a potential treatment option,more research is necessary to establish its efficacy and explore other potential treatments.

Abnormal liver function in children hospitalized with acute respiratory infection of adenoviruses:a retrospective study

Human adenoviruses(HAdVs)can cause acute hepatitis in immunocompromised patients.However,it is unclear whether HAdVs are contributors to hepatitis in immunocompetent children.In this study,the liver function test(LFT)results were retrospectively analyzed among children hospitalized(age<14 years)between January 2016 and October 2019 for acute respiratory infection caused by adenoviruses.Alanine transaminase(ALT)and aspartate aminotransferase(AST)levels were elevated in 7.74%and 46.89%of patients,respectively.All patients with>2 folds of the upper limit of ALT or AST levels were infected with HAdV-7 or HAdV-55.Significantly higher levels of ALT,AST,γ-glutamyl transpeptidase(γ-GT),and lower albumin levels were observed in the HAdV-7 infection group than in the HAdV-3 infection group.HAdV-55 infection led to significantly higherγ-GT,total bilirubin,and direct bilirubin levels than the other infection types.The records of four patients with serial monitoring of the LFT results were further analyzed.Multiple indicators remained abnormal during the entire hospitalization in these patients.These results indicate that HAdV infection is often accompanied by abnormal liver function,and HAdV-7 and HAdV-55 might be under-recognized contributors to hepatitis among children.

Clinical indicators for progression of nonalcoholic steatohepatitis to cirrhosis

Non-alcoholic fatty liver disease(NAFLD),is a disease spectrum characterized by fat accumulation in hepatocytes presenting as hepatic steatosis to advance disease with active hepatic inflammation,known as nonalcoholic steatohepatitis.Chronic steatohepatitis will lead to progressive hepatic fibrosis causing cirrhosis and increased risk for developing hepatocellular carcinoma(HCC).Fatty liver disease prevalence has increased at alarming rates alongside obesity,diabetes and metabolic syndrome to become the second most common cause of cirrhosis after alcohol related liver disease worldwide.Given this rise in prevalence,it is becoming increasingly more important to find non-invasive methods to diagnose disease early and stage hepatic fibrosis.Providing clinicians with the tools to diagnose and treat the full spectrum of NAFLD will help prevent known complications such as cirrhosis and HCC and improve quality of life for the patients suffering from this disease.This article discusses the utility of current noninvasive liver function testing in the clinical progression of fatty liver disease along with the imaging modalities that are available.Additionally,we summarize available treatment options including targeted medical therapy through four different pathways,surgical or endoscopic intervention.

Downregulation of endothelin-1 by somatostatin improves liver function of recipients undergoing adult-to-adult living donor liver transplantation

Background The aim of this study was to investigate the possible effect of somatostatin on the liver function of recipients undergoing living donor liver transplantation.Methods Forty recipients were randomized into group A （n=20） and group B （n=20）. Recipients in group A received no somatostatin whereas somatostatin was administrated for recipients in group B perioperatively. Liver function, the plasma concentration of endothelin-1 and nitric oxide, the intragraft expressions of endothelin-1 and inducible nitric oxide syntheses at 2 hours after declamping of the portal vein were compared between the two groups.Results Compared to group A, alanine transaminase values in group B were significantly reduced at 2 hours after portal vein declamping, at the end of the operation and postoperation day 1 （P 〈0.05）, whereas aspartate aminotransferase values in group B decreased at 30 minutes after portal vein clamping, at 2 hours after portal vein declamping and at the end of the operation （P 〈0.05）. Total bilirubin values in group B were reduced significantly at 2 hours after portal vein declamping and at the end of the operation when compared to group A （P 〈0.05）. Intragraft expression of endothelin-1 was significantly downregulated at 2 hours after declamping of the portal vein accompanied with a reduction of plasma concentration of endothelin-1 in the peripheral blood （P 〈0.05）.Conclusions Somatostatin had a protective effect on liver function during the early phase after declamping of portal vein for recipients undergoing living donor liver transplantation, and the possible mechanism might be partially attributed to the downregulation of endothelin-1.