Hemostatic and liver function parameters as COVID-19 severity markers.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a disease newly discovered in December 2019 which affects coagulation cascade and liver functions. The aim of this study was to investigate the potential of hemostatic and liver function parameters as severity markers in COVID-19 patients. This study was an observational analytic with cohort retrospective design using total sampling method. Data were retrieved from medical record of COVID-19 patients admitted to provincial hospital in Banda Aceh, Indonesia from March 2020 to March 2022. There were 1208 data eligible for the study after applying certain criteria. Mann-Whitney, logistic regression, and receiving operating characteristic (ROC) analyses were used to analysis the data. Thrombocyte count (p<0.001), prothrombin time (p<0.001), activated partial thromboplastin time (p<0.001), D-dimer (p<0.001), fibrinogen (p<0.001), aspartate aminotransferase (p<0.001), and alanine transaminase (p<0.001) significantly increased in severe compared to mild COVID-19 patients. After being adjusted, age (odds ratio (OR); 1.026 (95% confidence interval (CI): 1.016-1.037) was the most significant factor in predicting COVID-19 severity. Fibrinogen (cut-off 526.5 mg/L) was the best parameter associated with COVID-19 severity with 70% sensitivity and 66.4% specificity. Meanwhile, D-dimer (cut-off 805 ng/mL) had a sensitivity of 72.3% and specificity of 66.4%. Combining the parameters resulted in improved sensitivity to 82.0% with a slight decline of specificity to 65.5%. In conclusion, fibrinogen and D-dimer level on admission could be used as biomarkers in predicting COVID-19 prognosis. Routine monitoring and evaluation of laboratory testing especially D-dimer and fibrinogen could be implemented in order to reduce morbidity and mortality rate of COVID-19.

Organokines and liver enzymes in adolescent girls with polycystic ovary syndrome during randomized treatments.

Introduction: Polycystic ovary syndrome (PCOS) is often associated with metabolic-associated fatty liver disease (MAFLD). MAFLD has been associated with altered hepatic function, systemic dysmetabolism, and abnormal circulating levels of signaling molecules called organokines. Here, we assessed the effects of two randomized treatments on a set of organokines in adolescent girls with PCOS and without obesity, and report the associations with circulating biomarkers of liver damage, which were assessed longitudinally in the aforementioned studies as safety markers. Materials and methods: Liver enzymes [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT)] were assessed as safety markers in previous randomized pilot studies comparing the effects of an oral contraceptive (OC) with those of a low-dose combination of spironolactone-pioglitazone-metformin (spiomet) for 1 year. As a post hoc endpoint, the organokines fibroblast growth factor-21 (FGF21), diazepam-binding protein-1 (DBI), and meteorin-like protein (METRNL) were assessed by ELISA after 6 months of OC (N = 26) or spiomet (N = 28). Auxological, endocrine-metabolic, body composition (using DXA), and abdominal fat partitioning (using MRI) were also evaluated. Healthy, age-matched adolescent girls (N = 17) served as controls. Results: Circulating ALT and GGT levels increased during OC treatment and returned to baseline concentrations in the post-treatment phase; in contrast, spiomet treatment elicited no detectable changes in ALT and GGT concentrations. In relation to organokines after 6 months of treatment, (1) FGF21 levels were significantly higher in PCOS adolescents than in control girls; (2) DBI levels were lower in OC-treated girls than in controls and spiomet-treated girls; and (3) no differences were observed in METRNL concentrations between PCOS girls and controls. Serum ALT and GGT levels were directly correlated with circulating METRNL levels only in OC-treated girls (R = 0.449, P = 0.036 and R = 0.552, P = 0.004, respectively). Conclusion: The on-treatment increase in ALT and GGT levels occurring only in OC-treated girls is associated with circulating METRNL levels, suggesting enhanced METRNL synthesis as a reaction to the hepatic changes elicited by OC treatment. Clinical Trial Registration: https://doi.org, identifiers 10.1186/ISRCTN29234515, 10.1186/ISRCTN11062950.

