Fuzzy ontology-based approach for liver fibrosis diagnosis

Objective To analyze the levels of serum thrombin-activatable fibrinolysis inhibitor (TAFI) in patients with chronic hepatitis B (CHB) with different degrees of hepatic fibrosis, and to evaluate the value of TAFI in the evaluation of liver fibrosis. Methods Forty six patients with CHB who underwent liver biopsy from June 2016 to March 2017 in Zhejiang Provincial People’s Hospital were enrolled. According to liver fibrosis stage (S0-4), they were divided into mild liver fibrosis group (S0-1, n=16), significant liver fibrosis group (S2, n=15) and severe liver fibrosis group (S3-4, n=15). At the same time, 16 healthy subjects were randomly selected as health controls in the physical examination center of the hospital. Serum TAFI levels were analyzed in each group, and the receiver operating curve (ROC) was used to evaluate the diagnostic value of TAFI in CHB patients with significant liver fibrosis and severe liver fibrosis (S≥2). The SPSS 23.0 software was used to analyze the data. Results Serum TAFI levels in the mild liver fibrosis group, significant liver fibrosis group, severe liver fibrosis group and health controls were (63.4±18.2), (43.8±20.4), (27.5±19.2) and (71.3±25.6) ng/mL, the difference between the four groups was statistically significant (F=13.512, P 0.05). Conclusion The serum TAFI level is negatively correlated with the degree of liver fibrosis in CHB patients, which has a good diagnostic value for liver fibrosis (S≥2) in patients with CHB. Key words: Hepatitis B, chronic; Liver fibrosis; Thrombin-activatable fibrinolysis inhibitor

Serum markers detect the presence of liver fibrosis: A cohort study

ObjectiveTo investigate the diagnostic efficiency of FibroTouch, FibroScan, and acoustic radiation force impulse (ARFI) for liver fibrosis in patients with primary biliary cholangitis (PBC). MethodsA retrospective analysis was performed for the patients who underwent liver biopsy and were then diagnosed with PBC in Beijing Friendship Hospital, Capital Medical University, from September 2014 to October 2018, and the METAVIR scoring system was used to evaluate the degree of liver fibrosis and inflammation. Within 1 week after liver biopsy, FibroTouch, FibroScan, and ARFI were used to measure liver stiffness (LS); with pathological results as the gold standard, the area under the ROC curve (AUC) was used to compare the value of FibroTouch, FibroScan, and ARFI in the diagnosis of liver fibrosis in PBC patients, and related influencing factors were analyzed; Youden index was used to calculate the cut-off values of LS for different degrees of liver fibrosis. The Kruskal-Wallis H test was used for comparison between multiple groups, and P value corrected by the Bonferroni method was used for further comparison between two groups. A Spearman correlation analysis was performed, and a multiple linear regression model was used for multivariate analysis. ResultsA total of 68 patients with PBC were enrolled in the study, among whom 13 had F0 liver fibrosis, 15 had F1 liver fibrosis, 18 had F2 liver fibrosis, 12 had F3 liver fibrosis, and 10 had F4 liver fibrosis. LS obtained by FibroTouch (FT-LS), LS obtained by FibroScan (FS-LS), and LS obtained by ARFI (ARFI-LS) were strongly positively correlated with the degree of liver fibrosis (r=0.798, 0.782, and 0.742, all P＜0.001). FT-LS had AUCs of 0.922, 0.881, and 0.926, respectively, in the diagnosis of F≥2, F≥3, and F=4 liver fibrosis, and the corresponding cut-off values were 10.5 kPa, 15.8 kPa, and 17.5 kPa, respectively; FS-LS had AUCs of 0.918, 0.878, and 0.939, respectively, in the diagnosis of F≥2, F≥3, and F=4 liver fibrosis, and the corresponding cut-off values were 10.1 kPa, 12.9 kPa, and 18.2 kPa, respectively; ARFI-LS had AUCs of 0.904, 0.869, and 0.928, respectively, in the diagnosis of F≥2, F≥3, and F=4 liver fibrosis, and the corresponding cut-off values were 1.45 m/s, 1.83 m/s, and 2.08 m/s, respectively. There was no significant difference in diagnosing the same stage of liver fibrosis between FibroTouch, FibroScan, and ARFI (P＞0.05). The multivariate analysis showed that degree of liver fibrosis (β=0.399, P＜0.001), total bilirubin (β=0.466, P＜0.001), and prothrombin time activity (β=-0.195, P=0.020) were influencing factors for FT-LS; degree of liver fibrosis (β=0370, P＜0.001), aspartate aminotransferase (β=0.450, P＜0.001), prothrombin time activity (β=-0.303, P=0.001), and alkaline phosphatase (β=-0.187, P=0.042) were influencing factors for FS-LS; degree of liver fibrosis (β=0.489, P＜0.001), aspartate aminotransferase (β=0.467, P＜0.001), and platelet count (β=-0.188, P=0.028) were influencing factors for ARFI-LS. ConclusionFibroTouch has similar efficiency to FibroScan and ARFI in the diagnosis of liver fibrosis in PBC patients, with relatively high diagnostic efficiency for significant liver fibrosis (F≥2) and liver cirrhosis (F=4), and therefore, it can be used as a reliable method for the diagnosis of liver fibrosis in PBC patients.

