Validation of FIB-6 score in assessment of liver fibrosis in chronic hepatitis B.

BACKGROUND: We recently developed a simple novel index called fibrosis 6 (FIB-6) using machine learning data analysis. We aimed to evaluate its performance in the diagnosis of liver fibrosis and cirrhosis in chronic hepatitis B (CHB). METHODS: A retrospective observational analysis of data was obtained from seven countries (Egypt, Kingdom of Saudi Arabia (KSA), Turkey, Greece, Oman, Qatar, and Jordan) of CHB patients. The inclusion criteria were receiving an adequate liver biopsy and a complete biochemical and hematological data. The diagnostic performance analysis of the FIB-6 index was conducted and compared with other non-invasive scores. RESULTS: A total of 603 patients were included for the analysis; the area under the receiver operating characteristic curve (AUROC) of FIB-6 for the discrimination of patients with cirrhosis (F4), compensated advanced chronic liver disease (cACLD) (F3 and F4), and significant fibrosis (F2-F4) was 0.854, 0.812, and 0.745, respectively. The analysis using the optimal cut-offs of FIB-6 showed a sensitivity of 70.9%, specificity of 84.1%, positive predictive value (PPV) of 40.3%, and negative predictive value (NPV) of 95.0% for the diagnosis of cirrhosis. For the diagnosis of cACLD, the results were 71.5%, 69.3%, 40.8%, and 89.2%, respectively, while for the diagnosis of significant fibrosis, the results were 68.3%, 67.5%, 59.9%, and 75.0%, respectively. When compared to those of fibrosis 4 (FIB-4) index, aspartate aminotransferase (AST)-to-platelet ratio index (APRI), and AST-to-alanine aminotransferase (ALT) ratio (AAR), the AUROC for the performance of FIB-6 was higher than that of FIB-4, APRI, and AAR in all fibrosis stages. FIB-6 gave the highest sensitivity and NPV (89.1% and 92.4%) in ruling out cACLD and cirrhosis, as compared to FIB-4 (63.8% and 83.0%), APRI (53.9% and 86.6%), and AAR (47.5% and 82.3%), respectively. CONCLUSIONS: The FIB-6 index could be used in ruling out cACLD, fibrosis, and cirrhosis with good reliability.

Assessment of the Relationship Between Liver Enzymes and Cardiovascular Disease: A Study in Bangladeshi Adults.

OBJECTIVES: Elevated liver enzyme levels are suggested to be associated with an increased risk of cardiovascular disease (CVD). However, few studies have explored the relationship between liver enzymes and myocardial infarction (MI). This study aimed to evaluate the potential association of elevated liver enzymes with MI within a population group in Bangladesh. METHODS: In this cross-sectional study, 348 participants were enrolled, 189 with MI in the CVD group and 159 in the control group. Serum levels of liver enzymes (AST, ALT and GGT) and other biochemical parameters were measured using standard methods. Multivariate logistic regression models were applied to determine the associations between elevated liver enzymes and CVD. RESULT: In the CVD group, 51.6%, 30.9% and 67.7% of individuals had elevated serum AST, ALT and GGT levels, respectively. On the contrary, the control group had 17.0%, 15.1% and 35.2% of individuals with high serum AST, ALT and GGT levels, respectively. Overall, 71.8% of the subjects in the CVD group and 44.7% of the subjects in the control group had at least one or more elevated liver enzymes (p < 0.001). The mean level of all three liver enzymes was significantly higher in the CVD group than in the control group (p < 0.001). In both the CVD and control groups, males had higher levels of liver enzymes than females. In the regression models, the serum levels of AST, ALT and GGT showed a positive and independent association with the prevalence of CVD (p < 0.001). However, GGT showed the strongest association among the three enzymes. CONCLUSIONS: This study shows a high prevalence of liver enzyme abnormalities in individuals with CVD. Serum levels of AST, ALT and GGT were independently associated with the prevalence of CVD. This suggests that measuring liver enzyme levels could be a useful marker in predicting CVD at an early stage.

Genome-wide association study identifies multiple loci influencing duck serum biochemical indicators in the laying period.