FibroScan-aspartate transaminase: A superior non-invasive model for diagnosing high-risk metabolic dysfunction-associated steatohepatitis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) with hepatic histological NAFLD activity score ≥ 4 and fibrosis stage F ≥ 2 is regarded as "at risk" non-alcoholic steatohepatitis (NASH). Based on an international consensus, NAFLD and NASH were renamed as metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), respectively; hence, we introduced the term "high-risk MASH". Diagnostic values of seven non-invasive models, including FibroScan-aspartate transaminase (FAST), fibrosis-4 (FIB-4), aspartate transaminase to platelet ratio index (APRI), etc. for high-risk MASH have rarely been studied and compared in MASLD. AIM: To assess the clinical value of seven non-invasive models as alternatives to liver biopsy for diagnosing high-risk MASH. METHODS: A retrospective analysis was conducted on 309 patients diagnosed with NAFLD via liver biopsy at Beijing Ditan Hospital, between January 2012 and December 2020. After screening for MASLD and the exclusion criteria, 279 patients were included and categorized into high-risk and non-high-risk MASH groups. Utilizing threshold values of each model, sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV), were calculated. Receiver operating characteristic curves were constructed to evaluate their diagnostic efficacy based on the area under the curve (AUROC). RESULTS: MASLD diagnostic criteria were met by 99.4% patients with NAFLD. The MASLD population was analyzed in two cohorts: Overall population (279 patients) and the subgroup (117 patients) who underwent liver transient elastography (FibroScan). In the overall population, FIB-4 showed better diagnostic efficacy and higher PPV, with sensitivity, specificity, PPV, NPV, and AUROC of 26.9%, 95.2%, 73.5%, 72.2%, and 0.75. APRI, Forns index, and aspartate transaminase to alanine transaminase ratio (ARR) showed moderate diagnostic efficacy, whereas S index and gamma-glutamyl transpeptidase to platelet ratio (GPR) were relatively weaker. In the subgroup, FAST had the highest diagnostic efficacy, its sensitivity, specificity, PPV, NPV, and AUROC were 44.2%, 92.3%, 82.1%, 67.4%, and 0.82. The FIB-4 AUROC was 0.76. S index and GPR exhibited almost no diagnostic value for high-risk MASH. CONCLUSION: FAST and FIB-4 could replace liver biopsy as more effectively diagnostic methods for high-risk MASH compared to APRI, Forns index, ARR, S index, and GPR; FAST is superior to FIB-4.

Association Between Insulin Resistance Indices and Liver Function Parameters Among Women With Polycystic Ovary Syndrome.

OBJECTIVE: This study aimed to investigate whether polycystic ovary syndrome (PCOS) status changes the association between insulin resistance (IR) indices and liver function parameters among women. METHODS: This is a cross-sectional, population-based study. We selected 1101 subjects aged ≥20 years from participants of Tehran Lipid and Glucose Study (TLGS). All of them had known the status of PCOS, and all variables were related to the IR indices and liver function parameters. The main outcome measures were TG/HDL-C and triglyceride-glucose (TyG) and liver function parameters (hepatic steatosis index [HSI], alanine transaminase [ALT] and aspartate transaminase [AST]). RESULT: In the present study, there was no significant difference between the PCOS and the non-PCOS regarding the presence of liver function abnormalities. A model adjusted by age and BMI showed that the upper tertile of TyG index was positively associated with high AST (OR = 3.04 [95% CI: 1.20-7.68], p < 0.05), high ALT (4.76 [3.07-7.36], p < 0.05) and high HSI (8.44 [1.82-39.17], p < 0.05). Although the history of diabetes had a positive impact on elevated AST (1.66 [1.15, 2.40], p < 0.05), the third tertile of TG/HDL-C was associated with increased odds of elevated ALT (3.35 [2.21-5.06]) and HSI (6.55 [1.17-36.46]), whereas the second tertile of TG/HDL-C (OR = 2.65, CI 95%: 1.74-4.03) was also positively associated with elevated ALT. PCOS had no significant association with elevated liver function tests. CONCLUSION: The highest tertile of TyG index and the TG/HDL-C ratio as a surrogate of IR might play a role in detecting abnormalities of liver function parameters among women. However, PCOS status cannot change the association between IR and liver dysfunction.

Significance of serum ferritin and De Ritis ratio in non-alcoholic fatty liver disease as diagnostic markers.