AIMTo investigate whether serum interleukin (IL)-34 levels are correlated with hepatic inflammation and fibrosis in patients with chronic hepatitis B virus (HBV) infection.METHODSIn this study, serum IL-34 levels were assessed by enzyme-linked immunosorbent assay in 19 healthy controls and 175 patients with chronic HBV infection undergoing biopsy. The frequently used serological markers of liver fibrosis were based on laboratory indexes measured at the Clinical Laboratory of the Second Affiliated Hospital of Anhui Medical University. Liver stiffness was detected by transient elastography with FibroTouch. The relationships of non-invasive makers of liver fibrosis and IL-34 levels with inflammation and fibrosis were analyzed. The diagnostic value of IL-34 and other liver fibrosis makers were evaluated using areas under the receiver operating characteristic curves, sensitivity and specificity.RESULTSSerum IL-34 levels were associated with inflammatory activity in the liver, and IL-34 levels differed among phases of chronic HBV infection (P = 0.001). By comparing serum IL-34 levels among patients with various stages of liver fibrosis determined by liver biopsy, we found that IL-34 levels ≥ 15.83 pg/mL had a high sensitivity of 86.6% and a specificity of 78.7% for identifying severe fibrosis (S3-S4). Furthermore, we showed that IL-34 is superior to the fibrosis-4 score, one of the serum makers of liver fibrosis, in identifying severe liver fibrosis and early cirrhosis in patients with HBV-related liver fibrosis in China.CONCLUSIONOur results indicate that IL-34, a cytokine involved in the induction of activation of profibrogenic macrophages, can be an indicator of liver inflammation and fibrosis in patients with chronic HBV infection.

ObjectiveThe objective of this study was to investigate the association between sarcopenia and liver fibrosis in patients aged 18–59 years with metabolic dysfunction-associated steatotic liver disease (MASLD) and to assess the potential of sarcopenia as a risk factor for the progression of liver fibrosis.MethodsThe study included 821 patients with MASLD in the US cohort and 3,405 patients with MASLD in the Chinese cohort. Liver controlled attenuation parameters (CAP) and liver stiffness measurements (LSM) were assessed by vibration-controlled transient elastography (VCTE) to evaluate the extent of hepatic steatosis and fibrosis. Sarcopenia was assessed by measuring appendicular skeletal muscle mass (ASM) and calculating ASMI. To analyze the relationship between sarcopenia, ASMI, and liver fibrosis, logistic regression models, multivariate-adjusted models, and restricted cubic spline (RCS) models were employed, with stratification and interaction analyses.ResultsThe results demonstrated that patients with sarcopenia exhibited a markedly elevated risk of significant liver fibrosis, advanced liver fibrosis, and cirrhosis compared to those without sarcopenia in both cohorts. After adjusting for confounding variables, sarcopenia was identified as an independent risk factor for the progression of liver fibrosis in patients with MASLD. A significant negative correlation was observed between ASMI and the severity of liver fibrosis, with a progressive reduction in the risk of liver fibrosis associated with increasing ASMI. Additionally, a non-linear feature was evident in some liver fibrosis indicators. Subgroup analysis further corroborated the finding that the harmful effect of sarcopenia on liver fibrosis was consistent across all identified subgroups.ConclusionSarcopenia may be associated with the progression of liver fibrosis in patients with MASLD. Monitoring ASMI may assist in identifying individuals at an elevated risk of liver fibrosis in MASLD patients.