1. Laying performance is an important economic trait in poultry. The blood is essential in transporting nutrients to the yolk and albumen and is necessary for egg formation.2. This study calculated the phenotypic relationships of duck egg quality, egg production efficiency and 22 serum parameters in the egg-laying stage. Using a variety of methodologies, a genome-wide association study (GWAS) was carried out to uncover the genetic foundations of the 22 serum biochemical markers of laying ducks.3. Spearman correlation coefficients between the egg production (226-329 per day) and the serum parameters were all weak, being less than 0.3. This analysis was done on 22 serum parameters, with total protein (TP), total triglycerides (TG), calcium (Ca) and phosphorous (P) having the highest correlation coefficients (r = 0.56-0.88). The coefficients for blood markers, such as total cholesterol (CHOL), total bilirubin (TBIL), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) varied from 0.70-0.94.4. Based on single-marker single-trait genome-wide analyses by a mixed linear model program of EMMAX, nine candidate genes were associated with enzyme traits (AST/ALT aspartate transaminase/glutamic-pyruvic transaminase, creatine kinase) and 19 candidate genes were associated with metabolism and protein-related serum parameters (glucose, total bile acid, uric acid (UA), albumin (ALB).5. The mvLMM (multivariate linear mixed model) of GEMMA software was used to carry out multiple trait integrated GWAS. Two candidate genes were found in the TP-TG-CA-P analysis and seven candidate genes in the CHOL_LDL-C_HDL-C_TBIL study. There was a high genetic correlation between the two groups.

Assessment of the diagnostic accuracy of noninvasive scoring tools in predicting moderate-to-severe steatohepatitis via ultrasonography in asymptomatic healthy subjects admitted to family medicine outpatient clinics.

OBJECTIVE: Efficacies of the noninvasive scoring tools in screening and diagnosing nonalcoholic fatty liver disease (NAFLD) remain controversial. Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, AST-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) index are the most frequently used parameters for differentiating moderate and severe steatohepatitis. In this context, the objective of this study is to evaluate the diagnostic accuracy of noninvasive tools in predicting moderate-to-severe steatohepatitis via ultrasonography in asymptomatic healthy subjects admitted to family medicine outpatient clinics. PATIENTS AND METHODS: The population of this retrospective study consisted of healthy individuals tested within the scope of a medical check-up program between January and July 2021. All participants included in the study underwent relevant laboratory tests and liver ultrasonography (US). Steatohepatitis was graded using the US images as normal (grade 0), mild (grade 1), moderate (grade 2), and severe (grade 3). The participants with grade 0 and 1 steatohepatitis were categorized as Group 1, whereas those with grade 2 and 3 steatohepatitis (NAFLD) were categorized as Group 2. Any relationship between the aminotransferase/alanine aminotransferase (AST/ALT), AST-to-platelet ratio index (APRI), and fibrosis-4 index (FIB-4) parameters and the diagnostic powers thereof were analyzed based on the collected data. RESULTS: The mean age of the study sample (n=408) was 46.1±12.7 years. There were 352 (86.3%) and 56 individuals in Groups 1 and 2, respectively. Platelet-to-lymphocyte ratio (PLR) and AST/ALT values were significantly higher, whereas APRI values were significantly lower in Group 1 than in Group 2 (p=0.004, p<0.001, and p<0.001, respectively). There were significant correlations between the presence of NAFLD and PLR values of ≤90.78 [area under the curve (AUC)=0.619, 95% confidence interval (CI): 0.570-0.666, p=0.007], AST/ALT values of ≤0.91 (AUC=0.802, 95% CI: 0.760-0.840, p<0.001), and APRI values of >0.22 (AUC=0.687, 95% CI: 0.640-0.732, p<0.001). CONCLUSIONS: The composite noninvasive indices, including PLR, AST/ALT, and APRI, can be beneficial in predicting NAFLD in healthy individuals.

AST/ALT ratio, APRI, and FIB-4 compared to FibroScan for the assessment of liver fibrosis in patients with chronic hepatitis B in Bandar Abbas, Hormozgan, Iran.

BACKGROUND: Chronic hepatitis B (CHB) is a significant risk factor for liver-related disorders. Hepatic fibrosis staging by liver biopsy in these patients can lead to complications. This study aimed to compare aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, AST to platelet ratio index (APRI), and fibrosis-4 (FIB-4) with FibroScan results for the evaluation of hepatic fibrosis in CHB patients. METHODS: This cross-sectional study included patients with CHB referred to the outpatient clinics of Bandar Abbas, Hormozgan, Iran, in 2021. The age and sex of the participants were noted. FibroScan evaluation was done for all subjects. Moreover, AST, ALT, and platelet counts were measured in their blood samples within one month of the FibroScan evaluation. RESULTS: Of the 267 CHB patients evaluated in the present study (mean age: 45.45 ± 18.16 years), 173 (64.8%) were male. According to FibroScan results, 65 CHB patients (24.3%) had F1, 53 (19.9%) F2, 38 (14.2%) F3, and 20 (7.5%) F4 liver fibrosis. There was a significant correlation between FibroScan results and the three indices of AST/ALT ratio, APRI, and FIB-4 (P < 0.001), with the strongest correlation between FibroScan results and APRI (r = 0.682). With an area under the receiver operating characteristic (AUROC) curve of 0.852 (95% confidence interval [CI] 0.807; 0.897, P < 0.001), APRI ≥ 0.527 had the best diagnostic accuracy (77.15%) for the detection of any grade of liver fibrosis. Although the AUROC curve of APRI and FIB-4 was similar (0.864) for distinguishing between F3/F4 and F0-F2 of liver fibrosis, FIB-4 had the best diagnostic accuracy (82.02%). CONCLUSIONS: APRI can rule out 95.4% of F3/F4 of liver fibrosis and rule in any grade of liver fibrosis in CHB patients by 90.78%. Therefore, APRI appears to be the best substitute for FibroScan in the assessment of liver fibrosis in patients with CHB.