Objectives: To ascertain the significance of serum ferritin and De Ritis ratio as diagnostic markers in patients of nonalcoholic fatty liver disease with and without type 2 diabetes mellitus. METHODS: The comparative cross-sectional study was conducted from February to October 2022 at the Radiology Department of Combined Military Hospital, Rawalpindi, Pakistan, and comprised individuals aged 30-65 who were divided into 3 groups. Healthy controls formed group I, non-alcoholic fatty liver disease patients without type 2 diabetes mellitus formed group II and non-alcoholic fatty liver disease patients with type 2 diabetes mellitus were in group III. Blood 5ml was withdrawn and assessed for alkaline phosphatase, aspartate transaminase, alanine transaminase and ferritin. De Ritis ratio was calculated and subjected to intergroup comparison. Data was analysed using SPSS 22. RESULTS: Of the 210 subjects, 110(52.4%) were males and 100(47.6%) were females, with 70(33.3%) in each of the three groups. Group I had 38(54.3%) females and 32(45.7%) males with mean age 37.50±4.513. In group II, there were 27(38.6%) females and 43(61.4%) males with mean age 45.86±9.646, while in group III there were 35(50%) females and 35(50%) males with mean age 54.01±9.243 years. Serum ferritin levels were significantly increased in patient groups II and III compared to control group I (p<0.05). De Ritis ratio was markedly raised in groups II and III compared to group I (p<0.05). Ferritin was significantly correlated to age, weight, height, fasting blood glucose, haemoglobin, alkaline phosphatase, aspartate aminotransferase, alanine transaminase and bilirubin (p<0.05). De Ritis ratio had a significant correlation with body mass index and fasting blood glucose (p<0.05). CONCLUSIONS: Serum ferritin and De Ritis ratio were found to be useful diagnostic indicators for non-alcoholic fatty liver disease, highlighting their importance in improving disease screening.

Synchronizing positive effect of vitamin C and chromium on hyper lipidemia, hyperglycemia, liver enzymes and BMI of diabetes mellitus type 2 patients.

This study investigates the combined effect of vitamin C and chromium on BMI, lipid profile, LFTs and HbA1c of Diabetes Mellitus type 2 patients. This is randomized controlled trial study. For this study a total of 60 patients (n=28 female, n=32 male) Diabetes Mellitus type 2 patients were selected. They were divided into treatment group (vitamin C (500mg) Chromium (200µg) and control group (placebo) comprising thirty patients per group. Mean age in control group and treatment group is 33± 5.729 and 33±7.017 respectively. Statistical analysis showed significant results of lipid profile; total cholesterol (mg/dl) 198±66.1 P=0.008, High-Density Lipoprotein 38±7.5, P<0.001, Low Density Lipoprotein (LDL) (mg/dl) 105.1±22.4, P=0.002 and Triglycerides 191±64.3, P=0.02 are respectively. Levels of serum ALT (u/l) (34.7±9.1, P<0.001) and AST (u/l) (31.6 ±8.6, P<0.001) were significantly lower as compared to control group. HbA1c percentages were also normalized (5.45±0.2, P<.001) as compared to group 2. BMI values were also improved (P=0.01) after treatment. Combined supplementation of vitamin C and chromium reduce the plasma lipid percentage, blood glucose levels and also improve the ALT and AST functions.

Aspartate Transaminase-to-Albumin Ratio (ATAR), a Novel Prognostic Index, Predicts Outcomes in Patients with Small-Cell Lung Cancer.

BACKGROUND: Small cell lung cancer (SCLC) is characterized by high invasion rates, rapid progression, and poor prognoses. Thus, identifying SCLC patients at high risk of progression and death is critical to improve long-term survival. In this study, the aspartate transaminase-to-albumin ratio (ATAR) was examined as a prognostic factor for SCLC patients. METHODS: We screened 196 SCLC patients from December 2013 to September 2022 at the Sichuan Cancer Hospital. The data was collected from patients' medical information as well as from their blood results during diagnosis. Using the Youden index as a cutoff value, patients were divided into high-risk（> 0.54) and low-risk (≤ 0.54) ATAR groups. We analyzed the prognostic factors for overall survival (OS) using the Kaplan-Meier method, univariate and multivariate analyses, Cox regression, and the C-index. RESULTS: There were 109 (55.6%) smokers among the patients, and the median OS was 17.55 months. The Kaplan-Meier analysis indicated that patients with high-risk ATAR had significantly lower OS (p < 0.0001). A multivariate analysis demonstrated that elevated ATAR is an independent adverse predictor of OS (p < 0.001, HR = 1.907). Our study found that ATAR is an independent predictor of survival outcomes in SCLC, which was superior to ALB, PNI, and SII in predicting outcomes in low-risk and high-risk groups (all p < 0.05). Models combining ATAR with ALB, PNI, and SII showed more powerful prognostic value than their corresponding original models. Moreover, the prognostic indicator ATAR can significantly stratify stage I - II and III - IV SCLC patients (p ＜ 0.05). CONCLUSIONS: Peripheral blood ATAR prognostic index can be used as an independent predictor of SCLC patients before treatment.

Sustained virological response in chronic hepatitis C patients by direct-acting antiviral treatment significantly reduces liver stiffness over 24 weeks posttreatment.