To discuss the clinical value of hepatic and portal vein Doppler ultrasounds in assessing liver inflammation and fibrosis in patients with chronic hepatitis B virus (HBV) infection, and a normal alanine transaminase (ALT) level. 94 patients with chronic HBV infections who had undergone ultrasound-guided liver biopsies were enrolled and grouped by the liver tissue pathological results. Analyzed the differences and correlation between parameters of the hepatic and portal vein Doppler ultrasounds are discussed across different degrees of liver inflammation and fibrosis. There were 27 patients with no significant liver damage and 67 patients with significant liver damage, there were significant differences in the parameters of the hepatic and portal vein Doppler ultrasounds between them (p < 0.05). As liver inflammation was aggravated, the inner diameter of the portal vein increased, and the blood flow velocities of the portal and superior mesenteric veins decreased (p < 0.05). When liver fibrosis became more severe, the inner diameter of the portal vein increased, while the blood flow velocities of the portal, superior mesenteric, and splenic veins decreased, and the Doppler waveforms of hepatic veins became unidirectional or flat (p < 0.05). The receiver operating characteristic (ROC) curve showed the assessment efficacy of hepatic and portal vein Doppler ultrasounds was superior to abdominal Doppler ultrasound alone in assessing liver fibrosis, and the combination of the two examination techniques outperformed any technique used alone. The hepatic and portal vein Doppler ultrasounds have important clinical value for assessing liver fibrosis in patients with chronic HBV infection, to aid improve the diagnosis of liver fibrosis.

Relation of Liver Siderosis to Liver Fibrosis in Hemodialysis Patients With Severe Hyperferritinemia Secondary to High Doses of Intravenous Iron Supplementation

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. The more severe form is non-alcoholic steatohepatitis (NASH) which can progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). NASH is more common in patients with type 2 diabetes mellitus (T2DM). However, its true prevalence in unselected patients with T2DM in the United States remains unknown. In 2019, the American Diabetes Association recommended screening for NASH and liver fibrosis in all patients with T2DM with steatosis and/or elevated ALT. Screening focuses on liver fibrosis as associated with increased risk of cirrhosis and HCC. Still, a liver biopsy remains the gold standard to accurately assess the severity of liver disease. The aim of this study was to determine the prevalence of liver fibrosis in unselected patients with T2DM presenting to primary care or endocrinology clinics at a university hospital in the US. Secondary outcomes were to assess the prevalence of steatosis controlled attenuation parameter (CAP) and performance of vibration-controlled transient elastography (VCTE) as a non-invasive tool to identify patients with significant liver fibrosis. Patients with T2DM between ages of 21-79 and without a history of alcohol intake or other causes secondary causes of NAFLD were recruited for the study. Participants underwent screening for NAFLD at the time of their clinic visit by means of point-of-care CAP and VCTE. Initial evaluation also included obtaining patient demographics, routine chemistries, and fasting samples (on visit #2 if not fasting initially) for metabolic measurements and fibrosis biomarkers. Liver biopsies were offered to patients with a liver stiffness measurement (LSM) ≥8.0 kPa (i.e., highly likely to have moderate-to-severe fibrosis or ≥F2), or those with ≥7 kPa if AST ≥20 and had an APRI and/or FIB-4 score suggestive of being at high-risk of liver fibrosis (i.e., at least mild-to-moderate fibrosis or ≥F1). A total of 469 patients were recruited (age 59±12; 56% females; 60% non-Hispanic whites, 30% African Americans, 4% Asian; BMI 33±6 Kg/m2; A1c 7.5±1.7%; FPG 143±60 mg/dL; AST 22±11 U/L; ALT 24±17 U/L; triglycerides 156±151 mg/dL; LDL-C 88±37 mg/dL; HDL-C 47±13 mg/dL). The prevalence of NAFLD by CAP (≥280) was 67% with a mean CAP of 305±3. The prevalence of any fibrosis was 24% patients. Among those with fibrosis, 15% had moderate-to-severe fibrosis or ≥F2. In those that underwent a liver biopsy, 61% had moderate-to-severe fibrosis (F2-3). Our ongoing study demonstrates the high prevalence of liver steatosis and fibrosis in patients with T2DM. NASH is a common but under-recognized complication of T2DM that requires greater awareness among clinicians taking care of patients with diabetes. While the optimal screening strategy remains unclear, an approach based on plasma biomarkers and CAP/VCTE deserves further exploration moving forward.