Noninvasive assessment of liver disease severity in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes.

BACKGROUND AND AIMS: We evaluated the diagnostic accuracy of simple, noninvasive tests (NITs) in NAFLD patients with type 2 diabetes (T2D). METHODS AND RESULTS: This was an individual patient data meta-analysis of 1780 patients with biopsy-proven NAFLD and T2D. The index tests of interest were FIB-4, NAFLD Fibrosis Score (NFS), aspartate aminotransferase-to-platelet ratio index, liver stiffness measurement (LSM) by vibration-controlled transient elastography, and AGILE 3+. The target conditions were advanced fibrosis, NASH, and fibrotic NASH(NASH plus F2-F4 fibrosis). The diagnostic performance of noninvasive tests. individually or in sequential combination, was assessed by area under the receiver operating characteristic curve and by decision curve analysis. Comparison with 2278 NAFLD patients without T2D was also made. In NAFLD with T2D LSM and AGILE 3+ outperformed, both NFS and FIB-4 for advanced fibrosis (area under the receiver operating characteristic curve:LSM 0.82, AGILE 3+ 0.82, NFS 0.72, FIB-4 0.75, aspartate aminotransferase-to-platelet ratio index 0.68; p < 0.001 of LSM-based versus simple serum tests), with an uncertainty area of 12%-20%. The combination of serum-based with LSM-based tests for advanced fibrosis led to a reduction of 40%-60% in necessary LSM tests. Decision curve analysis showed that all scores had a modest net benefit for ruling out advanced fibrosis at the risk threshold of 5%-10% of missing advanced fibrosis. LSM and AGILE 3+ outperformed both NFS and FIB-4 for fibrotic NASH (area under the receiver operating characteristic curve:LSM 0.79, AGILE 3+ 0.77, NFS 0.71, FIB-4 0.71; p < 0.001 of LSM-based versus simple serum tests). All noninvasive scores were suboptimal for diagnosing NASH. CONCLUSIONS: LSM and AGILE 3+ individually or in low availability settings in sequential combination after FIB-4 or NFS have a similar good diagnostic accuracy for advanced fibrosis and an acceptable diagnostic accuracy for fibrotic NASH in NAFLD patients with T2D.

Non-invasive fibrosis markers for assessment of liver fibrosis in chronic hepatitis delta.

Assessment of liver fibrosis by non-invasive means is clinically important. Studies in chronic hepatitis delta (CHD) are scarce. We evaluated the performance of eight serum fibrosis markers [fibrosis-4 score (FIB-4), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), age-platelet index (API), AST-to platelet-ratio-index (APRI), Goteborg University Cirrhosis Index (GUCI), Lok index, cirrhosis discriminant score (CDS) and Hui score] in CHD and chronic hepatitis B (CHB). Liver stiffness was assessed by transient elastography (TE) in CHD. The ability of fibrosis markers to detect significant fibrosis and cirrhosis were evaluated in 202 CHB and 108 CHD patients using published and new cut-offs through receiver operating characteristics (ROC) analysis. The latter was also applied to obtain cut-offs for TE. APRI, Fib-4, API and Hui score were assessed for significant fibrosis, and APRI, GUCI, Lok index, CDS and AAR for cirrhosis determination. Fibrosis markers displayed weak performance in CHB for significant fibrosis with area under ROC (AUROC) curves between 0.62 and 0.71. They did slightly better for CHD. TE displayed an AUROC of 0.92 and performed better than serum fibrosis markers (p < 0.05 for fibrosis markers). For cirrhosis determination, CDS and Lok Index displayed an AUROC of 088 and 0.89 in CHB and GUCI, Lok index and APRI displayed AUROCs around 0.90 in CHD. TE displayed the best AUROC (0.95). Hence TE is superior to serum fibrosis markers for diagnosing significant liver fibrosis and cirrhosis. GUCI, Lok index and APRI displayed a reasonable performance in CHD, which needs further confirmation.

Development and validation of a potential biomarker to improve the assessment of liver fibrosis progression in patients with chronic hepatitis B.