To investigate whether direct-acting antiviral (DAA) treatment affected liver fibrosis testing, including transient elastography (TE), aspartate aminotransferase-to-platelet ratio index (APRI), and Fibrosis-4 (FIB-4) index, after establishing a sustained virological response for 24 weeks. This prospective cohort study was conducted between October 1, 2019, and September 30, 2020, at Rajavithi Hospital, Bangkok, Thailand. All the patients had significant liver fibrosis (TE ≥ 7.0 kPa) at baseline and completed 12 weeks of DAA therapy. After achieving SVR, liver stiffness measurements were repeated for at least 24 weeks. The primary outcome was a > 30% improvement in TE score at the end of the study compared to baseline. A multivariate logistic regression model was used to identify the parameters associated with the primary outcome. Temporal changes in APRI and FIB-4 indices from baseline to 24 weeks posttreatment were also examined. A total of 110 chronic HCV patients were included in our cohort, of which 57 (52.3%) achieved the primary outcome. The median TE decreased from 15.05 (8.76-23.68) kPa at pretreatment to 9.60 (6.50-14.40) kPa at 24 weeks posttreatment (P < .001). Those who had a baseline TE ≥ 9.5 kPa had higher odds of meeting the primary outcome, and this remained significant after adjusting for age, sex, baseline body mass index, underlying diabetes mellitus, HCV genotype 3, baseline laboratory levels, and treatment regimens (OR 3.04; 95% CI 1.22-7.60, P = .017). Similar to TE, the median APRI and FIB-4 index displayed a considerable reduction from baseline to 24 weeks after successful therapy. Modern DAA treatment has been associated with considerable improvement in liver stiffness measured by TE in chronic HCV patients who achieve SVR, with roughly 52% of patients experiencing a reduction of > 30% in TE over 24 weeks posttreatment compared to baseline. This probably indicates early fibrosis regression, although the effect of resolution of inflammation after treatment completion cannot be ruled out.

A new model of portal vein thrombosis in rats with cirrhosis induced by partial portal vein ligation plus carbon tetrachloride and intervened with rivaroxaban.

BACKGROUND AND AIMS: Portal vein thrombosis (PVT) is a common complication of liver cirrhosis that can aggravate portal hypertension. However, there are features of both PVT and cirrhosis that are not recapitulated in most current animal models. In this study, we aimed to establish a stable animal model of PVT and cirrhosis, intervene with anticoagulant, and explore the related mechanism. METHODS: First, 49 male SD rats received partial portal vein ligation (PPVL), and 44 survival rats were divided into 6 groups: PPVL control group; 4-week, 6 -week, 8-week, and 10-week model group; and the rivaroxaban (RIVA)-treated group. The rats were intoxicated with or without carbon tetrachloride (CCl4) for 4-10 weeks. Seven normal rats were used as the normal controls. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and parameters for blood coagulation were all assayed with kits. Liver inflammation, collagen deposition and hydroxyproline (Hyp) levels were also measured. The extrahepatic macro-PVT was observed via portal vein HE staining, etc. The intrahepatic microthrombi was stained via fibrin immunohistochemistry. The portal blood flow velocity (PBFV) and diameter were detected via color Doppler ultrasound. Vascular endothelial injury was evaluated by von Willebrand Factor (vWF) immunofluorescence. Fibrinolytic activity was estimated by western blot analysis of fibrin and plasminogen activator inhibitor-1 (PAI-1). RESULTS: After PPVL surgery and 10 weeks of CCl4 intoxication, a rat model that exhibited characteristics of both cirrhosis and extra and intrahepatic thrombi was established. In cirrhotic rats with PVT, the PBFV decreased, both factors of pro- and anti-coagulation decreased, but with relative hypercoagulable state, vascular endothelial injured, and fibrinolytic activity decreased. RIVA-treated rats had improved coagulation function, increased PBFV and attenuated thrombi. This effect was related to the improvements in endothelial injury and fibrinolytic activity. CONCLUSIONS: A new rat model of PVT with cirrhosis was established through partial portal vein ligation plus CCl4 intoxication, with the characteristics of macrothrombi at portal veins and microthrombi in hepatic sinusoids, as well as liver cirrhosis. Rivaroxaban could attenuate PVT in cirrhosis in the model rats. The underlying mechanisms of PVT formation in the rat model and pharmacological action of rivaroxaban are related to the regulation of portal blood flow, coagulant factors, and vascular endothelial cell function.

Genetic and Lifestyle Risk Factors of Metabolic Dysfunction-Associated Fatty Liver Disease and Its Relationship with Premature Coronary Artery Disease: A Study on the Pars Cohort.