Serum Ferritin Levels Lack Diagnostic Accuracy for Liver Fibrosis in Patients With Nonalcoholic Fatty Liver Disease

BackgroundIn beta-thalassemia major (TM) patients, levels of liver iron overload and the presence of chronic hepatitis C are directly correlated with the onset and severity of liver fibrosis. A noninvasive approach that can evaluate cirrhosis and liver fibrosis in these patients is transient elastography (TE). We aimed to find out the role of noninvasive elastography in the assessment of liver fibrosis in young beta-thalassemia major patients receiving frequent blood transfusions. Identifying the patients' risk factors for liver fibrosis is another goal. The study comprised 53 patients, all of whom had a thorough history-taking procedure, clinical examination, and investigations such as CBC, serum ferritin, HCV and HBV serology, and liver function testing. It was carried out transient elastography to find liver fibrosis.ResultsAccording to transient elastography, 52.8% of the patients had severe fibrosis (F2 and higher). 9.4% of people had positive HCV serology results. Significant liver fibrosis was correlated with all serum ferritin levels (708.2 ± 182.1, 3213.5 ± 1272.9, nonsignificant vs. significant fibrosis), HCV infection, age, blood transfusion frequency, and irregular chelation therapy. But no significant correlation regarding sex and BMI was detected.ConclusionTransient elastography is an alternate noninvasive approach that assesses liver fibrosis in beta-thalassemia major patients. The risk of liver fibrosis is related to iron overload, HCV seropositivity, advanced age, frequent blood transfusion, and irregular chelation therapy.

Several studies explored the association between vitamin D status and nonalcoholic fatty liver disease with contradictory results. We aimed to investigate the association between vitamin D status, inflammatory cytokines and liver fibrosis in nonalcoholic fatty liver disease patients. Two hundred nineteen nonalcoholic fatty liver disease patients and 166 age- and gender- matched healthy controls were recruited for this study. Serum 25(OH)D was measured by radioimmunoassay. Serum interleukin-8 and transforming growth factor-β1 were measured using ELISA. Serum 25(OH)D was only marginally decreased in nonalcoholic fatty liver disease patients. Interestingly, serum 25(OH)D was markedly reduced in nonalcoholic fatty liver disease patients with advanced liver fibrosis compared to nonalcoholic fatty liver disease patients with indeterminate liver fibrosis and no advanced fibrosis. Logistic regression analysis showed that there was an inverse association between serum 25(OH)D and severity of liver fibrosis in nonalcoholic fatty liver disease patients. Further analysis showed that serum interleukin-8 was elevated in nonalcoholic fatty liver disease patients, the highest interleukin-8 in patients with advanced fibrosis. An inverse correlation between serum 25(OH)D and interleukin-8 was observed in nonalcoholic fatty liver disease patients with and without liver fibrosis. Although serum transforming growth factor-β1 was slightly elevated in nonalcoholic fatty liver disease patients, serum transforming growth factor-β1 was reduced in nonalcoholic fatty liver disease patients with advanced fibrosis. Unexpectedly, a positive correlation between serum 25(OH)D and transforming growth factor-β1 was observed in nonalcoholic fatty liver disease patients with advanced fibrosis. In conclusion, low vitamin D status is associated with advanced liver fibrosis in nonalcoholic fatty liver disease patients. Interleukin-8 may be an important mediator for hepatic fibrosis in nonalcoholic fatty liver disease patients with low vitamin D status.