We aimed to develop and validate a novel combined score to improve the assessment of liver fibrosis progression in patients with chronic hepatitis B (CHB). In this study, a total of 331 CHB patients from three cohorts who underwent liver biopsy were enrolled, and the Scheuer system was used for liver fibrosis classification. The combined score was derived by principal component analysis of key differentially expressed genes. For significant liver fibrosis (≥S2), the areas under the receiver operating characteristics curves (AUROCs) of the combined score were 0.838, 0.842, and 0.881 in the three cohorts, respectively. And for advanced liver fibrosis (≥S3), the AUROCs were 0.794, 0.801, and 0.901, respectively. Compared with the results of AUROCs for aspartate aminotransferase≥to≥platelet ratio (APRI) and fibrosis index based on four factors (FIB-4) in the validation cohorts, better clinical diagnostic value for assessing the progression of liver fibrosis was found in the combined score. Additionally, univariate ordered logistic regression analysis indicated that the combined score could serve as a more superior and stable risk factor than APRI and FIB-4 in the assessment of liver fibrosis. For CHB patients with normal alanine aminotransferase (ALT), our results further emphasized the diagnostic value of the combined score for significant fibrosis (≥S2) and advanced fibrosis (≥S3). Moreover, it was found that patients with the high combined score, who were associated with the advanced fibrosis stage, had higher levels of drug sensitivity and immune checkpoint expression. In conclusion, the novel combined score could serve as a potential biomarker and contribute to improving the assessment of fibrosis stage in CHB patients.

Reliability of Non-invasive Liver Fibrosis Assessment Tools Versus Biopsy in Pre- and Post-bariatric Surgery Patients with Non-alcoholic Fatty Liver Disease.

PURPOSE: Liver biopsy (LBx) remains the gold standard to assess fibrosis in non-alcoholic fatty liver disease (NAFLD). Biochemical markers are also useful, but their reliability is not clear in patients with morbid obesity. We assessed the performance of six non-invasive fibrosis assessment tools before and after bariatric surgery (BSx) using LBx. MATERIALS AND METHODS: This is a cross-sectional and prospective cohort study. LBx was performed at the time of BSx and 12-month post-operatively and assessed using the Brunt system. Clinical and biochemical measurements were collected at the same time points and six non-invasive fibrosis assessment tools were calculated. RESULTS: One hundred seventy patients had BSx; 79.4% female; age was 46.6 ± 9.8 years, and BMI was 48.6 ± 7.5 kg/m2. From liver histology, 88% had F0-F2 and 11.2% F3-F4. At BSx, aspartate aminotransferase to platelet ratio index (APRI) and FIB-4 had better accuracy (0.86 and 0.88) with specificity of 96.6% and 94.0% and negative predictive values (NPV) of 88.9% and 93.7%. However, sensitivity (6.7% and 40.0%) and positive predictive values (PPV) (20.0% and 46.2%) were low. Twelve months post-surgery (n = 54), 88.9% of patients had F0-F2 and 11.1% had F3-F4. Fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS) had the best accuracy (0.79 and 0.77) with specificity of 83.7% and 86.9% and NPV of 92.3% and 86.9%. However, sensitivity (25% and 0%) and PPV (12.5% and 0%) were low. CONCLUSION: Overall, FIB-4, APRI, and NFS showed similar performances with higher accuracy, specificity, and NPV. Sensitivity and PPV were low. These tests are more useful at excluding advanced fibrosis.

Non-invasive liver fibrosis assessment: is transient elastography mandatory?

Real-time elastography (RTE) is a conventional ultrasonography-based liver stiffness assessment technique developed in chronic viral hepatitis. Evidence of its applicability in other aetiologies is lacking. This study aims to determine RTE diagnostic accuracy for advanced fibrosis in compensated chronic liver disease (cCLD) and to compare it with the biochemical scores FIB-4 and APRI, using transient elastography (TE) as the gold standard. A single center cross-sectional study including cCLD patients was conducted. RTE with assessment of Liver Fibrosis Index and TE were performed in the same day by different operators blind to the other technique result. The scores FIB-4 and APRI were calculated. Fibrosis cut-off values were inferred from previous evidence.

The Evaluation of Clinical Status of Endoscopic Retrograde Cholangiography for the Placement of Metal and Plastic Stents in Cholangiocarcinoma Therapy.