BACKGROUND: The main objective of this study is to identify the risk factors of metabolic dysfunction-associated fatty liver disease (MAFLD) in coronary artery disease (CAD) patients. METHODS: The present retrospective cohort study is part of the Pars Cohort Study (PCS). The participants were categorized as having MAFLD or not. The pattern of independent variables in patients was compared with those who did not have MAFLD. All variables were retained in the multivariable logistic regression model. RESULTS: Totally, 1862 participants with CAD were enrolled in this study. MAFLD was diagnosed in 647 (40.1%) participants. Gender, diabetes, hypertension, tobacco, opium, alcohol, age, weight, waist circumference, cholesterol, HDL, triglyceride, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were significantly different in MAFLD and non-MAFLD patients. Also, the results of multivariable logistic regression show male gender (OR=0.651, 95% CI: 0.470‒0.902, P value=0.01) and opium consumption (OR=0.563, 95% CI: 0.328‒0.968, P value<0.001) to be negative risk factors of MAFLD occurrence in CAD patients. Having diabetes (OR=2.414, 95% CI: 1.740-3.349, P value<0.001), high waist circumference (OR=1.078, 95% CI: 1.055‒1.102, P value<0.01), high triglyceride (OR=1.005, 95% CI: 1.001‒1.008, P value=0.006), and high ALT (OR=1.039, 95% CI: 1.026‒1.051, P value<0.01) were positive risk factors of MAFLD in CAD patients. CONCLUSION: Our study found that consuming opium decreases the likelihood of MAFLD in CAD patients, since these patients have decreased appetite and lower body mass index (BMI). On the other hand, female gender, having diabetes, high waist circumference, high triglyceride levels, and high ALT levels increase the probability of MAFLD in CAD patients.

Foot-and-mouth disease-associated myocarditis is age dependent in suckling calves.

Myocarditis is considered a fatal form of foot-and-mouth disease (FMD) in suckling calves. In the present study, a total of 17 calves under 4 months of age and suspected clinically for FMD were examined for clinical lesions, respiratory rate, heart rate, and heart rhythm. Lesion samples, saliva, nasal swabs, and whole blood were collected from suspected calves and subjected to Sandwich ELISA and reverse transcription multiplex polymerase chain reaction (RT-mPCR) for detection and serotyping of FMD virus (FMDV). The samples were found to be positive for FMDV serotype "O". Myocarditis was suspected in 6 calves based on tachypnoea, tachycardia, and gallop rhythm. Serum aspartate aminotransferase (AST), creatinine kinase myocardial band (CK-MB) and lactate dehydrogenase (LDH), and cardiac troponins (cTnI) were measured. Mean serum AST, cTn-I and LDH were significantly higher (P < 0.001) in < 2 months old FMD-infected calves showing clinical signs suggestive of myocarditis (264.833 ± 4.16; 11.650 ± 0.34 and 1213.33 ± 29.06) than those without myocarditis (< 2 months old: 110.00 ± 0.00, 0.06 ± 0.00, 1050.00 ± 0.00; > 2 months < 4 months: 83.00 ± 3.00, 0.05 ± 0.02, 1159.00 ± 27.63) and healthy control groups (< 2 months old: 67.50 ± 3.10, 0.047 ± 0.01, 1120.00 ± 31.62; > 2 months < 4 months: 72.83 ± 2.09, 0.47 ± 0.00, 1160.00 ± 18.44). However, mean serum CK-MB did not differ significantly amongst the groups. Four calves under 2 months old died and a necropsy revealed the presence of a pathognomic gross lesion of the myocardial form of FMD known as "tigroid heart". Histopathology confirmed myocarditis. This study also reports the relevance of clinical and histopathological findings and biochemical markers in diagnosing FMD-related myocarditis in suckling calves.

The Promising Effects of Erdosteine and Vitamin B in the Liver Ischemia/Reperfusion Model in Anesthetized Rats.