APRI and Forns (IF) index are noninvasive models consisting of routine laboratory data for the prediction of liver fibrosis in patients with chronic hepatitis C. The aim of our study was to confirm the value of these models to predict significant fibrosis in these patients and if they may decrease the need for performing liver biopsy specimens in coinfected and HIVnon-coinfected. We included 60 patients with chronic hepatitis C and histologic data, 33 were coinfected with HIV. Mild fibrosis (F0-F1) was found in 73% patients, severe fibrosis (F3-F4) in 23% and cirrhosis in 18.3%. We calculated and compared APRI and IF with the stage of liver fibrosis. The APRI score < 0.5 or > 1.5 and IF < 4.2 or > 6.9, as predictors of mild or severe fibrosis, were only available in 53% and 49%. Neither laboratory nor APRI and IF were associated with liver fibrosis in non-coinfected patients. We only found association in HIV coinfected patients: severe fibrosis (F3-4) whit higher gammaglobulins [24.5% vs. 30% (p < 0.05)] and Gamma-GT levels [77 (46.5) vs. 32 (48.5) (p < 0.05)], and lower prothrombin time [72% vs. 91% (p < 0.05) ] and platelets.109 count [129 (40) vs. 170 (78) (p < 0.05)]; APRI was lower than 0.5 in 41.6% patients with mild fibrosis (F0-1) against none with severe (F3-4) (p < 0.05); specifity (E) of APRI < 0.5 for predicting mild fibrosis was 100%, but sensivity (S) was very low (41%), with a positive preditive value (VPP) of 100%, but a negative predictive value (VPN) also very low ( 36.3%). Our study showed that these models don t avoid the need for liver biopsies. More than a half of patients are not appropriately classified according to findings on liver biopsy and S and VPN are very low. The combination of these index with gammaglobulins, Gamma-GT, AST, ALT and platelet levels and protrombine time, only may be an approach to degree of fibrosis or inflammation liver in HIV co-infected patients.

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide, with liver fibrosis (LF) being a crucial pathological feature in the progression of NAFLD. Insulin resistance (IR) is believed to play an important role in the pathogenesis of NAFLD and the development of LF. This study aims to explore the relationship between various IR indicators and LF in patients with NAFLD. This study utilized data from the National Health and Nutrition Examination Survey 2017-2020 cycles. Liver steatosis and fibrosis were assessed using liver ultrasound transient elastography. To assess the association between multiple IR indicators and LF, the study methodology included univariate and multivariate logistic regression, as well as restricted cubic spline (RCS) analysis. Subsequently, we used multivariate logistic regression to develop and validate a predictive model for LF, and evaluated the model's performance using the area under the curve (AUC) and calibration curve. A total of 904 patients were included in the final analysis. Among these NAFLD patients, 153 (16.92%) had LF. Compared to non-LF patients, LF patients had significantly higher body mass index (BMI), waist circumference (WC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), HbA1c, and fasting blood glucose (FBG) levels (all p < 0.05). Analysis of IR indicators showed that LF patients had significantly higher levels of TyG, TyG-WHtR, TyG-BMI, TyG-WC, TyG-GGT, METS-IR, and HOMA-IR (all p < 0.05). After adjusting for covariates, TyG-WHtR remained an independent risk factor (OR=2.69; 95% CI: 2.08-3.47), indicating a strong correlation with LF. The developed nomogram, incorporating AST, TyG, TyG-BMI, and diabetes, showed an AUC of 0.809 (95% CI: 0.771-0.847), indicating good predictive performance for LF in NAFLD patients. This study confirms that a significant association between various IR and LF in NAFLD patients, and the developed nomogram provides a practical tool for early risk assessment. These findings underscore the clinical value of incorporating IR indices into routine practice to identify high-risk patients, enabling timely interventions to prevent fibrosis progression and improve outcomes.

Prevalence and determinants of nonalcoholic fatty liver disease and liver fibrosis in patients with psoriasis vulgaris: A retrospective study

Objective To explore the diagnostic values of FibroTouch and FibroScan for liver fibrosis in patients with chronic hepatitis B(CHB). Methods This study enrolled patients with CHB who was accepted liver biopsy at Beijing Friendship Hospital, Capital Medical University between March 2014 to December 2017. FibroTouch and FibroScan were performed among these patients at same time. Liver stiffness measurement(LSM), optimal cut-off value, receiver operating characteristic(ROC) were compared. Results In our 103 patients, there were no significantly different between FibroTouch and FibroScan in LSM. The threshold of the optimal cut-off value for FibroTouch and FibroScan were 5.45 versus 5.55 kPa (≥S1), 7.10 versus 6.65 kPa (≥S2), 11.05 versus 9.20 kPa (≥S3), 15.50 versus 15.45 kPa (S4), respectively. The area under the ROC curve for the prediction of the stage1, stage2, stage2, stage 4 of liver fibrosis in these patients were 0.858 versus 0.765 (P=0.54), 0.812 versus 0.801 (P=0.68), 0.863 versus 0.878 (P=0.45), and 1.0 versus 0.99 (P=0.38) respectively. Conclusions FibroTouch and FibmScan have a good consistency in the evaluation of the degree of liver fibrosis in patients with CHB. Key words: Chronic hepatitis B; Fibrosis; FibroTouch; FibroScan