Objective: Cholangiocarcinoma is a common malignant tumor that occurs in the bile duct system, which can be treated by using the endoscopic retrograde cholangiography (ERCP). This study was aimed at exploring the therapeutic effect of ERCP with metal stent and plastic stent for cholangiocarcinoma. Methods: The clinical data of 71 patients with cholangiocarcinoma treated by ERCP in our hospital from June 2020 to October 2021 were retrospectively analyzed. According to different stent types, the patients were divided into plastic stent group (n = 43) and metal stent group (n = 28). Patients in the plastic stent group and metal stent group were received with plastic stent and metal stent, respectively. The indexes of liver function (serum alkaline phosphatase (ALT), direct bilirubin (DBIL), glutamic oxaloacetic transaminase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL)), postoperative complications, success rate of stent implantation, and survival time of patients in the two groups were determined. Logistic multivariate regression analysis was used to analyze the prognostic factors of postoperative cholangiocarcinoma. Results: The liver function indexes of the two groups were significantly improved after treatment with the stent, in which the ameliorative effect in the metal stent group was better than that in the plastic stent group (P < 0.05). The incidence of postoperative complications in the plastic stent group and the metal stent group was 53.49% and 14.29%, respectively, and the success rate of stent placement was 60.47% and 96.43%, respectively. The incidence of complications in the metal stent group was lower than that in the plastic stent group, and the success rate of stent placement was higher than that in the plastic stent group (P < 0.05). The median survival time of patients in the plastic stent group and the metal stent group was 8.15 and 11.83 months, respectively. The survival time of patients in the metal stent group was longer than that of the plastic stent group. The median survival time of patients with types I, II, III, and IV was 12.73, 11.54, 10.57, and 9.36 months, respectively. The survival time of patients with stage I was significantly higher than that of patients with types II, III, and IV. There was an inverse relationship between the disease type and the survival time of patients. Logistic multivariate regression analysis showed that tumor diameter ≥ 5 cm, portal vein invasion, lymph node metastasis, and classification of hilar cholangiocarcinoma were the risk factors (P < 0.05) and metal stent type was the protective factor (P < 0.05). Conclusion: In the clinical treatment of patients with cholangiocarcinoma, the placement of metal stent and plastic stent under ERCP plays an important role. The placement of the metal stent under ERCP has a higher success rate and better prognosis and can prolong the survival time of patients to a greater extent, but the price of the metal stent is relatively expensive. For patients with an expected survival period of more than 4-6 months, the metal stent should be considered; otherwise, the plastic stent can be used to maintain cost-effectiveness. Therefore, it is necessary to comprehensively analyze the patient's economic affordability, expected survival time, stent drainage time, and personal needs and then select an appropriate treatment method.

SARS-COV-ATE risk assessment model for arterial thromboembolism in COVID-19.

Patients with SARS-CoV-2 infection are at an increased risk of cardiovascular and thrombotic complications conferring an extremely poor prognosis. COVID-19 infection is known to be an independent risk factor for acute ischemic stroke and myocardial infarction (MI). We developed a risk assessment model (RAM) to stratify hospitalized COVID-19 patients for arterial thromboembolism (ATE). This multicenter, retrospective study included adult COVID-19 patients admitted between 3/1/2020 and 9/5/2021. Among 3531 patients from the training cohort, 15.5% developed acute in-hospital ATE, including stroke, MI, and other ATE, compared to 13.4% in the validation cohort. The 16-item final score was named SARS-COV-ATE (Sex: male = 1, Age [40-59 = 2, > 60 = 4], Race: non-African American = 1, Smoking = 1 and Systolic blood pressure elevation = 1, Creatinine elevation = 1; Over the range: leukocytes/lactate dehydrogenase/interleukin-6, B-type natriuretic peptide = 1, Vascular disease (cardiovascular/cerebrovascular = 1), Aspartate aminotransferase = 1, Troponin-I [> 0.04 ng/mL = 1, troponin-I > 0.09 ng/mL = 3], Electrolytes derangement [magnesium/potassium = 1]). RAM had a good discrimination (training AUC 0.777, 0.756-0.797; validation AUC 0.766, 0.741-0.790). The validation cohort was stratified as low-risk (score 0-8), intermediate-risk (score 9-13), and high-risk groups (score ≥ 14), with the incidence of ATE 2.4%, 12.8%, and 33.8%, respectively. Our novel prediction model based on 16 standardized, commonly available parameters showed good performance in identifying COVID-19 patients at risk for ATE on admission.

Using FIB-4 score as a screening tool in the assessment of significant liver fibrosis (F2) in patients with transfusion-dependent beta thalassaemia: a cross-sectional study.