Background and Objectives: Erdosteine (Erd) is an antioxidant and anti-inflammatory drug. Vitamin B has been reported to exert anti-inflammatory and antioxidant effects. In this study, we investigated the effect of erdosteine and vitamin B complex on a liver ischemia/reperfusion (I/R) model. Materials and Methods: Thirty-two Wistar Albino male rats weighing 350-400 g were used. The animals were randomly selected and divided into four groups. The groups are as follows: first group (Sham), second group (I/R), third group (I/R + vit B), and fourth group (I/R + vit B + Erd). Rats were subjected to 45 min of hepatic ischemia, followed by a 45 min reperfusion period in the I/R and Vitamin B + Erd groups. An amount of 150 mg/kg/day of erdosteine was given orally for 2 days, and 0.05 mL/kg of i.p. vitamin B complex was given 30 min before the reperfusion. Serum biochemical parameters were measured. Serum Total Antioxidant Status (TAS) and Total Oxidant Status (TOS) were measured, and the Oxidative Stress Index (OSI) was calculated. Hepatic tissue samples were taken for the evaluation of histopathological features. Results: In terms of all histopathological parameters, there were significant differences in the I/R + vit B group and I/R + vit B + Erd group compared with the I/R group (p < 0.01). In terms of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), TNF-alpha, and IL-6 levels, there were significant differences between the I/R group and treatment groups (p < 0.01). The lowest TOS and OSI levels were obtained in the treatment groups, and these groups had statistically significantly higher TAS levels compared with the sham and I/R groups (p < 0.01). Conclusions: As a preliminary experimental study, our study suggests that these agents may have potential diagnostic and therapeutic implications for both ischemic conditions and liver-related diseases. These results suggest that the combination of vit B + Erd may be used to protect against the devastating effects of I/R injury. Our study needs to be confirmed by clinical studies with large participation.

Preliminary study on the diagnostic value of LEAP-2 and CK18 in biopsy-proven MAFLD.

Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) has become the leading cause of chronic liver disease. Liver biopsy, as the diagnostic gold standard, is invasive and has sampling bias, making it particularly important to search for sensitive and specific biomarkers for diagnosis. Cytokeratin 18 (CK18) M30 and M65 are products of liver cell apoptosis and necrosis, respectively, and liver-expressed antimicrobial peptide 2 (LEAP-2) is a related indicator of glucose and lipid metabolism. Correlation studies have found that all three indicators positively correlate with the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Through comparison of diagnostic values, it was found that CK18 M65 can better distinguish between healthy individuals and MAFLD; LEAP-2 can effectively distinguish MAFLD from other liver diseases, especially ALD.

Noninvasive models for the prediction of liver fibrosis in patients with chronic hepatitis B.

OBJECTIVE: To evaluate the diagnostic accuracy of aspartate aminotransferase(AST)/ alanine transaminase (ALT), AST to platelet ratio index (APRI), fibrosis-4 score (FIB-4) and gamma-glutamyl transpeptidase to platelet count ratio (GPR) for hepatic fibrosis in patients with chronic hepatitis B (CHB). METHODS: A total of 1210 CHB patients who underwent liver biopsy were divided into two groups: patients with no significant fibrosis (control group) and patients with significant fibrosis, and routine laboratory tests were retrospectively included. Logistic regression models were used for the prediction, and the area under the receiver operating characteristic (AUROC) was used to assess the diagnostic accuracy. RESULTS: A total of 631 (52.1%) and 275 (22.7%) patients had significant fibrosis (≥ S2) and advanced fibrosis (≥ S3), respectively. The GPR showed significantly higher diagnostic accuracy than that of APRI, FiB-4, and AST/ALT to predict ≥ S2(significant fibrosis) and ≥ S3 fibrosis(advanced fibrosis), with an AUROC was 0.69 (95%CI: 0.66-0.71) and 0.72 (0.69-0.75), respectively. After stratified by the status of HBeAg ( positive or negative), GPR, APRI, and FiB-4 showed improved predicting performance for significant fibrosis and advanced fibrosis in HBeAg positive patients, with the most significant improvement was shown for GPR in predicting significant fibrosis (AUROC = 0.74, 95%CI: 0.70-0.78). CONCLUSIONS: Among the four noninvasive models, GPR has the best performance in the diagnosis of hepatic fibrosis in CHB patients and is more valuable in HBeAg-positive patients.

Hepatic function markers as prognostic factors in patients with acute kidney injury undergoing continuous renal replacement therapy.

Acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT), secondary to cardiovascular disease and sepsis, is associated with high in-hospital mortality. Although studies have examined cardiovascular disease and sepsis in AKI, the association between AKI and hepatic functional impairment remains unclear. We hypothesized that hepatic function markers would predict mortality in patients undergoing CRRT. We included 1,899 CRRT patients from a multi-centre database. In Phase 1, participants were classified according to the total bilirubin (T-Bil) levels on the day of, and 3 days after, CRRT initiation: T-Bil < 1.2, 1.2 ≤ T-Bil < 2, and T-Bil ≥ 2 mg/dL. In Phase 2, propensity score matching (PSM) was performed to examine the effect of a T-Bil cutoff of 1.2 mg/dL (supported by the Sequential Organ Failure Assessment score); creating two groups based on a T-Bil cutoff of 1.2 mg/dL 3 days after CRRT initiation. The primary endpoint was total mortality 90 days after CRRT initiation, which was 34.7% (n = 571). In Phase 1, the T-Bil, aspartate transaminase (AST), alanine transaminase (ALT), and AST/ALT (De Ritis ratio) levels at CRRT initiation were not associated with the prognosis, while T-Bil, AST, and the De Ritis ratio 3 days after CRRT initiation were independent factors. In Phase 2, T-Bil ≥1.2 mg/dL on day 3 was a significant independent prognostic factor, even after PSM [hazard ratio: 2.41 (95% CI; 1.84-3.17), p < 0.001]. T-Bil ≥1.2 mg/dL 3 days after CRRT initiation predicted 90-day mortality. Changes in hepatic function markers in acute renal failure may enable stratification of high-risk patients.

Effectiveness of the ALT/AST ratio for predicting insulin resistance in a Korean population: A large-scale, cross-sectional cohort study.

Insulin resistance is a common pathophysiology in patients with type 2 diabetes mellitus, cardiovascular disease, and non-alcoholic fatty liver disease. Thus, screening for the risk of insulin resistance is important to prevent disease progression. We evaluated the alanine aminotransferase/aspartate aminotransferase (ALT/AST) ratio to predict insulin resistance in the general population, regardless of comorbidities. Datasets from the 2015, 2019, and 2020 Korea National Health and Nutrition Examination Surveys were used, and the following four indices were implemented to indicate insulin resistance: fasting serum glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), and ß-cell function. We analyzed the degree of association between the liver enzyme profile and insulin resistance indices using Pearson's correlation coefficient and determined the associations using linear or logistic regression analysis. Accordingly, ALT levels in both sexes were positively and consistently correlated with the four aforementioned insulin resistance indices in stratification analyses based on diabetes, dyslipidemia, alcohol consumption, and obesity status. In multivariate linear regression, when comparing with ALT levels, the ALT/AST ratio exhibited superior predictive performance for fasting serum glucose and HOMA-ß in Korean men and improved outcomes for all insulin resistance indices in Korean women. In this analysis that included a large community-based population, the ALT/AST ratio was a more useful predictive marker than the HOMA-IR. Regarding the predicted presence or absence of insulin resistance, the ALT/AST ratio could better predict HOMA-IR than the ALT level alone in Koreans. A simple, precise marker that represents the ALT/AST ratio could be a practical method to screen for insulin resistance in the general population, regardless of diabetes mellitus, alcohol intake, and sex.

A potential new way to facilitate HCV elimination: The prediction of viremia in anti-HCV seropositive patients using machine learning algorithms.

BACKGROUND AND STUDY AIMS: The present study was undertaken to design a new machine learning (ML) model that can predict the presence of viremia in hepatitis C virus (HCV) antibody (anti-HCV) seropositive cases. PATIENTS AND METHODS: This retrospective study was conducted between January 2012-January 2022 with 812 patients who were referred for anti-HCV positivity and were examined for HCV ribonucleic acid (HCV RNA). Models were constructed with 11 features with a predictor (presence and absence of viremia) to predict HCV viremia. To build an optimal model, this current study also examined and compared the three classifier data mining approaches: RF, SVM and XGBoost. RESULTS: The highest performance was achieved with XGBoost (90%), which was followed by RF (89%), SVM Linear (85%) and SVM Radial (83%) algorithms, respectively. The four most important key features contributing to the models were: alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB) and anti-HCV levels, respectively, while "ALB" was replaced by the "AGE" only in the XGBoost model. CONCLUSION: This study has shown that XGBoost and RF based ML models, incorporating anti-HCV levels and routine laboratory tests (ALT, AST, ALB), and age are capable of providing HCV viremia diagnosis with 90% and 89% accuracy, respectively. These findings highlight the potential of ML models in the early diagnosis of HCV viremia, which may be helpful in optimizing HCV elimination programs.

The diagnostic utility of FIB-4 as a non-invasive tool for liver fibrosis scoring among NAFLD patients: a retrospective cross-sectional study.