OBJECTIVE: To evaluate the performance of the fibrosis-4 (FIB-4) score as a screening tool to detect significant liver fibrosis (F2) compared with transient elastography (TE), among chronic transfusion-dependent beta-thalassaemia (TDT) patients in a resource-poor setting. DESIGN: A cross-sectional study. SETTING: Adolescent and Adult Thalassaemia Care Centre (University Medical Unit), Kiribathgoda, Sri Lanka. PARTICIPANTS: 45 TDT patients who had undergone more than 100 blood transfusions with elevated serum ferritin >2000 ng/mL were selected for the study. Patients who were serologically positive for hepatitis C antibodies were excluded. OUTCOME MEASURES: TE and FIB-4 scores were estimated at the time of recruitment in all participants. Predefined cut-off values for F2, extracted from previous TE and FIB-4 scores studies, were compared. A new cut-off value for the FIB-4 score was estimated using receiver operating characteristics curve analysis to improve the sensitivity for F2 prediction. RESULTS: Of the selected 45 TDT patients, 22 (49%) were males. FIB-4 score showed a significant linear correlation with TE (r=0.52;p<0.0003). The FIB-4 score was improbable to lead to a false classification of TDT patients to have F2 when the FIB-4 cut-off value was 1.3. On the other hand, it had a very low diagnostic yield in missing almost all (except one) of those who had F2. Using a much-lowered cut-off point of 0.32 for FIB-4, we improved the pick-up rate of F2 to 72%. CONCLUSIONS: Regardless of the cut-off point, the FIB-4 score cannot be used as a good screening tool to pick up F2 in patients with TDT, irrespective of their splenectomy status. On the contrary, at a 1.3 cut-off value, though FIB-4 is a very poor detector for F2 fibrosis, it will not erroneously diagnose F2 fibrosis in those who do not have it.

Assessment of Clinical Outcomes, Clinical Manifestations, and Risk Factors for Hepatic Infarction After Transjugular Intrahepatic Portosystemic Shunt Placement (TIPS): A Retrospective Comparative Study.

PURPOSE: To describe the imaging findings of hepatic infarction after transjugular intrahepatic portosystemic shunt (TIPS) placement and identify risk factors, clinical manifestations, and outcomes of infarction after TIPS. MATERIALS AND METHODS: In this retrospective analysis of a TIPS registry (1995-2021), cirrhotic patients with hepatic infarction (n = 33) and control patients without infarct (n = 33) after TIPS were identified. Laboratory values, ultrasound findings, and clinical variables were compared between groups to identify risk factors and differences in outcomes. A Cox proportional hazards regression model with propensity score was used to assess the effect of hepatic infarction on mortality and acute-on-chronic liver failure (ACLF) score. RESULTS: Hepatic infarction involved the right posterior segments (segments VI or VII) in 32 of 33 patients. Prolonged vasopressor requirement (p = 0.003) and intensive care unit stay (p = 0.001) were seen in patients with hepatic infarct, as well as trends toward lower post-TIPS portosystemic pressure gradient (p = 0.061) and higher risk of ACLF (p = 0.056). Procedure-related portal vein thrombosis or hepatic artery injury was identified in 12 and 5 patients with infarct, respectively. Patients with infarct had higher postprocedural aspartate aminotransferase (p < 0.001) and alanine aminotransferase (p < 0.001) levels, higher international normalized ratio (p = 0.016), lower platelet count (p = 0.042), and a greater decrease in hemoglobin level (p = 0.003). CONCLUSION: Hepatic infarction most frequently affects the right posterior hepatic segments after TIPS and results in a worse postprocedural course. Procedure-related complications and critically low portosystemic pressure gradient may contribute to TIPS-associated hepatic infarct.

Liver Injury in COVID-19 Patients with Drugs as Causatives: A Systematic Review of 996 DILI Cases Published 2020/2021 Based on RUCAM as Causality Assessment Method.

Patients with coronavirus disease 19 (COVID-19) commonly show abnormalities of liver tests (LTs) of undetermined cause. Considering drugs as tentative culprits, the current systematic review searched for published COVID-19 cases with suspected drug-induced liver injury (DILI) and established diagnosis using the diagnostic algorithm of RUCAM (Roussel Uclaf Causality Assessment Method). Data worldwide on DILI cases assessed by RUCAM in COVID-19 patients were sparse. A total of 6/200 reports with initially suspected 996 DILI cases in COVID-19 patients and using all RUCAM-based DILI cases allowed for a clear description of clinical features of RUCAM-based DILI cases among COVID-19 patients: (1) The updated RUCAM published in 2016 was equally often used as the original RUCAM of 1993, with both identifying DILI and other liver diseases as confounders; (2) RUCAM also worked well in patients treated with up to 18 drugs and provided for most DILI cases a probable or highly probable causality level for drugs; (3) DILI was preferentially caused by antiviral drugs given empirically due to their known therapeutic efficacy in other virus infections; (4) hepatocellular injury was more often reported than cholestatic or mixed injury; (5) maximum LT values were found for alanine aminotransferase (ALT) 1.541 U/L and aspartate aminotransferase (AST) 1.076 U/L; (6) the ALT/AST ratio was variable and ranged from 0.4 to 1.4; (7) the mean or median age of the COVID-19 patients with DILI ranged from 54.3 to 56 years; (8) the ratio of males to females was 1.8-3.4:1; (9) outcome was favorable for most patients, likely due to careful selection of the drugs and quick cessation of drug treatment with emerging DILI, but it was fatal in 19 patients; (10) countries reporting RUCAM-based DILI cases in COVID-19 patients included China, India, Japan, Montenegro, and Spain; (11) robust estimation of the percentage contribution of RUCAM-based DILI for the increased LTs in COVID-19 patients is outside of the current scope. In conclusion, RUCAM-based DILI with its clinical characteristics in COVID-19 patients and its classification as a confounding variable is now well defined, requiring a new correct description of COVID-19 features by removing DILI characteristics as confounders.

Assessment of liver fibrosis using non-invasive screening tools in individuals with diabetes mellitus and metabolic syndrome.

Despite its rising prevalence, and its potential to lead to life threatening complications, there are no recommendations in the current guidelines for screening individuals with diabetes mellitus or high BMI for NAFLD(non-alcoholic fatty liver disease)/NASH (non alcoholic steatohepatitis),mainly due to the uncertain performance and feasibility of currently available screening tools. This research was carried out to assess the diagnostic accuracy of non-invasive screening tools in predicting liver fibrosis in individuals with diabetes mellitus and metabolic syndrome. MATERIAL: 140 patients with diabetes mellitus and metabolic syndrome, identified between March 2020 and October 2021 were studied. Liver stiffness measurement by point shear wave elastography was considered the gold standard. 5 non-invasive scores, AST/ALT (aspartate aminotransferase/alanine aminotransferase) Ratio, Aspartate aminotransferase/platelet ratio (APRI)Score, FIB-4 Index, BARD Score and NAFLD Fibrosis Score were determined in all of the study participants. Using receiver operator characteristic (ROC) curve analysis, sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) were calculated for each of these scores. The area under the ROC curve (AUROC) was used to calculate the diagnostic accuracy of these scores. OBSERVATION: Out of the140 participants in the study, (83 males (59.29%)), 30 (21.43%) had liver fibrosis as per liver stiffness measurement by point shear wave elastography. The mean age and mean BMI were 54.53±12.42 and 27.37±2.73 respectively in the 'Fibrosis' group and 56.20 ±11.76 and 27.10±4.22 in the 'No fibrosis' group. The major finding of our study was that all these scores had relatively high NPV (>85 %) for predicting liver fibrosis in our cohort. The AST/ALT Ratio had the highest negative predictive value (90.28 %) followed by APRI Score (88.94 %). The AUROC (for FIB-4 Score, NAFLD-Fibrosis Score, APRI Score, AST/ALT Ratio, BARD Score were 0.6669, 0.657, 0.655, 0.637 and 0.599 respectively. FIB-4 Index(p = 0.005) had the highest AUROC, followed by NAFLD-Fibrosis Score(p =0.009) .But, all the scores had relatively low specificity(<60 %), PPV(<35 %) and accuracy(<63 %). CONCLUSION: FIB- 4 Index and NAFLD-Fibrosis Score can be used to reliably exclude liver fibrosis in individuals with diabetes mellitus and metabolic syndrome in the Indian population, but may not be useful in accurately diagnosing liver fibrosis. Utilization of these non-invasive and cost-effective screening tools in routine practice, may have promising results in predicting liver fibrosis in 'at risk' populations.

Costs of unnecessary repeated diagnostic tests in cholecystectomy.

The purpose of this study was to calculate the number, rate and cost of unnecessarily repeated tests on the patients who underwent open cholecystectomy and laparoscopic cholecystectomy and figure out the share of the unnecessarily repeated test costs in total test expenditures and total treatment expenditures. Alkaline phosphatase, alanine aminotransferase, aspartate transaminase, gamma glutamyl transferase, Total bilirubin, whole abdominal ultrasonography, upper abdominal ultrasonography, hepatobiliary ultrasonography tests, which were among the tests used in the patients who underwent cholecystectomy. The research group included 1296 patients. All records of the patients within totally 180 days of period including 90 days of pre-cholecystectomy and 90 days of post-cholecystectomy period were analysed. Necessity/Unnecessary criteria of the tests were identified in accordance with literature data, expert opinions and American Society of Anaesthesiologists Physical Status Classification scores. It was determined that unnecessary test costs consisted of 8.48% of the total test costs and 0.93% of the total treatment expenditures. This study showed that age, gender, surgical technique, and American Society of Anesthesiologists scores significantly differentiated unnecessary repeated test costs. Reducing the use of excessive health service and the related health expenditures, working to reveal its financial and medical benefits are crucial for the reimbursement agency, health service hosts and patients.

Assessment of Liver Fibrosis by Transient Elastography in Children and Young Adults With Sickle Cell Disease With and Without Iron Overload.