OBJECTIVE: Liver biopsy is the gold standard method to evaluate patients with non-alcoholic fatty liver disease (NAFLD). However, due to its several limitations and complications, a reliable and non-invasive marker is required to assess liver fibrosis. In this study, we compared the performance of the FIB-4 index [based on age, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels and platelets count] with the Scheuer scoring system of liver biopsies to evaluate the diagnostic utility of FIB-4 among NAFLD patients with different liver fibrosis severities. PATIENTS AND METHODS: A cross-sectional study was conducted at An-Najah National University Hospital (NNUH) in Palestine. The FIB-4 index was calculated using laboratory data for 128 NAFLD patients who underwent liver biopsies between November 2014 and July 2022. The results of FIB-4 were compared with the Scheuer scoring system of liver biopsies (using F0, F1+F2, F3+F4) to determine the sensitivity and specificity of FIB-4 in detecting and staging liver fibrosis. RESULTS: Out of 128 patients involved in our study, 49 of them had advanced fibrosis according to liver biopsy (F3+F4), where their FIB-4 indices showed 87% sensitivity at 1.45 cut off point and 87% specificity at 3.25 cut off point. CONCLUSIONS: The FIB-4 index may be used as a screening tool in the primary care setting. To raise awareness of liver diseases, this non-invasive, inexpensive, simple, and quick marker could identify people in need of further liver fibrosis evaluation and diagnosis.

Cytokine storm modulation using cholecalciferol and low dose gamma radiation in Escherichia coli infected mice.

This work investigates the efficiency of cholecalciferol and low dose gamma radiation in modulating cytokine storm through their impact on inflammatory and anti-inflammatory cytokine and protecting against lung and liver injuries. Male Swiss albino mice were exposed to 0.2 Gy gamma radiation/week for four consecutive weeks then injected intraperitoneally (i.p) with a single dose of 8.3 × 106 CFU Escherichia coli/g b.w. then injected i.p. with 1.0 mg/kg cholecalciferol (Vit D3) for 7 days starting 4 h after E. coli injection. The results revealed that Cholecalciferol and low dose gamma radiation caused significant depletion in the severity of E. coli infection (colony forming unit per milliliter), log10 of E. coli, Tumor necrosis factor alpha, Interleukin 6, VEGF, alanine aminotransferase, and aspartate aminotransferase levels and significant elevation in IL-10, IL-4, and HO-1. Immunohistochemical analysis of caspase-3 expression in lung tissue section showed low caspase-3 expression in cholecalciferol and low dose gamma radiation treated group. Histopathological examinations were performed in both lung and liver tissues which also emphasis the biochemical findings. Our results exhibit the importance of cholecalciferol and low dose gamma radiation in improving liver function and providing anti-inflammatory response in diseases causing cytokine storm.

Relapse following withdrawal of D-penicillamine from combination (D-penicillamine + zinc) therapy in hepatic Wilson disease.

OBJECTIVES: Long-term D-penicillamine (D-pen) therapy in Wilson disease (WD) has numerous adverse effects which advocates its withdrawal, but with an inherent risk of relapse. This prospective observational study was conducted with the objective of evaluating incidence of relapse following withdrawal of D-pen from combination (D-pen + zinc) therapy in maintenance phase of previously symptomatic hepatic WD. METHODS: Hepatic WD patients <18 years of age and on combination therapy for >2 years with 6 months of biochemical remission were included. Biochemical remission was defined as achievement of (i) aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤1.5 times upper limit of normal (ULN), (ii) serum albumin >3.5 g/dL, international normalized ratio (INR) <1.5 and (iii) 24-h urinary copper excretion (UCE) <500 mcg/day, nonceruloplasmin-bound-copper (NCC) <15 mcg/dL. After D-pen withdrawal, monthly liver function test (LFT) and INR and 3 monthly UCE and NCC were done till 1 year or relapse (elevation of AST/ALT/both >2 times ULN or total bilirubin >2 mg/dL), whichever occurred earlier. RESULTS: Forty-five patients enrolled with median combination therapy duration of 36 months. Sixty percent of them had their index presentation as decompensated cirrhosis. Fourteen patients (31.8%) relapsed (cumulative incidence: 4 at 3 months, 11 at 6 months, and 14 at 12 months after D-pen discontinuation). All relapsers had index presentation as decompensated cirrhosis. On Cox-regression, ALT at D-pen withdrawal was an independent predictor of relapse (hazard ratio [HR]: 1.077, 95% confidence interval [CI]: 1.014-1.145, p = 0.017) with area under the receiver operating characteristic (AUROC) of 0.860. ALT ≥40 U/L predicted risk of relapse with 85.7% sensitivity, 70.9% specificity. CONCLUSION: Incidence of relapse after withdrawal of D-pen from combination therapy is 31.8% in hepatic WD. ALT ≥40 U/L, at the time of D-pen stoppage, predicts future relapse.