Transfusion-associated iron overload may cause liver fibrosis. We compared transient elastography (TE) and aspartate aminotransferase-platelet ratio index (APRI), noninvasive markers for hepatic fibrosis, to liver histology in children and young adults with sickle cell disease (SCD) who were iron overloaded (cohort 1). Age-matched subjects with SCD but without iron overload (cohort 2) were enrolled for APRI and TE assessments. Nineteen subjects ages 10 to 21 years were transfused for a mean of 9.67 years, had a mean serum ferritin of 4899±2849 ng/mL, and a liver iron concentration of 15.56±10.12 mg/g dry liver weight by R2-magnetic resonance imaging. Mean APRI was 0.33±0.13 in cohort 1 and 0.27±0.10 in cohort 2. The mean liver stiffness measures (LSM) in cohort 1, assessed by TE, was 8.46±3.95 kPa, ranging from 3.5 to 14.6 kPa (expected normal <7 kPa). Cohort 2 had a mean LSM of 5.72±1.74 kPa (4.6 to 8.7 kPa). There was a good correlation between LSM and histologic fibrosis (t value 6.94, P<0.0001). There was no significant correlation between APRI and histologic fibrosis and between APRI and LSM. A high LSM suggests liver fibrosis in children and adults with SCD with iron overload and may merit histologic confirmation especially if persistent.

Assessment of liver fibrosis by transient elastography and multi-parameters model in young children with chronic hepatitis B virus infection.

OBJECTIVE: This study aimed to compare the diagnostic value of the single or combined applications of transient elastography (TE) and multivariate indicators with biopsy for the detection of liver fibrosis in children caused by chronic hepatitis B (CHB). METHODS: This study included 148 CHB children treated at Hunan Children's Hospital from January 1st 2015 to December 31st 2018, aged from 0.83 to 14.58 years old. All patients underwent liver biopsy (LB), of which 43 patients underwent TE. Multiple clinical data, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), Platelet (PLT), and HBV-deoxyribonucleic acid (HBV DNA) of all patients were collected. The diagnostic values for CHB of TE and its combinations with these indicators were measured. The patients were classified in two ways: no hepatic fibrosis group (F0) versus fibrosis group (F ≥ 1), and no significant hepatic fibrosis group (F < 2) versus significant hepatic fibrosis group (F ≥ 2). The statistical assessment was performed between groups within each classification to compare the diagnostic value of different parameters. RESULTS: The operating characteristic area under curve (AUC) of liver fibrosis diagnosed by liver stiffness measurement (LSM) which obtained by TE, AST-to-PLT ratio index (APRI), and fibrosis-4 index (FIB-4) were 0.740, 0.701, and 0.651, while the corresponding cut-off values were 5.9 kPa, 0.50, and 0.10, respectively. The AUC of significant liver fibrosis diagnosed by LSM, APRI and FIB-4 were 0.849, 0.701, and 0.509, while the corresponding cut-off values were 8.4 kPa, 0.76, and 0.08, respectively. While with the combinations of LSM and APRI, LSM and FIB-4, LSM and APRI and FIB-4, APRI and FIB-4, the AUC of significant liver fibrosis were 0.866, 0.855, 0.869, and 0.684, respectively. The AUC of significant liver fibrosis diagnosed by the LSM was significantly higher than APRI and FIB-4. CONCLUSIONS: The diagnostic value of transient elastography was better than that of APRI and FIB-4 for CHB children with significant liver fibrosis. In addition, TE also has relatively high application values on the diagnosis of patients with different degrees of liver fibrosis caused by CHB.

Assessment of liver fibrosis markers in people with rheumatoid arthritis on methotrexate.

BACKGROUND: Up to 3% of methotrexate (MTX)-treated rheumatoid arthritis (RA) patients might develop liver fibrosis or cirrhosis, requiring effective screening algorithms. AIMS: To assess the utility of non-invasive liver fibrosis assessment in RA patients on MTX. METHODS: Fifty-six patients were recruited from rheumatology outpatient clinics in a public tertiary centre from July 2017 to October 2018. Clinical data was collected. Screening for hepatic fibrosis was performed using transient elastography (TE), aminoaspartate transaminase to platelet ratio index (APRI), Hepascore and Fibrosis-4 index (FIB-4). Those with suspected significant liver fibrosis based on these screening tests were assessed by a hepatologist. RESULTS: Twenty-seven patients were suspected to have liver fibrosis on screening, including 10/56 (18%) by TE, 20/56 (36%) by Hepascore, 2/56 by APRI (4%) and 1/56 by FIB-4 (2%). Of these 27 patients, 11 were reviewed by a hepatologist and one diagnosed with significant liver fibrosis. TE, but not APRI, Hepascore or FIB-4, was found to have 100% sensitivity and 84% specificity (P = 0.029) for hepatologist-diagnosed liver fibrosis. CONCLUSION: Liver fibrosis develops in a minority of MTX-treated RA patients. The present study suggests that TE is a more sensitive screening test than APRI, FIB-4 or Hepascore in the identification of people with RA at risk of hepatic fibrosis.